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Paroxetine  is indicated in:

• Major Depressive Disorder
• Obsessive Compulsive Disorder
• Panic Disorder
• Social Anxiety Disorder
• Generalized Anxiety Disorder
• Posttraumatic Stress Disorder.

SSRIs & related anti-depressant drugs

The efficacy of Paroxetine is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5 HT). Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1, alpha2, beta adrenergic, dopamine (D2), 5-HT1, 5 HT2 and histamine (H1)-receptors; antagonism of muscarinic, histaminergic and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative and cardiovascular effects for other psychotropic drugs. Because the relative potencies of paroxetine’s major metabolites are at most 1/50 of the parent compound, they are essentially inactive.

Major Depressive Disorder:

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dose is 20 mg/day. Some patients not responding to a 20 mg dose may benefit from dose increases, in 10 mg/day increments, up to a maximum of 50 mg/day. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Systematic evaluation of the efficacy of Paroxetine hydrochloride has shown that efficacy is maintained for periods of up to 1 year with doses that averaged about 30 mg.

Obsessive Compulsive Disorder (OCD):

• Usual Initial Dosage: Paroxetine (Paroxetine hydrochloride) should be administered as a single daily dose with or without food, usually in the morning. The recommended dose of Paroxetine in the treatment of OCD is 40 mg daily. Patients should be started on 20 mg/day and the dose can be increased in 10 mg/day increments. Dose changes should occur at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Panic Disorder:

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The target dose of Paroxetine in the treatment of panic disorder is 40 mg/day. Patients should be started on 10 mg/day. Dose changes should occur in 10 mg/day increments and at intervals of at least 1 week. The maximum dosage should not exceed 60 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Social Anxiety Disorder (SAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended initial dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Generalized Anxiety Disorder (GAD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Posttraumatic Stress Disorder (PTSD):

• Usual Initial Dosage: Paroxetine should be administered as a single daily dose with or without food, usually in the morning. The recommended starting dosage and the established effective dosage is 20 mg/day. Dose changes, if indicated, should occur in 10 mg/day increments and at intervals of at least 1 week.
• Maintenance Therapy: Dosage adjustments should be made to maintain the patient on the lowest effective dosage, and patients should be periodically reassessed to determine the need for continued treatment.

Major depressive disorder: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance and other male genital disorders.

Obsessive compulsive disorder: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence and abnormal ejaculation.

Panic disorder: Asthenia, sweating, decreased appetite, decreased libido , tremor, abnormal ejaculation, female genital disorders and impotence.

Social anxiety disorder: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, decreased libido, yawn, abnormal ejaculation, female genital disorders and impotence.

Generalised anxiety disorder: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, somnolence, tremor, sweating and abnormal
ejaculation.

Post-traumatic stress disorder: Asthenia, sweating nausea, dry mouth, diarrhoea, decreased appetite, somnolence, decreased libido, abnormal ejaculation, female genital disorders and impotence.

Concomitant use in patients taking either monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated. This is contraindicated in patients with a hypersensitivity to Paroxetine.

Cardiac conditions: Paroxetine does not produce clinically significant changes in blood pressure, heart rate and ECG. Nevertheless, as with all psychoactive drugs, caution is advised when treating patients with cardiac conditions.

Epilepsy: As with other antidepressants, Paroxetine should be used with caution in-patients with epilepsy.

Seizures: Overall, the incidence of seizures is < 0.1% in patients treated with Paroxetine. Paroxetine should be discontinued in any patient who develops seizures.

ECT: There is little clinical experience of concurrent administration of Paroxetine with ECT.

Ability to drive/use machines: Clinical experience has shown that therapy with Paroxetine is not associated with impairment of cognitive or psychomotor function. However, as with all psychoactive drugs, patients should be cautioned about their ability to drive a car and operate machinery.

Discontinuation of Treatment with Paroxetine: Recent clinical trials supporting the various approved indications of Paroxetine employed a taper phase regimen, rather than an abrupt discontinuation of treatment. The taper phase regimen used in GAD and PTSD clinical trials involved an incremental decrease in the daily dose by 10 mg/day at weekly intervals. When a daily dose of 20 mg/day was reached, patients were continued on this dose for 1 week before treatment was stopped.

Food/antacids: The absorption and pharmacokinetics of Paroxetine are not affected by food or antacids.

Tryptophan: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and Tryptophan may occur, resulting in a ‘serotonin syndrome’ suggested by a combination of agitation, restlessness and gastrointestinal symptoms including diarrhoea. 

Drug metabolizing enzyme inducers /inhibitors: The metabolism and pharmacokinetics of Paroxetine may be affected by drugs, which induce or inhibit hepatic drug metabolizing enzymes. When Paroxetine is to be coadministered with a known drug metabolizing inhibitor, consideration should be given to using doses at the lower end of the range. No initial dosage adjustment of Paroxetine is considered necessary when it is to be co-administered with known drug metabolizing enzyme inducers. Any subsequent dosage adjustment should be guided by clinical effect (tolerabilityand efficacy).

Alcohol: Although Paroxetine does not increase the impairment of mental and motor skill caused by alcohol, the concomitant use of Paroxetine and alcohol in depressed patients is not advised.

Haloperidol/amylobarbitone/oxazepam: Experience in a limited number of healthy subjects has shown that Paroxetine did not increase the sedation and drowsiness associated with haloperidol, amylobarbitone or oxazepam when given in combination.

MAOls: As with other 5-HT re uptake inhibitors, animal studies indicate that an interaction between Paroxetine and monoamine oxidase (MAO) inhibitors may occur.

Lithium: Since there is little clinical experience, and there have been reports of interaction of lithium with other 5-HT re-uptake inhibitors, the concurrent administration of Paroxetine and lithium should be undertaken with caution.

Lithium levels should be monitored. Phenytoin / anticonvulsants: Co-administration of Paroxetine and phenytoin is associated with decreased plasma concentrations of Paroxetine and increased adverse experiences. Co-administration of Paroxetine with other anticonvulsants may also be associated with an increased incidence of adverse experiences.

Warfarin: Preliminary data suggest that there may be a pharmacodynamic interaction between Paroxetine and warfarin, which may result in increased bleeding in the presence of unaltered prothrombin times. Paroxetine should therefore be administered with great caution to patients receiving oral anticoagulants.

This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery: The effect of Paroxetine on labor and delivery in humans is unknown.

Nursing Mothers: Like many other drugs, Paroxetine is secreted in human milk, and caution should be exercised when Paroxetine hydrochloride is administered to a nursing woman.

Dosage for Elderly or Debilitated, and Patients with Severe Renal or Hepatic Impairment: The recommended initial dose is 10 mg/day for elderly patients, debilitated patients, and/or patients with severe renal or hepatic impairment. Increases may be made if indicated. Dosage should not exceed 40 mg/day.

Keep out of the reach of children. Store at a cool and dry place. Protect from light and moisture.

Angiotensin-ll receptor blocker

Losartan Potassium is the first non-peptide orally active angiotensin II receptor blocker. It binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, kidneys and the heart) and reduces several important biological actions including vasoconstriction and the release of aldosterone responsible for hypertension.

The usual starting and maintenance dose is 50 mg once daily for most patients. If the antihypertensive effect using 50 mg once daily is inadequate, 25 mg twice daily is recommended prior to increasing the dose. For patients with intravascular volume-depletion (e.g., those treated with high-dose diuretics), a starting dose of 25 mg once daily should be considered. Losartan Potassium can be administered once or twice daily. The total daily dose ranges from 25 mg to 100 mg.

The side effects with the use of Losartan Potassium are mild and transient in nature. The most common side effects are dizziness, diarrhea, nasal congestion, cough, upper respiratory infection. Other side effects are fatigue, oedema, abdominal pain, chest pain, nausea, headache & pharyngitis.

