Ketoconazole

Indications

Ketoconazole is used for: Candidiasis, Fungal infections, Pityriasis versicolor, Seborrhoeic dermatitis

Adult Dose

Oral Fungal infections Adult: 200 mg once daily; may increase to 400 mg once daily if clinical response is insufficient. Continue treatment until symptoms have cleared and cultures have become negative. Chronic vag candidiasis 400 mg once daily for 5 days. Elderly: No dosage adjustment needed. Hepatic impairment: Contraindicated.

Child Dose

Oral Fungal infections Child: >2 yr 3.3-6.6 mg/kg/day once daily. Treatment duration: 1-2 wk for candidiasis; at least 4 wk in recalcitrant dermatophyte infections and up to 6 mth for other systemic mycoses.

Renal Dose

Renal impairment: No dosage adjustment needed.

Administration

Should be taken with food.

Contra Indications

Hypersensitivity; preexisting liver disease, porphyria. Concurrent use with cisapride, terfenadine or astemizole.

Precautions

Hepatic impairment; monitor liver function regularly. Pregnancy, lactation. Predisposition to adrenocortical insufficiency. Discontinue treatment if there is persistent or worsening of liver enzyme elevation.

Pregnancy-Lactation

Pregnancy category: C Lactation: Drug enters breast milk

Interactions

Reduced absorption w/ antimuscarinics, antacids, H2-blockers, PPIs, sucralfate. Reduced plasma concentrations w/ rifampicin, isoniazid, efavirenz, nevirapine, phenytoin. May also reduce concentrations of isoniazid and rifampicin. May reduce efficacy of oral contraceptives. May increase serum levels of CYP3A4 substrates e.g. digoxin, oral anticoagulants, sildenafil, tacrolimus. Potentially Fatal: May potentiate and prolong sedative and hypnotic effects of midazolam and triazolam. Increased plasma levels and prolonged QT intervals of astemizole, cisapride, dofetilide, pimozide, quinidine and terfenadine which may lead to torsade de pointes. Increased risk of myopathy w/ HMG-CoA reductase inhibitors (e.g. lovastatin, simvastatin). Markedly increased plasma levels of nisoldipine. Increased risk of hyperkalaemia and hypotension w/ eplerenone. Increased risk of vasospasm potentially leading to cerebral ischaemia w/ ergot alkaloids (e.g. ergotamine, dihydroergotamine).

Adverse Effects

Side effects of Ketoconazole : 1-10% Nausea and vomiting (3-10%), Pruritus (2%), Abdominal pain (1%) <1% Alopecia, Headache, Dizziness, Hyperlipidemia, Somnolence, Fever, Chills, Bulging fontanelles, Depression, Gynecomastia, Diarrhea, Impotence, Thrombocytopenia, Leukopenia, Hemolytic anemia, Erythema multiforme, Orthostatic hypotension, Jaundice, Dyspepsia, Dysgeusia, Hepatotoxicity, Decreased platelet count, Xeroderma, Photophobia Potentially Fatal: Hepatotoxicity.

Mechanism of Action

Ketoconazole interferes w/ biosynthesis of triglycerides and phopholipids by blocking fungal CYP450, thus altering cell membrane permeability in susceptible fungi. It also inhibits other fungal enzymes resulting in the accumulation of toxic concentrations of hydrogen peroxide.