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Velpanex

Sofosbuvir + Velpatasvir

Tablet 400 mg+100 mg Allopathic Hepatic viral infections (Hepatitis C)

Indications

Chronic hepatitis C

Indication detailsView

Sofosbuvir and Velpatasvir combination is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection-

Without cirrhosis or with compensated cirrhosis
With decompensated cirrhosis for use in combination with ribavirin

Therapeutic classView

Hepatic viral infections (Hepatitis C)

PharmacologyView

It is a fixed-dose combination tablet containing sofosbuvir and velpatasvir for oral administration. Sofosbuvir is a nucleotide analog HCV NS5B polymerase inhibitor and velpatasvir is an NS5A inhibitor.

DosageView

The recommended dosage is one tablet (400 mg of Sofosbuvir and 100 mg of Velpatasvir) taken orally once daily. Recommended treatment regimen:

Patients without cirrhosis and patients with compensated cirrhosis (Child-Pugh A): one tablet once daily for 12 weeks
Patients with decompensated cirrhosis (Child-Pugh B or C): one tablet once daily and Ribavirin for 12 weeks. The recommended dosage of Ribavirin is based on bodyweight (1000 mg/day for patients < 75 kg and 1200 mg/day for ≥ 75 kg, in two divided dose/day)

Side effectsView

The most common side effects of Sofosbuvir and Velpatasvir combination include headache and tiredness. Treatment may result in slowing of the heart rate along with other symptoms when taken with amiodarone (a medicine used to treat certain heart problems).

ContraindicationsView

Sofosbuvir, Velpatasvir and Ribavirin combination regimen is contraindicated in patients for whom Ribavirin is contraindicated.

PrecautionsView

Serious symptomatic bradycardia may occur in patients taking amiodarone, particularly in patients also receiving beta blockers, or those with underlying cardiac comorbidities and/or advanced liver disease. Coadministration of amiodarone with Sofosbuvir and Velpatasvir combination is not recommended. In patients without alternative viable treatment options, cardiac monitoring is recommended.

InteractionsView

Drugs may decrease the concentrations of sofosbuvir and/or velpatasvir: Antacids, H2-receptor antagonists, Proton-pump inhibitors etc.

Coadministration is not recommended with: topotecan, Carbamazepine, Phenytoin, Phenobarbital, Oxcarbazepine, Rifabutin, Rifampin, Rifapentine, efavirenz, Tipranavir, Ritonavir, Hypericum perforatum.

Coadministration of Sofosbuvir and Velpatasvir combination, with Rosuvastatin, Atorvastatin may significantly increase the concentration of Rosuvastatin, Atorvastatin.

Pregnancy & lactationView

No adequate human data are available to establish whether or not Sofosbuvir and Velpatasvir combination poses a risk to pregnancy outcomes. If Sofosbuvir and Velpatasvir combination administered with Ribavirin, the combination regimen is contraindicated in pregnant women and in men whose female partner is pregnant or going to be pregnant in next six months.

Pediatric usageView

Renal impairment patient: No dosage recommendation can be given for patients with severe renal impairment (eGFR ≤30 mL/min/1.73 m²) or with ESRD, due to higher exposures of the predominant sofosbuvir metabolite.

Overdose effectsView

If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose includes monitoring of vital signs as well as observation of the clinical status of the patient.

StorageView

Store in a cool and dry place (preferably below 30° C). Keep out of reach of children.

Velvin

Vinblastine Sulfate

Injection 10 mg/10 ml Allopathic Cytotoxic Chemotherapy

Indications

Testicular cancer

Indication detailsView

Vinblastine is effective as a single agent, but its therapeutic effect is enhanced when used in combination with other antineoplastic drugs. Vinblastine has been used in the treatment of Hodgkin’s disease (Stages III and IV) in combination therapy (with adriamycin (doxorubicin), bleomycin and dacarbazine as ABVD) and in the treatment of advanced testicular carcinoma (with cisplatin and bleomycin). Vinblastine has been used in the palliative treatment of lymphocytic lymphoma, histiocytic lymphoma, advanced stages of mycosis fungoides, Kaposi's sarcoma and Histiocytosis X.

Vinblastine may be used in the treatment of choriocarcinoma resistant to other chemotherapeutic agents; carcinoma of the breast, unresponsive to appropriate endocrine surgery and hormonal therapy. One of the most effective single agents for treatment of Hodgkin’s disease is vinblastine. A protocol substituting cyclophosphamide for nitrogen mustard and vinblastine for vincristine in MOPP is an alternative therapy for previously untreated patients with advanced Hodgkin’s disease. Patients suffering relapse have also responded to combination therapy that included vinblastine. Advanced testicular germ-cell cancers are sensitive to vinblastine alone but the administration of vinblastine concomitantly with other antineoplastic agents, produces better clinical results. Bleomycin effectiveness is enhanced when vinblastine is administered 6 to 8 hours prior to bleomycin administration; this schedule permits more cells to be arrested during metaphase, in which bleomycin is active.

Therapeutic classView

Cytotoxic Chemotherapy

PharmacologyView

Vinblastine is M phase specific. It binds to microtubular proteins and arrests mitosis at the metaphase by disrupting mitotic spindle formation. It blocks glutamic acid utilization, thus inhibiting purine synthesis, the citric acid cycle, and the formation of urea. It may also interfere with nucleic acid and protein synthesis.

DosageView

Adult (Intravenous): Initially, 3.7 mg/m², increase dose wkly based on WBC counts in increments of about 1.8 mg/m² until leukocyte count decreases to about 3000/mm³, or max wkly dose of 18.5 mg/m² reached. Do not increase dose if leukocyte count is reduced to approximately 3000 cells/mm³; administer the max dose that does not cause leucopenia for maintenance. Do not increase subsequent doses if onolytic activity occurs before leucopenic effect. Usual dose: 5.5-7.4 mg/m² per wk. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm³.

Child (Intravenous): Initial 2.5 mg/m² of BSA, increased dose at wkly intervals in increments of about 1.25 mg/m² until leukocyte count decreases to about 3000/ mm³, or max wkly dose of 12.5 mg/m² reached. Do not increase dose once leukocyte count reaches approximately 3000 cells/mm³, instead, a dose of 1 increment smaller to be admin at wkly intervals for maintenance i.e. patient receives the max dose that does not cause leucopenia. If onolytic activity is encountered before leucopenic effect, then there is no need to increase subsequent doses. Do not admin next dose, even though 7 days have lapsed unless the leukocyte count has returned to at least 4000/mm³. Duration of maintenance therapy depends on disease state and the antineoplastic agent combination.

Side effectsView

Alopecia, constipation, malaise, stomatitis, dose-limiting bone marrow suppression (e.g. granulocytopenia, thrombocytopenia, anaemia), hypertension, central and peripheral neurotoxicity, 8th cranial nerve damage resulting in vestibular and auditory toxicity, ischaemic cardiac toxicity, breathlessness, bone, tumour or jaw pain. Nausea, vomiting, GI bleed, syndrome of inappropriate antidiuretic hormone. Necrosis, cellulitis if extravasation occurs.

ContraindicationsView

Severe bone marrow suppression; presence of bacterial infection; maglignant cell infiltration of bone marrow; Inj into extremity with poor circulation; porphyria; granulocytopenia. Elderly with cachexia or extreme skin ulcerations. Pregnancy; lactation. Intrathecal use may result in death.

PrecautionsView

Hepatic impairment; neurotoxicity; ischemic heart disease; preexisting pulmonary dysfunction; extravasation may cause tissue damage and pain. Discontinue immediately if extravasation occurs, with local Inj of hyaluronidase and local heat application to decrease discomfort and risk of cellulitis; remaining Inj to be injected into another vein. Routine prophylaxis against constipation recommended especially in high doses. Nadir in leukocyte count occur 4-10 days after vinblastine admin; recovery observed 7-14 days after treatment.

InteractionsView

Possible increase in vinblastine levels with aprepitant. Reduced vinblastine metabolism with miconazole. Variable interactions with phenytoin, monitor serum phenytoin levels. Reduced immune response with vaccines. Additive myelotoxicity with zidovudine. Concurrent admin of vinblastine with CYP3A inhibitors may cause an earlier onset and/or an increased severity of side effects.

Pregnancy & lactationView

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Pediatric usageView

Hepatic Impairment: Serum bilirubin >3 mg/100ml: Reduce dose by 50%.

Overdose effectsView

Symptoms: Severe bone marrow suppression and extensions of its usual side effects.

Management: Treatment is supportive. Restrict fluid and use of loop diuretics to counteract the effects of syndrome of inappropriate secretion of antidiuretic hormone. Monitor the patient's CV system and daily blood counts for transfusion requirement.

StorageView

Store at 2-8° C.

Vencur

Vecuronium Bromide

IV Injection 10 mg/vial Allopathic Non depolarizing muscle relaxants

Indications

Skeletal muscle relaxation

Indication detailsView

Vecuronium Bromide is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery.

Therapeutic classView

Non depolarizing muscle relaxants

PharmacologyView

Vecuronium bromide is a non-depolarising neuromuscular blocking agent. It blocks the transmission process between the motor nerve-ending and striated muscle by binding competitively with acetylcholine to the nicotinic receptors located in the motor end-plate region of striated muscle.

Unlike depolarising neuromuscular blocking agents, such as suxamethonium, Vecuronium bromide does not cause muscle fasciculations.

Within the clinical dosage range, Vecuronium bromide exerts neither vagolytic nor ganglion blocking activity.

DosageView

Like other neuromuscular blocking agents, Vecuronium should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these agents.

Like with other neuromuscular blocking agents, the dosage of Vecuronium should be individualised in each patient. The anaesthetic method used, the expected duration of surgery, the possible interaction with other medicines that are administered before or during anaesthesia and the condition of the patient should be taken into account when determining the dose. The use of an appropriate neuromuscular monitoring technique is recommended to monitor neuromuscular block and recovery.

Inhalational anaesthetics do potentiate the neuromuscular blocking effects of Vecuronium. This potentiation however, becomes clinically relevant in the course of anaesthesia, when the volatile agents have reached the tissue concentrations required for this interaction. Consequently, adjustments with Vecuronium should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Vecuronium during long lasting procedures (longer than 1 hour) under inhalational anaesthesia.

In adult patients the following dosage recommendations may serve as a general guideline for tracheal intubation and muscle relaxation for short to long lasting surgical procedures.

Tracheal intubation: The standard intubating dose during routine anaesthesia is 0.08 to 0.1 mg vecuronium bromide per kg body weight, after which adequate intubation conditions are established within 90 to 120 seconds in nearly all patients.

Dosages of Vecuronium for surgical procedures after intubation with suxamethonium:

Recommended doses:

0.03 to 0.05 mg vecuronium bromide per kg body weight.
If suxamethonium is used for intubation, the administration of Vecuronium should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.

Maintenance dosing:

The recommended maintenance dose is 0.02 to 0.03 mg vecuronium bromide per kg body weight. These maintenance doses should best be given when twitch height has recovered to 25% of control twitch height.
Dose requirements for administration of Vecuronium by continuous infusion.
If Vecuronium is administered by continuous infusion, it is recommended to give a loading dose first (see 'Tracheal intubation') and, when neuromuscular block starts to recover, to start administration of Vecuronium by infusion. The infusion rate should be adjusted to maintain twitch response at 10% of control twitch height or to maintain 1 to 2 responses to train of four stimulation. In adults, the infusion rate required to maintain neuromuscular block at this level, ranges from 0.8 to 1.4 µg vecuronium bromide/kg/min. For neonates and infants, see below. Repeat monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used.

Dosing in elderly patients:

The same intubation and maintenance doses as for younger adults (0.08-0.1 mg/kg and 0.02-0.03 mg/kg, respectively) can be used. However, the duration of action is prolonged in elderly compared to younger subjects due to changes in pharmacokinetic mechanisms. The onset time in elderly is similar to younger adults.
In caesarean section and neonatal surgery the dose should not exceed 0.1 mg/kg.

Dosing in paediatric patients:

Because of the possible variation of the sensitivity of the neuromuscular junction, especially in neonates (up to 4 weeks) and probably in infants up to 4 months of age, an initial test dose of 0.01 to 0.02 mg vecuronium bromide per kg body weight followed by incremental doses until 90 to 95% depression of twitch response is achieved is recommended. In neonatal surgery the dose should not exceed 0.1 mg/kg. Dose requirements in neonates and infants (1-12 months) are the same as in adults. However, since the onset time of Vecuronium in these patients is considerably shorter than in adults and children, the use of high intubating doses in general is not required for early development of good intubating conditions.
Since the duration of action and recovery time with Vecuronium is longer in neonates and infants than in children and adults, maintenance doses are required less frequently.

Dose requirements in children (2-10 years) are higher. However, the same intubation and maintenance doses as for adults (0.08-0.1 mg/kg and 0.02-0.03 mg/kg, respectively) are usually sufficient. Since the duration of action is shorter in children, maintenance doses are required more frequently.

Although there is very little information on dosage in adolescents, it is advised to use the same dose as in adults, based on the physiological development at this age.
Dosing in overweight and obese patients
When used in overweight or obese patients (defined as patients with a body weight of 30% or more above ideal body weight) doses should be reduced taking into account an ideal body weight.

Higher doses: Should there be reason for selection of larger doses in individual patients; initial doses ranging from 0.15 mg up to 0.30 mg vecuronium bromide per kg body weight have been administered during surgery both under halothane and neurolept anaesthesia without adverse cardiovascular effects being noted as long as ventilation is properly maintained. The use of these high dosages of Vecuronium pharmacodynamically decreases the onset time and increases the duration of action.

AdministrationView

Vecuronium should be administered following reconstitution. Vecuronium is administered intravenously either as a bolus injection or as a continuous infusion

Side effectsView

Side effects are rare (<1/1000). The most commonly occurring side effects include changes in vital signs and prolonged neuromuscular block. The most frequently reported side effects during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms (reporting frequency <1/100,000).

PrecautionsView

Since Vecuronium causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this medicine until adequate spontaneous respiration is restored.

As with other neuromuscular blocking agents, residual curarization has been reported for Vecuronium. In order to prevent complications resulting from residual curarization, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual curarization after extubation in the post-operative phase (such as medicine interactions or patient condition) should also be considered. If not used as part of standard clinical practice, the use of a reversal agent should be considered, especially in those cases where residual curarization is more likely to occur.
Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. Particularly in the case of previous anaphylactic reactions to muscle relaxants, special precautions should be taken since allergic cross-reactivity to muscle relaxants has been reported.

