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Leucita AqVida
Filgrastim
Leucita AqVida
Filgrastim
Indications
Peripheral blood progenitor cell collection and therapy
Indication detailsView
Filgrastim is indicated to those:
- Cancer patients receiving myelosuppressive chemotherapy
- Patients with Acute Myeloid Leukemia receiving induction or consolidation chemotherapy
- Cancer patients receiving bone marrow transplant
- Patients with severe neutropenia
- Peripheral blood progenitor cell collection and therapy
Therapeutic classView
Haematopoietic Agents
PharmacologyView
Filgrastim is a granulocyte-colony stimulating factor which binds to cell surface receptors on haemetopoietic cells thus stimulating the development of granulocytes to increase their migration and cytotoxicity.
Filgrastim is a glycoprotein which regulates the production and release of functional neutrophils from the bone marrow. Filgrastim causes marked increases in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes. Elevations of neutrophil counts are dose-dependent at recommended doses. Following termination of Filgrastim therapy, circulating neutrophil counts decrease by 50% within 1 to 2 days, and to normal levels within 1 to 7 days.
Filgrastim is a glycoprotein which regulates the production and release of functional neutrophils from the bone marrow. Filgrastim causes marked increases in peripheral blood neutrophil counts within 24 hours, with minor increases in monocytes. Elevations of neutrophil counts are dose-dependent at recommended doses. Following termination of Filgrastim therapy, circulating neutrophil counts decrease by 50% within 1 to 2 days, and to normal levels within 1 to 7 days.
DosageView
Parenteral-
Chemotherapy-induced neutropenia: 5 mcg/kg daily as a single daily SC inj, as a continuous IV or SC infusion, or as a daily IV infusion over 15-30 minutes, starting notBone marrow transplantation: 10 mcg/kg daily by IV infusion over 30 min or 4 hr or continuous IV or SC infusion over 24 hr. Adjust according to response.
Subcutaneous-
Mobilisation of peripheral blood progenitor cells for autologous peripheral blood stem cell transplantation: 10 mcg/kg daily, as a single inj or by continuous infusion, for 4-7 days until the last leucapheresis procedure. If it is given after myelosuppressive chemotherapy: 5 mcg/kg daily by inj; given from the 1st day after chemotherapy completion until expected neutrophil nadir is passed and neutrophil count has returned to normal range, so that leucapheresis can be performed.Congenital neutropenia: 12 mcg/kg daily in single or divided doses. Adjust according to response. In patients with cyclic or idiopathic neutropenia: 5 mcg/kg daily in single or divided doses. Adjust according to response.
HIV infection and persistent neutropenia: Initially, 1 mcg/kg daily. Dose may be increased to 4 mcg/kg daily until normal neutrophil count is achieved. Maintenance: 300 mcg daily. Max: 4 mcg/kg daily.
Side effectsView
Musculoskeletal pain, bone pain, hypersensitivity reactions, splenic enlargement, hepatomegaly, thrombocytopaenia, anaemia, epistaxis, headache, nausea, vomiting, diarrhoea, urinary abnormalities (dysuria, proteinuria, haematuria), osteoporosis, exacerbation of rheumatoid arthritis, transient decrease in blood glucose, raised uric acid, cutaneous vasculitis, transient hypotension.
ContraindicationsView
Filgrastim is contraindicated in patients hypersensitive to the drug, any ingredient in the formulation, or proteins derived from Escherichia coli.
PrecautionsView
Filgrastim should not be administered within 24 hours before and after chemotherapy The possibility of Filgrastim acting as a growth factor for any tumor type cannot be excluded. To avoid adverse effects of excessive neutrophils complete blood count is recommended twice per week during treatment. Filgrastim is given by subcutaneous or intravenous infusion as required
InteractionsView
Drug interactions between Filgrastim and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils, such as lithium should be used with caution.
Pregnancy & lactationView
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Pediatric usageView
Pediatric precautions: Filgrastim has been used in children 3 months to 18 years of age without unusual adverse effect. However, safety and efficacy of the drug in neonates or patients with autoimmune neutropenia of infancy have not been established.
Overdose effectsView
The possibility of Filgrastim acting as a growth factor for any tumor type and adverse effects of excessive neutrophils may occur in overdose of Filgrastim.
ReconstitutionView
Dilution of Filgrastim conc less than 5 mcg/ml is not recommended at any time. Filgrastim may be diluted in 5% dextrose as required
StorageView
Refrigerate at 2-8° C. Do not freeze.
Leucodar
Fluconazole
Leucodar
Fluconazole
Indications
Vaginal candidiasis or thrush
Indication detailsView
Fluconazole is indicated for the treatment of vaginal candidiasis, oropharyngeal & esophageal candidiasis and cryptococcal meningitis. It is also effective for the treatment of urinary tract infection caused by candida, peritonitis and systemic candida infections (including candidemia, disseminated candidiasis and pneumonia).
Therapeutic classView
Drugs for subcutaneous and mycoses
PharmacologyView
Fluconazole is a triazole antifungal agent. It is a potent inhibitor of fungal cytochrome P-450 dependent enzymes. Cytochrome P-450 enzyme system is essential component of fungal cell membrane which is responsible for the synthesis of ergosterol.
DosageView
Adult (oral)-
Intravenous-
- Vaginal candidiasis: 150 mg as a single dose.
- Oropharyngeal candidiasis: 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of this infection generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.
- Esophageal candidiasis: 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used. Patients should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.
- Systemic candida infections: Optimal therapeutic dosage and duration of therapy have not been established. Sometimes, doses of up to 400 mg daily have been used.
- Urinary tract infections caused by candida and peritonitis: 50-200 mg daily have been used.
- Cryptococcal meningitis: 400 mg on the first day, followed by 200 mg once daily.
- Prophylaxis in patients undergoing bone marrow transplantation: 400 mg once daily.
- Doses of 3-6 mg/kg daily have been used. Doses up to 12 mg/kg is recommended.
Intravenous-
- Adult: Invasive candidal infections including candidaemia and disseminated candidiasis and cryptococcal infections including meningitis, by IV, 400 mg initially then 200 mg daily, increased if necessary to 400 mg daily, treatment continued according to response (at least 6-8 weeks for cryptococcal meningitis)
- Child: 6-12 mg/kg daily (every 72 hours in neonate up to 2 weeks old, every 48 hours in neonate 2-4 weeks old); maximum 400 mg daily. Prevention of relapse of cryptococcal meningitis, by IV, 100-200 mg daily.
Side effectsView
Fluconazole is well tolerated. Most common side effects of using Fluconazole includes nausea, vomiting, abdominal pain, diarrhoea, headache and skin rash.
ContraindicationsView
Fluconazole should not be used in patients with known hypersensitivity to Fluconazole or to related triazole compounds.
PrecautionsView
Fluconazole should be administered with caution to patients having proarrhythmic conditions.
InteractionsView
Concomitant use of cyclosporin or phenytoin with Fluconazole increases the plasma level of cyclosporin or phenytoin. Concomitant use of Fluconazole & warfarin prolongs the prothrombin time. Rifampicin level is decreased when used with Fluconazole.
Pregnancy & lactationView
US FDA Pregnancy category of Fluconazole is C. So, Fluconazole should be avoided in pregnancy and lactation unless the potential benefits to the other outweigh the possible risks to the fetus.
StorageView
Keep in a dry place away from light and heat. Keep out of the reach of children.
Leucofil
Ambroxol Hydrochloride
Leucofil
Ambroxol Hydrochloride
Indications
Sore throat
Indication detailsView
This is indicated in-
- Productive cough
- Acute and chronic inflammatory disorders of upper and lower respiratory tracts associated with viscid mucus including acute and chronic bronchitis
- Inflammatory disease of rhinopharyngeal tract (laryngitis, pharyngitis, sinusitis and rhinitis) associated with viscid mucus
- Asthmatic bronchitis bronchial asthma with thick expectoration
- Bronchiectasis
- Chronic pneumonia etc.
Therapeutic classView
Cough expectorants & mucolytics
PharmacologyView
Ambroxol is the active metabolite of bromhexine and it has been proven that this metabolite possesses a greater bronchosecretolytic effect than bromhexine. It improves sputum rheology by hydrating mechanism leading to liquefaction of mucus in the lumen of respiratory tract, thus facilitating expectoration of mucus and reducing dyspnea. It stimulates production of phospholipids of surfactant by alveolar cells, thus contributing to the lowering of superficial tension in the alveoli. It also reduces bronchial hyperactivity. Ambroxol has anti inflammatory properties owing to the inhibitory effect on the production of cellular cytokines and arachidonic acid metabolites. In patients with COPD it traditionally improves airway patency.
DosageView
Average daily dose (preferably after meal):
Pediatric Drops:
Pediatric Drops:
- 0-6 months: 0.5 ml 2 times a day
- 6-12 months: 1 ml 2 times a day
- 1-2 years: 1.25 ml 2 times a day
- 2-5 years: 2.5 ml (1/2 teaspoonful) 2-3 times a day
- 5-10 years: 5 ml (1 teaspoonful) 2-3 times a day
- 10 years and adults: 10 ml (2 teaspoonful) 3 times a day.
Side effectsView
Gastrointestinal side effects like epigastric pain, stomach overfill feeling may occur occasionally. Rarely allergic responses such as eruption, urticaria or angioneurotic edema have been reported.
ContraindicationsView
Contraindicated in known hypersensitivity to Ambroxol or Bromhexine.
PrecautionsView
Ambroxol should be given cautiously to patients with gastric and duodenal ulceration or convulsive disorders. Patients with hepatic and renal insufficiency should take it with caution.
InteractionsView
Ambroxol should not be taken simultaneously with antitussives (e.g.Codeine) because phlegm, which has been liquefied by Ambroxol might not be expectorated.
Pregnancy & lactationView
Teratogenic and fetal toxicity studies have shown no harmful effect of Ambroxol. However, it is advised not to use it in pregnancy, especially during the1st trimester. Safety during lactation has not been established yet.
StorageView
Protect from direct light exposure, Store in a dry place at a temperature not exceeding 30°C, Keep out of the reach of children.
Leufol
Calcium Folinate [Folinic Acid]
Leufol
Calcium Folinate [Folinic Acid]
Indications
Methotrexate toxicity
Indication detailsView
Calcium Folinate is indicated in:
- To diminish the toxicity and counteract the effect of impaired Methotrexate elimination.
- To treat the Megaloblastic anemia due to folate deficiency, as in sprue, nutritional deficiency.
- To treat the Megaloblastic anemia of pregnancy and infancy.
Therapeutic classView
Supportive Care Therapy
PharmacologyView
Calcium Folinate is a Calcium salt of Folinic acid (citrovorum factor), is a mixture of the diastereoisomers of the 5-formyl derivative of Tetrahydrofolic acid. It is a metabolite of Folic acid and an essential co-enzyme for nucleic acid synthesis used in cytotoxic therapy.