Losartan Potassium is contraindicated in pregnant women and in patients who are hypersensitive to any component of this product. Losartan Potassium should not be administered with Aliskiren in patients with diabetes.

Use of Losartan Potassium during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. In patients who are intravascularly volume-depleted (e.g., those treated with high-dose diuretics), symptomatic hypotension may occur. Plasma concentration of Losartan Potassium is significantly increased in cirrhotic patients. Changes in renal function including renal failure have been reported in renal impaired patient.

Rifampicin and fluconazole reduce levels of active metabolite of Losartan Potassium. Concomitant use of Losartan Potassium and hydrochlorothiazide may lead to potentiation of the antihypertensive effects. Concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium may lead to increases in serum potassium. The antihypertensive effect of losartan may be attenuated by the non-steroidal anti-inflammatory drug indomethacin. The use of ACE-inhibitor, angiotensin receptor antagonist, an anti-inflammatory drug and a thiazide diuretic at the same time increases the risk of renal impairment.

Pregnancy Category D. The risk to the fetus increases if Losartan Potassium is administered during the second or third trimesters of pregnancy. It is not known whether Losartan Potassium is excreted in human milk, as many drugs are excreted in human milk and because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

keep in a dry place away from light and heat. Keep out of the reach of children.

This is indicated for the treatment of hypertension. It is also indicated to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy.

Combined antihypertensive preparations

Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT₁ receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT₁ receptor. Neither Losartan nor its active metabolite inhibits ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of Sodium and Chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in Aldosterone secretion, increases in urinary Potassium loss, and decreases in serum Potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an angiotensin II receptor antagonist tends to reverse the Potassium loss associated with these diuretics.

Hypertension-

• The usual starting dose of 50/12.5 is one tablet once daily.
• For patients who do not respond adequately to one tablet the dosage may be increased to 100/25 once daily.
• A patient whose blood pressure is not adequately controlled with Losartan 100 mg monotherapy may be switched to this combination 100/12.5 once daily.
• In hypertensive patients with left ventricular hypertrophy initial dose is 50/12.5, if additional blood pressure reduction is needed, 100/12.5 may be given, followed by 100/25 if required. The maximum dose is 100/25 once daily.
• In general, the antihypertensive effect is attained within three weeks after initiation of therapy.
• No initial dosage adjustment of 50/12.5 is necessary for elderly patients. But maximum dose of 100/25 once daily dose should not be used as initial therapy in elderly patients.

Severe Hypertension:

• The starting dose for initial treatment of severe hypertension is one tablet of 50/12.5 once daily.
• For patients who do not respond adequately to this dose after 2 to 4 weeks of therapy, the dosage may be increased to 100/25 once daily. The maximum dose is one tablet of 100/25 once daily.

This preparation may be administered with other antihypertensive agents. This may be administered with or without food.

Side-effects are usually mild. Symptomatic hypotension including dizziness may occur, particularly in patients with intravascular volume depletion (e.g. those taking high-dose diuretics). Hyperkalaemia occurs occasionally; angioedema has also been reported with some angiotensin-II receptor antagonists. Vertigo; less commonly gastro-intestinal disturbances, angina, palpitation, oedema, dyspnoea, headache, sleep disorders, malaise, urticaria, pruritus, rash; rarely hepatitis, atrial fibrillation, cerebrovascular accident, syncope, paraesthesia; also reported pancreatitis, anaphylaxis, cough, depression, erectile dysfunction, anaemia, thrombocytopenia, hyponatraemia, arthralgia, myalgia, renal impairment, rhabdomyolysis, tinnitus, photosensitivity, and vasculitis (including Henoch-Schonlein purpura)

The combination of Losartan and Hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product. Because of the Hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Losartan Potassium: No significant drug-drug pharmacokinetic interactions have been found in interaction studies with Hydrochlorothiazide, Digoxin, Warfarin, Cimetidine and Phenobarbital. As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (e.g. Spironolactone, Triamterene, Amiloride), potassium supplements, or salt substitutes containing potassium may lead to increase in serum potassium. As with other antihypertensive agents, the antihypertensive effect of Losartan may be blunted by the non-steroidal anti-inflammatory drug Indomethacin.

Hydrochlorothiazide: When administered concurrently, the following drugs may interact with Thiazide diuretics: alcohol, barbiturates, or narcotics-potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and Insulin): dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs: additive effect or potentiation.

Cholestyramine and colestipol resins: absorption of Hydrochlorothiazide is impaired in the presence of anionic exchange resins

Angiotensin-II receptor antagonists should be avoided in pregnancy unless essential. They may adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohy dramnios have also been reported. Information on the use of angiotensin-II receptor antagonists in breastfeeding is limited. They are not recommended in breastfeeding and alternative treatment options, with better-established safety information during breastfeeding, are available.

Use in Patients with Renal Impairment: The usual regimens of therapy with 50/12.5 may be followed as long as the patient's creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides. In that case, hydrochlorothiazide is not recommended.

Use in Patients with Hepatic Impairment: The combination of Losartan and Hydrochlorothiazide is not recommended for titration in patients with hepatic impairment because the appropriate 25 mg starting dose of Losartan cannot be given.

Use in pediatric patients: The safety and effectiveness in pediatric patients have not been established.

Losartan Potassium: Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor its metabolite can be removed by hemodialysis.

Hydrochlorothiazide: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia, may accentuate cardiac arrhythmias. The degree to which Hydrochlorothiazide is removed by hemodialysis has not been established.

Do not store above 30°C. Keep out of the reach of children.

Adjunct anti-epileptic drugs, Benzodiazepine hypnotics

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects. The central actions of benzodiazepines are mediated through an enhancement of the GABAergic neurotransmission at inhibitory synapses. In the presence of benzodiazepines the affinity of the GABA receptor for the neurotransmitter is enhanced through positive allosteric modulation resulting in an increased action of released GABA on the postsynaptic transmembrane chloride ion flux.

There are also animal data showing an effect of clonazepam on serotonin. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absences seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations as well as irregular spikes and waves. Generalized EEG abnormalities are more regularly suppressed than focal abnormalities. According to these findings clonazepam has beneficial effects in generalized and focal epilepsies.

Oral:

• Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

• The initial dose for adults with panic disorder is 0.25 mg given in two divided dose. An increase to the target dose for most patients of 1 mg/day may be made after 3 days.
• Pediatric Patients: In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses.

Injection:

• Infants and children: half of a vial (0.5 mg) by slow IV injection or by IV infusion.

• Adults: 1 vial (1 mg) by slow IV injection or by IV infusion. This dose can be repeated as required (1-4 mg are usually sufficient to reverse the status). In adults, the rate of injection must not exceed 0.25 - 0.5 mg per minute (0.5-1.0 ml of the prepared solution) and a total dose of 10 mg should not be exceeded.

The most frequently occurring side effects of Clonazepam are referable to CNS depression. Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior problems have been noted in approximately 25% of patients. Abnormal eye movements, aphonia, coma, tremor, vertigo, confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis & palpitations may also occur.

It should not be used in patients with a history of hypersensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.

When used in patients in whom several different types of seizure disorders coexist, Clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures. This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Clonazepam may produce absence status.

Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital. The effect of Clonazepam on the metabolism of other drugs has not been investigated.

Pregnancy: From preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations. From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens. However, it is difficult to determine from published epidemiological reports which drug or combination of drugs is responsible for defects in the newborn. The possibility also exists that other factors e.g. genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. Under these circumstances, the drug should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus. During pregnancy, Clonazepam may be administered only if there is a compelling indication. Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heartbeat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feeding in the neonate. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy. Withdrawal symptoms in newborn infants have occasionally been reported with benzodiazepines.

Nursing Mothers: Although the active ingredient of Clonazepam has been found to pass into the maternal milk in small amounts only, mothers undergoing treatment with this drug should not breastfeed. If there is a compelling indication for Clonazepam, breastfeeding should be discontinued.