Since Vecuronium has no cardiovascular effects within the clinical dosage range, it does not attenuate bradycardia that may occur due to the use of some types of anaesthetics and opiates or due to vagal reflexes during surgery. Therefore, reassessment of the use and/or dosage of vagolytic medicines such as atropine for premedication or at induction of anaesthesia, may be of value for surgical procedures during which vagal reactions are more likely to occur (e.g. surgical procedures where anaesthetic medicines with known vagal stimulatory effects are used, ophthalmic, abdominal or anorectal surgery, etc).

In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of muscle relaxants. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques. Myopathy after long term administration of non-depolarizing neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported frequently. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.

InteractionsView

The following agents have been shown to influence the magnitude and/or duration of action of non-depolarizing neuromuscular blocking agents:

Effect of Other Agents on Vecuronium:

Increased Effect:

Halogenated volatile anaesthetics potentiate the neuromuscular block of Vecuronium. The effect only becomes apparent with maintenance dosing (see also Dosage and Administration). Reversal of the block with anticholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium
Long-term concomitant use of corticosteroids and Vecuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy.

Other medicines:

antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylaminopenicillin antibiotics,
diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts, cimetidine, lidocaine and acute administration of phenytoin or β-blocking agents
Recurarization has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine and magnesium salts

Decreased Effect (possible higher dose requirements):

prior chronic administration of phenytoin or carbamazepine
Variable Effect
Administration of other non-depolarizing neuromuscular blocking agents in combination with Vecuronium may produce attenuation or potentiation of the neuromuscular block, depending on the order of administration and the neuromuscular blocking agent used.
Suxamethonium given after the administration of Vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of Vecuronium.

Effect of Vecuronium on other agents:

Effect of Vecuronium on lidocaine: Vecuronium combined with lidocaine may result in a quicker onset of action of lidocaine.

Pregnancy & lactationView

There are insufficient data on the use of Vecuronium during animal or human pregnancy to assess potential harm to the foetus. Vecuronium should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.

Caesarean section: Studies with Vecuronium, administered in doses up to 0.1mg/kg, have shown its safety for use in caesarean section. In caesarean section the dose should not exceed 0.1mg/kg. In several clinical studies Vecuronium did not affect Apgar score, foetal muscle tonus or cardiorespiratory adaptation. From umbilical cord blood sampling it is apparent that only very little placental transfer of Vecuronium occurs which did not lead to the observation of any clinical adverse effect in the newborn.

Reversal of a Vecuronium induced neuromuscular block may be inhibited or unsatisfactory in patients receiving magnesium sulphate for toxaemia of pregnancy because magnesium salts enhance neuromuscular block.Therefore, in patients receiving magnesium sulphate, the dosage of Vecuronium should be reduced and be carefully titrated to twitch response.

Lactation: There are no human data on the use of Vecuronium during lactation. Vecuronium should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

Overdose effectsView

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. Upon start of spontaneous recovery an acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) should be administered in adequate doses.
When administration of an acetylcholinesterase-inhibiting agent fails to reverse the neuromuscular effects of Vecuronium, ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.

ReconstitutionView

Addition of 5 mL water for injections results in an isotonic solution of pH 4 containing 2 mg vecuronium bromide per ml. (2 mg/ml)

Alternatively, in order to obtain a solution with a lower concentration, Vecuronium 10 mg may be reconstituted with a volume up to 10 ml respectively of the following infusion fluids:

5% glucose injection fluid
0.9% sodium chloride injection fluid
Lactated Ringer's solution
Lactated Ringer's injection and 5% glucose
Glucose 5% and 0.9% sodium chloride injection

StorageView

Store between 20-25° C. Protect from light.

Vencuron

Vecuronium Bromide

IV Injection 10 mg/vial Allopathic Non depolarizing muscle relaxants

Indications

Skeletal muscle relaxation

Indication detailsView

Vecuronium Bromide is indicated as an adjunct to general anaesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery.

Therapeutic classView

Non depolarizing muscle relaxants

PharmacologyView

Vecuronium bromide is a non-depolarising neuromuscular blocking agent. It blocks the transmission process between the motor nerve-ending and striated muscle by binding competitively with acetylcholine to the nicotinic receptors located in the motor end-plate region of striated muscle.

Unlike depolarising neuromuscular blocking agents, such as suxamethonium, Vecuronium bromide does not cause muscle fasciculations.

Within the clinical dosage range, Vecuronium bromide exerts neither vagolytic nor ganglion blocking activity.

DosageView

Like other neuromuscular blocking agents, Vecuronium should only be administered by, or under supervision of, experienced clinicians who are familiar with the action and use of these agents.

Like with other neuromuscular blocking agents, the dosage of Vecuronium should be individualised in each patient. The anaesthetic method used, the expected duration of surgery, the possible interaction with other medicines that are administered before or during anaesthesia and the condition of the patient should be taken into account when determining the dose. The use of an appropriate neuromuscular monitoring technique is recommended to monitor neuromuscular block and recovery.

Inhalational anaesthetics do potentiate the neuromuscular blocking effects of Vecuronium. This potentiation however, becomes clinically relevant in the course of anaesthesia, when the volatile agents have reached the tissue concentrations required for this interaction. Consequently, adjustments with Vecuronium should be made by administering smaller maintenance doses at less frequent intervals or by using lower infusion rates of Vecuronium during long lasting procedures (longer than 1 hour) under inhalational anaesthesia.

In adult patients the following dosage recommendations may serve as a general guideline for tracheal intubation and muscle relaxation for short to long lasting surgical procedures.

Tracheal intubation: The standard intubating dose during routine anaesthesia is 0.08 to 0.1 mg vecuronium bromide per kg body weight, after which adequate intubation conditions are established within 90 to 120 seconds in nearly all patients.

Dosages of Vecuronium for surgical procedures after intubation with suxamethonium:

Recommended doses:

0.03 to 0.05 mg vecuronium bromide per kg body weight.
If suxamethonium is used for intubation, the administration of Vecuronium should be delayed until the patient has clinically recovered from the neuromuscular block induced by suxamethonium.

Maintenance dosing:

The recommended maintenance dose is 0.02 to 0.03 mg vecuronium bromide per kg body weight. These maintenance doses should best be given when twitch height has recovered to 25% of control twitch height.
Dose requirements for administration of Vecuronium by continuous infusion.
If Vecuronium is administered by continuous infusion, it is recommended to give a loading dose first (see 'Tracheal intubation') and, when neuromuscular block starts to recover, to start administration of Vecuronium by infusion. The infusion rate should be adjusted to maintain twitch response at 10% of control twitch height or to maintain 1 to 2 responses to train of four stimulation. In adults, the infusion rate required to maintain neuromuscular block at this level, ranges from 0.8 to 1.4 µg vecuronium bromide/kg/min. For neonates and infants, see below. Repeat monitoring of neuromuscular block is recommended since infusion rate requirements vary from patient to patient and with the anaesthetic method used.

Dosing in elderly patients:

The same intubation and maintenance doses as for younger adults (0.08-0.1 mg/kg and 0.02-0.03 mg/kg, respectively) can be used. However, the duration of action is prolonged in elderly compared to younger subjects due to changes in pharmacokinetic mechanisms. The onset time in elderly is similar to younger adults.
In caesarean section and neonatal surgery the dose should not exceed 0.1 mg/kg.

Dosing in paediatric patients:

Because of the possible variation of the sensitivity of the neuromuscular junction, especially in neonates (up to 4 weeks) and probably in infants up to 4 months of age, an initial test dose of 0.01 to 0.02 mg vecuronium bromide per kg body weight followed by incremental doses until 90 to 95% depression of twitch response is achieved is recommended. In neonatal surgery the dose should not exceed 0.1 mg/kg. Dose requirements in neonates and infants (1-12 months) are the same as in adults. However, since the onset time of Vecuronium in these patients is considerably shorter than in adults and children, the use of high intubating doses in general is not required for early development of good intubating conditions.
Since the duration of action and recovery time with Vecuronium is longer in neonates and infants than in children and adults, maintenance doses are required less frequently.

Dose requirements in children (2-10 years) are higher. However, the same intubation and maintenance doses as for adults (0.08-0.1 mg/kg and 0.02-0.03 mg/kg, respectively) are usually sufficient. Since the duration of action is shorter in children, maintenance doses are required more frequently.

Although there is very little information on dosage in adolescents, it is advised to use the same dose as in adults, based on the physiological development at this age.
Dosing in overweight and obese patients
When used in overweight or obese patients (defined as patients with a body weight of 30% or more above ideal body weight) doses should be reduced taking into account an ideal body weight.

Higher doses: Should there be reason for selection of larger doses in individual patients; initial doses ranging from 0.15 mg up to 0.30 mg vecuronium bromide per kg body weight have been administered during surgery both under halothane and neurolept anaesthesia without adverse cardiovascular effects being noted as long as ventilation is properly maintained. The use of these high dosages of Vecuronium pharmacodynamically decreases the onset time and increases the duration of action.

AdministrationView

Vecuronium should be administered following reconstitution. Vecuronium is administered intravenously either as a bolus injection or as a continuous infusion

Side effectsView

Side effects are rare (<1/1000). The most commonly occurring side effects include changes in vital signs and prolonged neuromuscular block. The most frequently reported side effects during post-marketing surveillance is 'anaphylactic and anaphylactoid reactions' and associated symptoms (reporting frequency <1/100,000).

PrecautionsView

Since Vecuronium causes paralysis of the respiratory muscles, ventilatory support is mandatory for patients treated with this medicine until adequate spontaneous respiration is restored.

As with other neuromuscular blocking agents, residual curarization has been reported for Vecuronium. In order to prevent complications resulting from residual curarization, it is recommended to extubate only after the patient has recovered sufficiently from neuromuscular block. Other factors which could cause residual curarization after extubation in the post-operative phase (such as medicine interactions or patient condition) should also be considered. If not used as part of standard clinical practice, the use of a reversal agent should be considered, especially in those cases where residual curarization is more likely to occur.
Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. Particularly in the case of previous anaphylactic reactions to muscle relaxants, special precautions should be taken since allergic cross-reactivity to muscle relaxants has been reported.

Since Vecuronium has no cardiovascular effects within the clinical dosage range, it does not attenuate bradycardia that may occur due to the use of some types of anaesthetics and opiates or due to vagal reflexes during surgery. Therefore, reassessment of the use and/or dosage of vagolytic medicines such as atropine for premedication or at induction of anaesthesia, may be of value for surgical procedures during which vagal reactions are more likely to occur (e.g. surgical procedures where anaesthetic medicines with known vagal stimulatory effects are used, ophthalmic, abdominal or anorectal surgery, etc).

In general, following long term use of neuromuscular blocking agents in the ICU, prolonged paralysis and/or skeletal muscle weakness has been noted. In order to help preclude possible prolongation of neuromuscular block and/or overdosage it is strongly recommended that neuromuscular transmission is monitored throughout the use of muscle relaxants. In addition, patients should receive adequate analgesia and sedation. Furthermore, muscle relaxants should be titrated to effect in the individual patients by or under supervision of experienced clinicians who are familiar with their actions and with appropriate neuromuscular monitoring techniques. Myopathy after long term administration of non-depolarizing neuromuscular blocking agents in the ICU in combination with corticosteroid therapy has been reported frequently. Therefore, for patients receiving both neuromuscular blocking agents and corticosteroids, the period of use of the neuromuscular blocking agent should be limited as much as possible.

InteractionsView

The following agents have been shown to influence the magnitude and/or duration of action of non-depolarizing neuromuscular blocking agents:

Effect of Other Agents on Vecuronium:

Increased Effect:

Halogenated volatile anaesthetics potentiate the neuromuscular block of Vecuronium. The effect only becomes apparent with maintenance dosing (see also Dosage and Administration). Reversal of the block with anticholinesterase inhibitors could also be inhibited.
After intubation with suxamethonium
Long-term concomitant use of corticosteroids and Vecuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy.

Other medicines:

antibiotics: aminoglycoside, lincosamide and polypeptide antibiotics, acylaminopenicillin antibiotics,
diuretics, quinidine, magnesium salts, calcium channel blocking agents, lithium salts, cimetidine, lidocaine and acute administration of phenytoin or β-blocking agents
Recurarization has been reported after post-operative administration of: aminoglycoside, lincosamide, polypeptide and acylamino-penicillin antibiotics, quinidine and magnesium salts

Decreased Effect (possible higher dose requirements):

prior chronic administration of phenytoin or carbamazepine
Variable Effect
Administration of other non-depolarizing neuromuscular blocking agents in combination with Vecuronium may produce attenuation or potentiation of the neuromuscular block, depending on the order of administration and the neuromuscular blocking agent used.
Suxamethonium given after the administration of Vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of Vecuronium.

Effect of Vecuronium on other agents:

Effect of Vecuronium on lidocaine: Vecuronium combined with lidocaine may result in a quicker onset of action of lidocaine.

Pregnancy & lactationView

There are insufficient data on the use of Vecuronium during animal or human pregnancy to assess potential harm to the foetus. Vecuronium should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.

Caesarean section: Studies with Vecuronium, administered in doses up to 0.1mg/kg, have shown its safety for use in caesarean section. In caesarean section the dose should not exceed 0.1mg/kg. In several clinical studies Vecuronium did not affect Apgar score, foetal muscle tonus or cardiorespiratory adaptation. From umbilical cord blood sampling it is apparent that only very little placental transfer of Vecuronium occurs which did not lead to the observation of any clinical adverse effect in the newborn.

Reversal of a Vecuronium induced neuromuscular block may be inhibited or unsatisfactory in patients receiving magnesium sulphate for toxaemia of pregnancy because magnesium salts enhance neuromuscular block.Therefore, in patients receiving magnesium sulphate, the dosage of Vecuronium should be reduced and be carefully titrated to twitch response.

Lactation: There are no human data on the use of Vecuronium during lactation. Vecuronium should be given to lactating women only when the attending physician decides that the benefits outweigh the risks.

Overdose effectsView

In the event of overdosage and prolonged neuromuscular block, the patient should continue to receive ventilatory support and sedation. Upon start of spontaneous recovery an acetylcholinesterase inhibitor (e.g. neostigmine, edrophonium, pyridostigmine) should be administered in adequate doses.
When administration of an acetylcholinesterase-inhibiting agent fails to reverse the neuromuscular effects of Vecuronium, ventilation must be continued until spontaneous breathing is restored. Repeated dosage of an acetylcholinesterase inhibitor can be dangerous.

ReconstitutionView

Addition of 5 mL water for injections results in an isotonic solution of pH 4 containing 2 mg vecuronium bromide per ml. (2 mg/ml)

Alternatively, in order to obtain a solution with a lower concentration, Vecuronium 10 mg may be reconstituted with a volume up to 10 ml respectively of the following infusion fluids:

5% glucose injection fluid
0.9% sodium chloride injection fluid
Lactated Ringer's solution
Lactated Ringer's injection and 5% glucose
Glucose 5% and 0.9% sodium chloride injection

StorageView

Store between 20-25° C. Protect from light.