DosageView
Oral-
- Reduction of harmful effects of folic acid antagonists: The dose is usually one 5-15 mg tablet every 6 hours for 2 to 3 days.
- Megaloblastic anemia: In the treatment of Megaloblastic anemia, the dose is one 5-15 mg tablet daily.
- Advanced Colorectal Cancer: Folinic Acid is administered at 200 mg/m2 by slow intravenous injection followed by 5-fluorouracil at 370 mg/m2 by intravenous injection. Or 20 mg/m 2 by slow intravenous injection followed by 5-fluorouracil at 425 mg/m2 by intravenous injection. Treatment is repeated daily for 5 days. This 5 day treatment course may be repeated at 4 weeks interval, for 2 courses and then may repeated at 4-5 weekly intervals if the patient has recovered completely from the toxic effects of the prior treatment course.
- Folinic acid rescue after high dose Methotrexate Therapy: Calcium Folinate starts 24 hours after the beginning of the methotrexate infusion at dose of 15mg (10 mg/m2 ) every 6 hours for 10 doses.
- Folate deficient megaloboastic anaemia: Up to 1 mg/day. Or, as directed by the registered physician.
Side effectsView
- Allergic reaction: one may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing).
- Fits and fainting.
ContraindicationsView
Calcium Folinate therapy is contraindicated for the following:
- Known hypersensitivity to Calcium Folinate, or to any components of the product formulation.
- Pernicious anemia or other Megaloblastic anemia where Vitamin B12 is deficient.
PrecautionsView
Calcium Folinate treatment may mask pernicious anemia and other Megaloblastic anemia resulting from Vitamin B12 deficiency.
Calcium Folinate should only be used with 5-fluorouracil or Methotrexate under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.
Many cytotoxic medicinal products- direct or indirect DNA synthesis inhibitors- lead to macrocytosis (hydroxycarbamide, cytarabine, mercaptopurine, thioguanine). Such macrocytosis should not be treated with Folinic acid.
In epileptic patients treated with Phenobarbital, Phenytoin, Primidone, and Succinimides, there is a risk to increase the frequency of seizures due to a decrease of plasma concentrations of anti-epileptic drug.
Calcium Folinate should only be used with 5-fluorouracil or Methotrexate under the direct supervision of a clinician experienced in the use of cancer chemotherapeutic agents.
Many cytotoxic medicinal products- direct or indirect DNA synthesis inhibitors- lead to macrocytosis (hydroxycarbamide, cytarabine, mercaptopurine, thioguanine). Such macrocytosis should not be treated with Folinic acid.
In epileptic patients treated with Phenobarbital, Phenytoin, Primidone, and Succinimides, there is a risk to increase the frequency of seizures due to a decrease of plasma concentrations of anti-epileptic drug.
Pregnancy & lactationView
There are no adequate and well-controlled clinical studies conducted in pregnant or breastfeeding women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Calcium Folinate is administered to a nursing mother.
Overdose effectsView
There have been no reported sequelae in patients who have received significantly more Calcium Folinate than the recommended dosage. However, excessive amounts of Calcium Folinate may nullify the chemotherapeutic effect of folic acid antagonists.
StorageView
Do not store above 30°C. Keep away from light and out of the reach of children.
Leukenib
Imatinib Mesylate
Leukenib
Imatinib Mesylate
Indication detailsView
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+CML) in chronic phase.
- Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
- Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy
- Adult patients with myelodysplastic/myeloproliferative diseases associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
- Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.
- Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFR a fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRa fusion kinase negative or unknown.
- Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.
- Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.
- Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.
Therapeutic classView
Targeted Cancer Therapy, Tyrosine Kinase Inhibitor
PharmacologyView
Imatinib is a small molecule protein-tyrosine kinase inhibitor that potently inhibits the activity of the Bcr-Abl tyrosine kinase (TK), as well as several receptor TKs: Kit, the receptor for stem cell factor (SCF) coded for by the c-Kit proto-oncogene, the discoidin domain receptors (DDR1 and DDR2), the colony stimulating factor receptor (CSF-1R) and the platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and PDGFR beta). Imatinib can also inhibit cellular events mediated by activation of these receptor kinases.
Absorption and Distribution: Imatinib is well absorbed after oral administration with Cmax achieved within 2 4 hours post-dose. Mean absolute bioavailability is 98%. Mean Imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of Imatinib on repeated dosing, and accumulation is 1.5- to 2.5- fold at a steady state when Imatinib is dosed once daily. At clinically relevant concentrations of Imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and 1-acid glycoprotein.
Metabolism: CYP3A4 is the major enzyme responsible for metabolism of Imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent Imatinib. The plasma AUC for this metabolite is about 15% of the AUC for Imatinib. The plasma protein binding of N-demethylated metabolite CGP74588 is similar to that of the parent compound.
Excretion: Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of Imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged Imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites. Following oral administration in healthy volunteers, the elimination half-lives of Imatinib and its major active metabolite, the N-demethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.
Absorption and Distribution: Imatinib is well absorbed after oral administration with Cmax achieved within 2 4 hours post-dose. Mean absolute bioavailability is 98%. Mean Imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of Imatinib on repeated dosing, and accumulation is 1.5- to 2.5- fold at a steady state when Imatinib is dosed once daily. At clinically relevant concentrations of Imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and 1-acid glycoprotein.
Metabolism: CYP3A4 is the major enzyme responsible for metabolism of Imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent Imatinib. The plasma AUC for this metabolite is about 15% of the AUC for Imatinib. The plasma protein binding of N-demethylated metabolite CGP74588 is similar to that of the parent compound.
Excretion: Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of Imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged Imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites. Following oral administration in healthy volunteers, the elimination half-lives of Imatinib and its major active metabolite, the N-demethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.
DosageView
Adults with Ph+ CML CP: 400 mg/day
Adults with Ph+ CML AP or BC: 600 mg/day
Pediatrics with Ph+ CML CP: 340 mg/m2/day
Adults with Ph+ ALL: 600 mg/day
Pediatrics with Ph+ ALL: 340 mg/m2/day
Adults with MDS/MPD: 400 mg/day
Adults with ASM: 100 mg/day or 400 mg/day
Adults with HES/CEL: 100 mg/day or 400 mg/day
Adults with DFSP: 800 mg/day
Adults with metastatic and/or unresectable GIST: 400 mg/day
Adjuvant treatment of adults with GIST: 400 mg/day
Patients with mild to moderate hepatic impairment: 400 mg/day
Patients with severe hepatic impairment: 300 mg/day
All doses of Imatinib should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. Daily dosing of 800 mg and above should be accomplished using the 400-mg tablet to reduce exposure to iron.
Adults with Ph+ CML AP or BC: 600 mg/day
Pediatrics with Ph+ CML CP: 340 mg/m2/day
Adults with Ph+ ALL: 600 mg/day
Pediatrics with Ph+ ALL: 340 mg/m2/day
Adults with MDS/MPD: 400 mg/day
Adults with ASM: 100 mg/day or 400 mg/day
Adults with HES/CEL: 100 mg/day or 400 mg/day
Adults with DFSP: 800 mg/day
Adults with metastatic and/or unresectable GIST: 400 mg/day
Adjuvant treatment of adults with GIST: 400 mg/day
Patients with mild to moderate hepatic impairment: 400 mg/day
Patients with severe hepatic impairment: 300 mg/day
All doses of Imatinib should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. Daily dosing of 800 mg and above should be accomplished using the 400-mg tablet to reduce exposure to iron.
Side effectsView
The following serious adverse reactions are described elsewhere in the labeling:
- Fluid Retention and Edema
- Hematologic Toxicity
- Congestive Heart Failure and Left Ventricular Dysfunction
- Hepatotoxicity
- Hemorrhage
- Gastrointestinal Disorders
- Hypereosinophilic Cardiac Toxicity
- Dermatologic Toxicities
- Hypothyroidism
- Growth Retardation in Children and Adolescents
- Tumor Lysis Syndrome
- Impairments Related to Driving and Using Machinery
- Renal Toxicity
PrecautionsView
- Edema and severe fluid retention have occurred. Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics.
- Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred. Manage with dose reduction, dose interruption, or discontinuation of treatment. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter.
- Severe congestive heart failure and left ventricular dysfunction have been reported, particularly in patients with comorbidities and risk factors. Monitor and treat patients with cardiac disease or risk factors for cardiac failure.
- Severe hepatotoxicity, including fatalities may occur. Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated. Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction.
- Grade 3/4 hemorrhage has been reported in clinical studies in patients with newly diagnosed CML and with GIST. Gl tumor sites may be the source of Gl bleeds in GIST. Gastrointestinal (Gl) perforations, some fatal, have been reported.
- Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of Imatinib in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM).
- Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of Imatinib.
- Hypothyroidism has been reported in thyroidectomy ZyvaxatX patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients.
- Fetal harm can occur when administered to a pregnant woman. Apprise women of the potential harm to the fetus, and to avoid pregnancy when taking Imatinib.
- Growth retardation occurring in children and pre-adolescents receiving Imatinib has been reported. Close monitoring of growth in children under Imatinib treatment is recommended.
- Tumor Lysis Syndrome. Close monitoring is recommended.
- Reports of motor vehicle accidents have been received in patients receiving Imatinib. Caution patients about driving a car or operating machinery.
- Renal Toxicity. A decline in renal function may occur in patients receiving Imatinib. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.
InteractionsView
Agents Inducing CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inducers may reduce total exposure of imatinib; consider alternative agents.
Agents Inhibiting CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice).
Interactions with Drugs Metabolized by CYP3A4: Imatinib will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Use caution when administering Imatinib with CYP3A4 substrates that have a narrow therapeutic window. Because warfarin is metabolized by CYP2C9 and CYP3A4, use low-molecular weight or standard heparin instead of warfarin in patients who require anticoagulation.
Interactions with Drugs Metabolized by CYP2D6: Use caution when administering Imatinib with CYP2D6 substrates that have a narrow therapeutic window.
Agents Inhibiting CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice).
Interactions with Drugs Metabolized by CYP3A4: Imatinib will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Use caution when administering Imatinib with CYP3A4 substrates that have a narrow therapeutic window. Because warfarin is metabolized by CYP2C9 and CYP3A4, use low-molecular weight or standard heparin instead of warfarin in patients who require anticoagulation.
Interactions with Drugs Metabolized by CYP2D6: Use caution when administering Imatinib with CYP2D6 substrates that have a narrow therapeutic window.
Pregnancy & lactationView
Women of childbearing potential: Women of childbearing potential must be advised to use effective contraception during treatment and for at least 15 days after stopping treatment with Imatinib.
