Itraconazole is a synthetic triazole agent with antimycotic properties. Formulated for both topical and systemic use, itraconazole preferentially inhibits fungal cytochrome P450 enzymes, resulting in a decrease in fungal ergosterol synthesis. Because of its low toxicity profile, this agent can be used for long-term maintenance treatment of chronic fungal infections
Itraconazole is an orally administered, triazole antifungal agent used in the treatment of systemic and superficial fungal infections. Itraconazole therapy is associated with transient, mild-to-moderate serum elevations and can lead to clinically apparent acute drug-induced liver injury.
Mechanism of Action of Itraconazole
Itraconazole 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. Itraconazole is an imidazole/triazole-type antifungal agent. Itraconazole 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. Itraconazole 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.
Indications of Itraconazole
- Systemic fungal infection
- Candida urinary tract infections
- Aspergillosis, aspergilloma
- Aspergillosis, invasive
- Cryptococcal meningitis, immunosuppressed host
- Esophageal candidiasis
- Febrile neutropenia
- Fungal infection prophylaxis
- Onychomycosis, Fingernail
- Onychomycosis, toenail
- Oral thrush
- Tinea capitis
- Tinea versicolor
- Vaginal yeast Infection
- Coccidioidal meningitis
- Esophageal candidiasis
- Infections, fungal
- Oropharyngeal candidiasis
- Penicillium marneffei infection
- Pulmonary coccidiosis
- Vulvovaginal candidiasis
- Disseminated Other specified protozoal diseases
- For the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: pulmonary and extrapulmonary blastomycosis, histoplasmosis, aspergillosis, and onychomycosis.
- Psittaciformes, Falconiformes, Accipitriformes, Strigiformes, and Anseriformes:
- For the treatment of aspergillosis.
- Also for the treatment of candidiasis.
- Antimycotic active against infections caused by yeasts and fungi
- Treatment of naevoid basal-cell carcinoma syndrome (Gorlin syndrome)
- Itraconazole capsules are also indicated for the treatment of the following fungal infections in non-immunocompromised patients: Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguium) and Onychomycosis of the fingernail due to dermatophytes (tinea unguium).
- Itraconazole capsules are indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: Blastomycosis, pulmonary and extrapulmonary; Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis and Aspergillosis, pulmonary and extrapulmonary, in patients who are intolerant of or who are refractory to amphotericin B therapy.
Contra Indications of Itraconazole
- Have known hypersensitivity to other azole medicines such as itraconazole;
- Are taking terfenadine, if 400 mg per day multidose of fluconazole is administered;
- Concomitant administration of itraconazole and quinidine, especially when itraconazole is administered in high dosages;
- Take SSRIs such as fluoxetine or sertraline.
Dosage of Itraconazole
Dosages may vary in the differant disease condition
DURATION OF TREATMENT
|– Vulvovaginal candidosis||
200 mg b.i.d. or
200 mg o.d.
|– Pityriasis versicolor||
200 mg o.d.
|– Tinea corporis, tinea cruris||
100 mg o.d. or
15 days or
200 mg o.d.
|– Tinea pedis, tinea manuum||
100 mg o.d.
|– Oral candidiasis||
100 mg o.d.
In some patients with compromised immune systems, such as neutropenic, AIDS or transplant patients, the bioavailability of oral itraconazole may be diminished. In these cases the dose may have to be doubled.
The length of treatment for systemic fungal infections should be dictated by the mycological and clinical response to therapy:
|Aspergillosis||200 mg o.d.||2-5 months||Increase dose to 200 mg b.i.d. in the case of widespread infection|
|Candidiasis||100-200 mg o.d.||3 weeks-7 months|
|Non-meningeal cryptococcosis||200 mg o.d.||10 weeks||Maintenance therapy (meningeal cases):
200 mg o.d.
|Cryptococcal meningitis||200 mg b.i.d.||2 months – 6 months|
|Histoplasmosis||200 mg o.d.||8 months|
|200 mg b.i.d.|
Side Effects of Itraconazole
The most common
- Abdominal or stomach pain
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- liver problems,
- stomach pain,
- Burning, itching, stinging, redness, or other sign of irritation at the application site ,rash
- a headache,
- increased intracranial pressure,
- meningeal signs,
- reversible hair loss or thinning, and
- chills or fever
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes)
- decreased amount of urine
- change in vision
- chest pain or tightness
- a cough
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- extra heartbeats
- a headache
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- severe pain in your upper stomach spreading to your back, nausea, and vomiting;
- signs of congestive heart failure–shortness of breath (even with mild exertion), cough with mucus, fast heartbeats, swelling, rapid weight gain, sleep problems; or.
Drug Interactions of Itraconazole
Many drugs can interact with itraconazole, and some drugs should not be used together. Tell your doctor about all your current medicines and any you start or stop using, especially
- an antibiotic;
- antipsychotic medicine or a sedative;
- an antiviral medicine to treat hepatitis C or HIV/AIDS;
- medicine to prevent blood clots;
- cancer medicine;
- heart or blood pressure medication;
- immunosuppressants, or medicine to prevent organ transplant rejection;
- medicine to treat high cholesterol;
- migraine headache medication;
- narcotic (opioid) pain medicine;
- seizure medicine; or
- steroid medication.
Never take itraconazole if you
are taking any of the medicines listed below. Dangerous or even life-threatening abnormal heartbeats could result:
are taking any of the following medicines
- have ever had an allergic reaction to itraconazole or any of the other ingredients in itraconazole. Ask your doctor or pharmacist for a list of these ingredients.
Itraconazole 100mg Capsules, hard must not be used during pregnancy except for life-threatening cases where the potential benefits to the mother outweigh the potential harm to the fetus
There is limited information on the use of itraconazole during pregnancy. During post-marketing experience, cases of congenital abnormalities have been reported. These cases included skeletal, genitourinary tract, cardiovascular and ophthalmic malformations as well as chromosomal and multiple malformations. A causal relationship with itraconazole has not been established.
A very small amount of itraconazole is excreted in human milk. The expected benefits of itraconazole capsules therapy should, therefore, be weighed against the potential risk of breastfeeding. In case of doubt, the patient should not breastfeed. Women of childbearing potential taking Itraconazole 100mg Capsules, hard should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of Itraconazole 100mg Capsules, hard therapy.