Venesa

Dienogest

Tablet 2 mg Allopathic Female Sex hormones

Indications

Endometriosis

Indication detailsView

Dienoaest is indicated for the treatment of endometriosis. This is the preparation of Dienogest which belongs to the class of medications called progestins. Progestins reduce the effects of estrogen on tissues such as the endometrium (lining of the uterus) and the breast. By reducing the growth effect of estrogen on the endometrium, Dienogest helps to reduce the pelvic pain experienced by women with endometriosis.

Therapeutic classView

Female Sex hormones

PharmacologyView

Dienogest acts as an agonist at the progesterone receptor (PR) with weak affinity that is comparable to that of progesterone but has a very potent progestagenic effect in the endometrium, causing endometrial atrophy after prolonged use. It promotes antiproliferative, immunologic and antiangiogenic effects on endometrial tissue. Dienogest reduces the level of endogenous production of oestradiol and thereby suppressing the trophic effects of oestradiol on both the eutopic and ectopic endometrium. Continous administration of dienogest results in hyperprogestogenic and moderately hypoestrogenic endocrine environment, which causes initial decidualization of endometrial tissue. It is an antagonist at androgen receptors, improve androgenic symptoms such as acne and hirsutism [A16570].

DosageView

Tablet-taking can be started on any day of the menstrual cycle. The dosage of Dienogest is 2 mg daily without any break, taken preferably at the same time each day with some liquid as needed. Tablet must be taken continuously without regard to vaginal bleeding. When a pack is finished, the next one should be started without interruption.

In the event of missed tablet(s), the woman should take 2 mg only, as soon as she remembers, and should then continue the next day to take the tablet at her usual time. A tablet not absorbed due to vomiting or diarrhea should likewise be replaced by 2 mg.

Side effectsView

Undesirable effects are more common during the 1st months after start of intake of Dienogest, and subside with duration of treatment. The following undesirable effects have been reported in users of Dienogest. The most frequently reported undesirable effects during treatment that were considered at least possibly related to Dienogest were headache (9%), breast discomfort (5.4%), depressed mood (5.1%) and acne (5.1%).

Nervous System Disorders: Headache, migraine.
Cardiac Disorders: Uncommon: Unspecified circulatory system disorder, palpitations.
Vascular Disorders: Uncommon: Hypotension.
Gastrointestinal Disorders: Common: Nausea, abdominal pain, flatulence.
Metabolism and nutrition disorders: Weight increase (3.6%)
Psychiatric Disorders: Depressed mood, irritability, nervousness, altered mood.

ContraindicationsView

Hypersensitivity to dienogest or to any of the excipients of Dienogest. Dienogest should not be used in the presence of any of the conditions such as, Active venous thromboembolic disorder; arterial and cardiovascular disease, (e.g, myocardial infarction, cerebrovascular accident, ischemic heart disease); diabetes mellitus with vascular involvement; presence or history of severe hepatic disease as long as liver function values have not returned to normal; presence or history of liver tumors (benign or malignant); known or suspected sex hormone-dependent malignancies and undiagnosed vaginal bleeding.

PrecautionsView

Before starting Dienogest treatment, pregnancy must be excluded. During treatment, patients are advised to use nonhormonal methods of contraception (e.g, barrier method) if contraception is required.

As Dienogest is a progestogen-only preparation, it can be assumed that special warnings and special precautions for use of other progestogen-only preparations are also valid for the use of Dienogest .

Changes in Bleeding Pattern: Dienogest treatment affects the menstrual bleeding pattern in the majority of women.
Hepatic Impairment: Dienogest is contraindicated in patients with present or past severe hepatic disease.
Impairment of Fertility: Based on available data, ovulation is inhibited in the majority of patients during treatment with Dienogest. However, Dienogest is not a contraceptive. If contraception is required, a nonhormonal method should be used.

InteractionsView

Progestogens including Dienogest are metabolized mainly by the cytochrome P450 3A4 system . Therefore, inducers or inhibitors of CYP3A4 may affect the progestogen drug metabolism. Known CYP3A4 inhibitors like azole antifungals (e.g, ketoconazole, itraconazole, fluconazole), cimetidine, verapamil, macrolides (e.g, erythromycin, clarithromycin and roxithromycin), diltiazem, protease inhibitors (e.g, ritonavir, saquinavir, indinavir, nelfinavir), antidepressants (e.g, nefazodone, fluvoxamine, fluoxetine) may increase plasma levels of progestogens and result in adverse reactions.

Pregnancy & lactationView

There are limited data from the use of Dienogest in pregnant women. Animal studies and data from women exposed to Dienogest during pregnancy reveal no special risks on pregnancy, embryonic/fetal development, birth or development after birth for humans. However, Dienogest should not be administered to pregnant women because there is no need to treat endometriosis during pregnancy.

Treatment with Dienogest during lactation is not recommended. Physiochemical properties and animal data indicate excretion of Dienogest in breast milk. A decision must be made whether to discontinue breastfeeding or to abstain from Dienogest therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Pediatric usageView

Use in Children: Dienogest is not indicated in children prior to menarche. The safety and efficacy of Dienogest in adolescents (menarche to 18 years) has not yet been established.

Use in the Elderly: There is no relevant indication for the use of Dienogest in the geriatric population.

Overdose effectsView

Acute toxicity studies performed with Dienogest did not indicate a risk of acute adverse effects in case of inadvertent intake of a multiple of the daily therapeutic dose. There is no specific antidote. Dienogest 20-30 mg/day (10-15 times higher dose than in Dienogest) over 24 weeks of use were very well tolerated.

StorageView

Keep in a cool and dry place. Protect from light. Keep out of the reach of children.

Veneta

Venetoclax

Tablet 50 mg Allopathic Cytotoxic Chemotherapy

Indications

Chronic lymphocytic leukemia

Indication detailsView

Venetoclax in combination with Rituximab is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

Venetoclax monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

Therapeutic classView

Cytotoxic Chemotherapy

PharmacologyView

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

DosageView

The starting dose is 20 mg of Venetoclax once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. The 5-week dose-titration schedule is designed to gradually reduce tumour burden (debulk) and decrease the risk of tumor lysis syndrome.

Post-titration dose for Venetoclax in combination with Rituximab: The recommended dose of Venetoclax in combination with Rituximab is 400 mg once daily. Rituximab should be administered after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg Venetoclax for 7 days. Venetoclax should be taken for 24 months from Cycle 1 Day 1 of Rituximab.

Post-titration dose for Venetoclax monotherapy: The recommended dose of Venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient.

Side effectsView

The most commonly occurring side effects (>20%) of any grade in patients receiving Venetoclax in the combination study with Rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common side effects were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection. The most frequently reported serious side effects (>2%) in patients receiving Venetoclax in combination with Rituximab were pneumonia, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious side effects (>2%) were pneumonia and febrile neutropenia.

ContraindicationsView

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John's wort

PrecautionsView

Tumour lysis syndrome: Tumour lysis syndrome, including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with Venetoclax. Venetoclax can cause rapid reduction in tumour, and thus poses a risk for TLS in the initial 5-weeks dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venetoclax and at each dose increase. The risk of TLS is a continuum based on multiple factors, including comorbidities. Patients with high tumour burden (e.g., any lymph node with a diameter >5 cm or high ALC >25 x 109/1) are at greater risk of TLS when initiating enetoclax. Reduced renal function (CrCI <80 ml/min) further increases the risk. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricaemics. Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed. More intensive measures (intravenous hydration, frequent monitoring, hospitalization) should be employed as overall risk increases. The instructions for "Prevention of tumour lysis syndrome" should be followed. Concomitant use of this medicinal product with strong or moderate CYP3A inhibitors increases Venetoclax exposure and may increase the risk for TLS at initiation and during the dose-titration phase. Also, inhibitors of P-gp or BCRP may increase Venetoclax exposure.

Neutropenia: Grade 3 or 4 neutropenia has been reported in patients treated with Venetoclax in the combination study with Rituximab (G028667/MURANO) and in the monotherapy studies. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Immunization: The safety and efficacy of immunization with live attenuated vaccines during or following Venetoclax therapy have not been studied. Live vaccines should not be administered during treatment and thereafter until B-cell recovery.

CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venetoclax exposure and consequently a risk for lack of efficacy. Concomitant use of Venetoclax with strong or moderate CYP3A4 inducers should be avoided.

Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venetoclax.

InteractionsView

CYP3A inhibitors: Co-administration of 400 mg once daily ketoconazole, a strong CYP3A, P-gp and BCRP inhibitor, for 7 days in 11 previously treated patients with NHL increased Venetoclax Cmax by 2.3-fold and AUC by 6.4-fold. Co-administration of 50 mg once daily ritonavir, a strong CYP3A and P-gp inhibitor, for 14 days in 6 healthy subjects increased Venetoclax Cmax by 2.4-fold and AUC by 7.9-fold. Co-administration of Venetoclax with other strong CYP3A4 inhibitors is predicted to increase Venetoclax AUC by on average 5.8- to 7.8-fold. Concomitant use of Venetoclax with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS.

At initiation and during the dose-titration phase, concomitant use of Venetoclax with moderate CYP3A inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. Alternative treatments should be considered. If a moderate CYP3A inhibitor must be used, the initiation dose of Venetoclax and the doses for the titration phase should be reduced by at least 50%. Patients should be monitored more closely for signs and symptoms of TLS.

For patients who have completed the dose-titration phase and are on a steady daily dose of Venetoclax, the Venetoclax dose should be reduced by 50% when used concomitantly with moderate CYP3A inhibitors and by 75% when used concomitantly with strong CYP3A inhibitors. Patients should be monitored more closely for signs of toxicities and the dose may need to be further adjusted. The Venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with Venetoclax as they contain inhibitors of CYP3A.

P-gp and BCRP inhibitors: Venetoclax is a substrate for P-gp and BCRP , Co-administration of a 600 mg single dose of rifampin, a P-gp inhibitor, in 11 healthy subjects increased Venetoclax Cmax by 106% and AUC by 78%. Concomitant use of Venetoclax with P-gp and BCRP inhibitors at initiation and during the dose-titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities.

CYP3A inducers: Co-administration of 600 mg once daily rifampin, a strong CYP3A inducer, for 13 days in 10 healthy subjects decreased Venetoclax Cmax by 42% and AUC°° by 71%. Concomitant use of Venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided. Alternative treatments with less CYP3A induction should be considered. Preparations containing St. John's wort are contraindicated during treatment with Venetoclax, as efficacy may be reduced.

Pregnancy & lactationView

Women of childbearing potential/Contraception in females: Women should avoid becoming pregnant while taking Venetoclax and for at least 30 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking Venetoclax and for 30 days after stopping treatment. It is currently unknown whether Venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

Pregnancy: Based on embryo-foetal toxicity studies in animals, Venetoclax may harm the fetus when administered to pregnant women. There is no adequate and well-controlled data from the use of Venetoclax in pregnant women. Studies in animals have shown reproductive toxicity. Venetoclax is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception.

Breast-feeding: It is unknown whether Venetoclax or its metabolites are excreted in human milk. A risk to the breast-feeding child cannot be excluded. Breast-feeding should be discontinued during treatment with Venetoclax.

Fertility: No human data on the effect of Venetoclax on fertility are available. Based on testicular toxicity in dogs at clinically relevant exposures, male fertility may be compromised by treatment with Venetoclax. Before starting treatment, counselling on sperm storage may be considered in some male patients.

Pediatric usageView

Elderly: No specific dose adjustment is required for elderly patients (aged >65 years).

Renal impairment: No dose adjustment is needed for patients with mild or moderate renal impairment (CrCI >30 ml/min and <90 mi/min). Patients with reduced renal function (CrCI <80 ml/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCI <30 ml/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. Venetoclax should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity.

Pediatric population: The safety and efficacy of Venetoclax in children aged less than 18 years have not been established. No data is available.

Overdose effectsView

There is no specific antidote for Venetoclax. Patients who experience overdose should be closely monitored and appropriate supportive treatment provided. During dose-titration phase, treatment should be interrupted and patients should be monitored carefully for signs and symptoms of TLS (fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or joint pain, abdominal pain and distension) along with other toxicities.

StorageView

Store below 30°C. Keep Venetoclax out of the sight and reach of children. Protect from moisture and light.

Veneta

Venetoclax

Tablet 100 mg Allopathic Cytotoxic Chemotherapy

Indications

Chronic lymphocytic leukemia

Indication detailsView

Venetoclax in combination with Rituximab is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

Venetoclax monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

Therapeutic classView

Cytotoxic Chemotherapy

PharmacologyView

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an antiapoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics. Venetoclax helps restore the process of apoptosis by binding directly to the BCL-2 protein, displacing pro-apoptotic proteins like BIM, triggering mitochondrial outer membrane permeabilization and the activation of caspases. In nonclinical studies, venetoclax has demonstrated cytotoxic activity in tumor cells that overexpress BCL-2.

DosageView

The starting dose is 20 mg of Venetoclax once daily for 7 days. The dose must be gradually increased over a period of 5 weeks up to the daily dose of 400 mg. The 5-week dose-titration schedule is designed to gradually reduce tumour burden (debulk) and decrease the risk of tumor lysis syndrome.

Post-titration dose for Venetoclax in combination with Rituximab: The recommended dose of Venetoclax in combination with Rituximab is 400 mg once daily. Rituximab should be administered after the patient has completed the dose-titration schedule and has received the recommended daily dose of 400 mg Venetoclax for 7 days. Venetoclax should be taken for 24 months from Cycle 1 Day 1 of Rituximab.

Post-titration dose for Venetoclax monotherapy: The recommended dose of Venetoclax is 400 mg once daily. Treatment should be continued until disease progression or no longer tolerated by the patient.

Side effectsView

The most commonly occurring side effects (>20%) of any grade in patients receiving Venetoclax in the combination study with Rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common side effects were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection. The most frequently reported serious side effects (>2%) in patients receiving Venetoclax in combination with Rituximab were pneumonia, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious side effects (>2%) were pneumonia and febrile neutropenia.