Pregnancy: There are limited data on the use of imatinib in pregnant women. There have been post-marketing reports of spontaneous abortions and infant congenital anomalies from women who have taken Imatinib. Studies in animals have however shown reproductive toxicity and the potential risk for the foetus is unknown. Imatinib should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Breast-feeding: There is limited information on imatinib distribution on human milk. Studies in two breast feeding women revealed that both imatinib and its active metabolite can be distributed into human milk. The milk plasma ratio studied in a single patient was determined to be 0.5 for imatinib and 0.9 for the metabolite, suggesting greater distribution of the metabolite into the milk. Considering the combined concentration of imatinib and the metabolite and the maximum daily milk intake by infants, the total exposure would be expected to be low (-10% of a therapeutic dose). However, since the effects of low-dose exposure of the infant to imatinib are unknown, women should not breast-feed during treatment and for at least 15 days after stopping treatment with Imatinib.
Fertility: In non-clinical studies, the fertility of male and female rats was not affected, although effects on reproductive parameters were observed. Studies on patients receiving Imatinib and its effect on fertility and gametogenesis have not been performed. Patients concerned about their fertility on Imatinib treatment should consult with their physician.
Pregnancy: There are limited data on the use of imatinib in pregnant women. There have been post-marketing reports of spontaneous abortions and infant congenital anomalies from women who have taken Imatinib. Studies in animals have however shown reproductive toxicity and the potential risk for the foetus is unknown. Imatinib should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Breast-feeding: There is limited information on imatinib distribution on human milk. Studies in two breast feeding women revealed that both imatinib and its active metabolite can be distributed into human milk. The milk plasma ratio studied in a single patient was determined to be 0.5 for imatinib and 0.9 for the metabolite, suggesting greater distribution of the metabolite into the milk. Considering the combined concentration of imatinib and the metabolite and the maximum daily milk intake by infants, the total exposure would be expected to be low (-10% of a therapeutic dose). However, since the effects of low-dose exposure of the infant to imatinib are unknown, women should not breast-feed during treatment and for at least 15 days after stopping treatment with Imatinib.
Fertility: In non-clinical studies, the fertility of male and female rats was not affected, although effects on reproductive parameters were observed. Studies on patients receiving Imatinib and its effect on fertility and gametogenesis have not been performed. Patients concerned about their fertility on Imatinib treatment should consult with their physician.
Overdose effectsView
Experience with doses higher than the recommended therapeutic dose is limited. In the event of overdose the patient should be observed and an appropriate symptomatic treatment given. Generally, the reported outcome in these cases was "improved" or "recovered". Events that have been reported at different dose ranges are as follows:
Adult Population:
Adult Population:
- 1200 to 1600 mg (duration varying between 1 to 10 days): Nausea, vomiting, diarrhoea, rash, erythema, oedema, swelling, fatigue, muscle spasms, thrombocytopenia, pancytopenia, abdominal pain, headache, decreased appetite.
- 1800 to 3200 mg (as high as 3200 mg daily for 6 days): Weakness, myalgia, increased creatine phosphokinase,
- increased bilirubin, gastrointestinal pain.
- 6400 mg (single dose): One case reported in the literature of one patient who experienced nausea, vomiting, abdominal pain, pyrexia, facial swelling, decreased neutrophil count, and increased transaminases.
- 8 to 10 g (single dose): Vomiting and gastrointestinal pain have been reported.
StorageView
Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.
Leukenib
Imatinib Mesylate
Leukenib
Imatinib Mesylate
Indication detailsView
- Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+CML) in chronic phase.
- Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy.
- Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy
- Adult patients with myelodysplastic/myeloproliferative diseases associated with platelet-derived growth factor receptor (PDGFR) gene re-arrangements.
- Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown.
- Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFR a fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRa fusion kinase negative or unknown.
- Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.
- Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors.
- Adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive GIST.
Therapeutic classView
Targeted Cancer Therapy, Tyrosine Kinase Inhibitor
PharmacologyView
Imatinib is a small molecule protein-tyrosine kinase inhibitor that potently inhibits the activity of the Bcr-Abl tyrosine kinase (TK), as well as several receptor TKs: Kit, the receptor for stem cell factor (SCF) coded for by the c-Kit proto-oncogene, the discoidin domain receptors (DDR1 and DDR2), the colony stimulating factor receptor (CSF-1R) and the platelet-derived growth factor receptors alpha and beta (PDGFR-alpha and PDGFR beta). Imatinib can also inhibit cellular events mediated by activation of these receptor kinases.
Absorption and Distribution: Imatinib is well absorbed after oral administration with Cmax achieved within 2 4 hours post-dose. Mean absolute bioavailability is 98%. Mean Imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of Imatinib on repeated dosing, and accumulation is 1.5- to 2.5- fold at a steady state when Imatinib is dosed once daily. At clinically relevant concentrations of Imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and 1-acid glycoprotein.
Metabolism: CYP3A4 is the major enzyme responsible for metabolism of Imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent Imatinib. The plasma AUC for this metabolite is about 15% of the AUC for Imatinib. The plasma protein binding of N-demethylated metabolite CGP74588 is similar to that of the parent compound.
Excretion: Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of Imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged Imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites. Following oral administration in healthy volunteers, the elimination half-lives of Imatinib and its major active metabolite, the N-demethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.
Absorption and Distribution: Imatinib is well absorbed after oral administration with Cmax achieved within 2 4 hours post-dose. Mean absolute bioavailability is 98%. Mean Imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg. There is no significant change in the pharmacokinetics of Imatinib on repeated dosing, and accumulation is 1.5- to 2.5- fold at a steady state when Imatinib is dosed once daily. At clinically relevant concentrations of Imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and 1-acid glycoprotein.
Metabolism: CYP3A4 is the major enzyme responsible for metabolism of Imatinib. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. It shows in vitro potency similar to the parent Imatinib. The plasma AUC for this metabolite is about 15% of the AUC for Imatinib. The plasma protein binding of N-demethylated metabolite CGP74588 is similar to that of the parent compound.
Excretion: Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of Imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose). Unchanged Imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites. Following oral administration in healthy volunteers, the elimination half-lives of Imatinib and its major active metabolite, the N-demethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.
DosageView
Adults with Ph+ CML CP: 400 mg/day
Adults with Ph+ CML AP or BC: 600 mg/day
Pediatrics with Ph+ CML CP: 340 mg/m2/day
Adults with Ph+ ALL: 600 mg/day
Pediatrics with Ph+ ALL: 340 mg/m2/day
Adults with MDS/MPD: 400 mg/day
Adults with ASM: 100 mg/day or 400 mg/day
Adults with HES/CEL: 100 mg/day or 400 mg/day
Adults with DFSP: 800 mg/day
Adults with metastatic and/or unresectable GIST: 400 mg/day
Adjuvant treatment of adults with GIST: 400 mg/day
Patients with mild to moderate hepatic impairment: 400 mg/day
Patients with severe hepatic impairment: 300 mg/day
All doses of Imatinib should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. Daily dosing of 800 mg and above should be accomplished using the 400-mg tablet to reduce exposure to iron.
Adults with Ph+ CML AP or BC: 600 mg/day
Pediatrics with Ph+ CML CP: 340 mg/m2/day
Adults with Ph+ ALL: 600 mg/day
Pediatrics with Ph+ ALL: 340 mg/m2/day
Adults with MDS/MPD: 400 mg/day
Adults with ASM: 100 mg/day or 400 mg/day
Adults with HES/CEL: 100 mg/day or 400 mg/day
Adults with DFSP: 800 mg/day
Adults with metastatic and/or unresectable GIST: 400 mg/day
Adjuvant treatment of adults with GIST: 400 mg/day
Patients with mild to moderate hepatic impairment: 400 mg/day
Patients with severe hepatic impairment: 300 mg/day
All doses of Imatinib should be taken with a meal and a large glass of water. Doses of 400 mg or 600 mg should be administered once daily, whereas a dose of 800 mg should be administered as 400 mg twice a day. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. Daily dosing of 800 mg and above should be accomplished using the 400-mg tablet to reduce exposure to iron.
Side effectsView
The following serious adverse reactions are described elsewhere in the labeling:
- Fluid Retention and Edema
- Hematologic Toxicity
- Congestive Heart Failure and Left Ventricular Dysfunction
- Hepatotoxicity
- Hemorrhage
- Gastrointestinal Disorders
- Hypereosinophilic Cardiac Toxicity
- Dermatologic Toxicities
- Hypothyroidism
- Growth Retardation in Children and Adolescents
- Tumor Lysis Syndrome
- Impairments Related to Driving and Using Machinery
- Renal Toxicity
PrecautionsView
- Edema and severe fluid retention have occurred. Weigh patients regularly and manage unexpected rapid weight gain by drug interruption and diuretics.
- Cytopenias, particularly anemia, neutropenia, and thrombocytopenia, have occurred. Manage with dose reduction, dose interruption, or discontinuation of treatment. Perform complete blood counts weekly for the first month, biweekly for the second month, and periodically thereafter.
- Severe congestive heart failure and left ventricular dysfunction have been reported, particularly in patients with comorbidities and risk factors. Monitor and treat patients with cardiac disease or risk factors for cardiac failure.
- Severe hepatotoxicity, including fatalities may occur. Assess liver function before initiation of treatment and monthly thereafter or as clinically indicated. Monitor liver function when combined with chemotherapy known to be associated with liver dysfunction.
- Grade 3/4 hemorrhage has been reported in clinical studies in patients with newly diagnosed CML and with GIST. Gl tumor sites may be the source of Gl bleeds in GIST. Gastrointestinal (Gl) perforations, some fatal, have been reported.
- Cardiogenic shock/left ventricular dysfunction has been associated with the initiation of Imatinib in patients with conditions associated with high eosinophil levels (e.g., HES, MDS/MPD, and ASM).
- Bullous dermatologic reactions (e.g., erythema multiforme and Stevens-Johnson syndrome) have been reported with the use of Imatinib.
- Hypothyroidism has been reported in thyroidectomy ZyvaxatX patients undergoing levothyroxine replacement. Closely monitor TSH levels in such patients.
- Fetal harm can occur when administered to a pregnant woman. Apprise women of the potential harm to the fetus, and to avoid pregnancy when taking Imatinib.
- Growth retardation occurring in children and pre-adolescents receiving Imatinib has been reported. Close monitoring of growth in children under Imatinib treatment is recommended.
- Tumor Lysis Syndrome. Close monitoring is recommended.
- Reports of motor vehicle accidents have been received in patients receiving Imatinib. Caution patients about driving a car or operating machinery.
- Renal Toxicity. A decline in renal function may occur in patients receiving Imatinib. Evaluate renal function at baseline and during therapy, with attention to risk factors for renal dysfunction.
InteractionsView
Agents Inducing CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inducers may reduce total exposure of imatinib; consider alternative agents.
Agents Inhibiting CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice).
Interactions with Drugs Metabolized by CYP3A4: Imatinib will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Use caution when administering Imatinib with CYP3A4 substrates that have a narrow therapeutic window. Because warfarin is metabolized by CYP2C9 and CYP3A4, use low-molecular weight or standard heparin instead of warfarin in patients who require anticoagulation.