Pediatric Use: In infants and small children Rivotril may cause increased production of saliva and bronchial secretion. Therefore special attention must be paid to maintaining patency of the airways. 

Geriatric Use: Benzodiazepine pharmacologic effects appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug–receptor interactions, post-receptor mechanisms and organ function.

Renal Impairment: Renal impairment does not affect the pharmacokinetics of clonazepam. Based on pharmacokinetic criteria, no dose adjustment is required in patients with renal impairment.

Hepatic Impairment: Plasma protein binding of clonazepam in cirrhotic patients is significantly different from that in healthy subjects (free fraction 17.1±1.0% vs 13.9±0.2%). Although the influence of hepatic impairment on clonazepam pharmacokinetics has not been further investigated, experience with another closely related nitrobenzodiazepine (nitrazepam) indicates that clearance of unbound clonazepam might be reduced in liver cirrhosis.

Symptoms: Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Clonazepam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Treatment: Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.

Slow intravenous injection: The contents of the vial must be diluted with 1 ml of water for injection prior to administration so as to avoid local irritation of the veins. The injection solution should be prepared immediately before use. IV injection should be administered slowly with continuous monitoring of EEG, respiration and blood pressure.

Intravenous infusion: Clonazepam (the vial) can be diluted for infusion in a ratio of 1 vial (1 mg) to at least 85 ml diluting media. The diluting media can be any of the following: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5% or glucose 10%. These mixtures are stable for 24 hours at room temperature. Infusion bags other than PVC should be used for infusing Clonazepam. If PVC infusion bags are used then the mixture should be infused immediately or within 4 hours. The infusion time should not exceed 8 hours. Do not prepare Clonazepam infusions using sodium bicarbonate solution, as precipitation of the solution may occur.

Intramuscular injection: The IM route should be used only in exceptional cases or if IV administration is not feasible.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Adjunct anti-epileptic drugs, Benzodiazepine hypnotics

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects. The central actions of benzodiazepines are mediated through an enhancement of the GABAergic neurotransmission at inhibitory synapses. In the presence of benzodiazepines the affinity of the GABA receptor for the neurotransmitter is enhanced through positive allosteric modulation resulting in an increased action of released GABA on the postsynaptic transmembrane chloride ion flux.

There are also animal data showing an effect of clonazepam on serotonin. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absences seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations as well as irregular spikes and waves. Generalized EEG abnormalities are more regularly suppressed than focal abnormalities. According to these findings clonazepam has beneficial effects in generalized and focal epilepsies.

Oral:

• Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

• The initial dose for adults with panic disorder is 0.25 mg given in two divided dose. An increase to the target dose for most patients of 1 mg/day may be made after 3 days.
• Pediatric Patients: In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses.

Injection:

• Infants and children: half of a vial (0.5 mg) by slow IV injection or by IV infusion.

• Adults: 1 vial (1 mg) by slow IV injection or by IV infusion. This dose can be repeated as required (1-4 mg are usually sufficient to reverse the status). In adults, the rate of injection must not exceed 0.25 - 0.5 mg per minute (0.5-1.0 ml of the prepared solution) and a total dose of 10 mg should not be exceeded.

The most frequently occurring side effects of Clonazepam are referable to CNS depression. Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior problems have been noted in approximately 25% of patients. Abnormal eye movements, aphonia, coma, tremor, vertigo, confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis & palpitations may also occur.

It should not be used in patients with a history of hypersensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.

When used in patients in whom several different types of seizure disorders coexist, Clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures. This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Clonazepam may produce absence status.

Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital. The effect of Clonazepam on the metabolism of other drugs has not been investigated.

Pregnancy: From preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations. From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens. However, it is difficult to determine from published epidemiological reports which drug or combination of drugs is responsible for defects in the newborn. The possibility also exists that other factors e.g. genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. Under these circumstances, the drug should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus. During pregnancy, Clonazepam may be administered only if there is a compelling indication. Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heartbeat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feeding in the neonate. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy. Withdrawal symptoms in newborn infants have occasionally been reported with benzodiazepines.

Nursing Mothers: Although the active ingredient of Clonazepam has been found to pass into the maternal milk in small amounts only, mothers undergoing treatment with this drug should not breastfeed. If there is a compelling indication for Clonazepam, breastfeeding should be discontinued.

Pediatric Use: In infants and small children Rivotril may cause increased production of saliva and bronchial secretion. Therefore special attention must be paid to maintaining patency of the airways. 

Geriatric Use: Benzodiazepine pharmacologic effects appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug–receptor interactions, post-receptor mechanisms and organ function.

Renal Impairment: Renal impairment does not affect the pharmacokinetics of clonazepam. Based on pharmacokinetic criteria, no dose adjustment is required in patients with renal impairment.

Hepatic Impairment: Plasma protein binding of clonazepam in cirrhotic patients is significantly different from that in healthy subjects (free fraction 17.1±1.0% vs 13.9±0.2%). Although the influence of hepatic impairment on clonazepam pharmacokinetics has not been further investigated, experience with another closely related nitrobenzodiazepine (nitrazepam) indicates that clearance of unbound clonazepam might be reduced in liver cirrhosis.

Symptoms: Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Clonazepam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Treatment: Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.

Slow intravenous injection: The contents of the vial must be diluted with 1 ml of water for injection prior to administration so as to avoid local irritation of the veins. The injection solution should be prepared immediately before use. IV injection should be administered slowly with continuous monitoring of EEG, respiration and blood pressure.

Intravenous infusion: Clonazepam (the vial) can be diluted for infusion in a ratio of 1 vial (1 mg) to at least 85 ml diluting media. The diluting media can be any of the following: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5% or glucose 10%. These mixtures are stable for 24 hours at room temperature. Infusion bags other than PVC should be used for infusing Clonazepam. If PVC infusion bags are used then the mixture should be infused immediately or within 4 hours. The infusion time should not exceed 8 hours. Do not prepare Clonazepam infusions using sodium bicarbonate solution, as precipitation of the solution may occur.

Intramuscular injection: The IM route should be used only in exceptional cases or if IV administration is not feasible.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Adjunct anti-epileptic drugs, Benzodiazepine hypnotics

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects. The central actions of benzodiazepines are mediated through an enhancement of the GABAergic neurotransmission at inhibitory synapses. In the presence of benzodiazepines the affinity of the GABA receptor for the neurotransmitter is enhanced through positive allosteric modulation resulting in an increased action of released GABA on the postsynaptic transmembrane chloride ion flux.

There are also animal data showing an effect of clonazepam on serotonin. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absences seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations as well as irregular spikes and waves. Generalized EEG abnormalities are more regularly suppressed than focal abnormalities. According to these findings clonazepam has beneficial effects in generalized and focal epilepsies.

Oral:

• Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

• The initial dose for adults with panic disorder is 0.25 mg given in two divided dose. An increase to the target dose for most patients of 1 mg/day may be made after 3 days.
• Pediatric Patients: In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses.

Injection:

• Infants and children: half of a vial (0.5 mg) by slow IV injection or by IV infusion.

• Adults: 1 vial (1 mg) by slow IV injection or by IV infusion. This dose can be repeated as required (1-4 mg are usually sufficient to reverse the status). In adults, the rate of injection must not exceed 0.25 - 0.5 mg per minute (0.5-1.0 ml of the prepared solution) and a total dose of 10 mg should not be exceeded.

The most frequently occurring side effects of Clonazepam are referable to CNS depression. Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior problems have been noted in approximately 25% of patients. Abnormal eye movements, aphonia, coma, tremor, vertigo, confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis & palpitations may also occur.

It should not be used in patients with a history of hypersensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.

When used in patients in whom several different types of seizure disorders coexist, Clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures. This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Clonazepam may produce absence status.

Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital. The effect of Clonazepam on the metabolism of other drugs has not been investigated.

Pregnancy: From preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations. From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens. However, it is difficult to determine from published epidemiological reports which drug or combination of drugs is responsible for defects in the newborn. The possibility also exists that other factors e.g. genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. Under these circumstances, the drug should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus. During pregnancy, Clonazepam may be administered only if there is a compelling indication. Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heartbeat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feeding in the neonate. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy. Withdrawal symptoms in newborn infants have occasionally been reported with benzodiazepines.

Nursing Mothers: Although the active ingredient of Clonazepam has been found to pass into the maternal milk in small amounts only, mothers undergoing treatment with this drug should not breastfeed. If there is a compelling indication for Clonazepam, breastfeeding should be discontinued.

Pediatric Use: In infants and small children Rivotril may cause increased production of saliva and bronchial secretion. Therefore special attention must be paid to maintaining patency of the airways. 

Geriatric Use: Benzodiazepine pharmacologic effects appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug–receptor interactions, post-receptor mechanisms and organ function.

Renal Impairment: Renal impairment does not affect the pharmacokinetics of clonazepam. Based on pharmacokinetic criteria, no dose adjustment is required in patients with renal impairment.

Hepatic Impairment: Plasma protein binding of clonazepam in cirrhotic patients is significantly different from that in healthy subjects (free fraction 17.1±1.0% vs 13.9±0.2%). Although the influence of hepatic impairment on clonazepam pharmacokinetics has not been further investigated, experience with another closely related nitrobenzodiazepine (nitrazepam) indicates that clearance of unbound clonazepam might be reduced in liver cirrhosis.

Symptoms: Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Clonazepam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Treatment: Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.

Slow intravenous injection: The contents of the vial must be diluted with 1 ml of water for injection prior to administration so as to avoid local irritation of the veins. The injection solution should be prepared immediately before use. IV injection should be administered slowly with continuous monitoring of EEG, respiration and blood pressure.

Intravenous infusion: Clonazepam (the vial) can be diluted for infusion in a ratio of 1 vial (1 mg) to at least 85 ml diluting media. The diluting media can be any of the following: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5% or glucose 10%. These mixtures are stable for 24 hours at room temperature. Infusion bags other than PVC should be used for infusing Clonazepam. If PVC infusion bags are used then the mixture should be infused immediately or within 4 hours. The infusion time should not exceed 8 hours. Do not prepare Clonazepam infusions using sodium bicarbonate solution, as precipitation of the solution may occur.

Intramuscular injection: The IM route should be used only in exceptional cases or if IV administration is not feasible.

Keep in a dry place away from light and heat. Keep out of the reach of children.

Adjunct anti-epileptic drugs, Benzodiazepine hypnotics

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects. The central actions of benzodiazepines are mediated through an enhancement of the GABAergic neurotransmission at inhibitory synapses. In the presence of benzodiazepines the affinity of the GABA receptor for the neurotransmitter is enhanced through positive allosteric modulation resulting in an increased action of released GABA on the postsynaptic transmembrane chloride ion flux.

There are also animal data showing an effect of clonazepam on serotonin. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absences seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations as well as irregular spikes and waves. Generalized EEG abnormalities are more regularly suppressed than focal abnormalities. According to these findings clonazepam has beneficial effects in generalized and focal epilepsies.

Oral:

• Adults: The initial dose for adults with seizure disorders should not exceed 1.5 mg/day divided into three doses. Dosage may be increased in increments of 0.5 to 1 mg every 3 days until seizures are adequately controlled or until side effects preclude any further increase. Maintenance dosage must be individualized for each patient depending upon response. Maximum recommended daily dose is 20 mg.

• The initial dose for adults with panic disorder is 0.25 mg given in two divided dose. An increase to the target dose for most patients of 1 mg/day may be made after 3 days.
• Pediatric Patients: In order to minimize drowsiness, the initial dose for infants and children (up to 10 years of age or 30 kg of body weight) should be between 0.01 and 0.03 mg/kg/day but not to exceed 0.05 mg/kg/day given in two or three divided doses.

Injection:

• Infants and children: half of a vial (0.5 mg) by slow IV injection or by IV infusion.

• Adults: 1 vial (1 mg) by slow IV injection or by IV infusion. This dose can be repeated as required (1-4 mg are usually sufficient to reverse the status). In adults, the rate of injection must not exceed 0.25 - 0.5 mg per minute (0.5-1.0 ml of the prepared solution) and a total dose of 10 mg should not be exceeded.

The most frequently occurring side effects of Clonazepam are referable to CNS depression. Experience in treatment of seizures has shown that drowsiness has occurred in approximately 50% of patients and ataxia in approximately 30%. In some cases, these may diminish with time; behavior problems have been noted in approximately 25% of patients. Abnormal eye movements, aphonia, coma, tremor, vertigo, confusion, depression, amnesia, hallucinations, hysteria, increased libido, insomnia, psychosis & palpitations may also occur.

It should not be used in patients with a history of hypersensitivity to benzodiazepines, nor in patients with clinical or biochemical evidence of significant liver disease. It may be used in patients with open angle glaucoma who are receiving appropriate therapy but is contraindicated in acute narrow angle glaucoma.

When used in patients in whom several different types of seizure disorders coexist, Clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures. This may require the addition of appropriate anticonvulsants or an increase in their dosages. The concomitant use of valproic acid and Clonazepam may produce absence status.

Clonazepam does not appear to alter the pharmacokinetics of phenytoin, carbamazepine or phenobarbital. The effect of Clonazepam on the metabolism of other drugs has not been investigated.

Pregnancy: From preclinical studies it cannot be excluded that clonazepam possesses the possibility of producing congenital malformations. From epidemiological evaluations there is evidence that anticonvulsant drugs act as teratogens. However, it is difficult to determine from published epidemiological reports which drug or combination of drugs is responsible for defects in the newborn. The possibility also exists that other factors e.g. genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. Under these circumstances, the drug should only be administered to pregnant women if the potential benefits outweigh the risk to the foetus. During pregnancy, Clonazepam may be administered only if there is a compelling indication. Administration of high doses in the last trimester of pregnancy or during labour can cause irregularities in the heartbeat of the unborn child and hypothermia, hypotonia, mild respiratory depression and poor feeding in the neonate. It should be borne in mind that both pregnancy itself and abrupt discontinuation of the medication can cause exacerbation of epilepsy. Withdrawal symptoms in newborn infants have occasionally been reported with benzodiazepines.

Nursing Mothers: Although the active ingredient of Clonazepam has been found to pass into the maternal milk in small amounts only, mothers undergoing treatment with this drug should not breastfeed. If there is a compelling indication for Clonazepam, breastfeeding should be discontinued.

Pediatric Use: In infants and small children Rivotril may cause increased production of saliva and bronchial secretion. Therefore special attention must be paid to maintaining patency of the airways. 

Geriatric Use: Benzodiazepine pharmacologic effects appear to be greater in elderly patients than in younger patients even at similar plasma benzodiazepine concentrations, possibly because of age-related changes in drug–receptor interactions, post-receptor mechanisms and organ function.

Renal Impairment: Renal impairment does not affect the pharmacokinetics of clonazepam. Based on pharmacokinetic criteria, no dose adjustment is required in patients with renal impairment.

Hepatic Impairment: Plasma protein binding of clonazepam in cirrhotic patients is significantly different from that in healthy subjects (free fraction 17.1±1.0% vs 13.9±0.2%). Although the influence of hepatic impairment on clonazepam pharmacokinetics has not been further investigated, experience with another closely related nitrobenzodiazepine (nitrazepam) indicates that clearance of unbound clonazepam might be reduced in liver cirrhosis.