ContraindicationsView

Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John's wort

PrecautionsView

Tumour lysis syndrome: Tumour lysis syndrome, including fatal events, has occurred in patients with previously treated CLL with high tumour burden when treated with Venetoclax. Venetoclax can cause rapid reduction in tumour, and thus poses a risk for TLS in the initial 5-weeks dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of Venetoclax and at each dose increase. The risk of TLS is a continuum based on multiple factors, including comorbidities. Patients with high tumour burden (e.g., any lymph node with a diameter >5 cm or high ALC >25 x 109/1) are at greater risk of TLS when initiating enetoclax. Reduced renal function (CrCI <80 ml/min) further increases the risk. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricaemics. Blood chemistries should be monitored and abnormalities managed promptly. Dosing should be interrupted if needed. More intensive measures (intravenous hydration, frequent monitoring, hospitalization) should be employed as overall risk increases. The instructions for "Prevention of tumour lysis syndrome" should be followed. Concomitant use of this medicinal product with strong or moderate CYP3A inhibitors increases Venetoclax exposure and may increase the risk for TLS at initiation and during the dose-titration phase. Also, inhibitors of P-gp or BCRP may increase Venetoclax exposure.

Neutropenia: Grade 3 or 4 neutropenia has been reported in patients treated with Venetoclax in the combination study with Rituximab (G028667/MURANO) and in the monotherapy studies. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Immunization: The safety and efficacy of immunization with live attenuated vaccines during or following Venetoclax therapy have not been studied. Live vaccines should not be administered during treatment and thereafter until B-cell recovery.

CYP3A inducers: Co-administration of CYP3A4 inducers may lead to decreased Venetoclax exposure and consequently a risk for lack of efficacy. Concomitant use of Venetoclax with strong or moderate CYP3A4 inducers should be avoided.

Women of childbearing potential: Women of childbearing potential must use a highly effective method of contraception while taking Venetoclax.

InteractionsView

CYP3A inhibitors: Co-administration of 400 mg once daily ketoconazole, a strong CYP3A, P-gp and BCRP inhibitor, for 7 days in 11 previously treated patients with NHL increased Venetoclax Cmax by 2.3-fold and AUC by 6.4-fold. Co-administration of 50 mg once daily ritonavir, a strong CYP3A and P-gp inhibitor, for 14 days in 6 healthy subjects increased Venetoclax Cmax by 2.4-fold and AUC by 7.9-fold. Co-administration of Venetoclax with other strong CYP3A4 inhibitors is predicted to increase Venetoclax AUC by on average 5.8- to 7.8-fold. Concomitant use of Venetoclax with strong CYP3A inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) at initiation and during the dose-titration phase is contraindicated due to increased risk for TLS.

At initiation and during the dose-titration phase, concomitant use of Venetoclax with moderate CYP3A inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. Alternative treatments should be considered. If a moderate CYP3A inhibitor must be used, the initiation dose of Venetoclax and the doses for the titration phase should be reduced by at least 50%. Patients should be monitored more closely for signs and symptoms of TLS.

For patients who have completed the dose-titration phase and are on a steady daily dose of Venetoclax, the Venetoclax dose should be reduced by 50% when used concomitantly with moderate CYP3A inhibitors and by 75% when used concomitantly with strong CYP3A inhibitors. Patients should be monitored more closely for signs of toxicities and the dose may need to be further adjusted. The Venetoclax dose that was used prior to initiating the CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with Venetoclax as they contain inhibitors of CYP3A.

P-gp and BCRP inhibitors: Venetoclax is a substrate for P-gp and BCRP , Co-administration of a 600 mg single dose of rifampin, a P-gp inhibitor, in 11 healthy subjects increased Venetoclax Cmax by 106% and AUC by 78%. Concomitant use of Venetoclax with P-gp and BCRP inhibitors at initiation and during the dose-titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities.

CYP3A inducers: Co-administration of 600 mg once daily rifampin, a strong CYP3A inducer, for 13 days in 10 healthy subjects decreased Venetoclax Cmax by 42% and AUC°° by 71%. Concomitant use of Venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided. Alternative treatments with less CYP3A induction should be considered. Preparations containing St. John's wort are contraindicated during treatment with Venetoclax, as efficacy may be reduced.

Pregnancy & lactationView

Women of childbearing potential/Contraception in females: Women should avoid becoming pregnant while taking Venetoclax and for at least 30 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking Venetoclax and for 30 days after stopping treatment. It is currently unknown whether Venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

Pregnancy: Based on embryo-foetal toxicity studies in animals, Venetoclax may harm the fetus when administered to pregnant women. There is no adequate and well-controlled data from the use of Venetoclax in pregnant women. Studies in animals have shown reproductive toxicity. Venetoclax is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception.

Breast-feeding: It is unknown whether Venetoclax or its metabolites are excreted in human milk. A risk to the breast-feeding child cannot be excluded. Breast-feeding should be discontinued during treatment with Venetoclax.

Fertility: No human data on the effect of Venetoclax on fertility are available. Based on testicular toxicity in dogs at clinically relevant exposures, male fertility may be compromised by treatment with Venetoclax. Before starting treatment, counselling on sperm storage may be considered in some male patients.

Pediatric usageView

Elderly: No specific dose adjustment is required for elderly patients (aged >65 years).

Renal impairment: No dose adjustment is needed for patients with mild or moderate renal impairment (CrCI >30 ml/min and <90 mi/min). Patients with reduced renal function (CrCI <80 ml/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCI <30 ml/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. Venetoclax should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

Hepatic impairment: No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase. A dose reduction of at least 50% throughout treatment is recommended for patients with severe hepatic impairment. These patients should be monitored more closely for signs of toxicity.

Pediatric population: The safety and efficacy of Venetoclax in children aged less than 18 years have not been established. No data is available.

Overdose effectsView

There is no specific antidote for Venetoclax. Patients who experience overdose should be closely monitored and appropriate supportive treatment provided. During dose-titration phase, treatment should be interrupted and patients should be monitored carefully for signs and symptoms of TLS (fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle or joint pain, abdominal pain and distension) along with other toxicities.

StorageView

Store below 30°C. Keep Venetoclax out of the sight and reach of children. Protect from moisture and light.

Veniron

Iron Sucrose Injection [Elemental Iron]

IV Injection or Infusion 100 mg/5 ml Allopathic Parenteral Iron Preparations

Indications

Peritoneal dialysis dependent-chronic kidney disease (PDD-CKD) patients receiving an erythropoietin

Indication detailsView

This is indicated for the treatment of Iron deficiency in the following indications:

Where there is a clinical need for a rapid Iron supply
In patients who can not tolerate oral Iron therapy or who are non-compliant
In active inflammatory bowel disease where oral Iron preparations are ineffective
Non-dialysis dependent-chronic kidney disease (NDD-CKD) patients receiving an erythropoietin
Non-dialysis dependent-chronic kidney disease (NDD-CKD) patients not receiving an erythropoietin
Hemodialysis dependent-chronic kidney disease (HDD-CKD) patients receiving an erythropoietin
Peritoneal dialysis dependent-chronic kidney disease (PDD-CKD) patients receiving an erythropoietin
It is also indicated in the treatment of Iron deficiency anaemia in patients undergoing surgical procedures, patients donating blood, postpartum patients.

Therapeutic classView

Parenteral Iron Preparations

PharmacologyView

The therapeutic class of Iron Sucrose is haematinic. Iron Sucrose Injection USP is a brown, sterile, aqueous, complex of Polynuclear Iron (III) Hydroxide in Sucrose for Intravenous use. The drug product contains approximately 30% Sucrose w/v (300 mg/ml) and has a pH of 10.5-11.1. Following intravenous administration, Iron Sucrose Injection is dissociated into Iron and Sucrose by the reticuloendothelial system, and Iron is transferred from the blood to a pool of Iron in the liver and bone marrow. Ferritin, an Iron storage protein, binds and sequesters Iron in a nontoxic form, from which Iron is easily available. Iron binds to plasma transferrin, which carries Iron within the plasma and the extracellular fluid to supply the tissues. The transferrin receptor, located in the cell, and the transferrin-receptor complex is returned to the cell membrane. Transferrin without Iron (apotransferrin) is then released to the plasma. The intracellular Iron becomes (mostly) haemoglobin in circulating red blood cells (RBCs). Transferrin synthesis is increased and ferritin production reduced in Iron deficiency. The converse is true when Iron is plentiful. Its elimination halflife is 6 h, total clearance is 1.2 L/h, non-steady state apparent volume of distribution is 10.0 L and steady state apparent volume of distribution is 7.9 L. In Iron Sucrose, its Iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A significant amount of the administered Iron distributes in the liver, spleen and bone marrow and that the bone marrow is an Iron trapping compartment and not a reversible volume distribution. The sucrose component is eliminated mainly through urinary excretion.

DosageView

Adults and Elderly: 5-10 ml Iron Sucrose Injection (100-200 mg Iron) once to three times a week depending on the hemoglobin level.

Children: There is limited data on children under study conditions. If there is a clinical need, it is recommended not to exceed 0.15 ml Iron Sucrose Injection (3 mg Iron) per kg body weight once to three times per week depending on the haemoglobin level.

AdministrationView

Intravenous injection: Iron Sucrose Injection can also be administered undiluted by slow intravenous injection at the (normal) recommended rate of 1 ml Iron Sucrose Injection (20 mg Iron) per minute [5 ml Iron Sucrose Injection (100 mg Iron) in 2 to 5 minutes]. A maximum of 10 ml Iron Sucrose Injection (200 mg Iron) can be injected per injection. Before administration of the therapeutic dose in a new patient, a test dose of 1 ml Iron Sucrose Injection (20 mg Iron) in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg Iron/kg) in children with a body weight less than 14 kg should be injected over 1 to 2 minutes. If no adverse reactions occur within a waiting period of 15 minutes, the remaining portion of the injection can be administered at recommended speed. After an injection the arm of the patient should be extended.

Infusion: Iron Sucrose Injection should preferably be administered by drip infusion (in order to reduce the risk of hypotensive episodes and paravenous injection) in a dilution of 1 ml Iron Sucrose Injection (20 mg Iron) in max. 20 ml 0.9% w/v Sodium Chloride [5 ml (100 mg Iron) in max. 100 ml 0.9% w/v NaCI etc. up to 25 ml (500 mg Iron) in max. 500 ml 0.9% w/v NaCI]. Dilution must take place immediately prior to infusion and the solution should be administered as follows: 100 mg Iron in at least 15 minutes; 200 mg Iron in at least 30 minutes; 400 mg Iron In at least 1.5 hours, and 500 mg Iron in at least 3.5 hours. Further of the maximum tolerated single dose of 7 mg Iron/kg body weight, an Infusion time of at least 3.5 hours has to be respected, independently of the total dose.

Before administration of the therapeutic dose in a new patient the first 20 mg Iron in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg lron/kg) in children with a body weight less than 14 kg should be infused over 15 minutes as a test dose. If no adverse reactions occur, the remaining portion of the infusion can be administered at recommended speed.

Side effectsView

Adverse reactions, whether or not related to Iron Sucrose injection are as follows: hypotension, cramps/leg cramps, nausea, headache, vomiting, and diarrhea. Some of these symptoms may be seen in patients with chronic renal failure or on hemodialysis not receiving intravenous iron.
Body as a Whole: headache, fever, pain, asthenia, unwell, malaise, accidental injury. Cardiovascular Disorders
General: hypotension, chest pain, hypertension, hypervolemia.
Gastrointestinal Disorders: nausea, vomiting, abdominal pain, elevated liver enzymes.
Central and Peripheral Nervous System: dizziness.
Musculoskeletal System: cramps/leg cramps, musculoskeletal pain.
Respiratory System: dyspnea pneumonia, cough.
Skin and appendages: pruritus, application site reaction.
Hypersensitivity reactions: In safety studies, several patients experienced mild or moderate hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. Anaphylactoid reactions including patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Iron Sucrose administration can occur. So, patients should be given a small test dose initially.

ContraindicationsView

The use of Iron Sucrose is contraindicated in patients with evidence of Iron overload, in patients with known hypersensitivity to Iron Sucrose or any of its inactive components, and in patients with anaemia not caused by Iron deficiency. It is also contraindicated in patients with history of allergic disorders including asthma, eczema and anaphylaxis, liver disease and infections.

PrecautionsView

General: Because body Iron excretion is limited and excess tissue Iron can be hazardous, caution should be exercised to withhold Iron administration in the presence of evidence of tissue Iron overload. Patients receiving Iron Sucrose require periodic monitoring of hematologic and haematinic parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Iron therapy should be withheld in patients with evidence of Iron overload. Transferrin saturation values increase rapidly after IV administration of Iron Sucrose; thus, serum Iron values may be reliably obtained 48 hours after IV dosing.

Hypersensitivity Reactions: Serious hypersensitivity reactions have been rarely reported in patients receiving Iron Sucrose. Several cases of mild or moderate hypersensitivity reactions were observed in these studies.

Hypotension: Hypotension has been reported frequently in hemodialysis patients receiving intravenous Iron. Hypotension following administration of Iron Sucrose may be related to rate of administration and total dose administered. Caution should be taken to administer Iron Sucrose according to recommended guidelines.

InteractionsView

Drug-drug interactions involving Iron Sucrose have not been studied. Iron Sucrose Injection should not be administered concomitantly with oral iron preparations since the absorption of oral Iron is reduced. Even oral Iron therapy should not be given until 5 days after last injection.

Pregnancy & lactationView

Pregnancy Category-B. No adequate and well controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Iron Sucrose is administered to a nursing woman.

Pediatric usageView

Pediatric Use: Safety and effectiveness of Iron Sucrose in pediatric patients have not been established.

Geriatric Use: No overall differences in safety were observed between the elder subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Injection into dialyser: Iron Sucrose Injection may be administered directly into the venous limb of the dialyser under the same conditions as for intravenous injection.

Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD): Iron Sucrose Injection may be administered undiluted as a 100 mg slow intravenous injection over 2 to 5 minutes or as an infusion of 100 mg, diluted in a maximum of 100 ml of 0.9% NaCI over a period of at least 15 minutes per consecutive hemodialysis session for a total cumulative dose of 1,000 mg.

Non-Dialysis Dependent-Chronic Kidney Disease Patient (NDD-CKD): Iron Sucrose Injection is administered as a total cumulative dose 1000 mg over a 14 day period as a 200 mg slow IV injection undiluted over 2 to 5 minutes on 5 different occasions within the 14 day period.

Overdose effectsView

Dosages of Iron Sucrose Injection in excess of Iron needs may lead to accumulation of Iron in storage sites leading to hemosiderosis. Periodic monitoring of Iron parameters such as serum ferritin and transferrin saturation may assist in recognizing Iron accumulation. Iron Sucrose should not be administered to patients with Iron overload and should be discontinued when serum ferritin levels equal or exceed established guidelines. Particular caution should be exercised to avoid Iron overload where anaemia unresponsive to treatment has been incorrectly diagnosed as Iron deficiency anaemia. Symptoms associated with overdosage or infusing Iron Sucrose too rapidly included hypotension, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema. and cardiovascular collapse. Most symptoms have been successfully treated with IV fluids, hydrocortisone, and/or antihistamines. Infusing the solution as recommended or at a slower rate may also alleviate symptoms.