Interactions with Drugs Metabolized by CYP2D6: Use caution when administering Imatinib with CYP2D6 substrates that have a narrow therapeutic window.
Agents Inhibiting CYP3A Metabolism: Concomitant administration of Imatinib and strong CYP3A4 inhibitors may result in a significant imatinib exposure increase. Grapefruit juice may also increase plasma concentrations of imatinib; avoid grapefruit juice).
Interactions with Drugs Metabolized by CYP3A4: Imatinib will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Use caution when administering Imatinib with CYP3A4 substrates that have a narrow therapeutic window. Because warfarin is metabolized by CYP2C9 and CYP3A4, use low-molecular weight or standard heparin instead of warfarin in patients who require anticoagulation.
Interactions with Drugs Metabolized by CYP2D6: Use caution when administering Imatinib with CYP2D6 substrates that have a narrow therapeutic window.
Pregnancy & lactationView
Women of childbearing potential: Women of childbearing potential must be advised to use effective contraception during treatment and for at least 15 days after stopping treatment with Imatinib.
Pregnancy: There are limited data on the use of imatinib in pregnant women. There have been post-marketing reports of spontaneous abortions and infant congenital anomalies from women who have taken Imatinib. Studies in animals have however shown reproductive toxicity and the potential risk for the foetus is unknown. Imatinib should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Breast-feeding: There is limited information on imatinib distribution on human milk. Studies in two breast feeding women revealed that both imatinib and its active metabolite can be distributed into human milk. The milk plasma ratio studied in a single patient was determined to be 0.5 for imatinib and 0.9 for the metabolite, suggesting greater distribution of the metabolite into the milk. Considering the combined concentration of imatinib and the metabolite and the maximum daily milk intake by infants, the total exposure would be expected to be low (-10% of a therapeutic dose). However, since the effects of low-dose exposure of the infant to imatinib are unknown, women should not breast-feed during treatment and for at least 15 days after stopping treatment with Imatinib.
Fertility: In non-clinical studies, the fertility of male and female rats was not affected, although effects on reproductive parameters were observed. Studies on patients receiving Imatinib and its effect on fertility and gametogenesis have not been performed. Patients concerned about their fertility on Imatinib treatment should consult with their physician.
Pregnancy: There are limited data on the use of imatinib in pregnant women. There have been post-marketing reports of spontaneous abortions and infant congenital anomalies from women who have taken Imatinib. Studies in animals have however shown reproductive toxicity and the potential risk for the foetus is unknown. Imatinib should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus.
Breast-feeding: There is limited information on imatinib distribution on human milk. Studies in two breast feeding women revealed that both imatinib and its active metabolite can be distributed into human milk. The milk plasma ratio studied in a single patient was determined to be 0.5 for imatinib and 0.9 for the metabolite, suggesting greater distribution of the metabolite into the milk. Considering the combined concentration of imatinib and the metabolite and the maximum daily milk intake by infants, the total exposure would be expected to be low (-10% of a therapeutic dose). However, since the effects of low-dose exposure of the infant to imatinib are unknown, women should not breast-feed during treatment and for at least 15 days after stopping treatment with Imatinib.
Fertility: In non-clinical studies, the fertility of male and female rats was not affected, although effects on reproductive parameters were observed. Studies on patients receiving Imatinib and its effect on fertility and gametogenesis have not been performed. Patients concerned about their fertility on Imatinib treatment should consult with their physician.
Overdose effectsView
Experience with doses higher than the recommended therapeutic dose is limited. In the event of overdose the patient should be observed and an appropriate symptomatic treatment given. Generally, the reported outcome in these cases was "improved" or "recovered". Events that have been reported at different dose ranges are as follows:
Adult Population:
Adult Population:
- 1200 to 1600 mg (duration varying between 1 to 10 days): Nausea, vomiting, diarrhoea, rash, erythema, oedema, swelling, fatigue, muscle spasms, thrombocytopenia, pancytopenia, abdominal pain, headache, decreased appetite.
- 1800 to 3200 mg (as high as 3200 mg daily for 6 days): Weakness, myalgia, increased creatine phosphokinase,
- increased bilirubin, gastrointestinal pain.
- 6400 mg (single dose): One case reported in the literature of one patient who experienced nausea, vomiting, abdominal pain, pyrexia, facial swelling, decreased neutrophil count, and increased transaminases.
- 8 to 10 g (single dose): Vomiting and gastrointestinal pain have been reported.
StorageView
Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.
Leukeran
Chlorambucil
Leukeran
Chlorambucil
Indications
Waldenstrom's macroglobulinaemia
Indication detailsView
Hodgkin's disease, certain forms of non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, Waldenstrom's macroglobulinaemia.
Therapeutic classView
Cytotoxic Chemotherapy
PharmacologyView
Chlorambucil produces its anti-cancer effects by interfering with DNA replication and damaging the DNA in a cell. The DNA damage induces cell cycle arrest and cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of Bax, an apoptosis promoter.
Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, inducing DNA damage via three different methods of covalent adduct generation with double-helical DNA:
Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, inducing DNA damage via three different methods of covalent adduct generation with double-helical DNA:
- Attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA.
- DNA damage via the formation of cross-links which prevents DNA from being separated for synthesis or transcription.
- Induction of mispairing of the nucleotides leading to mutations.
DosageView
Hodgkin's disease: 200 mcg/kg/day for 4-8 wk.
Non-Hodgkin's lymphoma: 100-200 mcg/kg/day for 4-8 wk. Maintenance: Reduced daily dosage of intermittent courses of treatment.
Chronic lymphocytic leukaemia: Initially, 150 mcg/kg/day until the total leukocyte count falls to 10,000 microliter. Treatment may be resumed 4 wk after at a dose of 100 mcg/kg/day.
Waldenstrom's macroglobulinaemia: Starting dose of 6-12 mg daily until leucopenia occurs followed by 2-8 mg daily.
Non-Hodgkin's lymphoma: 100-200 mcg/kg/day for 4-8 wk. Maintenance: Reduced daily dosage of intermittent courses of treatment.
Chronic lymphocytic leukaemia: Initially, 150 mcg/kg/day until the total leukocyte count falls to 10,000 microliter. Treatment may be resumed 4 wk after at a dose of 100 mcg/kg/day.
Waldenstrom's macroglobulinaemia: Starting dose of 6-12 mg daily until leucopenia occurs followed by 2-8 mg daily.
AdministrationView
Should be taken on an empty stomach: Ensure adequate hydration. Swallow whole, do not chew/crush.
Side effectsView
Bone marrow suppression, seizures in childn with nephrotic syndrome, nausea, vomiting, diarrhoea, oral ulceration. Rarely, irreversible bone marrow failure, allergic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures, movement disorders, interstitial pulmonary fibrosis, interstitial pneumonia, hepatotoxicity, jaundice, sterile cystitis, drug fever
ContraindicationsView
Pregnancy (1st trimester) & lactation.
PrecautionsView
Monitor FBC closely. Bone marrow suppression reversible only if withdrawn early enough. Should not be given to patients who have recently undergone radio- or chemotherapy. In lymphocytic infiltration of bone marrow or hypoplastic bone marrow, max daily dose is 0.1 mg/kg. Childn with nephrotic syndrome, patients on high pulse dosing regimens, history of seizure disorders. Renal or hepatic impairment. Ensure adequate contraceptive precautions. Pregnancy.
Pregnancy & lactationView
Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Leukin
Mercaptopurine
Leukin
Mercaptopurine
Indications
Leukemia
Indication detailsView
Mercaptopurine is indicated for maintenance therapy of acute lymphatic (lymphocytic, lymphoblastic) leukemiaas part of a combination regimen. The response to this agent depends upon the particular subclassification of acute lymphatic leukemia and the age of the patient (pediatric or adult).
Mercaptopurine is not effective for prophylaxis or treatment of central nervous system leukemia. Mercaptopurine is not effective in acute myelogenous leukemia, chronic lymphatic leukemia, the lymphomas (including Hodgkins Disease), or solid tumors.
Mercaptopurine is not effective for prophylaxis or treatment of central nervous system leukemia. Mercaptopurine is not effective in acute myelogenous leukemia, chronic lymphatic leukemia, the lymphomas (including Hodgkins Disease), or solid tumors.
Therapeutic classView
Cytotoxic Chemotherapy
PharmacologyView
Mercaptopurine is a purine antagonist which is converted intracellularly into its active nucleotides, including thioinosinic acid. The nucleotides inhibit several reactions which ultimately interferes with nucleic acid synthesis and prevents the formation of RNA and DNA.
DosageView
Crohn's disease:
- Adult: Initially 1-1.5 mg/kg daily, may increase to 125 mg daily.
- Child: Initially 1-1.5 mg/kg daily increased to a max of 75 mg daily
- Adult: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.
- Child: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.
AdministrationView
Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. Ensure adequate fluid intake.
Side effectsView
Hyperuricaemia, bone marrow toxicity, hypoplasia, anorexia, diarrhoea, leukopenia, thrombocytopenia, intestinal ulceration, crystalluria with haematuria, immunosuppression, interstitial pneumonitis. Cutaneous hyperpigmentation, alopecia.
ContraindicationsView
Pregnancy and lactation. Prior resistance to mercaptopurine or thioguanine; severe liver disease; severe bone marrow suppression.
PrecautionsView
Hepatic or renal dysfunction; monitor hepatic function periodically. Mercaptopurine is potentially carcinogenic. Thiopurine S-methyl transferase (TPMT) deficiency; porphyria.
InteractionsView
Anticoagulant action of warfarin may be inhibited by mercaptopurine. Enhanced toxicity with myelosuppressive drugs.
Pregnancy & lactationView
Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Pediatric usageView
Renal Impairment: Dosage may need to be reduced.
Hepatic Impairment:
For patients with homozygous TPMT deficiency: Substantial reduction is required.
For patients with heterozygous TPMT deficiency: Some may require reduction but most will tolerate the usual dosages.
Hepatic Impairment:
- Crohn's disease: Dosage may need to be reduced.
- Acute lymphocytic leukemia: Dosage may need to be reduced
For patients with homozygous TPMT deficiency: Substantial reduction is required.
For patients with heterozygous TPMT deficiency: Some may require reduction but most will tolerate the usual dosages.
StorageView
Store at 20-25° C
Levair
Levosalbutamol (Oral)
Levair
Levosalbutamol (Oral)
Indications
COPD
Indication detailsView
Levosalbutamol is indicated for the treatment or prevention of bronchospasm in adults, adolescents and children 6 years of age and older with reversible obstructive airway disease.
Therapeutic classView
Short-acting selective & β2-adrenoceptor stimulants
PharmacologyView
Levosalbutamol is a single isomer beta 2-agonist that differs from racemic salbutamol by elimination of (S)-salbutamol. Levosalbutamol is an effective bronchodilator whose primary mechanism of action is unimpeded by (S)-salbutamol. Thus, when compared with racemic salbutamol, clinically comparable bronchodilation can be achieved with doses that substantially lessen beta-mediated side effects.
