Each hard gelatin capsule contains Itraconazole 100 mg (As itraconazole pellets 22%).
Excipients/Inactive Ingredients: Sugar spheres, hypromellose, eudragit E 100, polyethylene glycol 20000.
Pharmacotherapeutic group: Antimycotics for systemic use; Triazole derivatives. ATC Code: J02AC02.
Pharmacology: Pharmacodynamics: Itraconazole, a synthetic triazole derivative, is an antifungal agent. Itraconazole inhibits cytochrome P450-dependent enzymes in sensitive fungi resulting in impairment of ergosterol synthesis in fungal cell membranes. It has a lightly wider spectrum of activity than ketoconazole. It is active against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Epidermophyton spp., Histoplasma capsulatum, Malassezia furfur, Microsporum spp., Paracoccidioides brasiliensis, Sporothrix schenckii, and Trichophyton spp.
Pharmacokinetics: Itraconazole is absorbed from the gastrointestinal tract. Absorption from the capsule formulation is enhanced by an acidic gastric environment and is greatest when doses are taken with food. Peak plasma concentrations are achieved between 1.5 and 5 hours, about 2 mcg/ml after daily doses of 200 mg.
Itraconazole is highly protein bound; only 0.2% circulates as free drug. Itraconazole is widely distributed but only small amounts diffuse into the CSF. Concentrations attained in the skin, pus, and many organs and tissues are several times higher than simultaneous plasma concentrations.
Therapeutic concentrations of itraconazole remain in the skin and mucous membranes for 1 to 4 weeks after the drug is discontinued. Small amounts are distributed into breast milk.
Itraconazole is metabolised in the liver mainly by cytochrome P450 isoenzyme CYP3A4. The major metabolite, hydroxyitraconazole, has antifungal activity comparable with that of itraconazole.
Itraconazole is also excreted as inactive metabolites in the bile or urine; 3 to 18% is excreted in the faeces as unchanged drug. Small amounts are eliminated in the stratum corneum and hair. Itraconazole is not removed by dialysis.
The elimination half-life following a single 100 mg dose has been reported as 20 hours, increasing to 30-40 hours with continued use.
Dermatophytosis caused by organisms susceptible to itraconazole (Trichophyton spp., Microsporum spp., Epidermophyton floccosum) e.g. tinea pedis, tinea cruris, tinea corporis, tinea manuum.
Onychomycosis (tinea unguium).
Blastomycosis (pulmonary and extrapulmonary).
Histoplasmosis (including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis).
Aspergillosis (pulmonary and extrapulmonary in patients who do not respond to or cannot tolerate amphotericin B).
Maintenance therapy in AIDS patients to prevent relapse of underlying fungal infection.
Itraconazole is also indicated in the prevention of fungal infection during prolonged neutropenia when standard therapy is considered inappropriate.
Adults: Short-term therapy: Oropharyngeal candidosis: 100 mg once daily for 15 days. Increase dose to 200 mg once daily for 15 days in AIDS or neutropenic patients because of impaired absorption in these groups.
Vulvovaginal candidosis: 200 mg twice daily for 1 day or 200 mg once daily for 3 days.
Pityriasis versicolor: 200 mg once daily for 7 days.
Dermatophytoses: 100 mg once daily for 15 days. In highly keratinized regions: require an additional treatment of 15 days at 100 mg daily.
Long-term therapy (for systemic fungal infections) should be dictated by the mycological and clinical response to therapy: Onychomycosis: 200 mg once daily for 3 months.
Aspergillosis: 200 mg once daily for 2-5 months; increase dose to 200 mg twice daily in case of invasive or disseminated disease.
Candidosis: 100-200 mg once daily for 3 weeks to 7 months; increase dose to 200 mg twice daily in case of invasive or disseminated disease.
Non-meningeal cryptococcosis: 200 mg once daily, for 2 months to 1 year.
Meningeal cryptococcosis: 200 mg twice daily. Maintenance dose: 200 mg once daily.
Histoplasmosis and Blastomycosis: 200 mg once daily or twice daily for 8 months.
Maintenance in AIDS: 200 mg once daily.
Prophylaxis in neutropenia: 200 mg once daily.
Children: Safety and efficacy of itraconazole in children younger than 18 years of age have not been established.
Method of Administration: Itranstad is administered orally and should be swallowed whole immediately after a meal.
Symptoms: There are limited data on the outcomes of patients ingesting high doses of itraconazole. In patients taking up to 3000 mg of itraconazole capsules, the adverse event profile was similar to that observed at recommended doses.
Treatment: In the event of overdosage, supportive measures should be employed. Within the first hour after ingestion, gastric lavage may be performed. Activated charcoal may be given if considered appropriate. Itraconazole cannot be removed by haemodialysis. No specific antidote is available.
Patients with known hypersensitivity to itraconazole and other azoles or any ingredient in the formulation.
Patients with ongoing treatment with terfenadine, astemizole, oral triazolam, oral midazolam and cisapride.
Use of itraconazole for the treatment of onychomycosis in pregnant women or to women contemplating pregnancy.
Itraconazole should not be used for the treatment of onychomycosis in patients with evidence of ventricular dysfunction, such as congestive heart failure or history of congestive heart failure; should be discontinued in patients who develop congestive heart failure while receiving the drug.