StorageView

Store in a cool (15°C- 30°C) & dry place, protected from light. Keep out of the reach of children. Do not freeze.

Venium

Clobazam

Tablet 10 mg Allopathic Benzodiazepine hypnotics

Indications

Tension

Indication detailsView

Acute and chronic anxiety states which may produce the following symptoms in particular: anxiety, tension, restlessness, excitement, irritability, sleep disturbances from emotional causes, psychovegetative and psychosomatic disorders (for example, in the cardiovascular or gastrointestinal area), and emotional instability.

In patients with depression or anxiety associated with depression, Clobazam must be used only in conjunction with adequate concomitant treatment. Use of benzodiazepines alone, can precipitate suicide in such patients. Before treatment of anxiety states associated with emotional instability, it must first be determined whether the patient suffers from a depressive disorder requiring adjunctive or different treatment.

In patients with schizophrenic or other psychotic illnesses, use of benzodiazepines is recommended only for adjunctive, i.e. not for primary treatment.

As adjunctive therapy in patients with epilepsy who are not adequately stabilized with their anticonvulsant monotherapy.

Therapeutic classView

Benzodiazepine hypnotics

PharmacologyView

Clobazam binds at distinct binding sites associated with the chloride ionopore at the post-synaptic GABA receptor. These GABA receptors are in various locations in the CNS (limbic, reticular formation) and clobazam increases the duration of time for which the chloride ionopore is open. As a result, hyper polarization and stabilization of the membrane occur as the post-synaptic inhibitory effect of GABA is enhanced.

DosageView

General Dosage: Dosage and duration of treatment must be adjusted to the indication, the severity of the condition and the individual clinical response. Due regard must be paid to the possibility of interference with alertness and reaction time. The fundamental principle is to keep the dose as low as possible.

Treatment of anxiety states-

Adults and adolescents over 15 years of age: The initial dose is usually 20 mg clobazam daily. If necessary, the daily dose may be increased. Generally, it is recommended that a total daily dose of 30 mg is not exceeded.

Elderly: Increased responsiveness and higher susceptibility to adverse effects may be present in elderly patients and require low initial doses and gradual dose increments under careful observation. A maintenance dose of 10 to 15 mg clobazam daily is frequently sufficient.

Children from 3 to 15 years of age: Increased responsiveness and higher susceptibility to adverse effects may be present in children and require low initial doses and gradual dose increments under careful observation. A daily dose of 5 to 10 mg clobazam is frequently sufficient. Benzodiazepines must not be given to children without careful assessment of the need for their use.

Secondary dosage adjustment: After the improvement of the symptoms, the dose may be reduced.

Timing of doses: If the dose is to be spread throughout the day, it is recommended that the larger portion be taken in the evening.

Duration of treatment: The duration of treatment must be as short as possible. The patient must be reassessed after a period not exceeding 4 weeks and regularly thereafter in order to evaluate the need for continued treatment, especially where the patient is free of symptoms. Generally, the overall duration of treatment (i.e. including tapering-of process) must not exceed 8 to 12 weeks. In certain cases, extension beyond the maximum treatment period may be necessary; treatment must not be extended without a re-evaluation of the patient's status using special expertise. It is strongly recommended that prolonged periods of uninterrupted treatment be avoided, since they may lead to dependence.

Discontinuation of treatment: It is strongly recommended that after prolonged treatment clobazam is not withdrawn suddenly but rather that the dose is reduced gradually under medical supervision; otherwise, withdrawal symptoms may occur.

Treatment of epilepsy in combination with one or more other anticonvulsants-

Adults and adolescents over 15 years of age: It is recommended that administration be started at small doses (5 to 15 mg daily), if necessary, increasing the dose gradually to a maximum daily dose of about 80 mg.

Children from 3 to 15 years of age: It is recommended that normally treatment be started at 5 mg daily. A maintenance dose of 0.3 to 1.0 mg/kg body weight daily is usually sufficient. Higher susceptibility to adverse effects may be present in children and require gradual dose increments under careful observation; Benzodiazepines must not be given to children without careful assessment of the need for their use.

Elderly: Higher susceptibility to adverse effects may be present in elderly patients and require low initial doses and gradual dose increments under careful observation.

Timing of doses: If the dose is spread throughout the day, it is recommended that the larger portion be taken in the evening. Doses of up to 30 mg clobazam can also be administered as a single evening dose.

Duration of treatment: The patient must be re-assessed after a period not exceeding 4 weeks and regularly thereafter in order to evaluate the need for continued treatment.

Discontinuation of treatment: At the end of treatment- to include cases in which response to therapy has been poor- it is strongly recommended that clobazam is not withdrawn suddenly but rather that the dose is reduced gradually; otherwise an increased susceptibility to seizures as well as other withdrawal symptoms may occur.

AdministrationView

The tablets can be administered whole, or crushed and mixed in applesauce. The 10 mg tablets can be divided into equal halves of 5 mg. Clobazam can be given with or without food.

Side effectsView

Metabolism and nutrition disorders: Common: decreased appetite

Psychiatric disorders: Common: irritability, aggression, restlessness, depression (pre-existing depression may be unmasked), drug tolerance (especially during prolonged use), agitation.

Nervous system disorders: Very common: somnolence, especially at the beginning of treatment and when higher doses are used; Common: sedation, dizziness, disturbance in attention, slow speech/dysarthria/ speech disorder (particularly with high doses or in long-term treatment, and are reversible), headache, tremor, ataxia.

Eye Disorders: Uncommon: diplopia (particularly with high doses or in long-term treatment and is reversible)

Respiratory, thoracic and mediastinal disorders: Not known: respiratory depression respiratory failure (particularly in patients with pre-existing compromised respiratory function e.g. in patients with bronchial asthma or brain damage)

Gastrointestinal disorders: Common: dry mouth, nausea, constipation

Skin and subcutaneous disorders: Uncommon: rash; Not known: photosensitivity reaction urticaria; Steven Johnson syndrome, toxic epidermal necrolysis (including some cases with fatal outcome);

Musculoskeleteal and connective tissue disorders: Not known: muscle spasms, muscle weakness

General disorders and administration site conditions: Very common: fatigue, especially at the beginning of treatment and when higher doses are used. Not known: slow response to stimuli, hypothermia

Investigations: Uncommon: weight increased (particularly with high doses or in long-term treatment).

ContraindicationsView

Clobazam must not be used-

In patients with hypersensitivity to clobazam or any of the excipients of Clobazam.
In patients with myasthenia gravis (risk of aggravation of muscle weakness).
In patients with severe respiratory insufciency (risk of deterioration).
In patients with sleep apnoea syndrome (risk of deterioration).
In patients with severe impairment of liver function (risk of precipitating encephalopathy).
In breast-feeding women Benzodiazepines must not be given to children without careful assessment of the need for their use.
Clobazam must not be used in children between the ages of 6 months and 3 years, other than in exceptional cases for anticonvulsant treatment where there is a compelling indication.

PrecautionsView

Serious Skin Reactions: Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with clobazam in both children and adults during the post-marketing experience. A majority of the reported cases involved the concomitant use of other drugs, including antiepileptic drugs that are associated with serious skin reactions. SJS/TEN could be associated with a fatal outcome. Patients should be closely monitored for signs or symptoms of SJS/TEN, especially during the first 8 weeks of treatment. Clobazam should be immediately discontinued when SJS/TEN is suspected. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.

Respiratory depression: Clobazam can cause respiratory depression, especially if administered in high doses. Therefore in patients with chronic or acute respiratory insufficiency, respiratory function must be monitored and a dose reduction may be necessary. Clobazam is contraindicated in patients with severe respiratory insufficiency.

Muscle weakness: Clobazam can cause muscle weakness. Clobazam is contraindicated in patients with myasthenia gravis.

Renal and hepatic impairment: In patients with impairment of renal or hepatic function, responsiveness to clobazam and susceptibility to adverse effects are increased, and a dose reduction may be necessary. In long-term treatment, renal and hepatic function must be checked regularly.

Elderly patients: In the elderly, due to the increased sensitivity to adverse reactions such as drowsiness, dizziness, muscle weakness, there is an increased risk of fall that may result in serious injury. A dose reduction is recommended.

Tolerance in epilepsy: In the treatment of epilepsy with benzodiazepines- including Clobazam, consideration must be given to the possibility of a decrease in anticonvulsant efficacy (development of tolerance) in the course of treatment.

CYP2C19 poor metabolizers: In patients who are CYP2C19 poor metabolizers, levels of the active metabolite N-desmethylclobazam are expected to be increased as compared to extensive metabolizers. Dosage adjustment of clobazam may be necessary (e.g. low starting dose with careful dose titration).

Suicidality: Several epidemiological studies show an increased incidence of suicide and suicide attempt in patients with or without depression, treated with other benzodiazepines and hypnotics. There are very limited data available for clobazam in these studies. Cases of suicidal behavior have been reported with clobazam in post-marketing surveillance. All of these cases had confounding factors.

Concomitant use of CYP2C19 inhibitors: The concomitant use of clobazam with CYP2C19 inhibitors, including cannabidiol containing medicinal products, dietary supplements and recreational products may result in increased exposure to N-desmethylclobazam (NCLB). Such increases might lead to increased adverse effects, such as somnolence and sedation. When used with medicinal products that are CYP2C19 inhibitors dosage adjustment of clobazam may be necessary. Dietary supplements and recreational products containing cannabidiol must not be taken in combination with clobazam as they contain unknown quantities of cannabidiol and are of variable quality

InteractionsView

Alcohol: Concomitant consumption of alcohol can increase the bioavailability of clobazam by 50% and therefore lead to increased clobazam effects.

Central nervous system depressant drugs: Especially when clobazam is administered in higher doses, a mutually potentiating effect is to be expected if other central nervous system depressant drugs (such as antipsychotics, anxiolytics, certain antidepressant agents, anticonvulsant drugs, sedative antihistamines, anaesthetics, hypnotics or narcotic analgesics, or other sedatives) are taken at the same time. Special caution is also necessary when clobazam is administered in cases of intoxication with such substances or with lithium.

Opioids: The concomitant use of benzodiazepines, including clobazam, and opioids increases the risk of sedation, respiratory depression, coma, and death because of the additive CNS depressant effect. Limit dosage and duration of concomitant use of benzodiazepines and opioids.

Anticonvulsants: If clobazam is administered simultaneously with anticonvulsants in the treatment of epilepsy, the dosage must be adjusted under regular medical supervision (EEG monitoring), as there may be interactions with the patient's basic anticonvulsant medication. In patients receiving concomitant treatment with valproic acid, there may be a slight to moderate rise in plasma valproic acid concentration. Phenytoin plasma levels may rise if patients receive concomitant treatment with clobazam. Where possible, it is recommended that blood levels of concomitantly administered valproic acid or phenytoin be monitored. Carbamazepine and phenytoin may cause an increase in the metabolic conversion of clobazam to the active metabolite N-desmethyl clobazam. Stiripentol increases plasma levels of clobazam and its active metabolite N-desmethylclobazam, through inhibition of CYP3A and CYP2C19. Monitoring of blood levels is recommended, prior to initiation of stiripentol, and then once new steady-state concentration has been reached, i.e. after 2 weeks approximately.

Narcotic analgesics: If clobazam is used concomitantly with narcotic analgesics, possible euphoria may be enhanced; this may lead to increased psychological dependence.

Muscle relaxants: The effects of muscle relaxants and nitrous oxide may be enhanced.

CYP 2C19 inhibitors: Strong and moderate inhibitors of CYP2C19 may result in increased exposure to N-desmethylclobazam (N-CLB), the active metabolite of clobazam. Dosage adjustment of clobazam may be necessary when co-administered with strong CYP2C19 inhibitors (e.g., cannabidiol containing medicinal products, fuconazole, fuvoxamine, ticlopidine) or moderate CYP2C19 inhibitors (e.g. omeprazole).

CYP 2D6 substrates: Clobazam is a weak CYP2D6 inhibitor. Dose adjustment of drugs metabolized by CYP2D6 (e.g. dextromethorphan, pimozide, paroxetine, nebivolol) may be necessary.

Pregnancy & lactationView

Pregnancy: Clobazam is not recommended during the first trimester of pregnancy and in women of childbearing potential not using contraception. Clobazam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have demonstrated reproductive toxicity. Clobazam crosses the placenta. In the post-marketing safety database, limited data on exposed pregnancies are available with clobazam. A large amount of data collected from cohort studies has not demonstrated evidence of the occurrence of malformations following exposure to benzodiazepines during the first trimester of pregnancy. However, in certain epidemiological case-control studies, an increased incidence of cleft lip and palate was observed with benzodiazepines. Cases of reduced fetal movement and fetal heart rate variability have been described after administration of benzodiazepines during the second and/or third trimester of pregnancy. Administration of clobazam during the late phase of pregnancy or during childbirth can result in the occurrence of neonatal respiratory depression (including respiratory distress and apnea), which may be associated with other disorders such as sedation signs, hypothermia, hypotonia, and feeding difficulties (which may result in poor weight gain) in the newborn (signs and symptoms of the so-called "floppy infant syndrome"). Moreover, infants born to mothers who have taken benzodiazepines over longer periods during the later stages of pregnancy may have developed physical dependence and may be at risk of developing a withdrawal syndrome in the postnatal period. Appropriate monitoring of the newborn in the postnatal period is recommended. Women of childbearing potential should be informed of the risks and benefits of the use of Clobazam during pregnancy. If a woman plans a pregnancy or becomes pregnant, carefully evaluate the risks and benefits and whether treatment with Clobazam should be discontinued. If Clobazam treatment is to be continued, use Clobazam at the lowest effective dose.

Lactation: Clobazam must not be used in breastfeeding women, since clobazam passes into breast milk.

StorageView

Do not use the medicine later than the date of expiry. Store below 30° and protect from light. Keep out of the reach of children.

Veniz XR

Venlafaxine Hydrochloride

Capsule (Extended Release) 75 mg Allopathic Serotonin-norepinephrine reuptake inhibitor (SNRI)

Indications

Social anxiety disorder

Indication detailsView

Venlafaxine tablets is indicated for the treatment of major depressive disorder.

The efficacy of venlafaxine tablets, in the treatment of major depressive disorder was established in 6 week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-III-R category of major depression and in a 4 week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia

A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.

The efficacy of venlafaxine hydrochloride extended-release capsules in maintaining an antidepressant response for up to 26 weeks following 8 weeks of acute treatment was demonstrated in a placebocontrolled trial. The efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then followed for a period of up to 52 weeks was demonstrated in a second placebo-controlled trial (see Clinical Trials). Nevertheless, the physician who elects to use venlafaxine tablets / extended-release capsules for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Therapeutic classView

Serotonin-norepinephrine reuptake inhibitor (SNRI)

PharmacologyView

The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.