DosageView
Tablet-
- Adults and adolescents above 12 years: 1-2 mg three times daily.
- Children (6 -11 years): 1 mg three times daily.
- Adults : 5-10 ml three times daily.
- Childrn (6-11 years): 5 ml three times daily.
Side effectsView
Hypocalcaemia, palpitation, fine tremors of the skeletal muscle and muscle cramps may occur. The other likely side effects are nausea, vomiting, burning substernal or epigastric pain and diarrhoea.
ContraindicationsView
Levosalbutamol is contraindicated in patients with a history of hypersensitivity to levosalbutamol or any of its components.
PrecautionsView
Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.
InteractionsView
Other short acting sympathomimetic bronchodilators or epinephrine should be used with caution with Levosalbutamol. If additional adrenergic drugs are to be administered by any route, they will be used with caution to avoid deleterious cardiovascular effects.
Pregnancy & lactationView
The drug should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus. It is not known whether Levosalbutamol is excreted in human milk. Caution should be exercised when oral Levosalbutamol is administered to a nursing woman.
Overdose effectsView
The expected symptoms with over dosage are those of excessive beta-adrenergic stimulation and the symptoms listed under side effects. In the event of serious poisoning, the stomach should be emptied and, if necessary, a beta-blocker administered with caution in patients with a history of bronchospasm.
StorageView
Keep all medicines out of reach of children. Store in a cool and dry place, protected from light.
Levamin
Levamisole
Levamin
Levamisole
Indications
Helminthiasis
Indication detailsView
Levamisole is a fast acting drug which acts on nematode nerve ganglia paralysing the worm’s musculature within seconds of contact. Unable to maintain their position, the worms are then ejected by normal peristaltic movement, usually within 24 hours of levamisole administration. Although it is certain that levamisole primarily influences the neuromuscular system of nematodes, it is possible that in some helminthes the inhibition of the fumarate reductase system contributes to the anthelmintic efficacy of levamisole. Levamisole is indicated for the treatment of infections by the following gastrointestinal worm
species:
species:
- Ascaris lumbricoides: Roundworm
- Necator americanus: Hookworm
- Ancylostoma duodenal: Hookworm
- E nterobius vermicularis: Pinworm
- Trichuris trichuria: Whipworm
- Strongyloides stercoralis: Threadworm
- Trichostrongylus colubriformis
Therapeutic classView
Anthelmintic
PharmacologyView
Levamisole is the active laevo-isomer of tetramisole. It works by paralysing susceptible intestinal worms which are then excreted from the intestines. Levamisole also enhances cellular immune responses in humans.
DosageView
The following doses of Levamisole are given as a single administration, preferably after a light meal.
- Age 1-4 year: 1 Tablets or 5 ml Syrup
- Age 5-15 year: 2 Tablets or 10 ml Syrup
- Age 16 year and over: 3 Tablets or 15 ml Syrup
Side effectsView
Side-effects are infrequent. They are usually mild and transient and include nausea, vomiting, abdominal pain, giddiness(dizziness) and headache. An encephalopathylike syndrome has been reported to have occurred in a few patients two or three weeks after treatment.
ContraindicationsView
There is no absolute contra-indication to the use of Levamisole
PrecautionsView
Effect on ability to drive or operate machinery: There is no evidence to suggest that Levamisole , used for anthelmintic purpose, will produce sedation. Mild and transient giddiness is an infrequent side-effect of treatment. No precautions are suggested concerning the ability to drive or operate machinery.
In case of concurrent microfilaraemia transient fever may occur.
In case of concurrent microfilaraemia transient fever may occur.
InteractionsView
May increase toxicity of phenytoin. Increases bioavailability of ivermectin; decreases bioavailability of albendazole. Alcohol causes disulfiram-like reaction.
Pregnancy & lactationView
Although studies in animals have shown that Levamisole produces no teratogenic effects, current medical practice requires that the benefits of any drug used during pregnancy should be weighed against the possible dangers.
Overdose effectsView
Counter possible anticholinesterase activity with e.g. atropine. Control blood pressure and respiration . Do not use sedatives.
StorageView
Tablet: Store in room temperature and protect from moisture.
Syrup: Store in room temperature and protect from light.
Syrup: Store in room temperature and protect from light.
Levamin
Levamisole
Levamin
Levamisole
Indications
Helminthiasis
Indication detailsView
Levamisole is a fast acting drug which acts on nematode nerve ganglia paralysing the worm’s musculature within seconds of contact. Unable to maintain their position, the worms are then ejected by normal peristaltic movement, usually within 24 hours of levamisole administration. Although it is certain that levamisole primarily influences the neuromuscular system of nematodes, it is possible that in some helminthes the inhibition of the fumarate reductase system contributes to the anthelmintic efficacy of levamisole. Levamisole is indicated for the treatment of infections by the following gastrointestinal worm
species:
species:
- Ascaris lumbricoides: Roundworm
- Necator americanus: Hookworm
- Ancylostoma duodenal: Hookworm
- E nterobius vermicularis: Pinworm
- Trichuris trichuria: Whipworm
- Strongyloides stercoralis: Threadworm
- Trichostrongylus colubriformis
Therapeutic classView
Anthelmintic
PharmacologyView
Levamisole is the active laevo-isomer of tetramisole. It works by paralysing susceptible intestinal worms which are then excreted from the intestines. Levamisole also enhances cellular immune responses in humans.
DosageView
The following doses of Levamisole are given as a single administration, preferably after a light meal.
- Age 1-4 year: 1 Tablets or 5 ml Syrup
- Age 5-15 year: 2 Tablets or 10 ml Syrup
- Age 16 year and over: 3 Tablets or 15 ml Syrup
Side effectsView
Side-effects are infrequent. They are usually mild and transient and include nausea, vomiting, abdominal pain, giddiness(dizziness) and headache. An encephalopathylike syndrome has been reported to have occurred in a few patients two or three weeks after treatment.
ContraindicationsView
There is no absolute contra-indication to the use of Levamisole
PrecautionsView
Effect on ability to drive or operate machinery: There is no evidence to suggest that Levamisole , used for anthelmintic purpose, will produce sedation. Mild and transient giddiness is an infrequent side-effect of treatment. No precautions are suggested concerning the ability to drive or operate machinery.
In case of concurrent microfilaraemia transient fever may occur.
In case of concurrent microfilaraemia transient fever may occur.
InteractionsView
May increase toxicity of phenytoin. Increases bioavailability of ivermectin; decreases bioavailability of albendazole. Alcohol causes disulfiram-like reaction.
Pregnancy & lactationView
Although studies in animals have shown that Levamisole produces no teratogenic effects, current medical practice requires that the benefits of any drug used during pregnancy should be weighed against the possible dangers.
Overdose effectsView
Counter possible anticholinesterase activity with e.g. atropine. Control blood pressure and respiration . Do not use sedatives.
StorageView
Tablet: Store in room temperature and protect from moisture.
Syrup: Store in room temperature and protect from light.
Syrup: Store in room temperature and protect from light.
Levamolin
S-Amlodipine Besilate (Levamlodipine)
Levamolin
S-Amlodipine Besilate (Levamlodipine)
Indications
Stroke
Indication detailsView
S-Amlodipine is calcium channel blocker and may be used alone or in combination with other antihypertensive agents for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
Therapeutic classView
Calcium-channel blockers
PharmacologyView
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine is a 1:1 racemic mixture of levamlodipine and dextro amlodipine, it has been demonstrated that levamlodipine is the pharmacologically active, anti-hypertensive isomer.
DosageView
Adults: The usual initial antihypertensive oral dose of S-Amlodipine is 2.5 mg once daily, and the maximum dose is 5 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dose may be used when adding S-Amlodipine to other antihypertensive therapy. Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.
Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.
Side effectsView
Most common adverse reactions to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain and somnolence.
ContraindicationsView
S-Amlodipine is contraindicated in patients with known sensitivity to amlodipine.
PrecautionsView
Hypotension: Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
InteractionsView
Impact of Other Drugs on Amlodipine-
- CYP3A Inhibitors: Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment
- CYP3A Inducers: No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.
- Sildenafil: Monitor for hypotension when sildenafil is coadministered with amlodipine.
- Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
- Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate
Pregnancy & lactationView
The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.
Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.
Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.
Pediatric usageView
Pediatric Use: S-Amlodipine (1.25 to 2.5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years. The effect of S-Amlodipine on blood pressure in patients less than 6 years of age is not known.
Geriatric Use: Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required
Geriatric Use: Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required
Overdose effectsView
Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
StorageView
Store bottles at 20°C to 25°C.
Levamolin
S-Amlodipine Besilate (Levamlodipine)
Levamolin
S-Amlodipine Besilate (Levamlodipine)
Indications
Stroke
Indication detailsView
S-Amlodipine is calcium channel blocker and may be used alone or in combination with other antihypertensive agents for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.
Therapeutic classView
Calcium-channel blockers
PharmacologyView
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. Amlodipine is a 1:1 racemic mixture of levamlodipine and dextro amlodipine, it has been demonstrated that levamlodipine is the pharmacologically active, anti-hypertensive isomer.
DosageView
Adults: The usual initial antihypertensive oral dose of S-Amlodipine is 2.5 mg once daily, and the maximum dose is 5 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dose may be used when adding S-Amlodipine to other antihypertensive therapy. Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently.
Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.
Children: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.
Side effectsView
Most common adverse reactions to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain and somnolence.
ContraindicationsView
S-Amlodipine is contraindicated in patients with known sensitivity to amlodipine.
PrecautionsView
Hypotension: Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.
Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.
InteractionsView
Impact of Other Drugs on Amlodipine-
- CYP3A Inhibitors: Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment
- CYP3A Inducers: No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers.
- Sildenafil: Monitor for hypotension when sildenafil is coadministered with amlodipine.
- Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.
- Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate
Pregnancy & lactationView
The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy.
Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.
Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.
Pediatric usageView
Pediatric Use: S-Amlodipine (1.25 to 2.5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years. The effect of S-Amlodipine on blood pressure in patients less than 6 years of age is not known.
Geriatric Use: Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required
Geriatric Use: Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required
Overdose effectsView
Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.
StorageView
Store bottles at 20°C to 25°C.
Levant
Levocetirizine Dihydrochloride
Levant
Levocetirizine Dihydrochloride
Indications
Urticaria
Indication detailsView
Levocetirizine is indicated in the treatment of symptoms associated with allergic conditions such as perennial allergic rhinitis, seasonal allergic rhinitis and chronic idiopathic urticaria.
Therapeutic classView
Non-sedating antihistamines
PharmacologyView
This preparation contains Levocetirizine Dihydrochloride. Levocetirizine is the active (Levo) isomer of cetirizine. It is a new highly effective and well-tolerated nonsedating antihistamine with potent antiallergic properties. It has a two-fold higher affinity for H1 receptors than cetirizine. Levocetirizine has a rapid and long-acting action, allowing once-a-day administration.