Symptoms: Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Overdose of Clonazepam is seldom life-threatening if the drug is taken alone, but may lead to areflexia, apnoea, hypotension, cardiorespiratory depression and coma. Coma, if it occurs, usually lasts a few hours but it may be more protracted and cyclical, particularly in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease. Benzodiazepines increase the effects of other central nervous system depressants, including alcohol.

Treatment: Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state. In particular, patients may require symptomatic treatment for cardiorespiratory effects or central nervous system effects. Further absorption should be prevented using an appropriate method e.g. treatment within 1-2 hours with activated charcoal. If activated charcoal is used airway protection is imperative for drowsy patients. In case of mixed ingestion gastric lavage may be considered, however not as a routine measure. If CNS depression is severe consider the use of flumazenil, a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is to be used with extreme caution in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil, for further information on the correct use of this drug.

Slow intravenous injection: The contents of the vial must be diluted with 1 ml of water for injection prior to administration so as to avoid local irritation of the veins. The injection solution should be prepared immediately before use. IV injection should be administered slowly with continuous monitoring of EEG, respiration and blood pressure.

Intravenous infusion: Clonazepam (the vial) can be diluted for infusion in a ratio of 1 vial (1 mg) to at least 85 ml diluting media. The diluting media can be any of the following: sodium chloride 0.9%; sodium chloride 0.45% + glucose 2.5%; glucose 5% or glucose 10%. These mixtures are stable for 24 hours at room temperature. Infusion bags other than PVC should be used for infusing Clonazepam. If PVC infusion bags are used then the mixture should be infused immediately or within 4 hours. The infusion time should not exceed 8 hours. Do not prepare Clonazepam infusions using sodium bicarbonate solution, as precipitation of the solution may occur.

Intramuscular injection: The IM route should be used only in exceptional cases or if IV administration is not feasible.

Keep in a dry place away from light and heat. Keep out of the reach of children.

হায়োসিন বিউটাইলব্রোমাইড একটি এন্টিকোলিনার্জিক ওষুধ, এবডোমিনাল ক্যাভিটির বিভিন্ন অংশের নরম মাংসপেশীর (smooth muscle) উপর যার খিঁচুনিবিরোধী (antispasmodic) ক্রিয়া রয়েছে। হায়োসিন বিউটাইলব্রোমাইড ট্যাবলেট গ্যাসট্রো ইন্টেসটিনাল ট্র্যাক্টে অথবা জেনিটো-ইউরিনারী ট্র্যাক্টের ভিসেরাল খিঁচুনি জনিত লক্ষণসমূহে নির্দেশিত। স্পাসমোডিক ডিসমেনোরিয়াতেও এটি নির্দেশিত। হায়োসিন বিউটাইলব্রোমাইড ইনজেকশন গ্যাসট্রো-ইন্টেসটিনাল খিঁচুনি এবং রেনাল অথবা পিত্তের (billary) তীব্র ব্যথাতেও নির্দেশিত। রেডিওলজীতে প্রতিবন্ধকতার পার্থক্যমূলক রোগ নির্ণয়ে, পাইলোগ্রাফীতে খিঁচুনি ও ব্যথা কমাতে এবং গ্যাসট্রো-ডিওডেনাল এনডোস্কোপীর মত রোগ নির্ণয়ের অন্যান্য পদ্ধতিতেও খিঁচুনির সমস্যা দূর করার জন্য হায়োসিন বিউটাইলব্রোমাইড ইনজেকশন ব্যবহার করা হয়।

Anticholinergics (antimuscarinics)/ Anti-spasmodics

খাওয়ার জন্য-

• প্রাপ্ত বয়স্ক: ২০ মিগ্রা দিনে চার বার। স্পাসমোডিক ডিসমেনোরিয়ার ক্ষেত্রে ঋতুস্রাব (menstruation) শুরুর সম্ভাব্য তারিখের কমপক্ষে দুদিন আগে থেকে চিকিৎসা শুরু করতে হবে এবং স্রাব শুরুর তিনদিন পরে পর্যন্ত তা অব্যাহত রাখতে হবে।
• শিশু ৬ থেকে ১২ বৎসর পর্যন্ত: ১০ মিগ্রা দিনে তিনবার অথবা চিকিৎসকের নির্দেশ অনুযায়ী। 

ইনজেকশন হিসেবে-

• প্রাপ্তবয়স্ক: মাংসপেশীতে বা শিরাপথে প্রয়োগের জন্য সাধারণ মাত্রা হচ্ছে ২০ মিগ্রা (১টি এ্যাম্পুল), প্রয়োজনে যা কিনা ৩০ মিনিট পর পুনরায় প্রয়োগ করতে হবে। এনডোস্কোপীর ক্ষেত্রে এই মাত্রা আরো ঘন ঘন প্রয়োগ করতে হবে।

হায়োসিন বিউটাইলব্রোমাইড এর পার্শ্ব-প্রতিক্রিয়ার মধ্যে রয়েছে মুখ শুকিয়ে যাওয়া, পিউপিল এর প্রসরণ (dilatation), ইন্ট্রা-অকিউলার প্রেসার বৃদ্ধি, ফ্লাসিং, ত্বক শুকিয়ে যাওয়া, ব্র্যাডিকার্ডিয়া এবং তারপরেই ট্যাকিকার্ডিয়া ও এরিমিয়া। কখনো কখনো ক্লান্তি, বমি, মাথা ঝিমঝিম (giddiness) এবং ষ্ট্যাগারিং হতে পারে।

যে সব রোগীর প্রস্টেটিক বৃদ্ধি ঘটেছে তাদের ক্ষেত্রে এর ব্যবহার নিষিদ্ধ এবং বৃদ্ধদের ক্ষেত্রে এটি সতর্কতার সাথে ব্যবহার করতে হবে। যে সব রোগী প্যারালাইটিক ইলিয়াস অথবা পাইলোরিক ষ্টেনোসিসে ভুগছেন তাদের ক্ষেত্রেও ওষুধটির ব্যবহার নিষিদ্ধ। সম্ভাব্য মাইড্রিয়াটিক ক্ষতির কারণে যে সব রোগীর গ্লুকোমা রয়েছে তাদের ক্ষেত্রেও এটির ব্যবহার নিষিদ্ধ ।

সাবধানতা: হায়োসিন ঝিমুনি সৃষ্টি করতে পারে ও মানসিক সতর্কতা নিজে করে নিস্তেজ করে দিতে পারে। যে সকল রোগী হায়োসিন দিয়ে চিকিৎসাধীন রয়েছে তাদের গাড়ী বা অন্যান্য যানবাহন অথবা মানসিক একাগ্রতার অভাবে দুর্ঘটনা ঘটতে পারে এমন কোন যন্ত্রপাতি চালানো উচিত নয়। রোগীদের মদ্যপান করা থেকেও বিরত থাকা উচিত।

সতর্কতা: থাইরোটক্সিকোসিস, কার্ডিয়াক অপর্যাপ্ততা (insufficiency) বা ফেলিওর এবং হৃদপিন্ডে অস্ত্রোপচারের ক্ষেত্রে এই ওষুধ হৃদপিন্ডের গতি আরো বাড়িয়ে দিতে পারে বলে এর ব্যবহারে সতর্কতা অবলম্বন করা উচিত। অন্যান্য এন্টিকোলিনার্জিক ওষুধসমূহ যেমন এমানটেডিন, কোন কোন এন্টিহিস্টামিন, বিউটাইরোফেনন ও ফেনোথায়াজিন এবং ট্রাইসাইক্লিক এন্টিডিপ্রেসেন্ট হায়োসিনের সাথে একত্রে প্রয়োগের ফলে হায়োসিনের ক্রিয়া বেড়ে যেতে পারে বিধায় এ সব ক্ষেত্রে হায়োসিন ব্যবহার করতে হলে এর মাত্রা কমিয়ে নেয়া প্রয়োজন হতে পারে।