DosageView

Initial Treatment: The recommended starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses

Dosage For Elderly Patients: No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment: It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extendedrelease capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets / extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Venlafaxine Tablet: Symptoms associated with discontinuation of venlafaxine tablets, other SNRIs, and SSRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Side effectsView

Changes in behaviour, suicidal ideation, agitation, tremor, nervousness, anxiety, insomnia, confusions, abnormal dreams, HTN, nausea, headache, asthenia, somnolence, dizziness, dry mouth, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain, anorexia, sexual dysfunction, urinary frequency, visual disturbances, mydriasis, vasodilatation, paraesthesia, hypertonia, chills or fever, palpitations, wt gain or loss, arthralgia, myalgia, tinnitus, pruritus, dyspnoea, yawning, rashes, sweating, increased serum cholesterol, may impair platelet aggregation.

ContraindicationsView

Concomitant use with MAOIs or within 14 days of discontinuing the MAOI. Use with linezolid or IV methylene blue.

PrecautionsView

History of MI or unstable cardiac disease, seizure; hypomania or mania, increased intraocular pressure or at risk of acute narrow-angle galaucoma, at risk of bleeding. Renal and hepatic impairment. Gradual dose reduction is recommended rather than abrupt withdrawal. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery.

InteractionsView

Increased risk of serotonin syndrome with TCA, SSRI, SNRI, lithium, sibutramine, tramadol. May increase serum levels with CYP3A4 inhibitors (e.g. ketoconazole, atazanavir, clarithromycin). May increase serum levels of haloperidol. May decrease serum levels of indinavir. May increase bleeding risk with aspirin, NSAIDs, warfarin and other anticoagulants.

Pregnancy & lactationView

Treatment Of Pregnant Women During The Third Trimester
Neonates exposed to venlafaxine tablets, USP, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with venlafaxine tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Pediatric usageView

Dosage For Patients With Hepatic Impairment: Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects, it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Dosage For Patients With Renal Impairment: Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals, it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Overdose effectsView

Symptoms: Sweating, dizziness, somnolence, mydriasis, convulsions, vomiting, ECG changes, cardiac arrhythmias and seizures.

Management: Symptomatic and supportive treatment. Ensure adequate airway, oxygenation and ventilation. Initiate gastric lavage immediately after ingestion. Admin activated charcoal to reduce absorption. Monitor cardiac rhythm and vital signs.

StorageView

Store between 20-25° C.

Venlax

Venlafaxine Hydrochloride

Tablet 75 mg Allopathic Serotonin-norepinephrine reuptake inhibitor (SNRI)

Indications

Social anxiety disorder

Indication detailsView

Venlafaxine tablets is indicated for the treatment of major depressive disorder.

The efficacy of venlafaxine tablets, in the treatment of major depressive disorder was established in 6 week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-III-R category of major depression and in a 4 week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia

A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.

The efficacy of venlafaxine hydrochloride extended-release capsules in maintaining an antidepressant response for up to 26 weeks following 8 weeks of acute treatment was demonstrated in a placebocontrolled trial. The efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then followed for a period of up to 52 weeks was demonstrated in a second placebo-controlled trial (see Clinical Trials). Nevertheless, the physician who elects to use venlafaxine tablets / extended-release capsules for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Therapeutic classView

Serotonin-norepinephrine reuptake inhibitor (SNRI)

PharmacologyView

The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.

DosageView

Initial Treatment: The recommended starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses

Dosage For Elderly Patients: No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment: It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extendedrelease capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets / extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Venlafaxine Tablet: Symptoms associated with discontinuation of venlafaxine tablets, other SNRIs, and SSRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Side effectsView

Changes in behaviour, suicidal ideation, agitation, tremor, nervousness, anxiety, insomnia, confusions, abnormal dreams, HTN, nausea, headache, asthenia, somnolence, dizziness, dry mouth, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain, anorexia, sexual dysfunction, urinary frequency, visual disturbances, mydriasis, vasodilatation, paraesthesia, hypertonia, chills or fever, palpitations, wt gain or loss, arthralgia, myalgia, tinnitus, pruritus, dyspnoea, yawning, rashes, sweating, increased serum cholesterol, may impair platelet aggregation.

ContraindicationsView

Concomitant use with MAOIs or within 14 days of discontinuing the MAOI. Use with linezolid or IV methylene blue.

PrecautionsView

History of MI or unstable cardiac disease, seizure; hypomania or mania, increased intraocular pressure or at risk of acute narrow-angle galaucoma, at risk of bleeding. Renal and hepatic impairment. Gradual dose reduction is recommended rather than abrupt withdrawal. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery.

InteractionsView

Increased risk of serotonin syndrome with TCA, SSRI, SNRI, lithium, sibutramine, tramadol. May increase serum levels with CYP3A4 inhibitors (e.g. ketoconazole, atazanavir, clarithromycin). May increase serum levels of haloperidol. May decrease serum levels of indinavir. May increase bleeding risk with aspirin, NSAIDs, warfarin and other anticoagulants.

Pregnancy & lactationView

Treatment Of Pregnant Women During The Third Trimester
Neonates exposed to venlafaxine tablets, USP, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with venlafaxine tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Pediatric usageView

Dosage For Patients With Hepatic Impairment: Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects, it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Dosage For Patients With Renal Impairment: Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals, it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Overdose effectsView

Symptoms: Sweating, dizziness, somnolence, mydriasis, convulsions, vomiting, ECG changes, cardiac arrhythmias and seizures.

Management: Symptomatic and supportive treatment. Ensure adequate airway, oxygenation and ventilation. Initiate gastric lavage immediately after ingestion. Admin activated charcoal to reduce absorption. Monitor cardiac rhythm and vital signs.

StorageView

Store between 20-25° C.

Venlax

Venlafaxine Hydrochloride

Tablet 37.5 mg Allopathic Serotonin-norepinephrine reuptake inhibitor (SNRI)

Indications

Social anxiety disorder

Indication detailsView

Venlafaxine tablets is indicated for the treatment of major depressive disorder.

The efficacy of venlafaxine tablets, in the treatment of major depressive disorder was established in 6 week controlled trials of adult outpatients whose diagnoses corresponded most closely to the DSM-III or DSM-III-R category of major depression and in a 4 week controlled trial of inpatients meeting diagnostic criteria for major depression with melancholia

A major depressive episode implies a prominent and relatively persistent depressed or dysphoric mood that usually interferes with daily functioning (nearly every day for at least 2 weeks); it should include at least 4 of the following 8 symptoms: change in appetite, change in sleep, psychomotor agitation or retardation, loss of interest in usual activities or decrease in sexual drive, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, and a suicide attempt or suicidal ideation.

The efficacy of venlafaxine hydrochloride extended-release capsules in maintaining an antidepressant response for up to 26 weeks following 8 weeks of acute treatment was demonstrated in a placebocontrolled trial. The efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then followed for a period of up to 52 weeks was demonstrated in a second placebo-controlled trial (see Clinical Trials). Nevertheless, the physician who elects to use venlafaxine tablets / extended-release capsules for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Therapeutic classView

Serotonin-norepinephrine reuptake inhibitor (SNRI)

PharmacologyView

The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.

DosageView

Initial Treatment: The recommended starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided doses

Dosage For Elderly Patients: No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.

Maintenance Treatment: It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extendedrelease capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets / extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Discontinuing Venlafaxine Tablet: Symptoms associated with discontinuation of venlafaxine tablets, other SNRIs, and SSRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.

Side effectsView

Changes in behaviour, suicidal ideation, agitation, tremor, nervousness, anxiety, insomnia, confusions, abnormal dreams, HTN, nausea, headache, asthenia, somnolence, dizziness, dry mouth, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain, anorexia, sexual dysfunction, urinary frequency, visual disturbances, mydriasis, vasodilatation, paraesthesia, hypertonia, chills or fever, palpitations, wt gain or loss, arthralgia, myalgia, tinnitus, pruritus, dyspnoea, yawning, rashes, sweating, increased serum cholesterol, may impair platelet aggregation.

ContraindicationsView

Concomitant use with MAOIs or within 14 days of discontinuing the MAOI. Use with linezolid or IV methylene blue.

PrecautionsView

History of MI or unstable cardiac disease, seizure; hypomania or mania, increased intraocular pressure or at risk of acute narrow-angle galaucoma, at risk of bleeding. Renal and hepatic impairment. Gradual dose reduction is recommended rather than abrupt withdrawal. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery.

InteractionsView

Increased risk of serotonin syndrome with TCA, SSRI, SNRI, lithium, sibutramine, tramadol. May increase serum levels with CYP3A4 inhibitors (e.g. ketoconazole, atazanavir, clarithromycin). May increase serum levels of haloperidol. May decrease serum levels of indinavir. May increase bleeding risk with aspirin, NSAIDs, warfarin and other anticoagulants.

Pregnancy & lactationView

Treatment Of Pregnant Women During The Third Trimester
Neonates exposed to venlafaxine tablets, USP, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with venlafaxine tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Pediatric usageView

Dosage For Patients With Hepatic Impairment: Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects, it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Dosage For Patients With Renal Impairment: Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals, it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Overdose effectsView

Symptoms: Sweating, dizziness, somnolence, mydriasis, convulsions, vomiting, ECG changes, cardiac arrhythmias and seizures.

Management: Symptomatic and supportive treatment. Ensure adequate airway, oxygenation and ventilation. Initiate gastric lavage immediately after ingestion. Admin activated charcoal to reduce absorption. Monitor cardiac rhythm and vital signs.

StorageView

Store between 20-25° C.

Venofer

Iron Sucrose Injection [Elemental Iron]

IV Injection or Infusion 100 mg/5 ml Allopathic Parenteral Iron Preparations

Indications

Peritoneal dialysis dependent-chronic kidney disease (PDD-CKD) patients receiving an erythropoietin

Indication detailsView

This is indicated for the treatment of Iron deficiency in the following indications:

Where there is a clinical need for a rapid Iron supply
In patients who can not tolerate oral Iron therapy or who are non-compliant
In active inflammatory bowel disease where oral Iron preparations are ineffective
Non-dialysis dependent-chronic kidney disease (NDD-CKD) patients receiving an erythropoietin
Non-dialysis dependent-chronic kidney disease (NDD-CKD) patients not receiving an erythropoietin
Hemodialysis dependent-chronic kidney disease (HDD-CKD) patients receiving an erythropoietin
Peritoneal dialysis dependent-chronic kidney disease (PDD-CKD) patients receiving an erythropoietin
It is also indicated in the treatment of Iron deficiency anaemia in patients undergoing surgical procedures, patients donating blood, postpartum patients.

Therapeutic classView

Parenteral Iron Preparations

PharmacologyView

The therapeutic class of Iron Sucrose is haematinic. Iron Sucrose Injection USP is a brown, sterile, aqueous, complex of Polynuclear Iron (III) Hydroxide in Sucrose for Intravenous use. The drug product contains approximately 30% Sucrose w/v (300 mg/ml) and has a pH of 10.5-11.1. Following intravenous administration, Iron Sucrose Injection is dissociated into Iron and Sucrose by the reticuloendothelial system, and Iron is transferred from the blood to a pool of Iron in the liver and bone marrow. Ferritin, an Iron storage protein, binds and sequesters Iron in a nontoxic form, from which Iron is easily available. Iron binds to plasma transferrin, which carries Iron within the plasma and the extracellular fluid to supply the tissues. The transferrin receptor, located in the cell, and the transferrin-receptor complex is returned to the cell membrane. Transferrin without Iron (apotransferrin) is then released to the plasma. The intracellular Iron becomes (mostly) haemoglobin in circulating red blood cells (RBCs). Transferrin synthesis is increased and ferritin production reduced in Iron deficiency. The converse is true when Iron is plentiful. Its elimination halflife is 6 h, total clearance is 1.2 L/h, non-steady state apparent volume of distribution is 10.0 L and steady state apparent volume of distribution is 7.9 L. In Iron Sucrose, its Iron component appears to distribute mainly in blood and to some extent in extravascular fluid. A significant amount of the administered Iron distributes in the liver, spleen and bone marrow and that the bone marrow is an Iron trapping compartment and not a reversible volume distribution. The sucrose component is eliminated mainly through urinary excretion.

DosageView

Adults and Elderly: 5-10 ml Iron Sucrose Injection (100-200 mg Iron) once to three times a week depending on the hemoglobin level.

Children: There is limited data on children under study conditions. If there is a clinical need, it is recommended not to exceed 0.15 ml Iron Sucrose Injection (3 mg Iron) per kg body weight once to three times per week depending on the haemoglobin level.

AdministrationView

Intravenous injection: Iron Sucrose Injection can also be administered undiluted by slow intravenous injection at the (normal) recommended rate of 1 ml Iron Sucrose Injection (20 mg Iron) per minute [5 ml Iron Sucrose Injection (100 mg Iron) in 2 to 5 minutes]. A maximum of 10 ml Iron Sucrose Injection (200 mg Iron) can be injected per injection. Before administration of the therapeutic dose in a new patient, a test dose of 1 ml Iron Sucrose Injection (20 mg Iron) in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg Iron/kg) in children with a body weight less than 14 kg should be injected over 1 to 2 minutes. If no adverse reactions occur within a waiting period of 15 minutes, the remaining portion of the injection can be administered at recommended speed. After an injection the arm of the patient should be extended.

Infusion: Iron Sucrose Injection should preferably be administered by drip infusion (in order to reduce the risk of hypotensive episodes and paravenous injection) in a dilution of 1 ml Iron Sucrose Injection (20 mg Iron) in max. 20 ml 0.9% w/v Sodium Chloride [5 ml (100 mg Iron) in max. 100 ml 0.9% w/v NaCI etc. up to 25 ml (500 mg Iron) in max. 500 ml 0.9% w/v NaCI]. Dilution must take place immediately prior to infusion and the solution should be administered as follows: 100 mg Iron in at least 15 minutes; 200 mg Iron in at least 30 minutes; 400 mg Iron In at least 1.5 hours, and 500 mg Iron in at least 3.5 hours. Further of the maximum tolerated single dose of 7 mg Iron/kg body weight, an Infusion time of at least 3.5 hours has to be respected, independently of the total dose.

Before administration of the therapeutic dose in a new patient the first 20 mg Iron in adults and in children with a body weight greater than 14 kg and half the daily dose (1.5 mg lron/kg) in children with a body weight less than 14 kg should be infused over 15 minutes as a test dose. If no adverse reactions occur, the remaining portion of the infusion can be administered at recommended speed.

