Ketoconazole

Ketoconazole is an azole antifungal that interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability due to reduced amounts of ergosterol present in the fungal cell membrane. It is available as shampoo, cream, and tablets.

• Fungal skin infections (tinea pedis, tinea corporis, tinea cruris)
• Seborrheic dermatitis
• Dandruff (pityriasis capitis)
• Pityriasis versicolor
• Vaginal candidiasis
• Other systemic mycoses

Adult Dose (Shampoo):

• Seborrheic dermatitis/Dandruff: twice weekly × 2-4 weeks (treatment); once every 1-2 weeks (prophylaxis)
• Pityriasis versicolor: once daily × 5 days

Adult Dose (Cream):

• Tinea pedis: twice daily × 1 week (mild); more severe until symptoms resolve
• Other infections: once or twice daily; tinea versicolor 2-3 weeks; tinea corporis 3-4 weeks

Adult Dose (Tablet):

• Vaginal candidiasis: 200 mg twice daily × 5 days
• Other: 200 mg once daily until 1 week after symptoms resolve

Child Dose (Tablet): 3.3-6.6 mg/kg/day once daily

Shampoo:

• Local burning sensation
• Itching
• Contact dermatitis
• Oily and dry hair (rare)

Cream:

• Application site burning
• Erythema
• Pruritus
• Skin exfoliation
• Dry skin

Tablet:

• Nausea
• Headache
• Diarrhea
• Abdominal pain
• Vomiting

Precautions:

• After prolonged topical corticosteroid use, gradually withdraw over 2-3 weeks (to prevent rebound effect)
• If shampoo gets into eyes, bathe with water
• Not for ophthalmic use (cream)
• Monitor liver enzymes in patients with previous liver disease (tablet)
• Discontinue tablet if signs of liver reaction (nausea, fatigue, pale stools, dark urine, jaundice)

Contraindications:

• Known hypersensitivity to ketoconazole
• Pre-existing liver disease (tablet)
• Porphyria (tablet)
• Concurrent use with cisapride, terfenadine or astemizole

Drug Interactions (Tablet):

• Reduced absorption with antimuscarinics, antacids, H2-blockers, PPIs, sucralfate
• Reduced plasma concentrations with rifampicin, isoniazid, efavirenz, nevirapine, phenytoin
• May increase serum levels of CYP3A4 substrates
• May potentiate sedative and hypnotic effects of midazolam and triazolam

Use in Pregnancy: May be unsafe; animal studies have shown harmful effects; doctor will weigh benefits and risks.

Use in Lactation: Safe during breastfeeding; does not pass into breastmilk in significant amount (cream & shampoo); tablets are excreted in milk, do not breastfeed.

Renal Impairment: No interaction found/established; no dose adjustment needed.

Hepatic Impairment: No interaction found/established; pre-existing liver disease contraindicated for tablets.

Overdose (Shampoo/Cream): Topical overdose may cause erythema, edema and burning sensation; resolves upon discontinuation; accidental ingestion requires no special measures.