DosageView
Adult and children 12 years of age and older: The recommended dose is 5 mg once daily.
Children 6 to 11 years of age: The recommended dose is 2.5 mg (1/2 tablet or 1 teaspoon oral solution) once daily.
Children 6 months to 5 years of age: The recommended dose is 1.25 mg (1/2 teaspoon oral solution) once daily.
Children 6 to 11 years of age: The recommended dose is 2.5 mg (1/2 tablet or 1 teaspoon oral solution) once daily.
Children 6 months to 5 years of age: The recommended dose is 1.25 mg (1/2 teaspoon oral solution) once daily.
Side effectsView
Generally, levocetirizine is well tolerated. However, a few side effects like headache, dry mouth, fatigue and skin rash have been reported rarely.
ContraindicationsView
Hypersensitivity to levocetirizine, cetirizine or its parent compound hydroxyzine. Patients with severe renal impairment (creatinine clearance: <10 ml/min) should not be administered levocetirizine.
PrecautionsView
Epileptic patients and patients at risk of convulsions. Renal impairment. Pregnancy and lactation.
InteractionsView
Levocetirizine is not known to have any interactions with other drugs.
Pregnancy & lactationView
Pregnancy Catagory B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, levocetirizine should be used during pregnancy only if clearly needed. Since levocetirizine is excreted in breast milk it is not recommended for use by nursing mothers.
Pediatric usageView
Pediatric use: The recommended dose for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in patients 6 months to 17 years of age is based on extrapolation of efficacy from adults 18 years of age and older.
Geriatric use: In clinical studies, each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.
Hepatic impairment: No dosage adjustment is required in patients with solely hepatic impairment.
Renal impairment:
Geriatric use: In clinical studies, each approved indication did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently than younger patients.
Hepatic impairment: No dosage adjustment is required in patients with solely hepatic impairment.
Renal impairment:
- Mild renal impairment (creatinine clearance: 50-80 ml/min): a dose of 2.5 mg once daily is recommended.
- Moderate renal impairment (creatinine clearance: 30-50 ml/min): a dose of 2.5 mg once every other day is recommended.
- Severe renal impairment (creatinine clearance: 10-30 ml/min): a dose of 2.5 mg twice weekly (administered once every 3-4 days) is recommended.
- End-stage renal disease patients (creatinine clearance: <10 ml/min) and patients undergoing hemodialysis: should not receive Levocetirizine.
Overdose effectsView
No clinically relevant adverse events have been reported in case of overdose. However in the event of overdosage, symptomatic and supportive treatment is recommended.
StorageView
Store at a temperature not exceeding 30°C in a dry place. Protect from light.
Levat
Lenvatinib Mesylate
Levat
Lenvatinib Mesylate
Indication detailsView
Lenvatinib is a kinase inhibitor that is indicated:
- Differentiated Thyroid Cancer: Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC).
- Renal Cell Carcinoma: Lenvatinib is indicated in combination with Everolimus for the treatment of patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy.
- Hepatocellular Carcinoma: Lenvatinib is indicated for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).
- Endometrial Carcinoma: Lenvatinib, in combination with Pembrolizumab, is indicated for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation.
PharmacologyView
Lenvatinib is a kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; platelet-derived growth factor receptor alpha (PDGFR ), KIT, and RET. Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with concurrent inhibition of FGF-receptor substrate 2 (FRS2 ) phosphorylation.
Absorption: The time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours post-dose. Administration with a high-fat meal (approximately 900 calories of which approximately 55% were from fat, 15% from protein, and 30% from carbohydrates) did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.
Distribution: In vitro binding of Lenvatinib to human plasma proteins ranged from 98% to 99% at concentrations of 0.3 to 30 μg/mL. The blood-to-plasma concentration ratio ranged from 0.59 to 0.61 at concentrations of 0.1 to 10 μg/mL in vitro.
Metabolism: The main metabolic pathways for Lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and non-enzymatic processes. Excretion: Ten days after a single administration of radiolabeled Lenvatinib, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.
Elimination: The terminal elimination half-life of Lenvatinib was approximately 28 hours.
Absorption: The time to peak plasma concentration (Tmax) typically occurred from 1 to 4 hours post-dose. Administration with a high-fat meal (approximately 900 calories of which approximately 55% were from fat, 15% from protein, and 30% from carbohydrates) did not affect the extent of absorption, but decreased the rate of absorption and delayed the median Tmax from 2 hours to 4 hours.
Distribution: In vitro binding of Lenvatinib to human plasma proteins ranged from 98% to 99% at concentrations of 0.3 to 30 μg/mL. The blood-to-plasma concentration ratio ranged from 0.59 to 0.61 at concentrations of 0.1 to 10 μg/mL in vitro.
Metabolism: The main metabolic pathways for Lenvatinib in humans were identified as enzymatic (CYP3A and aldehyde oxidase) and non-enzymatic processes. Excretion: Ten days after a single administration of radiolabeled Lenvatinib, approximately 64% and 25% of the radiolabel were eliminated in the feces and urine, respectively.
Elimination: The terminal elimination half-life of Lenvatinib was approximately 28 hours.
DosageView
Important Dosage Information: The dose reduction is needed for certain patients with renal or hepatic impairment. Lenvatinib should be taken once daily, with or without food, at the same time each day. If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration.
Recommended Dosage for Differentiated Thyroid Cancer (DTC): The recommended dosage of Lenvatinib is 24 mg orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Renal Cell Carcinoma (RCC): The recommended dosage of Lenvatinib is 18 mg in combination with 5 mg Everolimus orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Hepatocellular Carcinoma (HCC): The recommended dosage of Lenvatinib is based on actual body weight: 12 mg for patients greater than or equal to 60 kg or 8 mg for patients less than 60 kg. Lenvatinib should be taken orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Endometrial Carcinoma: The recommended dosage of Lenvatinib is 20 mg orally once daily, in combination with Pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression.
Recommended Dosage for Differentiated Thyroid Cancer (DTC): The recommended dosage of Lenvatinib is 24 mg orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Renal Cell Carcinoma (RCC): The recommended dosage of Lenvatinib is 18 mg in combination with 5 mg Everolimus orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Hepatocellular Carcinoma (HCC): The recommended dosage of Lenvatinib is based on actual body weight: 12 mg for patients greater than or equal to 60 kg or 8 mg for patients less than 60 kg. Lenvatinib should be taken orally once daily until disease progression or until unacceptable toxicity.
Recommended Dosage for Endometrial Carcinoma: The recommended dosage of Lenvatinib is 20 mg orally once daily, in combination with Pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression.
AdministrationView
Lenvatinib capsules can be swallowed whole or dissolved in a small glass of liquid. To dissolve in liquid, put capsules into 1 tablespoon of water or apple juice without breaking or crushing the capsules. Leave the capsules in the water or apple juice for at least 10 minutes. Stir for at least 3 minutes. After drinking the mixture, add 1 tablespoon of water or apple juice to the glass, swirl the contents a few times and swallow the water or apple juice.
Side effectsView
Hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, renal failure and impairment, proteinuria, diarrhea, fistula formation and gastrointestinal perforation, QT Interval Prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid stimulating hormone suppression/thyroid dysfunction, wound healing complications.
ContraindicationsView
It is contraindicated in patients with known hypersensitivity to Lenvatinib or to any component of the formulation.
PrecautionsView
Hypertension: Control blood pressure prior to initiating Lenvatinib. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue Lenvatinib is based on severity.
Cardiac Dysfunction: Serious and fatal cardiac dysfunction can occur with Lenvatinib. Monitor patients for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Arterial Thromboembolic Events: Permanently discontinue Lenvatinib following an arterial thrombotic event. The safety of resuming Lenvatinib after an arterial thromboembolic event has not been established and Lenvatinib has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
Hepatotoxicity: Monitor liver function prior to initiating Lenvatinib, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Renal Failure or Impairment: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib for renal failure or impairment based on severity.
Proteinuria: Monitor for proteinuria prior to initiating Lenvatinib and periodically during treatment. If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24-hour urine protein. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Diarrhea: Diarrhea was the most frequent cause of dose interruption/reduction and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Fistula Formation and Gastrointestinal Perforation: Permanently discontinue Lenvatinib in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula.
QT Interval Prolongation: Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at a reduced dose of Lenvatinib upon recovery based on severity.
Hypocalcemia: Hypocalcemia improved or resolved following calcium supplementation, with or without dose interruption or dose reduction.
Reversible Posterior Leukoencephalopathy Syndrome: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib depending on severity and persistence of neurologic symptoms.
Hemorrhagic Events: Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue Lenvatinib based on the severity.
Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction: Monitor thyroid function prior to initiating Lenvatinib and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.
Wound Healing Complications: Wound healing complications, including fistula formation and wound dehiscence, can occur with Lenvatinib. Withhold Lenvatinib for at least 6 days prior to scheduled surgery. Resume Lenvatinib after surgery based on clinical judgment of adequate wound healing. Permanently discontinue Lenvatinib in patients with wound healing complications.
Cardiac Dysfunction: Serious and fatal cardiac dysfunction can occur with Lenvatinib. Monitor patients for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Arterial Thromboembolic Events: Permanently discontinue Lenvatinib following an arterial thrombotic event. The safety of resuming Lenvatinib after an arterial thromboembolic event has not been established and Lenvatinib has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.
Hepatotoxicity: Monitor liver function prior to initiating Lenvatinib, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Renal Failure or Impairment: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib for renal failure or impairment based on severity.
Proteinuria: Monitor for proteinuria prior to initiating Lenvatinib and periodically during treatment. If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24-hour urine protein. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Diarrhea: Diarrhea was the most frequent cause of dose interruption/reduction and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib based on severity.
Fistula Formation and Gastrointestinal Perforation: Permanently discontinue Lenvatinib in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula.
QT Interval Prolongation: Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at a reduced dose of Lenvatinib upon recovery based on severity.
Hypocalcemia: Hypocalcemia improved or resolved following calcium supplementation, with or without dose interruption or dose reduction.
Reversible Posterior Leukoencephalopathy Syndrome: Withhold and resume at a reduced dose upon recovery or permanently discontinue Lenvatinib depending on severity and persistence of neurologic symptoms.
Hemorrhagic Events: Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue Lenvatinib based on the severity.
Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction: Monitor thyroid function prior to initiating Lenvatinib and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.
Wound Healing Complications: Wound healing complications, including fistula formation and wound dehiscence, can occur with Lenvatinib. Withhold Lenvatinib for at least 6 days prior to scheduled surgery. Resume Lenvatinib after surgery based on clinical judgment of adequate wound healing. Permanently discontinue Lenvatinib in patients with wound healing complications.
InteractionsView
Drugs That Prolong the QT Interval: Lenvatinib has been reported to prolong the QT/QTc interval. Avoid coadministration of Lenvatinib with medicinal products with a known potential to prolong the QT/QTc interval.