গর্ভাবস্থার প্রথম তিন মাসে অন্যান্য ওষুধের মতো একেও সতর্কতার সাথে ব্যবহার করতে হবে।

ডেক্সট্রান কিংবা ০.৯% সোডিয়াম ক্লোরাইড ইনজেকশনের তরল দিয়ে হায়োসিন বিউটাইলব্রোমাইড ইনজেকশনকে তরলীকরণ করা যাবে।

মেয়াদ উত্তীর্ণের পর ব্যবহার করবেন না। সকল ওষুধ শিশুদের নাগালের বাইরে রাখুন।  কেবলমাত্র রেজিস্টার্ড চিকিৎসকের ব্যবস্থাপত্র অনুযায়ী বিতরণযোগ্য।

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Olopatadine is indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Ophthalmic Non-Steroid drugs

Olopatadine is an inhibitor of the release of histamine from the mast cell and a relatively selective histamine H1‐antagonist that inhibits the in vivo and in vitro type 1 immediate hypersensitivity reaction including inhibition of histamine induced effects on human conjunctival epithelial cells. Olopatadine is devoid of effects on alpha adrenergic, dopamine and muscarinic type 1 and 2 receptors. Following topical ocular administration in human, olopatadine was shown to have low systemic exposure.

0.1% Sterile Eye Drops: One drop in each affected eye two times per day at an interval of 6 to 8 hours.

0.2% Sterile Eye Drops: One drop in the affected eye once a day.

0.7% Sterile Eye Drops: One drop in each affected eye once a day.

Headaches have been reported at an incidence of 7%. The following adverse experiences have been reported in less than 5% of patients: Asthenia, blurred vision, burning or stinging, cold syndrome, dry eye, foreign body sensation, hyperemia, hypersensitivity, keratitis, lid edema, nausea, pharyngitis, pruritus, rhinitis, sinusitis, and taste perversion

Olopatadine Hydrochloride ophthalmic solution is contraindicated in persons with a known hypersensitivity to Olopatadine Hydrochloride.

Olopatadine HCl ophthalmic solution should not be used to treat contact lens related irritation. Patients who wear soft contact lenses should be instructed to wait at least ten minutes after instilling Olopatadine Hydrochloride ophthalmic solution before they insert their contact lenses.

May result in additive CNS depression with CNS depressants.

There are no adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the fetus.

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when Olopatadine Hydrochloride ophthalmic solution is administered to a nursing mother.

Geriatric Use: No overall differences in safety or effectiveness have been observed betweents.

Symptoms: Drowsiness in adults and, initially, agitation and restlessness, followed by drowsiness in childn.

Management: Symptomatic or supportive treatment.

Store below 30° C in a cool and dry place protected from light. Keep out of reach of children. Do not touch the dropper tip to surfaces since this may contaminate the solution. Do not use after 30 days of first opening.

Pantoprazole is indicated where suppression of acid secretion has therapeutic benefit; i.e 

• Peptic ulcer diseases
• Gastroesophageal reflux diseases
• Ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs)
• Eradication of Helicobacter pylori (in combination with antibiotics)
• Zollinger-Ellison Syndrome

Proton Pump Inhibitor

Pantoprazole is a proton pump inhibitor that suppresses the final step in gastric acid production by covalently binding to the H⁺/K⁺ATPase enzyme system at the surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus that persists longer than 24 hours.

Oral:

• Benign gastric ulcer: 40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed.
• Gastro-esophageal reflux disease: 20-40 mg daily in the morning for 4 weeks, continued for further 4 weeks, if not fully healed; maintenance dose is 20 mg daily, which may be increased to 40 mg daily.
• Duodenal ulcer: 40 mg daily in the morning for 2 weeks, continued for further 2 weeks if not fully healed.
• Duodenal ulcer associated with Helicobacter pylori: Pantoprazole is recommended at a dose of 40 mg twice daily in association with antimicrobial agents as detailed below: Amoxycillin 1 g and Clarithromycin 500 mg both twice daily for one week, or Clarithromycin 250 mg and Metronidazole 400 mg both twice daily for one week.
• Prophylaxis of NSAID-associated gastric or duodenal ulcer: 20 mg daily for those require long-term NSAID treatment.
• Zollinger-Ellison Syndrome: Initially 80 mg once daily adjusted according to response (elderly max. 40 mg daily); daily doses above 80 mg given in 2 divided doses.

IV Injection:

• Duodenal ulcer and gastric ulcer: 40 mg once daily for 7-10 days
• Gastroesophageal reflux disease associated with a history of erosive esophagitis: 40 mg once daily for 7-10 days
• Prevention of rebleeding in peptic ulcer: IV 80 mg, followed by 8 mg/hour infusion for 72 hours
• Prophylaxis of acid aspiration: 80 mg IV every 12 h for 24 h, followed by 40mg every 12 hour
• Long-term management of Zollinger-Ellison Syndrome and other pathological hypersecretory conditions: 80 mg IV every 12 hours, may increase to 80 mg every 8 hours if needed, may titrate to higher doses depending on acid output.

Pantoprazole is well tolerated in both short-term and long-term treatment. Headache and diarrhea are the common side effects and rarely included side effects are abdominal pain, flatulence, rash, insomnia and hyperglycemia.

Pantoprazole is contraindicated in patients with known hypersensitivity to any of the components of the formulation.

Patients should be cautioned that Pantoprazole tablet should not be split, chewed or crushed. Long-term therapy of Pantoprazole may lead to malabsorption of cyanocobalamin (Vitamin B12) or may increase the risk of osteoporosis related disorders.

No significant drug interactions have been observed in clinical studies.

US FDA Pregnancy Category of Pantoprazole is B. There are, however, no adequate and well-controlled studies in pregnant woman. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Pantoprazole has been shown to be excreted in human milk. So, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

There are no known symptoms of overdosage in humans. Since Pantoprazole is highly protein bound, it is not readily dialyzable. Apart from symptomatic and supportive management, no specific therapy is recommended.

Direction for use of IV injection: Pantoprazole lyophilized powder and 0.9% Sodium Chloride Injection is for intravenous administration only and must not be given by any other route. Pantoprazole IV injection should be given as a slow intravenous injection. The solution for IV injection is obtained by adding 10 ml 0.9% Sodium Chloride Injection to the vial containing powder. After reconstitution the injection should be given slowly over a period of at least 2 to 5 minutes. Use only freshly prepared solution. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours.

Direction for use of IV infusion: Pantoprazole IV infusion should be given as an intravenous infusion over a period of approximately 15 minutes. Pantoprazole IV infusion should be reconstituted with 10 ml of 0.9% Sodium Chloride Injection and further diluted (admixed) with 0.9% Sodium Chloride Injection or 5% Dextrose or Lactated Ringer's Injection to a final volume of 100 ml. The reconstituted solution may be stored at room temperature (up to 30° C) for a maximum 4 hours prior to further dilution. The admixed solution may be stored at room temperature (up to 30° C) and must be used within 24 hours from the time of initial reconstitution.

Keep in a dry place, away from light and heat. Keep out of the reach of children.

Cefprozil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains. Infections include:

• Lower respiratory tract infections: acute bronchitis, acute exacerbations of chronic bronchitis, community acquired pneumonia.
• Upper respiratory tract and ear infections: otitis media, sinusitis, tonsillitis and pharyngitis.
• Uncomplicated skin and soft tissue infections.

Second generation Cephalosporins

Cefprozil is a preparation of Cefprozil, which is a semi synthetic, second-generation cephalosporin antibiotic indicated for the treatment of patients with mild to moderate infections caused by susceptible strains.

