Itraconazol
Itraconazol Uses, Dosage, Side Effects, Food Interaction and all others data.
Itraconazol is an orally active triazole antifungal drug that has demonstrated a broad spectrum of activity and favorable pharmacokinetic profile. Itraconazol inhibits Cytochrome P-450 dependent enzymes resulting in impairment of the biosynthesis of ergosterol, a major component of the cell membrane of yeast and fungal cells. Being integral to the proper functioning of the cell membrane, inhibition of the synthesis of ergosterol leads to a cascade of abnormalities in permeability, membrane bound enzyme activity, and co-ordination of chitin synthesis leading to inhibition of growth, abnormal cell wall formation and accumulation of intracellular lipids and membranous vesicles.
Itraconazol is an imidazole/triazole type antifungal agent. Itraconazol is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazol exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.
| Trade Name | Itraconazol |
| Availability | Prescription only |
| Generic | Itraconazole |
| Itraconazole Other Names | Itraconazol, Itraconazole, Itraconazolum, Oriconazole |
| Related Drugs | ciprofloxacin, fluconazole, Augmentin, amoxicillin / clavulanate, vancomycin, nystatin, nystatin topical, gentamicin, clotrimazole, clotrimazole topical |
| Type | |
| Formula | C35H38Cl2N8O4 |
| Weight | Average: 705.633 Monoisotopic: 704.239307158 |
| Protein binding | 99.8% |
| Groups | Approved, Investigational |
| Therapeutic Class | Drugs for subcutaneous and systemic mycoses |
| Manufacturer | |
| Available Country | Netherlands |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Itraconazol 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 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 works
Itraconazol 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 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 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 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. 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. 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 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 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 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 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 is contraindicated in pregnancy. Breast feeding while receiving Itraconazol is not recommended.
Contraindication
Itraconazol 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. It is not advisable to use the drug in patients taking rifampin, which appears to initially inhibit and then enhance the metabolism of Itraconazol.
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.
Innovators Monograph
You find simplified version here Itraconazol
Itraconazol contains Itraconazole see full prescribing information from innovator Itraconazol Monograph, Itraconazol MSDS, Itraconazol FDA label
FAQ
What is Itraconazol used for?
Itraconazol is an antifungal medication that is used in adults to treat infections caused by fungus.
How safe is Itraconazol?
Itraconazol is effective and well tolerated, with most side effects being minor and reversible. The most common adverse events are gastrointestinal upset, headache, and transient skin reaction. There have also been rare reports of hepatitis.
How does Itraconazol work?
Itraconazol works by slowing the growth of fungi that cause infection.
What are the common side effects of Itraconazol?
Common side effects of Itraconazol are include:
- Decreased urine output.
- increased thirst.
- irregular heartbeat.
- mood changes.
- muscle pain or cramps.
- numbness or tingling in the hands, feet, or lips.
- unusual tiredness or weakness.
Is Itraconazol safe during pregnancy?
Itraconazol should still be avoided during pregnancy, especially during the first trimester.
Is Itraconazol safe during breastfeeding?
No information is available on the clinical use of Itraconazol during breastfeeding. However, limited data indicate that maternal Itraconazol produces levels in milk that are less than the 5 mg/kg daily doses that have been recommended to treat infants.
Can I drink alcohol with Itraconazol?
Avoid alcohol while taking this Itraconazol.
Can I drive after taking Itraconazol?
Avoid driving or hazardous activity until you know how this Itraconazol will affect you. Your reactions could be impaired. Avoid taking antacids within 1 hour before or 2 hours after you take Itraconazol.
When should be taken of Itraconazol?
Itraconazol capsules and tablets should be taken with a full meal. The oral liquid is best taken on an empty stomach.Take the tablets at the same time each day.
Can Itraconazol be taken at night?
The capsules are taken during the night or after a full meal.
Why is Itraconazol taken with food?
Food increases the absorption of Itraconazol capsules but decreases the absorption of Itraconazol oral solution. Capsules should be taken immediately after a full meal and the solution be taken on an empty stomach to ensure best results.
How long does Itraconazol take to work ?
Itraconazol takes around one to four weeks after treatment for its optimum action on the fungi that cause ringworm infections. It is essential to complete the dosage for the best results.
How long does Itraconazol stay in my system?
Itraconazol has a half-life of around 60 hours and therefore stays in the blood for a long time. Most of the drug elimination occurs through stool and urine. It may require two weeks for complete elimination.
Does Itraconazol affect my immune system?
The anti-fungal agent Itraconazol exerts immunosuppressive effects on alloreactivity but not on natural immunity in vitro.
Can Itraconazol be taken long term?
The results show that Itraconazol 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections.
How long can I take Itraconazol?
Itraconazol oral solution is usually taken on an empty stomach once or twice a day for 1 to 4 weeks or sometimes longer.
Who should not take Itraconazol?
You should not take Itraconazol if you have ever had heart failure.If you have liver or kidney disease, you should not take Itraconazol with colchicine, fesoterodine, or solifenacin.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
What happen if I overdose of Itraconazol?
If you think you took too much Itraconazol, call your doctor or local poison control center, or go to the nearest hospital emergency room right away.
What happen if I stop taking Itraconazol suddenly ?
If you experience any of the following symptoms, stop taking Itraconazol and call your doctor immediately: shortness of breath; coughing up white or pink phlegm; weakness; excessive tiredness; fast heartbeat; swelling of the feet, ankles, or legs; waking up at night; and sudden weight gain.
Is Itraconazol bad for my liver?
Some people taking Itraconazol have developed severe liver damage leading to liver transplant or death.
