Adults: The recommended starting dose of ketoconazole tablets is a single daily administration of 200 mg (one tablet). In very serious infections or if clinical responsiveness is insufficient within the expected time, the dose of ketoconazole tablets may be increased to 400 mg (two tablets) once daily.<br/>Pediatric Patients: In small numbers of pediatric patients over 2 years of age, a single daily dose of 3.3 to 6.6 mg/kg has been used. Ketoconazole tablets have not been studied in pediatric patients under 2 years of age. There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. Treatment should be continued until tests indicate that active fungal infection has subsided. Inadequate periods of treatment may yield poor response and lead to early recurrence of clinical symptoms. Minimum treatment for candidiasis is one or two weeks. Patients with chronic mucocutaneous candidiasis usually require maintenance therapy. Minimum treatment for the other indicated systemic mycoses is six months. Minimum treatment for recalcitrant dermatophyte infections is four weeks in cases involving glabrous skin. Palmar and plantar infections may respond more slowly. Apparent cures may subsequently recur after discontinuation of therapy in some cases.
Ketoconazole is a synthetic broad-spectrum antifungal agent. Each tablet, for oral administration, contains 200 mg ketoconazole base. In addition, each tablet contains the following inactive ingredients: lactose monohydrate, sodium starch glycolate, povidone, microcrystalline cellulose, and magnesium stearate. Ketoconazole is (��)-cis-1-Acetyl-4-[p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine and has the following structural formula: CHClNOM.W. 531.44 Ketoconazole is a white to slightly beige, odorless powder, soluble in acids, with a molecular weight of 531.44.
Mean peak plasma levels of approximately 3.5 mcg/mL are reached within 1 to 2 hours, following oral administration of a single 200 mg dose taken with a meal. Subsequent plasma elimination is biphasic with a half-life of 2 hours during the first 10 hours and 8 hours thereafter. Following absorption from the gastrointestinal tract, ketoconazole is converted into several inactive metabolites. The major identified metabolic pathways are oxidation and degradation of the imidazole and piperazine rings, oxidative O-dealkylation and aromatic hydroxylation. About 13% of the dose is excreted in the urine, of which 2 to 4% is unchanged drug. The major route of excretion is through the bile into the intestinal tract. In vitro, the plasma protein binding is about 99% mainly to the albumin fraction. Only a negligible proportion of ketoconazole reaches the cerebral-spinal fluid. Ketoconazole is a weak dibasic agent and thus requires acidity for dissolution and absorption. Ketoconazole tablets are active against clinical infections with Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Phialophora spp. Ketoconazole tablets are also active against Trichophyton spp., Epidermophyton spp., and Microsporum spp. Ketoconazole is also active in vitro against a variety of fungi and yeast. In animal models, activity has been demonstrated against Candida spp., Blastomyces dermatitidis, Histoplasma capsulatum, Malassezia furfur, Coccidioides immitis, and Cryptococcus neoformans. Mode of Action: In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes.
Ketoconazole Tablets, USP: 200 mg - White, round, scored tablets in bottles of 100, 500 and 1000. Debossed: PLIVA 621 Dispense in a tight container as defined in the USP. Store at 20��- 25��C (68��- 77��F) [See USP Controlled Room Temperature]. Protect from moisture. Manufactured by: PLIVA', Inc. East Hanover, NJ 07936 P21-0621 Rev. 8/06 c/n
WARNING: When used orally, ketoconazole has been associated with hepatic toxicity, including some fatalities. Patients receiving this drug should be informed by the physician of the risk and should be closely monitored. See WARNINGSand PRECAUTIONS sections. Coadministration of terfenadine with ketoconazole tablets is contraindicated. Rare cases of serious cardiovascular adverse events, including death, ventricular tachycardia and torsades de pointes have been observed in patients taking ketoconazole tablets concomitantly with terfenadine, due to increased terfenadine concentrations induced by ketoconazole tablets. See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections. Pharmacokinetic data indicate that oral ketoconazole inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and its active metabolite desmethylastemizole which may prolong QT intervals. Coadminstration of astemizole with ketoconazole tablets is therefore contraindicated. See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections. Coadministration of cisapride with ketoconazole is contraindicated. Serious cardiovascular adverse events including ventricular tachycardia, ventricular fibrillation and torsades de pointes have occurred in patients taking ketoconazole concomitantly with cisapride. See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections.
In rare cases, anaphylaxis has been reported after the first dose. Several cases of hypersensitivity reactions including urticaria have also been reported. However, the most frequent adverse reactions were nausea and/or vomiting in approximately 3%, abdominal pain in 1.2%, pruritus in 1.5%, and the following in less than 1% of the patients: headache, dizziness, somnolence, fever and chills, photophobia, diarrhea, gynecomastia, impotence, thrombocytopenia, leukopenia, hemolytic anemia, and bulging fontanelles. Oligospermia has been reported in investigational studies with the drug at dosages above those currently approved. Oligospermia has not been reported at dosages up to 400 mg daily, however sperm counts have been obtained infrequently in patients treated with these dosages. Most of these reactions were mild and transient and rarely required discontinuation of ketoconazole tablets. In contrast, the rare occurrences of hepatic dysfunction require special attention . In worldwide postmarketing experience with ketoconazole tablets there have been rare reports of alopecia, paresthesia, and signs of increased intracranial pressure including bulging fontanelles and papilledema. Hypertriglyceridemia has also been reported but a causal association with ketoconazole tablets is uncertain. Neuropsychiatric disturbances, including suicidal tendencies and severe depression, have occurred rarely in patients using ketoconazole tablets. Ventricular dysrhythmias (prolonged QT intervals) have occurred with the concomitant use of terfenadine with ketoconazole tablets. Data suggest that coadministration of ketoconazole tablets and cisapride can result in prolongation of the QT interval and has rarely been associated with ventricular arrhythmias.
Ketoconazole Tablets, USP are indicated for the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole tablets should not be used for fungal meningitis because it penetrates poorly into the cerebral-spinal fluid. Ketoconazole Tablets, USP are also indicated for the treatment of patients with severe recalcitrant cutaneous dermatophyte infections who have not responded to topical therapy or oral griseofulvin, or who are unable to take griseofulvin.