• Ensures treatment success in pediatric GAS pharyngitis/tonsillitis
• A drug of choice for pediatric patients with tonsilopharyngitis
• Guarantees treatment success in SSTI

Cefprozil is a semi synthetic, second-generation cephalosporin antibiotic. Cefprozil is active in vitro against both gram positive and gram negative bacteria. The bactericidal activity of cefprozil results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

Adults (13 years and older)-
Upper Respiratory Tract:

• Pharyngitis/Tonsillitis: 500 q24h for 10 days
• Acute Sinusitis (For moderate to severe infections, the higher dose should be used): 250 q12h or 500 q12h for 10 days

Lower Respiratory Tract:

• Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis: 500 q12h for 10 days.

Skin And Skin Structure:

• Uncomplicated Skin and Skin Structure Infections 250 q12h or 500 q24h or 500 q12h for 10 days.

Children (2 years–12 years)-
Upper Respiratory Tract:

• Pharyngitis/Tonsillitis: 7.5 mg/kg q12h for 10 days

Skin And Skin Structure:

• Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h for 10 days.

Infants & Children (6 months–12 years)-
Upper Respiratory Tract:

• Otitis Media: 15 mg/kg q12h for 10 days
• Acute Sinusitis (For moderate to severe infections, the higher dose should be used): 7.5 mg/kg q12h or 15 mg/kg q12h for 10 days.

The adverse reactions to cefprozil are similar to those observed with other orally administered cephalosporins. Cefprozil was usually well tolerated in controlled clinical trials. The most common adverse effects of cefprozil are diarrhea, nausea, vomiting, abdominal pain, rash, urticaria, dizziness, hyperactivity, insomnia, confusion etc.

Hypersensitivity to cephalosporin antibiotics.

In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. Prolonged use of cefprozil may result in the overgrowth of  nonsusceptible organisms. Cefprozil should be prescribed with caution in individuals with a history of gastrointestinal disease particularly colitis.

Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics. Concomitant administration of probenecid doubled the AUC for cefprozil.

Pregnancy category B. There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Small amounts of cefprozil (<0.3% of dose) have been detected in human milk following administration of a single 1 gram dose to lactating women. Caution should be exercised when cefprozil is administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.

Cefprozil powder for suspension should be stored in a cool, dry place (preferably below 30°C) and should be protected from light. Keep out of reach of children.

Cefprozil is indicated for the treatment of patients with mild to moderate infections caused by susceptible strains. Infections include:

• Lower respiratory tract infections: acute bronchitis, acute exacerbations of chronic bronchitis, community acquired pneumonia.
• Upper respiratory tract and ear infections: otitis media, sinusitis, tonsillitis and pharyngitis.
• Uncomplicated skin and soft tissue infections.

Second generation Cephalosporins

Cefprozil is a preparation of Cefprozil, which is a semi synthetic, second-generation cephalosporin antibiotic indicated for the treatment of patients with mild to moderate infections caused by susceptible strains.

• Ensures treatment success in pediatric GAS pharyngitis/tonsillitis
• A drug of choice for pediatric patients with tonsilopharyngitis
• Guarantees treatment success in SSTI

Cefprozil is a semi synthetic, second-generation cephalosporin antibiotic. Cefprozil is active in vitro against both gram positive and gram negative bacteria. The bactericidal activity of cefprozil results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

Adults (13 years and older)-
Upper Respiratory Tract:

• Pharyngitis/Tonsillitis: 500 q24h for 10 days
• Acute Sinusitis (For moderate to severe infections, the higher dose should be used): 250 q12h or 500 q12h for 10 days

Lower Respiratory Tract:

• Secondary Bacterial Infection of Acute Bronchitis and Acute Bacterial Exacerbation of Chronic Bronchitis: 500 q12h for 10 days.

Skin And Skin Structure:

• Uncomplicated Skin and Skin Structure Infections 250 q12h or 500 q24h or 500 q12h for 10 days.

Children (2 years–12 years)-
Upper Respiratory Tract:

• Pharyngitis/Tonsillitis: 7.5 mg/kg q12h for 10 days

Skin And Skin Structure:

• Uncomplicated Skin and Skin Structure Infections 20 mg/kg q24h for 10 days.

Infants & Children (6 months–12 years)-
Upper Respiratory Tract:

• Otitis Media: 15 mg/kg q12h for 10 days
• Acute Sinusitis (For moderate to severe infections, the higher dose should be used): 7.5 mg/kg q12h or 15 mg/kg q12h for 10 days.

The adverse reactions to cefprozil are similar to those observed with other orally administered cephalosporins. Cefprozil was usually well tolerated in controlled clinical trials. The most common adverse effects of cefprozil are diarrhea, nausea, vomiting, abdominal pain, rash, urticaria, dizziness, hyperactivity, insomnia, confusion etc.

Hypersensitivity to cephalosporin antibiotics.

In patients with known or suspected renal impairment, careful clinical observation and appropriate laboratory studies should be done prior to and during therapy. Prolonged use of cefprozil may result in the overgrowth of  nonsusceptible organisms. Cefprozil should be prescribed with caution in individuals with a history of gastrointestinal disease particularly colitis.

Nephrotoxicity has been reported following concomitant administration of aminoglycoside antibiotics and cephalosporin antibiotics. Concomitant administration of probenecid doubled the AUC for cefprozil.

Pregnancy category B. There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Small amounts of cefprozil (<0.3% of dose) have been detected in human milk following administration of a single 1 gram dose to lactating women. Caution should be exercised when cefprozil is administered to a nursing woman, since the effect of cefprozil on nursing infants is unknown.

Cefprozil powder for suspension should be stored in a cool, dry place (preferably below 30°C) and should be protected from light. Keep out of reach of children.

Anti-emetic drugs

Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT3 receptors that are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema, to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factorcs and is triggered by release of 5-HT3 in a cascade of neuronal event involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. Palonosetron works by blocking the actions of Serotonin, associated with nausea and vomiting, at 5-HTs receptor. It is likely that Palonosetron works in the small intestine but it may also work in the brain.

Pharmacokinetics: Palonosetron exhibits linear dose-proportional pharmacokinetics over the doserange 1-90 pg/kg in healthy subjects and in patients with cancer. In cancer patients receiving single intravenous doses of Palonosetron in this dose range, the mean maximum plasma concentration (Cmax) ranges from 0.89 to 336 ng/ml and the area under the plasma concentration-time curve from zero to infinity (AUCo-co) ranges from 13.8 to 957 ng.h/ml. Palonosetron has a volume of distribution of approximately 6.9-7.9 L/kg, with approximately 62% bound to plasma proteins. Approximately 50% of Palonosetron is metabolized into two inactive metabolites that exhibit <1% of the 5-HT3 receptor antagonist activity. Approximately 40% of the drug is metabolised via kidney, 50% by liver CYP2D6 (mainly), CYP3A4 and CYP1A2 isoenzymes. About 50% of the drug goes under metabolism. After a single intravenous dose, approximately 40% is excreted as unchanged drug in the urine after 144 hours. Total body clearance of Palonosetron is 160±35 ml/h/kg, and renal clearance is 66.5±18.2 ml/h/kg in healthy subjects. Palonosetron exhibits a longer half-life (40 hours) and has a greater 5-HT3 receptor binding affinity.

Usual dosage: Adult tablet dosage: 0.5 mg daily. Adult IV dosage: A single IV dose of 0.075 mg should be administered over 10 seconds.

Chemotherapy-induced nausea and vomiting: Adult tablet dosage: 0.5 mg administered approximately 1 hour prior to the start of chemotherapy. Adult IV dosage: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before the start of chemotherapy.

Radiotherapy-induced nausea and vomiting: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before each week of radiation fraction.

Post-operative nausea and vomiting: A single IV dose of 0.075 mg should be administered over 10 seconds immediately before induction of anesthesia.

Children dosage: (1 month to 17 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

The most common adverse reactions are headaches and constipation.

Palonosetron is contraindicated in patients known to have hypersensitivity to the drug or any of its components.