Side effectsView

Adverse reactions, whether or not related to Iron Sucrose injection are as follows: hypotension, cramps/leg cramps, nausea, headache, vomiting, and diarrhea. Some of these symptoms may be seen in patients with chronic renal failure or on hemodialysis not receiving intravenous iron.
Body as a Whole: headache, fever, pain, asthenia, unwell, malaise, accidental injury. Cardiovascular Disorders
General: hypotension, chest pain, hypertension, hypervolemia.
Gastrointestinal Disorders: nausea, vomiting, abdominal pain, elevated liver enzymes.
Central and Peripheral Nervous System: dizziness.
Musculoskeletal System: cramps/leg cramps, musculoskeletal pain.
Respiratory System: dyspnea pneumonia, cough.
Skin and appendages: pruritus, application site reaction.
Hypersensitivity reactions: In safety studies, several patients experienced mild or moderate hypersensitivity reactions presenting with wheezing, dyspnea, hypotension, rashes, or pruritus. Anaphylactoid reactions including patients who experienced serious or life-threatening reactions (anaphylactic shock, loss of consciousness or collapse, bronchospasm with dyspnea, or convulsion) associated with Iron Sucrose administration can occur. So, patients should be given a small test dose initially.

ContraindicationsView

The use of Iron Sucrose is contraindicated in patients with evidence of Iron overload, in patients with known hypersensitivity to Iron Sucrose or any of its inactive components, and in patients with anaemia not caused by Iron deficiency. It is also contraindicated in patients with history of allergic disorders including asthma, eczema and anaphylaxis, liver disease and infections.

PrecautionsView

General: Because body Iron excretion is limited and excess tissue Iron can be hazardous, caution should be exercised to withhold Iron administration in the presence of evidence of tissue Iron overload. Patients receiving Iron Sucrose require periodic monitoring of hematologic and haematinic parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Iron therapy should be withheld in patients with evidence of Iron overload. Transferrin saturation values increase rapidly after IV administration of Iron Sucrose; thus, serum Iron values may be reliably obtained 48 hours after IV dosing.

Hypersensitivity Reactions: Serious hypersensitivity reactions have been rarely reported in patients receiving Iron Sucrose. Several cases of mild or moderate hypersensitivity reactions were observed in these studies.

Hypotension: Hypotension has been reported frequently in hemodialysis patients receiving intravenous Iron. Hypotension following administration of Iron Sucrose may be related to rate of administration and total dose administered. Caution should be taken to administer Iron Sucrose according to recommended guidelines.

InteractionsView

Drug-drug interactions involving Iron Sucrose have not been studied. Iron Sucrose Injection should not be administered concomitantly with oral iron preparations since the absorption of oral Iron is reduced. Even oral Iron therapy should not be given until 5 days after last injection.

Pregnancy & lactationView

Pregnancy Category-B. No adequate and well controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Iron Sucrose is administered to a nursing woman.

Pediatric usageView

Pediatric Use: Safety and effectiveness of Iron Sucrose in pediatric patients have not been established.

Geriatric Use: No overall differences in safety were observed between the elder subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Injection into dialyser: Iron Sucrose Injection may be administered directly into the venous limb of the dialyser under the same conditions as for intravenous injection.

Hemodialysis Dependent-Chronic Kidney Disease Patients (HDD-CKD): Iron Sucrose Injection may be administered undiluted as a 100 mg slow intravenous injection over 2 to 5 minutes or as an infusion of 100 mg, diluted in a maximum of 100 ml of 0.9% NaCI over a period of at least 15 minutes per consecutive hemodialysis session for a total cumulative dose of 1,000 mg.

Non-Dialysis Dependent-Chronic Kidney Disease Patient (NDD-CKD): Iron Sucrose Injection is administered as a total cumulative dose 1000 mg over a 14 day period as a 200 mg slow IV injection undiluted over 2 to 5 minutes on 5 different occasions within the 14 day period.

Overdose effectsView

Dosages of Iron Sucrose Injection in excess of Iron needs may lead to accumulation of Iron in storage sites leading to hemosiderosis. Periodic monitoring of Iron parameters such as serum ferritin and transferrin saturation may assist in recognizing Iron accumulation. Iron Sucrose should not be administered to patients with Iron overload and should be discontinued when serum ferritin levels equal or exceed established guidelines. Particular caution should be exercised to avoid Iron overload where anaemia unresponsive to treatment has been incorrectly diagnosed as Iron deficiency anaemia. Symptoms associated with overdosage or infusing Iron Sucrose too rapidly included hypotension, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema. and cardiovascular collapse. Most symptoms have been successfully treated with IV fluids, hydrocortisone, and/or antihistamines. Infusing the solution as recommended or at a slower rate may also alleviate symptoms.

StorageView

Store in a cool (15°C- 30°C) & dry place, protected from light. Keep out of the reach of children. Do not freeze.

Venol

Salbutamol

Syrup 2 mg/5 ml Allopathic Short-acting selective & β2-adrenoceptor stimulants

Indications

Emphysema

Indication detailsView

Salbutamol is indicated as a bronchodilator for use in-

Asthma
Chronic Bronchitis
Emphysema and
Other conditions associated with airways obstruction.

Therapeutic classView

Short-acting selective & β2-adrenoceptor stimulants

PharmacologyView

Salbutamol is a synthetic sympathomimetic agent with predominant beta-2 adrenergic activity. Salbutamol produces bronchodilatation through stimulation of beta-2-adrenergic receptors in bronchial smooth muscles, thereby causing relaxation of bronchial muscle fibers. This action is manifested by an improvement in pulmonary function as demonstrated by spirometric measurements.

DosageView

Salbutamol tablet or syrup-
Children:

2-6 years: 2.5 ml syrup, 3-4 times daily
6-12 years: 5 ml syrup, 3-4 times daily
Over 12 years: 5-10 ml syrup, 3-4 times daily (2-4 mg tablet, 3-4 times daily)

Adults: 2-4 mg tablet, 3-4 times daily. Maximum single dose is 8 mg tablet.

Salbutamol Respirator Solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Method-1 (Intermittent Administration):

Adults (and the elderly): 0.5 ml-1.0 ml salbutamol up to four times a day. Up to 40mg per day can be given under strict medical direction in the hospital. 0.5-1 ml solution should be diluted to final volume of 2-4 ml with sterile normal saline solution. It will take time about 10 minutes.
Salbutamol respiratory solution may be used undiluted for intermittent administration. For this 2.0 ml of the solution is placed in the nebulizer and the patient allowed to inhale until bronchodilation is achieved. This usually takes 3-5 minutes.
Children under 12 years of age: 0.5 ml of the solution diluted to 2.0-4.0 ml with normal saline. Some children may however require higher doses of up to 1.0 ml of the solution. Intermittent treatment may be repeated four times a day.

Method-2 (Continuous administration): 1-2 ml solution is diluted to make up to 100 ml with normal saline solution. The diluted solution is administered by a suitable nebulizer devise. When there is risk of anoxia through hypoventilation, oxygen should be added to the inspired air.

Salbutamol nebulizer solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Adults & Elderly: 2.5 mg to 5 mg Salbutamol up to 4 times a day. Up to 40 mg/day may be given under strict medical direction in the hospital.
Children under 12 years: 2.5 mg up to 4 times a day. A higher dose up to 5 mg four times a day may be used if required.

Salbutamol injection:
Adults:

Salbutamol I.V. infusion solution is used to prepare a solution for continuous intravenous infusion. It should not be injected undiluted. A suitable solution for infusion may be prepared by diluting 5 mL of Salbutamol I.V. infusion solution (1000 mcg/mL) in 500 mL of a chosen i.v. solution to provide a salbutamol concentration of 10 mcg/mL.
The only recommended diluents are Sodium Chloride Injection, or Sodium Chloride and Dextrose Injection.
Infusion rates providing 3 to 20 micrograms salbutamol/minute (0.3 to 2ml/minute of the above infusion solution) are usually adequate. Infusion rates can be started at 5 mcg of salbutamol/min., and can be increased to 10 mcg/min., and 20 mcg/min. at 15 - 30 minute intervals, if necessary.
As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration.
All unused admixtures of Salbutamol infusion solution with infusion fluids should be discarded 24 hours after preparation.

Children and Adolescents (<18 years of age): The dosage of Salbutamol infusion solution in the pediatric age group has not been established. At present, there are insufficient data to recommend a dosage regimen for children.

Salbutamol Inhalation Capsule:

Adults: For the relief of bronchospasm and for managing intermittent episodes of asthma, one or two inhalation capsule may be administered as a single dose. The usual recommended dosage of Salbutamol inhalation capsule for inhalation for adults for maintenance or prophylactic therapy is the contents of one 200 microgram capsule every 4 to 6 hours using a device. In some patients, the contents of two 200 microgram capsules inhaled every 4 to 6 hours may be required. Large doses or more frequent administration is not recommended. The use of salbutamol powder for inhalation can be continued as medically indicated to control recurring/intermittent episodes of bronchospasm.
Children: One Salbutamol inhalation capsule is the recommended dose for relief of acute bronchospasm in the maintenance of episodic asthma or before exercise of children 4 years of age and older. One inhalation should be administered for three or four times a day for routine maintenance or prophylactic therapy. This dosage may be increased to inhalation of two inhalation capsule, if necessary. The bronchodilator effect of each administration of inhaled Salbutamol inhalation capsule lasts for at least four hours. Such patients should be warned not to increase the dose of inhaler, but should seek medical advice immediately.

Excercise-induced Asthma:

Adults: 400 microgram
Child: 200 microgram, 15-30 minutes prior to any physical exertion.

Side effectsView

Salbutamol may cause fine tremor of skeletal muscles (particularly the hands), palpitations and muscle cramps. Tachycardia, tenseness, headaches and peripheral vasodilatation have been reported after large doses.

PrecautionsView

Salbutamol should be used with caution in patients with hyperthyroidism, cardiovascular disease, occlusive vascular disorders, hypertension and aneurysms. Hypokalaemia associated with high doses of Salbutamol may result in increased susceptibility to digitalis-induced cardiac arrhythmia. Tachyphylaxis with resistance may occur with prolonged use of high dosage. Care is necessary when treating patients with diabetes mellitus or closed angle glaucoma, and in those receiving antihypertensive therapy.

Pregnancy & lactationView

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Overdose effectsView

The symptoms with overdosage are angina, headache, nausea, vomiting, tremor etc. The preferred antidote for overdosage with Salbutamol is a cardio-selective beta-blocking agent but beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

StorageView

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Ventair

Montelukast Sodium

Chewable Tablet 5 mg Allopathic Leukotriene receptor antagonists

Indications

Rhinitis

Indication detailsView

Montelukast Sodium is indicated for:

Prophylaxis and chronic treatment of asthma
Acute prevention of Exercise-Induced Bronchoconstriction (EIB)
Relief of symptoms of Allergic Rhinitis (AR): Seasonal & Perennial Allergic Rhinitis

Therapeutic classView

Leukotriene receptor antagonists

PharmacologyView

Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor (CysLT₁). The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma & allergic rhinitis, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

DosageView

Adults & adolescents (15 years & older)-

Asthma & Allergic Rhinitis: 10 mg/day
Exercise-Induced Bronchoconstriction: 10 mg/day

Pediatric patients (6 to 14 years)-

Asthma & Allergic Rhinitis: 5 mg/day
Exercise-Induced Bronchoconstriction: 5 mg/day

Pediatric patients (6 months to 5 years)-

Asthma & Allergic Rhinitis: 4 mg/day
Exercise-Induced Bronchoconstriction: Not recommended

Patients with both asthma and allergic rhinitis should take only one dose daily in the evening. For prevention of Acute prevention of Exercise-Induced Bronchoconstriction, a single dose should be taken at least 2 hours before exercise.

AdministrationView

Route of administration: Oral. Montelukast may be taken with or without food or as directed by the physician.

Side effectsView

Common: Diarrhoea, fever, gastrointestinal discomfort, headache, nausea, vomiting, skin reactions, upper respiratory tract infection.

Uncommon: Akathisia, anxiety, arthralgia, asthenia, abnormal behavior, depression, dizziness, drowsiness, dry mouth, haemorrhage, irritability, malaise, muscle complaints, oedema, seizure, abnormal sensation, sleep disorders.

Rare: Angioedema, concentration impaired, disorientation, eosinophilic granulomatosis with polyangiitis, erythema nodosum, hallucination, hepatic disorders, memory loss, palpitations, pulmonary eosinophilia, suicidal tendencies, tremor.

ContraindicationsView

Montelukast is contraindicated in patients who are hypersensitive to any component of this product.

PrecautionsView

Montelukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmatic. Neuropsychiatric events including agitation, hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide) and tremor.

InteractionsView

With medicine: No dose adjustment is needed when montelukast is co-administered with theophylline, prednisone, prednisolone, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative-hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, oral contraceptives, and Cytochrome P450 (CYP) enzyme inducers.

With food and others: Bioavailability and other conditions were not significantly observed with food & other conditions.

Pregnancy & lactationView

There are no adequate and well-controlled studies in pregnant women. Montelukast should be used during pregnancy only if clearly needed. Montelukast is excreted in breast milk. So caution should be exercised when Montelukast is given to a nursing mother.

Overdose effectsView

There were no adverse experiences in the majority of overdosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of Montelukast and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

StorageView

Store in cool & dry place below 30°C, protect from light & moisture. Keep out of reach of children.

Ventair

Montelukast Sodium

Tablet 10 mg Allopathic Leukotriene receptor antagonists

Indications

Rhinitis

Indication detailsView

Montelukast Sodium is indicated for:

Prophylaxis and chronic treatment of asthma
Acute prevention of Exercise-Induced Bronchoconstriction (EIB)
Relief of symptoms of Allergic Rhinitis (AR): Seasonal & Perennial Allergic Rhinitis

Therapeutic classView

Leukotriene receptor antagonists

PharmacologyView

Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene receptor (CysLT₁). The cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma & allergic rhinitis, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

DosageView

Adults & adolescents (15 years & older)-

Asthma & Allergic Rhinitis: 10 mg/day
Exercise-Induced Bronchoconstriction: 10 mg/day

Pediatric patients (6 to 14 years)-

Asthma & Allergic Rhinitis: 5 mg/day
Exercise-Induced Bronchoconstriction: 5 mg/day

Pediatric patients (6 months to 5 years)-

Asthma & Allergic Rhinitis: 4 mg/day
Exercise-Induced Bronchoconstriction: Not recommended

Patients with both asthma and allergic rhinitis should take only one dose daily in the evening. For prevention of Acute prevention of Exercise-Induced Bronchoconstriction, a single dose should be taken at least 2 hours before exercise.

AdministrationView

Route of administration: Oral. Montelukast may be taken with or without food or as directed by the physician.