Pregnancy & lactationView
Use in Pregnancy: Based on the mechanism of action, Lenvatinib can cause embryo-fetal harm when administered to a pregnant female. Pregnant women should be advised of the potential risk to a fetus. Females of reproductive potential should be advised to use effective contraception during treatment with Lenvatinib and for at least 30 days after the last dose.
Use in Lactation: It is not known whether Lenvatinib is present in human milk. Because of the potential for serious adverse reactions in breastfed infants, women should be advised to discontinue breastfeeding during treatment with Lenvatinib and for at least 1 week after the last dose.
Use in Lactation: It is not known whether Lenvatinib is present in human milk. Because of the potential for serious adverse reactions in breastfed infants, women should be advised to discontinue breastfeeding during treatment with Lenvatinib and for at least 1 week after the last dose.
Pediatric usageView
Dosage Modifications for Severe Renal Impairment: The recommended dosage of Lenvatinib for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment (creatinine clearance less than 30 mL/min calculated by Cockcroft-Gault equation using actual body weight) is:
- Differentiated thyroid cancer: 14 mg orally once daily
- Renal cell carcinoma: 10 mg orally once daily
- Endometrial carcinoma: 10 mg orally once daily
- Differentiated thyroid cancer: 14 mg taken orally once daily
- Renal cell carcinoma: 10 mg taken orally once daily
- Endometrial carcinoma: 10 mg orally once daily Or as directed by the registered physician.
Overdose effectsView
Due to the high plasma protein binding, Lenvatinib is not expected to be dialyzable. Death due to multiorgan dysfunction occurred in a patient who received a single dose of Lenvatinib 120 mg orally.
StorageView
Store below 30°C in a dry place. Protect from light. Keep out of the reach of children.
Levefix
Levetiracetam
Levefix
Levetiracetam
Indications
Seizures
Indication detailsView
Levetiracetam is indicated as monotherapy in the treatment of partial-onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy. Levetiracetam is indicated as adjunctive therapy-
- in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents, children and infants from 1 month of age with epilepsy.
- in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.
- in the treatment of primary generalized tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.
Therapeutic classView
Adjunct anti-epileptic drugs
DosageView
Adults and adolescents from 16 years of age: The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
- Monotherapy: The safety and efficacy of levetiracetam in children and adolescents below 16 years as monotherapy treatment have not been established.
- Add-on therapy: Oral solution is the preferred formulation for use in infants and children under the age of 6 years. For children 6 years and above, oral solution should be used for doses under 250 mg, for doses not in multiples of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets. The lowest effective dose should be used. The starting dose for a child or adolescent of 25 kg should be 250 mg twice daily with a maximum dose of 750 mg twice daily. Dosing for children 50 kg or greater is the same as in adults.
- Add-on therapy: For infants aged from 1 month to less than 6 months: The oral solution is the formulation to use in infants.
AdministrationView
The flm-coated tablets must be taken orally, swallowed with a sufcient quantity of liquid and may be taken with or without food. The daily dose is administered in two equally divided doses.
Side effectsView
Most common adverse reactions (incidence ≥ 5% more than placebo) include:
- Adult patients: somnolence, asthenia, infection and dizziness
- Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability
ContraindicationsView
Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients.
PrecautionsView
Renal impairment: The administration of levetiracetam to patients with renal impairment may require dose adjustment. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
InteractionsView
Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Pregnancy & lactationView
Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clinically necessary. Levetiracetam is excreted in human breast milk. Therefore, breastfeeding is not recommended. However, if levetiracetam treatment is needed during breastfeeding, the benefit/risk of the treatment should be weighed considering the importance of breastfeeding. No impact on fertility was detected in animal studies. No clinical data are available, the potential risk for humans is unknown.
Pediatric usageView
Elderly (65 years and older): Adjustment of the dose is recommended in elderly patients with compromised renal function.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Overdose effectsView
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with levetiracetam overdoses. After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specifc antidote for levetiracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74% for the primary metabolite.
StorageView
Store at a cool temperature (not exceeding 25°C) and dry place, protected from light.
Levefix
Levetiracetam
Levefix
Levetiracetam
Indications
Seizures
Indication detailsView
Levetiracetam is indicated as monotherapy in the treatment of partial-onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy. Levetiracetam is indicated as adjunctive therapy-
- in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents, children and infants from 1 month of age with epilepsy.
- in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.
- in the treatment of primary generalized tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.
Therapeutic classView
Adjunct anti-epileptic drugs
DosageView
Adults and adolescents from 16 years of age: The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
- Monotherapy: The safety and efficacy of levetiracetam in children and adolescents below 16 years as monotherapy treatment have not been established.
- Add-on therapy: Oral solution is the preferred formulation for use in infants and children under the age of 6 years. For children 6 years and above, oral solution should be used for doses under 250 mg, for doses not in multiples of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets. The lowest effective dose should be used. The starting dose for a child or adolescent of 25 kg should be 250 mg twice daily with a maximum dose of 750 mg twice daily. Dosing for children 50 kg or greater is the same as in adults.
- Add-on therapy: For infants aged from 1 month to less than 6 months: The oral solution is the formulation to use in infants.
AdministrationView
The flm-coated tablets must be taken orally, swallowed with a sufcient quantity of liquid and may be taken with or without food. The daily dose is administered in two equally divided doses.
Side effectsView
Most common adverse reactions (incidence ≥ 5% more than placebo) include:
- Adult patients: somnolence, asthenia, infection and dizziness
- Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability
ContraindicationsView
Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients.
PrecautionsView
Renal impairment: The administration of levetiracetam to patients with renal impairment may require dose adjustment. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
InteractionsView
Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Pregnancy & lactationView
Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clinically necessary. Levetiracetam is excreted in human breast milk. Therefore, breastfeeding is not recommended. However, if levetiracetam treatment is needed during breastfeeding, the benefit/risk of the treatment should be weighed considering the importance of breastfeeding. No impact on fertility was detected in animal studies. No clinical data are available, the potential risk for humans is unknown.
Pediatric usageView
Elderly (65 years and older): Adjustment of the dose is recommended in elderly patients with compromised renal function.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Overdose effectsView
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with levetiracetam overdoses. After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specifc antidote for levetiracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74% for the primary metabolite.
StorageView
Store at a cool temperature (not exceeding 25°C) and dry place, protected from light.
Levefix
Levetiracetam
Levefix
Levetiracetam
Indications
Seizures
Indication detailsView
Levetiracetam is indicated as monotherapy in the treatment of partial-onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy. Levetiracetam is indicated as adjunctive therapy-
- in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents, children and infants from 1 month of age with epilepsy.
- in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy.
- in the treatment of primary generalized tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy.
Therapeutic classView
Adjunct anti-epileptic drugs
DosageView
Adults and adolescents from 16 years of age: The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg twice daily.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
Adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more: The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decrease every two to four weeks.
Pediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Oral solution is the preferred formulation for use in this population. In addition, the available dose strengths of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases, oral solution should be used.
- Monotherapy: The safety and efficacy of levetiracetam in children and adolescents below 16 years as monotherapy treatment have not been established.
- Add-on therapy: Oral solution is the preferred formulation for use in infants and children under the age of 6 years. For children 6 years and above, oral solution should be used for doses under 250 mg, for doses not in multiples of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients unable to swallow tablets. The lowest effective dose should be used. The starting dose for a child or adolescent of 25 kg should be 250 mg twice daily with a maximum dose of 750 mg twice daily. Dosing for children 50 kg or greater is the same as in adults.
- Add-on therapy: For infants aged from 1 month to less than 6 months: The oral solution is the formulation to use in infants.
AdministrationView
The flm-coated tablets must be taken orally, swallowed with a sufcient quantity of liquid and may be taken with or without food. The daily dose is administered in two equally divided doses.
Side effectsView
Most common adverse reactions (incidence ≥ 5% more than placebo) include:
- Adult patients: somnolence, asthenia, infection and dizziness
- Pediatric patients: fatigue, aggression, nasal congestion, decreased appetite, and irritability
ContraindicationsView
Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients.
PrecautionsView
Renal impairment: The administration of levetiracetam to patients with renal impairment may require dose adjustment. In patients with severely impaired hepatic function, assessment of renal function is recommended before dose selection.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
Acute kidney injury: The use of levetiracetam has been very rarely associated with acute kidney injury with a time to onset ranging from a few days to several months.
Blood cell counts: Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, thrombocytopenia and pancytopenia) have been described in association with levetiracetam administration, generally at the beginning of the treatment. Complete blood cell counts are advised in patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders.
Suicide: Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and behaviour. The mechanism of this risk is not known. Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge.
Paediatric population: The tablet formulation is not adapted for use in infants and children under the age of 6 years. Available data in children did not suggest an impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown.
InteractionsView
Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low.
Methotrexate: Concomitant administration of levetiracetam and methotrexate has been reported to decrease methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients treated concomitantly with the two drugs.
Laxatives: There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should not be taken orally for one hour before and for one hour after taking levetiracetam.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Pregnancy & lactationView
Levetiracetam is not recommended during pregnancy and in women of childbearing potential not using contraception unless clinically necessary. Levetiracetam is excreted in human breast milk. Therefore, breastfeeding is not recommended. However, if levetiracetam treatment is needed during breastfeeding, the benefit/risk of the treatment should be weighed considering the importance of breastfeeding. No impact on fertility was detected in animal studies. No clinical data are available, the potential risk for humans is unknown.
Pediatric usageView
Elderly (65 years and older): Adjustment of the dose is recommended in elderly patients with compromised renal function.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Renal impairment: The daily dose must be individualized according to renal function.
Hepatic impairment: No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the creatinine clearance may underestimate renal insufficiency. Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine clearance is < 60 ml/min.
Overdose effectsView
Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma were observed with levetiracetam overdoses. After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specifc antidote for levetiracetam. Treatment of an overdose will be symptomatic and may include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74% for the primary metabolite.
StorageView
Store at a cool temperature (not exceeding 25°C) and dry place, protected from light.
Level-K
Sodium Polystyrene Sulfonate
Level-K
Sodium Polystyrene Sulfonate
Indications
Hyperkalemia
Indication detailsView
Indicated for the treatment of hyperkalemia. (Hyperkalemia is mainly caused by Acute or Chronic Kidney Disease. Other causes may include Liver failure, Adrenal insufficiency, Use of certain drugs like ARB, ACE inhibitors, Beta blockers or Excessive use of Potassium supplements.)
Therapeutic classView
Calcium Regulator
PharmacologyView
Sodium Polystyrene Sulfonate is a non-absorbed, cation exchange polymer that contains a sodium counterion. Sodium Polystyrene Sulfonate increases fecal potassium excretion through binding of potassium in the lumen of the gastrointestinal tract. Binding of potassium reduces the concentration of free potassium in the gastrointestinal lumen, resulting in a reduction of serum potassium levels. The practical exchange ratio is 1 mEq K per 1 gram of resin.