In controlled clinical trials, Palonosetron injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Palonosetron did not inhibit the antitumor activity of cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C in murine tumor models. Concomitant administration of Palonosetron and metoclopramide has no significant pharmacokinetic interactions. In vitro studies indicated that palonosetron is not inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 & CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6 or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with Palonosetron appears to be low.

Pregnancy category 'B'. It is not known whether Palonosetron is excreted in breast milk.

Use in elderly patients: No dosage adjustment is recommended in elderly patients >65 years of age.

Use in Children: (1 month to 10 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

Use in patients with impaired renal and hepatic function: No dosage adjustment is recommended in patients with renal and hepatic dysfunction.

There is no known antidote to Palonosetron. Overdose should be managed with supportive care.

Store in a cool & dry place, protected from light.

Anti-emetic drugs

Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT3 receptors that are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema, to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factorcs and is triggered by release of 5-HT3 in a cascade of neuronal event involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. Palonosetron works by blocking the actions of Serotonin, associated with nausea and vomiting, at 5-HTs receptor. It is likely that Palonosetron works in the small intestine but it may also work in the brain.

Pharmacokinetics: Palonosetron exhibits linear dose-proportional pharmacokinetics over the doserange 1-90 pg/kg in healthy subjects and in patients with cancer. In cancer patients receiving single intravenous doses of Palonosetron in this dose range, the mean maximum plasma concentration (Cmax) ranges from 0.89 to 336 ng/ml and the area under the plasma concentration-time curve from zero to infinity (AUCo-co) ranges from 13.8 to 957 ng.h/ml. Palonosetron has a volume of distribution of approximately 6.9-7.9 L/kg, with approximately 62% bound to plasma proteins. Approximately 50% of Palonosetron is metabolized into two inactive metabolites that exhibit <1% of the 5-HT3 receptor antagonist activity. Approximately 40% of the drug is metabolised via kidney, 50% by liver CYP2D6 (mainly), CYP3A4 and CYP1A2 isoenzymes. About 50% of the drug goes under metabolism. After a single intravenous dose, approximately 40% is excreted as unchanged drug in the urine after 144 hours. Total body clearance of Palonosetron is 160±35 ml/h/kg, and renal clearance is 66.5±18.2 ml/h/kg in healthy subjects. Palonosetron exhibits a longer half-life (40 hours) and has a greater 5-HT3 receptor binding affinity.

Usual dosage: Adult tablet dosage: 0.5 mg daily. Adult IV dosage: A single IV dose of 0.075 mg should be administered over 10 seconds.

Chemotherapy-induced nausea and vomiting: Adult tablet dosage: 0.5 mg administered approximately 1 hour prior to the start of chemotherapy. Adult IV dosage: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before the start of chemotherapy.

Radiotherapy-induced nausea and vomiting: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before each week of radiation fraction.

Post-operative nausea and vomiting: A single IV dose of 0.075 mg should be administered over 10 seconds immediately before induction of anesthesia.

Children dosage: (1 month to 17 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

The most common adverse reactions are headaches and constipation.

Palonosetron is contraindicated in patients known to have hypersensitivity to the drug or any of its components.

In controlled clinical trials, Palonosetron injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Palonosetron did not inhibit the antitumor activity of cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C in murine tumor models. Concomitant administration of Palonosetron and metoclopramide has no significant pharmacokinetic interactions. In vitro studies indicated that palonosetron is not inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 & CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6 or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with Palonosetron appears to be low.

Pregnancy category 'B'. It is not known whether Palonosetron is excreted in breast milk.

Use in elderly patients: No dosage adjustment is recommended in elderly patients >65 years of age.

Use in Children: (1 month to 10 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

Use in patients with impaired renal and hepatic function: No dosage adjustment is recommended in patients with renal and hepatic dysfunction.

There is no known antidote to Palonosetron. Overdose should be managed with supportive care.

Store in a cool & dry place, protected from light.

Anti-emetic drugs

Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. It is thought that chemotherapeutic agents produce nausea and vomiting by releasing serotonin from the enterochromaffin cells of the small intestine and that the released serotonin then activates 5-HT3 receptors that are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema, to initiate the vomiting reflex. Postoperative nausea and vomiting is influenced by multiple patient, surgical and anesthesia related factorcs and is triggered by release of 5-HT3 in a cascade of neuronal event involving both the central nervous system and the gastrointestinal tract. The 5-HT3 receptor has been demonstrated to selectively participate in the emetic response. Palonosetron works by blocking the actions of Serotonin, associated with nausea and vomiting, at 5-HTs receptor. It is likely that Palonosetron works in the small intestine but it may also work in the brain.

Pharmacokinetics: Palonosetron exhibits linear dose-proportional pharmacokinetics over the doserange 1-90 pg/kg in healthy subjects and in patients with cancer. In cancer patients receiving single intravenous doses of Palonosetron in this dose range, the mean maximum plasma concentration (Cmax) ranges from 0.89 to 336 ng/ml and the area under the plasma concentration-time curve from zero to infinity (AUCo-co) ranges from 13.8 to 957 ng.h/ml. Palonosetron has a volume of distribution of approximately 6.9-7.9 L/kg, with approximately 62% bound to plasma proteins. Approximately 50% of Palonosetron is metabolized into two inactive metabolites that exhibit <1% of the 5-HT3 receptor antagonist activity. Approximately 40% of the drug is metabolised via kidney, 50% by liver CYP2D6 (mainly), CYP3A4 and CYP1A2 isoenzymes. About 50% of the drug goes under metabolism. After a single intravenous dose, approximately 40% is excreted as unchanged drug in the urine after 144 hours. Total body clearance of Palonosetron is 160±35 ml/h/kg, and renal clearance is 66.5±18.2 ml/h/kg in healthy subjects. Palonosetron exhibits a longer half-life (40 hours) and has a greater 5-HT3 receptor binding affinity.

Usual dosage: Adult tablet dosage: 0.5 mg daily. Adult IV dosage: A single IV dose of 0.075 mg should be administered over 10 seconds.

Chemotherapy-induced nausea and vomiting: Adult tablet dosage: 0.5 mg administered approximately 1 hour prior to the start of chemotherapy. Adult IV dosage: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before the start of chemotherapy.

Radiotherapy-induced nausea and vomiting: A single IV dose of 0.25 mg should be administered over 30 seconds approximately 30 minutes before each week of radiation fraction.

Post-operative nausea and vomiting: A single IV dose of 0.075 mg should be administered over 10 seconds immediately before induction of anesthesia.

Children dosage: (1 month to 17 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

The most common adverse reactions are headaches and constipation.

Palonosetron is contraindicated in patients known to have hypersensitivity to the drug or any of its components.

In controlled clinical trials, Palonosetron injection has been safely administered with corticosteroids, analgesics, antiemetics/antinauseants, antispasmodics and anticholinergic agents. Palonosetron did not inhibit the antitumor activity of cisplatin, cyclophosphamide, cytarabine, doxorubicin and mitomycin C in murine tumor models. Concomitant administration of Palonosetron and metoclopramide has no significant pharmacokinetic interactions. In vitro studies indicated that palonosetron is not inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP2E1 & CYP3A4/5 (CYP2C19 was not investigated) nor does it induce the activity of CYP1A2, CYP2D6 or CYP3A4/5. Therefore, the potential for clinically significant drug interactions with Palonosetron appears to be low.

Pregnancy category 'B'. It is not known whether Palonosetron is excreted in breast milk.

Use in elderly patients: No dosage adjustment is recommended in elderly patients >65 years of age.

Use in Children: (1 month to 10 years): A single IV dose at 20 mcg/kg body weight. Which maximum dose is 1.5 mg.

Use in patients with impaired renal and hepatic function: No dosage adjustment is recommended in patients with renal and hepatic dysfunction.

There is no known antidote to Palonosetron. Overdose should be managed with supportive care.

Store in a cool & dry place, protected from light.