Side effectsView

Common: Diarrhoea, fever, gastrointestinal discomfort, headache, nausea, vomiting, skin reactions, upper respiratory tract infection.

Uncommon: Akathisia, anxiety, arthralgia, asthenia, abnormal behavior, depression, dizziness, drowsiness, dry mouth, haemorrhage, irritability, malaise, muscle complaints, oedema, seizure, abnormal sensation, sleep disorders.

Rare: Angioedema, concentration impaired, disorientation, eosinophilic granulomatosis with polyangiitis, erythema nodosum, hallucination, hepatic disorders, memory loss, palpitations, pulmonary eosinophilia, suicidal tendencies, tremor.

ContraindicationsView

Montelukast is contraindicated in patients who are hypersensitive to any component of this product.

PrecautionsView

Montelukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmatic. Neuropsychiatric events including agitation, hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide) and tremor.

InteractionsView

With medicine: No dose adjustment is needed when montelukast is co-administered with theophylline, prednisone, prednisolone, terfenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative-hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, oral contraceptives, and Cytochrome P450 (CYP) enzyme inducers.

With food and others: Bioavailability and other conditions were not significantly observed with food & other conditions.

Pregnancy & lactationView

There are no adequate and well-controlled studies in pregnant women. Montelukast should be used during pregnancy only if clearly needed. Montelukast is excreted in breast milk. So caution should be exercised when Montelukast is given to a nursing mother.

Overdose effectsView

There were no adverse experiences in the majority of overdosage reports. The most frequently occurring adverse experiences were consistent with the safety profile of Montelukast and included abdominal pain, somnolence, thirst, headache, vomiting and psychomotor hyperactivity. In the event of overdose, it is reasonable to employ the usual supportive measures; e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

StorageView

Store in cool & dry place below 30°C, protect from light & moisture. Keep out of reach of children.

Ventel

Salbutamol

Syrup 2 mg/5 ml Allopathic Short-acting selective & β2-adrenoceptor stimulants

Indications

Emphysema

Indication detailsView

Salbutamol is indicated as a bronchodilator for use in-

Asthma
Chronic Bronchitis
Emphysema and
Other conditions associated with airways obstruction.

Therapeutic classView

Short-acting selective & β2-adrenoceptor stimulants

PharmacologyView

Salbutamol is a synthetic sympathomimetic agent with predominant beta-2 adrenergic activity. Salbutamol produces bronchodilatation through stimulation of beta-2-adrenergic receptors in bronchial smooth muscles, thereby causing relaxation of bronchial muscle fibers. This action is manifested by an improvement in pulmonary function as demonstrated by spirometric measurements.

DosageView

Salbutamol tablet or syrup-
Children:

2-6 years: 2.5 ml syrup, 3-4 times daily
6-12 years: 5 ml syrup, 3-4 times daily
Over 12 years: 5-10 ml syrup, 3-4 times daily (2-4 mg tablet, 3-4 times daily)

Adults: 2-4 mg tablet, 3-4 times daily. Maximum single dose is 8 mg tablet.

Salbutamol Respirator Solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Method-1 (Intermittent Administration):

Adults (and the elderly): 0.5 ml-1.0 ml salbutamol up to four times a day. Up to 40mg per day can be given under strict medical direction in the hospital. 0.5-1 ml solution should be diluted to final volume of 2-4 ml with sterile normal saline solution. It will take time about 10 minutes.
Salbutamol respiratory solution may be used undiluted for intermittent administration. For this 2.0 ml of the solution is placed in the nebulizer and the patient allowed to inhale until bronchodilation is achieved. This usually takes 3-5 minutes.
Children under 12 years of age: 0.5 ml of the solution diluted to 2.0-4.0 ml with normal saline. Some children may however require higher doses of up to 1.0 ml of the solution. Intermittent treatment may be repeated four times a day.

Method-2 (Continuous administration): 1-2 ml solution is diluted to make up to 100 ml with normal saline solution. The diluted solution is administered by a suitable nebulizer devise. When there is risk of anoxia through hypoventilation, oxygen should be added to the inspired air.

Salbutamol nebulizer solution: To be used with a suitable nebulizer device under the direction of a physician. The solution must not be injected or ingested.

Adults & Elderly: 2.5 mg to 5 mg Salbutamol up to 4 times a day. Up to 40 mg/day may be given under strict medical direction in the hospital.
Children under 12 years: 2.5 mg up to 4 times a day. A higher dose up to 5 mg four times a day may be used if required.

Salbutamol injection:
Adults:

Salbutamol I.V. infusion solution is used to prepare a solution for continuous intravenous infusion. It should not be injected undiluted. A suitable solution for infusion may be prepared by diluting 5 mL of Salbutamol I.V. infusion solution (1000 mcg/mL) in 500 mL of a chosen i.v. solution to provide a salbutamol concentration of 10 mcg/mL.
The only recommended diluents are Sodium Chloride Injection, or Sodium Chloride and Dextrose Injection.
Infusion rates providing 3 to 20 micrograms salbutamol/minute (0.3 to 2ml/minute of the above infusion solution) are usually adequate. Infusion rates can be started at 5 mcg of salbutamol/min., and can be increased to 10 mcg/min., and 20 mcg/min. at 15 - 30 minute intervals, if necessary.
As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discoloration and leakage prior to administration.
All unused admixtures of Salbutamol infusion solution with infusion fluids should be discarded 24 hours after preparation.

Children and Adolescents (<18 years of age): The dosage of Salbutamol infusion solution in the pediatric age group has not been established. At present, there are insufficient data to recommend a dosage regimen for children.

Salbutamol Inhalation Capsule:

Adults: For the relief of bronchospasm and for managing intermittent episodes of asthma, one or two inhalation capsule may be administered as a single dose. The usual recommended dosage of Salbutamol inhalation capsule for inhalation for adults for maintenance or prophylactic therapy is the contents of one 200 microgram capsule every 4 to 6 hours using a device. In some patients, the contents of two 200 microgram capsules inhaled every 4 to 6 hours may be required. Large doses or more frequent administration is not recommended. The use of salbutamol powder for inhalation can be continued as medically indicated to control recurring/intermittent episodes of bronchospasm.
Children: One Salbutamol inhalation capsule is the recommended dose for relief of acute bronchospasm in the maintenance of episodic asthma or before exercise of children 4 years of age and older. One inhalation should be administered for three or four times a day for routine maintenance or prophylactic therapy. This dosage may be increased to inhalation of two inhalation capsule, if necessary. The bronchodilator effect of each administration of inhaled Salbutamol inhalation capsule lasts for at least four hours. Such patients should be warned not to increase the dose of inhaler, but should seek medical advice immediately.

Excercise-induced Asthma:

Adults: 400 microgram
Child: 200 microgram, 15-30 minutes prior to any physical exertion.

Side effectsView

Salbutamol may cause fine tremor of skeletal muscles (particularly the hands), palpitations and muscle cramps. Tachycardia, tenseness, headaches and peripheral vasodilatation have been reported after large doses.

PrecautionsView

Salbutamol should be used with caution in patients with hyperthyroidism, cardiovascular disease, occlusive vascular disorders, hypertension and aneurysms. Hypokalaemia associated with high doses of Salbutamol may result in increased susceptibility to digitalis-induced cardiac arrhythmia. Tachyphylaxis with resistance may occur with prolonged use of high dosage. Care is necessary when treating patients with diabetes mellitus or closed angle glaucoma, and in those receiving antihypertensive therapy.

Pregnancy & lactationView

The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether this drug is excreted in human milk. Because of the potential of tumorigenecity shown for Salbutamol in some animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Overdose effectsView

The symptoms with overdosage are angina, headache, nausea, vomiting, tremor etc. The preferred antidote for overdosage with Salbutamol is a cardio-selective beta-blocking agent but beta-blocking drugs should be used with caution in patients with a history of bronchospasm.

StorageView

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Venterol

Bambuterol Hydrochloride

Oral Solution 5 mg/5 ml Allopathic Short-acting selective & β2-adrenoceptor stimulants

Indications

H. pylori infection

Indication detailsView

Bambuterol is indicated for Bronchial asthma, chronic bronchitis, emphysema & other lung diseases where bronchospasm is a complicating factor.

Therapeutic classView

Short-acting selective & β2-adrenoceptor stimulants

PharmacologyView

Bambuterol is an adrenergic β2 receptor agonist which predominantly stimulates β2 receptor, thus producing relaxation of bronchial smooth muscle, inhibition of release of endogenous spasmogens, inhibition of edema caused by endogenous mediators & increased mucocilliary clearance.

DosageView

Adult or Elderly: The recommended initial dose 10 mg. The dose may be increased to 20 mg after 1-2 weeks depending on the clinical effect.

Children 2-5 years: The recommended normal dose 10 mg (10 ml syrup).

Children 6-12 years: The recommended normal dose 10 mg (10 ml syrup). The dose may be increased to 20 mg.

Side effectsView

Common side effects are fatigue, nausea, palpitation, headache, dizziness & tremor.

ContraindicationsView

Bambuterol is contraindicated in hepatic impairment, liver cirrhosis or severely impaired liver function.

PrecautionsView

Reduce the dose in renal impairment, avoid in cirrhosis and severe hepatic impairment. Caution should be observed in patients with severe cardiovascular disorder, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.

InteractionsView

Succinylcholin, MAOIs (monoamine oxidase inhibitors), β2-blockers, corticosteroids, diuretics, muscle relaxants, sympathomimetic xanthine derivatives. Bambuterol may partly or totally inhibit the effect of β-blockers.

Pregnancy & lactationView

Pregnant women: There is no definite evidence of ill consequence during pregnancy. Nevertheless, the drug should not be used during the first trimester of pregnancy, unless the expected benefit is thought to outweigh any possible risk to the fetus.

Lactating mother: It is excreted in breast milk. So, patients taking this drug should not breast-feed.

Pediatric usageView

Impaired renal function (GFR 50 ml/min): The recommended starting dose is 5 mg, which may be increased to 10 mg after one to two weeks, depending on the clinical effect.

Impaired hepatic function: Not recommended because of unpredictable conversion to terbutaline.

StorageView

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Venterol

Bambuterol Hydrochloride

Tablet 20 mg Allopathic Short-acting selective & β2-adrenoceptor stimulants

Indications

H. pylori infection

Indication detailsView

Bambuterol is indicated for Bronchial asthma, chronic bronchitis, emphysema & other lung diseases where bronchospasm is a complicating factor.

Therapeutic classView

Short-acting selective & β2-adrenoceptor stimulants

PharmacologyView

Bambuterol is an adrenergic β2 receptor agonist which predominantly stimulates β2 receptor, thus producing relaxation of bronchial smooth muscle, inhibition of release of endogenous spasmogens, inhibition of edema caused by endogenous mediators & increased mucocilliary clearance.

DosageView

Adult or Elderly: The recommended initial dose 10 mg. The dose may be increased to 20 mg after 1-2 weeks depending on the clinical effect.

Children 2-5 years: The recommended normal dose 10 mg (10 ml syrup).

Children 6-12 years: The recommended normal dose 10 mg (10 ml syrup). The dose may be increased to 20 mg.

Side effectsView

Common side effects are fatigue, nausea, palpitation, headache, dizziness & tremor.

ContraindicationsView

Bambuterol is contraindicated in hepatic impairment, liver cirrhosis or severely impaired liver function.

PrecautionsView

Reduce the dose in renal impairment, avoid in cirrhosis and severe hepatic impairment. Caution should be observed in patients with severe cardiovascular disorder, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.

InteractionsView

Succinylcholin, MAOIs (monoamine oxidase inhibitors), β2-blockers, corticosteroids, diuretics, muscle relaxants, sympathomimetic xanthine derivatives. Bambuterol may partly or totally inhibit the effect of β-blockers.

Pregnancy & lactationView

Pregnant women: There is no definite evidence of ill consequence during pregnancy. Nevertheless, the drug should not be used during the first trimester of pregnancy, unless the expected benefit is thought to outweigh any possible risk to the fetus.

Lactating mother: It is excreted in breast milk. So, patients taking this drug should not breast-feed.

Pediatric usageView

Impaired renal function (GFR 50 ml/min): The recommended starting dose is 5 mg, which may be increased to 10 mg after one to two weeks, depending on the clinical effect.

Impaired hepatic function: Not recommended because of unpredictable conversion to terbutaline.

StorageView

Keep away from light, store in a cool and dry place. Keep out of reach of children.

Venterol

Bambuterol Hydrochloride

Tablet 10 mg Allopathic Short-acting selective & β2-adrenoceptor stimulants

Indications

H. pylori infection

Indication detailsView

Bambuterol is indicated for Bronchial asthma, chronic bronchitis, emphysema & other lung diseases where bronchospasm is a complicating factor.

Therapeutic classView

Short-acting selective & β2-adrenoceptor stimulants

PharmacologyView

Bambuterol is an adrenergic β2 receptor agonist which predominantly stimulates β2 receptor, thus producing relaxation of bronchial smooth muscle, inhibition of release of endogenous spasmogens, inhibition of edema caused by endogenous mediators & increased mucocilliary clearance.

DosageView

Adult or Elderly: The recommended initial dose 10 mg. The dose may be increased to 20 mg after 1-2 weeks depending on the clinical effect.

Children 2-5 years: The recommended normal dose 10 mg (10 ml syrup).

Children 6-12 years: The recommended normal dose 10 mg (10 ml syrup). The dose may be increased to 20 mg.

Side effectsView

Common side effects are fatigue, nausea, palpitation, headache, dizziness & tremor.

ContraindicationsView

Bambuterol is contraindicated in hepatic impairment, liver cirrhosis or severely impaired liver function.

PrecautionsView

Reduce the dose in renal impairment, avoid in cirrhosis and severe hepatic impairment. Caution should be observed in patients with severe cardiovascular disorder, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.

InteractionsView

Succinylcholin, MAOIs (monoamine oxidase inhibitors), β2-blockers, corticosteroids, diuretics, muscle relaxants, sympathomimetic xanthine derivatives. Bambuterol may partly or totally inhibit the effect of β-blockers.

Pregnancy & lactationView

Pregnant women: There is no definite evidence of ill consequence during pregnancy. Nevertheless, the drug should not be used during the first trimester of pregnancy, unless the expected benefit is thought to outweigh any possible risk to the fetus.

Lactating mother: It is excreted in breast milk. So, patients taking this drug should not breast-feed.

Pediatric usageView

Impaired renal function (GFR 50 ml/min): The recommended starting dose is 5 mg, which may be increased to 10 mg after one to two weeks, depending on the clinical effect.

Impaired hepatic function: Not recommended because of unpredictable conversion to terbutaline.

StorageView

Keep away from light, store in a cool and dry place. Keep out of reach of children.