Ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine.
Synthetic broad-spectrum antifungal agent.
Pharmacology: Mechanism of Action: In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated that the therapeutic effect of ketoconazole in seborrheic dermatitis is due to the reduction of M. ovale, but this has not been proven.
Microbiology: Ketoconazole is a broad-spectrum synthetic antifungal agent which inhibits the in vitro growth of the following common dermatophytes and yeasts by altering the permeability of the cell membrane.
Dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouini, M. gypseum and Epidermophyton floccosum.
Yeasts: Candida albicans, Malassezia ovale (Pityrosporum ovale) and C. tropicalis and the organism responsible for tinea versicolor, Malassezia furfur (Pityrosporum orbiculare).
Ointment: Only those organisms listed under Indications have been proven to be clinically affected. Development of resistance to ketoconazole has not been reported.
Pharmacokinetics: Tablet: Mean plasma levels of approximately 3.5 mg/mL are reached within 1-2 hrs following oral administration of a single 200-mg dose taken with meal. Subsequent plasma elimination is biphasic with a half-life of 2 hrs during the first 10 hrs and 8 hrs, thereafter. Following absorption, ketoconazole is converted into several inactive metabolites. About 13% of the drug is excreted in urine, 2-4% as unchanged drug. The major route of excretion is through faeces (about 57% of a dose), consisting of 20-65% of the unchanged drug and the rest as metabolite.
Ointment: When ketoconazole 2% ointment was applied dermally to intact or abraded skin of beagle dogs for 28 consecutive days at a dose of 80 mg, there were no detectable plasma levels using an assay method having a lower detection limit of 2 ng/mL. After a single topical application to the chest, back and arms of normal volunteers, systemic absorption of ketoconazole was not detected at the 5 ng/mL level in blood over a 72-hr period. Ketoconazole does not penetrate beyond the epidermis, non-percutaneous absorption is detected.
Tablet: Treatment of the following systemic fungal infections: Candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis and paracoccidioidomycosis.
Ointment: Topical treatment of tinea corporis and tinea cruris caused by Trichophyton rubrum, T. mentagrophytes, and Epidermophyton floccosum; tinea versicolor caused by Malassezia furfur; cutaneous candidiasis caused by Candida sp and seborrheic dermatitis.
Tablet: Adults: Recommended Starting Dose: Single dose of 200 mg daily. In very severe infections, dosage can be doubled.
Children >2 years: Single daily dose of 3.3-6.6 mg/kg.
Ointment: Apply once daily to cover the affected area, for around 2 weeks. Seborrheic Dermatitis: Application should be twice daily for 4 weeks.
In the event of accidental overdosage, employ supportive measures, including gastric lavage with sodium bicarbonate.
Overdosage by topical application of ketoconazole ointment is not reported.
Tablet: Patients with known hypersensitivity to ketoconazole; concomitant use of ketoconazole with terfenadine and astemizole.
Ointment: Hypersensitivity to ketoconazole or any of the components of Phytoral Ointment.
Tablet: Hepatotoxicity, primarily of the hepatocellular type has been associated with the use of ketoconazole. Hence, it should not be given to patients with preexisting liver disease. Liver function tests should be performed before starting therapy. Patients should be instructed to report promptly any signs and symptoms of liver dysfunction eg, anorexia, nausea/vomiting, fatigue, jaundice, dark urine or pale stools.
Ointment: Ketoconazole ointment is not for ophthalmic use. If reaction suggesting sensitivity or chemical irritation should occur, use of Phytoral Ointment should be discontinued.
Use in pregnancy & lactation: There are no adequate and well-controlled studies in pregnant women. Ketoconazole should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.
Since ketoconazole is excreted in the milk, mothers who are under treatment should not breastfeed.
There are no adequate and well-controlled studies in pregnant women. Ketoconazole should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.
Since ketoconazole is excreted in the milk, mothers who are under treatment should not breastfeed.
Tablet: In rare cases, anaphylaxis has been reported after the 1st dose. Several cases of hypersensitivity reactions including urticaria have also been reported. The most frequent adverse reactions are nausea and/or vomiting, abdominal pain, pruritus.
In <1% of patients, headache, dizziness, somnolence, photophobia, gynecomastia, etc, have been reported. Most of these reactions are mild and transient.
Ointment: Reported adverse effects consist mainly of irritation, pruritus and stinging.
Concomitant administration of rugs that reduce stomach acidity eg, anticholinergic agents, antacids and H2-receptor antagonists may reduce the absorption of ketoconazole. If indicated, these drugs should be taken not <2 hrs after ketoconazole.
Ketoconazole has been shown to increase plasma concentration of cyclosporin in patients receiving both drugs.
There are no clinical studies of drug interaction with ketoconazole ointment.
Tablet: Store in a dry place, below 25°C.
Ointment: Store at 15-30°C.
J02AB02 - ketoconazole ; Belongs to the class of imidazole derivatives. Used in the systemic treatment of mycotic infections.
D01AC08 - ketoconazole ; Belongs to the class of imidazole and triazole derivatives. Used in the topical treatment of fungal infection.
Tab 200 mg (uncoated) x 3 x 10's, 10 x 10's. Oint 2% x 15 g.
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