Each capsule contains: Itraconazole 100 mg.
Pharmacology: Fungistatic; may be fungicidal, depending on concentration; azole antifungals interfere with cytochrome P450 enzyme activity, which is necessary for the demethylation of 14-alpha-methylsterols to ergosterol. Ergosterol, the principal sterol in the fungal cell membrane, becomes depleted. This damages the cell membrane, producing alterations in membrane functions and permeability. In Candida albicans, azole antifungals inhibit transformation of blastospores into invasive mycelial form.
Pharmacokinetics: Bioavailability: 40-50% (fasting); 90-100% (with food).
VolD: 796 Liters.
CSF/ Serum concentrations (%): < 10%.
Protein binding: 99%.
Half-life: 21 hours (single dose); 64 hours (steady state).
Time to peak serum concentration: 3-4 hours.
Peak serum concentration after dose: 0.132 mcg/mL - 100 mg (with food); 0.234 mcg/mL 200 mg (with food).
Distribution: Highly lipophilic; extensively distributed to tissues, concentrating in fatty tissues, the omentum, the liver, and the kidneys. Aqueous fluids, such as the CSF, aqueous humor, and saliva, contain negligible concentrations of Itraconazole. Itraconazole also does not distribute into peritoneal dialysate effluent. Exudates, such as pus, may have up to 3.5 times the simultaneous plasma concentration; tissues that are prone to fungal invasion, such as skin, lung tissue, and the female genital tract, have several times the plasma concentration.
Treatment of the following fungal infection: Aspergillosis caused by Aspergillus species in patients who are intolerant of or refractory to amphotericin B therapy in both immunocompromised and non-immunocompromised patients.
Pulmonary and extrapulmonary blastomycosis caused by Blastomyces dermatiditis in immunocompromised and non-immunocompromised patients.
Esophageal and oropharyngeal candidiasis (thrush) caused by Candida species.
Histoplasmosis, including chronic cavitary pulmonary disease and disseminated, non-meningeal disease caused by Histoplasma capsulatum, in immunocompromised and non-immunocompromised patients.
Non-immunocompromised patients for the treatment of onychomycosis caused by Tinea unguium, Trichophyton species and Candida species.
Usual adult and adolescent dose: Aspergillosis: 200 mg one or two times a day with meals for at least three months.
Blastomycosis or Histoplasmosis (treatment): 200 mg once a day with meals. The dose may be increased by 100 mg, up to a maximum of 400 mg a day, if there is no obvious improvement or if there is evidence of progressive fungal disease.
Candidiasis, esophageal or Candidiasis, oropharyngeal: 100 to 200 mg once a day with a meal for fourteen days; the dose for AIDS and neutropenic patients is increased to 200 mg for four weeks.
Onychomycosis: Fingernails only: 200 mg two times a day with meals for one week; this treatment is suspended for three weeks, then resumed for one week.
Toenails with or without fingernail involvement: 200 mg once a day with meals for twelve consecutive weeks.
Usual pediatric dose: Safety and efficacy have not been established. However, a small number of patients 3 to 16 years of age have been treated with Itraconazole capsules, 100 mg per day, for systemic fungal infections, and no serious adverse effects have been reported.
Cross-sensitivity: Patients allergic to one azole antifungal agent may also be allergic to the other antifungals.
Carcinogenicity/ Tumorigenicity: No evidence of carcinogenicity was found in mice.
Mutagenicity: No mutagenic effects in appropriate, non-mammalian and mammalian test system.
Fertility: Not affect the fertility of male and female rats.
Use in Children: Not been performed in pediatric population.
Use in Elderly: No information available in geriatric patients.
Achlorhydria or hypochlorhydria will decrease the absorption of Itraconazole.
Pregnancy: Adequate and well-controlled studies in humans have not been done.
Breast-feeding: Distributed into breast milk.
Those indicating need for medical attention: Incidence less frequent:
Incidence not determined:
Anaphylaxis, anaphylactoid and allergic reactions, angioedema, congestive heart failure, hepatitis, hyperglycemia, hypokalemia, liver failure, neutropenia, peripheral edema, peripheral neuropathy, pruritus, pulmonary edema, Stevens-Johnson syndrome, urticaria.
Those indicating need for medical attention only if they continue or are bothersome: Incidence less frequent:
Incidence not determined:
Abdominal pain, alopecia, constipation, diarrhea, dizziness, dyspepsia, headache, menstrual disorders, nausea, vomiting.
Antacids, anticholinergics/antispasmodics, histamine H-receptor antagonists, Omeprazole, or Sucralfate will increase the pH of the stomach and decrease the absorption of Itraconazole.
Use with Astemizole, Cisapride, Dofetilide, Pimozide, Quinidine, or Terfenadine is contraindicated and may increase the risk of cardiac arrhythmias, including QT prolongation, ventricular tachycardia, torsades de pointes, and death.
Didanosine contains a buffer to increase its absorption; this will decrease the absorption of Itraconazole since Itraconazole needs an acidic environment.
Use with oral antidiabetic agents has increased the plasma concentration of these sulfonylurea agents, leading to hypoglycemia.
Use with Carbamazepine may decrease Itraconzole plasma concentrations, leading to treatment failure or relapse.
Itraconazole may increase digoxin concentrations, leading to digoxin toxicity.
Use with Atorvastatin, Cerivastatin, Lovastatin or Simvastatin may increase the plasma concentrations of these cholesterol-lowering agents and may increase the risk of rhabdomyolysis.
Use with Alprazolam, Diazepam, Midazolam or Triazolam may potentiate the hypnotic and sedative effects of these benzodiazepines.
Use with Nifedipine, Felodipine, or Verapamil may cause additive negative inotropic effects.
Use with macrolide antibiotics such as Clarithromycin and Erythromycin may cause increased plasma concentrations of Itraconazole.
Use with Erythromycin also showed an adjusted rate of sudden death from cardiac causes to be five times as high as that among those who had used neither a CYP3A inhibitor nor any of the study antibiotic medications; concurrent use should be avoided.
Store at temperature not more than 30°C.
J02AC02 - itraconazole ; Belongs to the class of triazole derivatives. Used in the systemic treatment of mycotic infections.