Ketoconazole
KETOCONAZOLE
MOA:
- 2 types of action.
Block both testicular & adrenal androgen biosynthesis, reducing circulating testosterone levels.
- Via 17α-hydroxylase & 17, 20-lyase inhibition, both involved in synthesis & degradation of steroids, including testosterone precursors.
- Used as treatment for androgen-dependent prostate cancer.
- Due to its efficacy in reducing systemic androgen levels.
An androgen receptor antagonist.
- Competing with androgens like testosterone & dihydrotestosterone (DHT) for androgen receptor binding.
Pharmacokinetics:
- Plasma binding – 95%;
- t 1/2: 2-8h
- Along with food intake to avoid GI discomfort.
- Pregnancy category – C
Available Form:
- Oral Suspension: 100mg/ml
- Tablets: 200mg
Uses:
- For infections by Candida sp.
- Histoplasmosis,
- Dermatophytosis
- Blastomycosis and others treatment could last 1-6 months for systemic infections.
Indications:
- Systemic Candidiasis,
- Chronic mucocandidiasis,
- Oral candidiasis,
- Candiduria,
- Coccidioidomycosis,
- Blastomycosis,
- Histoplasmosis,
- Chromomycosis and
- Paracoccidioidomycosis;
- Medical adrenalectomy
- Pityriasis Versicolor
- Severe cutaneous dermatophyte infections resistant to therapy with topical or oral griseofulvin
CONTRA-INDICATIONS:
- In patients hypersensitive to drug.
SIDE EFFECTS:
- CNS: headache, nervousness, dizziness, somnolence, suicidal tendencies, severe depression
- ENT: photophobia
- GI: nausea, vomiting, abdominal pain, diarrhea
- GU: Impotence
- HEMATOLOGIC: thrombocytopenia, haemolytic anemia, leukopenia
- HEPATIC: fatal hepatoxicity
- METABOLIC: hyperlipidemia
- SKIN: pruritus
DRUG INTERACTION:
- Potent inhibitor of cytochrome P450 3A4
- Rifampin and phenytoin decrease ketoconazole levels
- Decreases efficacy of testosterone
- Ketoconazole increases cyclosporin, warfarin, astemizole, corticosteroid, and theophylline levels
- Many of these drug interactions are severe
- Drugs that increase gastric pH will decrease blood levels of ketoconazole Antacids, omeprazole, H2 blockers
Exam Question
- Anti-histamines associated with an increased risk of cardiac arrhythmias in patients receiving erythromycin or ketoconazole & Terfenadine.
- Ketoconazole would treat both dermatophytosis & candidal infection.
- Ketoconazole is Cyt. p450 inhibitor.
- Ketoconazole is effective in the treatment of pityriasis Versicolor.
- Ketoconazole is used for medical adrenalectomy.
- Ketoconazole decreases the efficacy of testosterone.
Don’t Forget to Solve all the previous Year Question asked on Ketoconazole