Itraconazole therapy should not be used in patients with increased serum hepatic enzymes, active liver disease, or a history of liver toxicity with other drugs unless the potential benefits exceed the risks. In addition, serum hepatic enzyme monitoring should be considered for all patients receiving itraconazole, especially those who receive itraconazole therapy continuously for longer than 1 month.
If neuropathy occurs that may be attributable to itraconazole, the drug should be discontinued.
In systemic candidosis, if fluconazole-resistant strains of Candida species are suspected, it cannot be assumed that these are sensitive to itraconazole. Hence sensitivity should be tested before start of itraconazole therapy.
Itranstad contains sucrose (sugar spheres). Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. When driving vehicles and operating machinery, the possibility of adverse reactions such as dizziness, visual disturbances and hearing loss, which may occur in some instances, must be taken into account.
Pregnancy: Itraconazole has caused abnormalities in foetal development in rats. There are no studies in pregnant women, itraconazole should be used in pregnancy only if the benefit outweighs the potential risk.
Lactation: Breast feeding while receiving itraconazole is not recommended.
Common (1/100 ≤ ADR <1/10): General:
Nausea, abdominal pain, constipation, dyspepsia.
Less common (1/1000 ≤ ADR <1/100): General:
Allergic reactions, such as itch, exanthema, urticaria and angioedema; Stevens-Johnson syndrome.
Reversible liver enzyme elevation, hepatitis, especially after long-term treatment.
Especially after long-time treatment (>1 month), there is risk of hepatitis, hypokalemia, edema and alopecia. In rare cases, there have also been reported cases of peripheral neuropathy.
Antiarrhythmic agents: Administration of itraconazole with quinidine or dofetilide would be expected to increase plasma concentrations of the antiarrhythmic agent which could result in serious adverse cardiovascular effects such as life-threatening cardiac dysrhythmias and/or sudden death. Concomitant use of itraconazole and these drugs is contraindicated.
Antilipemic agents: Concomitant use of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (e.g., atorvastatin, cerivastatin, lovastatin, simvastatin) and itraconazole may increase plasma concentrations of these antilipemic agents resulting in increased effects and increased risk of toxicity. Concomitant use of itraconazole and these drugs is contraindicated.
HIV protease inhibitors: Concomitant use of itraconazole with HIV protease inhibitors (PIs) (e.g., amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) may result in altered serum concentrations of the PIs and/or the antifungal.
Terfenadine: Serious adverse cardiovascular effects, including death, ventricular tachycardia, and atypical ventricular tachycardia, have occurred in patients receiving itraconazole and terfenadine concomitantly.
Benzodiazepines: Concomitant use of itraconazole and benzodiazepines (e.g., alprazolam, diazepam, oral midazolam, triazolam) may result in increased plasma concentrations of these benzodiazepines that could potentiate and prolong the sedative and hypnotic effects of the drugs.
Cisapride: Itraconazole inhibits metabolism of cisapride and such use can result in increased plasma cisapride concentrations and increase the potential for serious adverse cardiovascular effects.
Pimozide: Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients receiving pimozide concomitantly with itraconazole and/or other drugs that inhibit the CYP3A4 enzyme.
Phosphodiesterase inhibitors: Itraconazole is a potent inhibitor of the cytochrome P-450 isoenzyme 3A4, and concomitant use in patients receiving a phosphodiesterase (PDE) inhibitor (sildenafil, tadalafil, vardenafil) can substantially increase plasma concentrations of the PDE inhibitor and may increase the risk of adverse effects (e.g., hypotension, visual changes, priapism).
Combination of itraconazole with oral diazepam, midazolam or triazolam is contraindicated.
Coadministration of warfarin and itraconazole has led to increased levels and enhanced anticoagulant effect of warfarin. Therefore, prothrombin time should be carefully monitored in plasma of the patient and appropriate warfarin dosage adjustments may be necessary.
Coadministration of itraconazole and digoxin has led to increased levels of the latter drug. Digoxin concentrations should be monitored and digoxin dose should be adjusted appropriately.
Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. Blood glucose concentrations should be carefully monitored when itraconazole and oral hypoglycemic agents are coadministered and appropriate dosage adjustments may be necessary.
Itraconazole absorption requires gastric acidity. Therefore antacids, H2-antagonists (cimetidine and ranitidine), omeprazole, and sucralfate significantly reduce bioavailability of itraconazole resulting in treatment failure and should not be administered concomitantly; amphotericin B or fluconazole should be used instead.
Enzyme-inducing drugs such as rifampicin, isoniazid, phenobarbital, phenytoin reduce plasma levels of itraconazole. Alternative antifungal therapy should be considered if isoniazid or rifampicin therapy is necessary.
Incompatibilities: In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products.
Store in a well-closed container, in a dry place, protect from light. Do not store above 30°C.
Shelf-Life: 36 months from the date of manufacturing.
J02AC02 - itraconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.
Cap 100 mg (hard gelatin, size No. 0, transparent green cap imprinted logo Click on icon to see table/diagram/image
with edible white ink, transparent white body, containing off-white pellets) x 1 x 6's, 30's, 10 x 10's.