Itraconazol Actavis

Uses

Itraconazol Actavis is used for the treatment of oropharyngeal candidiasis, vulvovaginal candidiasis, pityriasis versicolor, tinea pedis, tinea cruris, tinea corporis, tinea manuum, onychomycosis, histoplasmosis. It is used for the treatment of systemic candidiasis, aspergillosis, and cryptococcosis (including cryptococcal meningitis). It is also used for maintenance therapy in AIDS patients to prevent relapse of underlying fungal infections and in the prevention of fungal infection during prolonged neutropenia.

Itraconazol Actavis is also used to associated treatment for these conditions: Aspergillosis, Blastomycosis, Chromomycosis, Coccidioidal meningitis, Dermatomycoses, Esophageal Candidiasis, Histoplasmosis, Infections, Fungal, Onychomycosis, Oropharyngeal Candidiasis, Paracoccidioidomycosis, Penicillium marneffei infection, Pulmonary coccidioides, Sporotrichosis, Vulvovaginal Candidiasis, Disseminated Other specified protozoal diseases

How Itraconazol Actavis works

Itraconazol Actavis interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Itraconazol Actavis may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.

Dosage

Itraconazol Actavis dosage

Oropharyngeal candidiasis: 100 mg daily (200 mg daily in AIDS or neutropenia) for 15 days.

Vulvovaginal candidiasis: 200 mg twice daily for 1 day.

Pityriasis versicolor: 200 mg daily for 7 days.

Tinea corporis and tinea cruris: either 100 mg daily for 15 days or 200 mg daily for 7 days.

Tinea pedis and tinea manuum: either 100 mg daily for 30 days or 200 mg twice daily for 7 days.

Onychomycosis: either 200 mg daily for 3 months or course (pulse) of 200 mg twice daily for 7 days, subsequent courses repeated after 21 days interval. Fingernails two courses, toenails three courses.

Systemic infections (aspergillosis, candidiasis and cryptococcosis including cryptococcal meningitis) where other antifungal drugs inappropriate or ineffective: 200 mg once daily, increased in invasive or disseminated disease and in cryptococcal meningitis to 200 mg twice daily.

Histoplasmosis: 200 mg 1-2 times daily.

Maintenance in AIDS patients to prevent relapse of underlying fungal infection and prophylaxis in neutropenia when standard therapy is inappropriate: 200 mg once daily, increased to 200 mg twice daily if low plasma Itraconazol Actavis concentration is detected. Child dose: the recommended dose is 3 to 5 mg/kg/day.

Should be taken with food. Take immediately after a full meal.

Side Effects

Nausea, abdominal pain, dyspepsia, constipation, headache, dizziness, raised liver enzymes, menstrual disorders, allergic reactions (including pruritus, rash, urticaria and angioedema), hepatitis and cholestatic jaundice, peripheral neuropathy and Stevens-Johnson syndrome reported. On prolonged use hypokalaemia, oedema and hair loss reported.

Toxicity

No significant lethality was observed when itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.

Precaution

Absorption is impaired when gastric acidity is reduced. In patients receiving acid neutralizing medicines (e.g. aluminium hydroxide), these should be administered at least 2 hours after the intake of Itraconazol Actavis. The drug should be administered after a full meal. Rarely, cases of hepatitis and jaundice have been reported mainly in patients treated for longer than one month. It is therefore, advised to monitor liver function in patients receiving continuous treatment of more than one month.

Interaction

The drugs like terfenadine, astemizole, cisapride, HMG-CoA reductase inhibitors such as simvastatin, oral midazolam or triazolam should not be given concurrently with Itraconazol Actavis. Significant interactions also observed during co-administration of rifampin, phenytoin, phenobarbital, digoxin, and calcium channel blockers.

Food Interaction

• Avoid grapefruit products.
• Avoid multivalent ions. Calcium, iron, and aluminum containing products taken up to 2 hours before and 6 hours after administration can decrease drug concentrations.
• Take with food.

[Moderate] ADJUST DOSING INTERVAL: Food increases the absorption of itraconazole capsules but decreases the absorption of itraconazole oral solution.

Cola beverages may increase the bioavailability of itraconazole capsules.

Itraconazol Actavis capsules require an acidic gastric pH for adequate dissolution and subsequent absorption.

Cola beverages help lower gastric pH and improve absorption.

GENERALLY AVOID: Grapefruit juice may impair the absorption of itraconazole capsules, resulting in decreased antifungal effects.

In a small, randomized, crossover study, the administration of itraconazole capsules with double-strength grapefruit juice (compared to water) was associated with significantly decreased (43%) plasma concentrations of itraconazole and its pharmacologically active hydroxy metabolite, as well as delayed times to reach peak concentrations of both.

The exact mechanism of interaction is unknown but may involve reduced absorption of itraconazole secondary to enhanced activity of intestinal P-glycoprotein drug efflux pumps and delayed gastric emptying induced by certain compounds present in grapefruits.

Another study reported no pharmacokinetic changes with single-strength grapefruit juice.

Whether or not these observations apply to itraconazole oral solution is unknown.

MANAGEMENT: The manufacturer recommends that the capsules be taken immediately after a full meal and the solution be taken on an empty stomach to ensure maximal absorption.

Cola beverages may help increase the bioavailability of itraconazole capsules, particularly in patients with hypochlorhydria or those treated concomitantly with gastric acid suppressants.

Until more information is available, it may be advisable to avoid the consumption of grapefruits and grapefruit juice during itraconazole therapy.

Itraconazol Actavis Drug Interaction

Unknown: diphenhydramine, diphenhydramine, celecoxib, celecoxib, duloxetine, duloxetine, acetaminophen, acetaminophen, montelukast, montelukast, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine

Itraconazol Actavis Disease Interaction

Major: CHF, hepatotoxicityModerate: QT prolongation, achlorhydria, cystic fibrosis, immunodeficiency, renal dysfunction

Volume of Distribution

• 796 ± 185 L

Elimination Route

The absolute oral bioavailability of itraconazole is 55%, and is maximal when taken with a full meal.

Half Life

21 hours

Clearance

• 381 +/- 95 mL/minute [IV administration]

Elimination Route

Itraconazol Actavis is metabolized predominately by the cytochrome P450 3A4 isoenzyme system (CYP3A4) in the liver, resulting in the formation of several metabolites, including hydroxyitraconazole, the major metabolite. Fecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is less than 0.03% of the dose. About 40% of the dose is excreted as inactive metabolites in the urine. No single excreted metabolite represents more than 5% of a dose.

Pregnancy & Breastfeeding use

Itraconazol Actavis is contraindicated in pregnancy. Breast feeding while receiving Itraconazol Actavis is not recommended.

Contraindication

Itraconazol Actavis is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation. Patients who have severe hepatic disease are not advised to take Itraconazol Actavis. It is not advisable to use the drug in patients taking rifampin, which appears to initially inhibit and then enhance the metabolism of Itraconazol Actavis.

Special Warning

Renal Impairment Intravenous: Severe: Contraindicated.

Acute Overdose

Symptoms: Same with adverse reactions.

Management: Supportive treatment. May admin activated charcoal if necessary.

Storage Condition

Protect from light. Store in a cool and dry place. Store between 15˚C and 30˚C.

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