As the resin passes along the intestine or is retained in the colon after administration by enema, the sodium ions are partially released and are replaced by potassium ions. This action occurs primarily in the large intestine, which excretes potassium ions to a greater degree than does the small intestine. The efficiency of this process is limited and unpredictably variable.
As the resin passes along the intestine or is retained in the colon after administration by enema, the sodium ions are partially released and are replaced by potassium ions. This action occurs primarily in the large intestine, which excretes potassium ions to a greater degree than does the small intestine. The efficiency of this process is limited and unpredictably variable.
DosageView
Adults (including the elderly)-
- Oral Dose: The average daily oral dose for adult is 15 gm to 60 gm (1 Sachet 1-4 times daily).
- Rectal dose: In patients who are unable to intake this medicine orally, rectal administration is possible (as enema). 30 gm to 50 gm of resin is given once or twice daily (at intervals of 6 hours). Each dose is administered as a warm emulsion (at body temperature) in 150 ml to 200 ml of aqueous vehicle (such as plain water, 10% dextrose in water or equal parts of water and 2% Methylcellulose suspension). The emulsion should be agitated gently during administration. The enema should be retained for as long as possible and should be followed by a cleansing enema.
- Oral dose: In smaller children and infants correspondingly lower doses should be employed. An appropriate initial dose is 1 gm/kg body weight daily in divided doses in acute hyperkalemia. For maintenance therapy, dosage may be reduced to 0.5 gm/kg body weight daily.
- Rectal dose: When refused by mouth, the resin may be given rectally using a dose at least as much as that which would have been given orally. The resin should be suspended in a proportional amount of 10% Dextrose in water. Following retention of the enema, the colon should be irrigated to ensure adequate removal of the resin.
- Rectal dose: Since it is advised that the oral route should not be employed, only rectal administration should be considered. With rectal administration, the minimum effective dosage within the range of 0.5 to 1 gm/kg of resin should be employed. The resultant suspension should be diluted as for adults. Following administration of the resin, the colon should be adequately irrigated to ensure recovery of the resin.
AdministrationView
Mixing procedure: Each dose should be given as a suspension in a small quantity of water or, for greater palatability, in sweetened liquid or syrup (but not with orange or other fruit juices which contain potassium). The amount of fluid usually ranges from 20 ml to 100 ml, depending on the dose. It may be simply determined by allowing 3 ml to 4 ml per gram of drug. The prepared suspension should be administered by placing and maintaining the patient in an upright position. The resin may be introduced into the stomach through a plastic tube. If desired, it may be mixed with a diet appropriate for a patient in renal failure.The intensity and duration of therapy depend upon the severity and resistance of hyperkalemia. Sodium Polystyrene Sulfonate should not be heated because it may alter the exchange properties of the resin.
Suspension of this drug should be freshly prepared and not to be stored beyond 24 hours.
Suspension of this drug should be freshly prepared and not to be stored beyond 24 hours.
Side effectsView
The drug may cause some degree of gastric irritation. Anorexia, nausea, vomiting, and constipation may occur especially if high doses are given. Also, hypokalemia, hypocalcemia, and significant sodium retention, and their related clinical manifestations, may occur. Occasionally diarrhea develops. Large doses in elderly individuals may cause fecal impaction. Rare instances of colonic necrosis have been reported. Intestinal obstruction due to concretions of aluminum hydroxide, when used in combination with such resin has been reported.
ContraindicationsView
Sodium Polystyrene Sulfonate is contraindicated in the following conditions: patients with hypokalemia, patients with a history of hypersensitivity to polystyrene sulfonate resins, obstructive bowel disease, neonates with reduced gut motility (postoperatively or drug induced) and oral administration in neonates.
PrecautionsView
Caution is advised when this product is administered to patients who cannot tolerate even a small increase in sodium loads (i.e., severe congestive heart failure, severe hypertension, or marked edema). In such instances compensatory restriction of sodium intake from other sources may be indicated. In the event of clinically signifcant constipation, treatment with this drug should be discontinued until normal bowel motion is resumed. Magnesium-containing laxatives or sorbitol should not be used.
InteractionsView
Sodium Polystyrene Sulfonate may cause drug interactions with Antacids, Non absorbable cation-donating antacids and laxatives, Digitalis, Sorbitol, Lithium, Thyroxine.
Pregnancy & lactationView
Pregnancy Category C. Animal reproduction studies have not been conducted with Sodium Polystyrene Sulfonate. It is also not known whether it can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. It should be given to a pregnant woman only if clearly needed.
Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.
Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this product is administered to a nursing woman.
Overdose effectsView
Overdosage may result in electrolyte disturbances including hypokalemia, hypocalcemia, and hypomagnesemia. Biochemical disturbances resulting from overdosage may give rise to clinical signs and symptoms of hypokalemia, including: irritability, confusion, delayed thought processes, muscle weakness, hyporeflexia, which may progress to frank paralysis and/or apnea.
StorageView
Store below 30°C. Keep out of the reach of children. Suspension of this drug should be freshly prepared and not to be stored beyond 24 hours.
Levemir Flexpen
Insulin Detemir
Levemir Flexpen
Insulin Detemir
Indications
Type 1 DM
Indication detailsView
Insulin Detemir is a long-acting human insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus.
Important Limitations of Use: Not recommended for treating diabetic ketoacidosis. Use intravenous, rapid acting or short-acting insulin instead.
Important Limitations of Use: Not recommended for treating diabetic ketoacidosis. Use intravenous, rapid acting or short-acting insulin instead.
Therapeutic classView
Long Acting Insulin
PharmacologyView
The primary activity of insulin detemir is the regulation of glucose metabolism. Insulins, including insulin detemir, exert their specific action through binding to insulin receptors. Receptor-bound insulin lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and adipose tissue and by inhibiting the output of glucose from the liver. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis, and enhances protein synthesis.
DosageView
Adult: In insulin-naive patients with type 2 DM who are not well controlled on oral antidiabetic drugs: Initial: 0.1 -0.2 unit/kg once daily in the evening or 10 unit 1-2 times/day, adjust subsequently based on glycaemic control.
In patients on basal insulin only: May substitute with insulin detemir on a unit-for-unit basis based on the current basal insulin dosage, adjust subsequently to achieve glycaemic targets.
In patients on basal insulin only: May substitute with insulin detemir on a unit-for-unit basis based on the current basal insulin dosage, adjust subsequently to achieve glycaemic targets.
Side effectsView
Hypoglycaemia, lipodystrophy, pruritus, rash, wt gain, sodium retention and oedema. Inj site reactions e.g. pain, itching, hives, swelling and inflammation. Influenza-like symptoms, Pallor, Palpitation, Tachycardia, Mental confusion, Weakness, Blurred vision, Itching, Hunger, Nausea.
ContraindicationsView
Insulin Detemir is contraindicated in patients with hypersensitivity to Insulin Detemir or any of its excipients. Reactions have included anaphylaxis
PrecautionsView
Renal or hepatic impairment. Regular monitoring of blood glucose and HbA1c. Continuous rotation of the inj site within a given area to reduce inj site reactions. Pregnancy, lactation
InteractionsView
Possible absence of hypoglycaemic warning symptoms with beta-blockers. Increased blood sugar with thiazide diuretics, corticosteriods, chlorpromazine, tibolone, isoniazid, niacin, some calcium-channel blockers such as diltiazem or nifedipine, diazoxide, lithium and thyroid hormones. Increased risk of hypoglycemia with disopyramide, larges doses of aspirin, gatifloxacin, MAOIs, mebanazine, nandrolone, pegvisomant, testosterone. Decreased insulin resistance with octreotide and lanreotide. Increased risk of wt gain and peripheral oedema with pioglitazone, rosiglitazone. Decreased effect of sermorelin.
Pregnancy & lactationView
Pregnancy Category B. Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women OR Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester.
Nursing Mothers: It is unknown whether Insulin detemir is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, use caution when administering Insulin detemir to a nursing woman. Women with diabetes who are lactating may require adjustments of their insulin doses.
Nursing Mothers: It is unknown whether Insulin detemir is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, use caution when administering Insulin detemir to a nursing woman. Women with diabetes who are lactating may require adjustments of their insulin doses.
Pediatric usageView
Pediatric Use: The pharmacokinetics, safety and effectiveness of subcutaneous injections of Insulin Detemir have been established in pediatric patients (age 6 to 17 years) with type 1 diabetes. Insulin Detemir has not been studied in pediatric patients younger than 6 years of age with type 1 diabetes. Insulin Detemir has not been studied in pediatric patients with type 2 diabetes. The dose recommendation when converting to Insulin Detemir is the same as that described for adults. As in adults, the dosage of Insulin Detemir must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose.
Geriatric Use: In controlled clinical trials comparing Insulin Detemir to NPH insulin or insulin glargine, 64 of 1624 patients (3.9%) in the type 1 diabetes trials and 309 of 1082 patients (28.6%) in the type 2 diabetes trials were≥65 years of age. A total of 52 (7 type 1 and 45 type 2) patients (1.9%) were ≥75 years of age. Nooverall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes, particularly for patients ≥65 years of age in the type 1 diabetes trials and for patients ≥75 years of age in all trials limits conclusions. Greater sensitivity of some older individuals cannot be ruled out. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the elderly.
Geriatric Use: In controlled clinical trials comparing Insulin Detemir to NPH insulin or insulin glargine, 64 of 1624 patients (3.9%) in the type 1 diabetes trials and 309 of 1082 patients (28.6%) in the type 2 diabetes trials were≥65 years of age. A total of 52 (7 type 1 and 45 type 2) patients (1.9%) were ≥75 years of age. Nooverall differences in safety or effectiveness were observed between these patients and younger patients, but small sample sizes, particularly for patients ≥65 years of age in the type 1 diabetes trials and for patients ≥75 years of age in all trials limits conclusions. Greater sensitivity of some older individuals cannot be ruled out. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be difficult to recognize in the elderly.
Overdose effectsView
An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia
StorageView
Unused (unopened) Insulin Detemir should be stored in the refrigerator between 2° and 8°C. Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze. Do not use Insulin Detemir if it has been frozen. Unused (unopened) Insulin Detemir can be kept until the expiration date printed on the label if it is stored in a refrigerator. Keep unused Insulin Detemir in the carton so that it stays clean and protected from light.
If refrigeration is not possible, unused (unopened) Insulin Detemir can be kept unrefrigerated at room temperature, below 30°C as long as it is kept as cool as possible and away from direct heat and light. Unrefrigerated Insulin Detemir should be discarded 42 days after it is first kept out of the refrigerator, even if the FlexPen or vial still contains insulin.
If refrigeration is not possible, unused (unopened) Insulin Detemir can be kept unrefrigerated at room temperature, below 30°C as long as it is kept as cool as possible and away from direct heat and light. Unrefrigerated Insulin Detemir should be discarded 42 days after it is first kept out of the refrigerator, even if the FlexPen or vial still contains insulin.