Ketoconazole

Available Form:
  • Oral Suspension: 100mg/ml
  • Tablets: 200mg
MOA: Ketoconazole operates through at least two mechanisms of action.
  • First, block both testicular and adrenal androgen biosynthesis, leading to a reduction in circulating testosterone levels.
  1. It produces this effect through inhibition of 17α-hydroxylase and 17,20-lyase, which are involved in the synthesis and degradation of steroids, including the precursors of testosterone.
  2. Due to its efficacy at reducing systemic androgen levels, ketoconazole has been used with some success as a treatment for androgen-dependent prostate cancer.
  •  Second, ketoconazole is an androgen receptor antagonist, competing with androgens such as testosterone and dihydrotestosterone (DHT) for binding to the androgen receptor.
 Uses and Considerations:
  • For infections by Candida spp.
  • Histoplasmosis, 
  • Dermatophytosis 
  • Blacstomycosis, and others Treatment could last 1-6 months for systemic infections. 
  • Take with food to avoid GI discomfort. Pregnancy category: C; PB: 95%; t 1/2 : 2-8h
Indications:
  • Systemic Candidiasis, 
  • Chronic mucocandidiasis, 
  • Oral candidiasis, 
  • Candiduri, 
  • Coccidioidomycosis, 
  • Blastomycosis, 
  • Histoplasmosis, 
  • Chromomycosis and 
  • Paracoccidioidomycosis; 
  • Medical adrenalectomy
  • Pityriasis versicolor
  • Severe cutaneous dermatophyte infections resistant to therapy with topical or oral griseofulvin
Contraindications: 
  •  Contraindicated 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 cyclosporine, 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
  • Antihistamines associated with an increased risk of cardiac arrhythmias in patients receiving erythromycin or ketoconazole include Terfenadine
  • Ketoconazole would treat both dermatophytes and candidal infection
  • Ketoconazole is Cyt. p450 inhibitor
  • Ketoconazole are effective in the treatment of pityriasis versicolor
  • Ketoconazole is used for medical adrenalectomy
  • Ketoconazole decreases efficacy of testosterone
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