Itraconazole (Sporanox Capsules 100 Mg)
Itraconazole is a triazole antifungal agent that inhibits the C-demethylation step in the synthesis of ergosterol, which is a vital component of fungal cell membranes.
Injection: used in treatment of aspergillosis, blastomycosis, histoplasmosis, and the empiric treatment of febrile neutropenic patients with suspected fungal infections.
Capsules: used in treatment of asper-gillosis, blastomycosis, histoplasmosis, and onychomycosis (nonimmunocompromised patients only).
Oral solution: used in treatment of oropharyngeal or esophageal candidiasis and empiric treatment of febrile neutropenic patients with suspected fungal infections.
Itraconazole (Sporonox) is available as a capsule and two solution formulations, one for oral and one for intravenous administration. The capsule form of the drug is best absorbed in the fed state, but the oral solution is better absorbed in the fasting state, providing peak plasma concentrations that are more than 150% of those obtained with the capsule. Both the oral solution and intravenous formulation are solubilized in a 40:1 weight ratio of itraconazole hydroxypropyl-β-cyclodextrin, so that administration of 200 mg of itraconazole provides 8 g of this excipient.
Itraconazole is metabolized in the liver. It is both a substrate for and a potent inhibitor of CYP3A4. Itraconazole is present in plasma with an approximately equal concentration of a biologically active metabolite, hydroxy-itraconazole. Bioassays may report up to 3.3 times as much itraconazole in plasma as do physical methods such as high-performance liquid chromatography, depending on the susceptibility of the bioassay organism to hydroxy-itraconazole. The native drug and metabolite are >99% bound to plasma proteins. Neither appears in urine or CSF. The half-life of itraconazole at steady state is approximately 30 to 40 hours. Steady-state levels of itraconazole are not reached for 4 days and those of hydroxy-itraconazole for 7 days; thus, loading doses are recommended when treating deep mycoses.
Severe liver disease will increase itraconazole plasma concentrations, but azotemia and hemodialysis have no effect. Some 80 to 90% of intravenously administered hydroxypropyl-β-cyclodextrin is excreted in the urine, and the compound accumulates in the presence of azotemia. Intravenous administration of itraconazole is contraindicated in patients with a creatinine clearance below 30 ml / min because of concern about potential hydroxypropyl-β-cyclodextrin toxicity.
It is not carcinogenic but is teratogenic in rats, and is contraindicated in the treatment of onychomycosis during pregnancy or for women contemplating pregnancy. Itraconazole given as a capsule is the drug of choice for patients with indolent, nonmeningeal infections due to B. dermatitidis, H. capsulatum, P. brasiliensis, and C. immitis. This dosage form also is useful in therapy of indolent invasive aspergillosis outside the CNS, particularly after the infection has been stabilized with amphotericin B. The intravenous formulation is approved for the initial 2 weeks of therapy with blastomycosis, histoplasmosis, and indolent aspergillosis, and for empirical therapy of febrile neutropenic patients not responding to antibacterial antibiotics and at high risk of fungal infections. The intravenous route would be most appropriate for patients unable to tolerate the oral formulation or unable to absorb itraconazole because of decreased gastric acid production.
Approximately half the patients with distal subungual onychomycosis respond to itraconazole. Although not an approved use, itraconazole is a reasonable choice for treatment of pseudallescheriasis, an infection not responding to amphotericin B therapy, as well as cutaneous and extracutaneous sporotrichosis, tinea corporis, and extensive tinea versicolor. HTV-infected patients with disseminated histoplasmosis or Penicillium marneffei infections have a decreased incidence of relapse if given prolonged itraconazole “maintenance” therapy. It is as yet unclear whether patients responding to highly active antiretroviral therapy (HAART) will require less than lifelong therapy for P. marneffei and disseminated histoplasmosis.
Itraconazole is not recommended for maintenance therapy of cryptococcal meningitis in HIV-infected patients because of a high incidence of relapse. Long-term therapy has been used in non-HIV-infected patients with allergic bronchopulmonary aspergillosis to decrease the dose of glucocorticoids and reduce attacks of acute bronchospasm.
Itraconazole, a synthetic triazole with antifungal properties, is indicated in the treatment of blastomycosis (pulmonary and extra-pulmonary), histoplasmosis (including chronic cavitary pulmonary disease and disseminated non-meningeal histoplasmosis) and aspergillosis (pulmonary and extra-pulmonary) in patients who are intolerant of or refractory to amphotericin B therapy. In addition, itraconazole has been used in the treatment of superficial mycoses (dermatophytoses, pityriasis versicolor, sebopsoriasis, candidiasis [vaginal, oral or chronic mucocutaneous], and onychomycosis), systemic mycoses (candidiasis, cryptococcal infections [meningitis, disseminated], dimorphic infections [paracoccidioidomycosis, coccidioidomycosis]), subcutaneous mycoses (sporotrichosis, chromomycosis), cutaneous leishmaniasis, fungal keratitis, alteranariosis, and zygomycosis. Itraconazole is an orally active, broad-spectrum, triazole antifungal agent that has a higher affinity for fungal cytochrome P450 than ketoconazole but a low affinity for mammalian cytochrome P450. Itraconazole has a broader spectrum of activity than other azole antifungals and shows interesting pharmacokinetic features in terms of its tissue distribution.
These properties have resulted in reduced treatment times for a number of diseases such as vaginal candidiasis, as well as effective oral treatment of several deep mycoses, including aspergillosis and candidiasis.