Ketoconazole
Ketoconazole is an imidazole antifungal agent. It was the first oral azole introduced into clinical use for the treatment of systemic mycoses. It has a broad spectrum of action. Ketoconazole is active against many Candida species, endemic mycoses and dermatophytes. It was approved by the FDA in 1981.Like other azole antifungals, it exerts its effect by altering the fungal cell membrane.it inhibits ergosterol synthesis by interacting with 14-¢ demethylase, a cytochrome P-450 enzyme that is necessary for the conversion of lanosterol to ergosterol, an essential component of the membrane.
Primary Characteristics
It is of Synthetic origin and belongs to Imidazole.
It is classified in Antifungals pharmacological group.
Molecular Weight: 531.4 · pKa: 6.5 , 2.94 · Solubility in Water: almost Insoluble · Solubility in Alcohol: Sparingly soluble · Non-proprietary name: Ketoconazole.
Pharmacokinetics
Absorption: Ketoconazole has an pre-systemic (first-pass) metabolism accounts for 60.5% (±9.5%).
Distribution: Ketoconazole has a volume of distribution is 0.36 l/kg. plasma protein binding is 90%.
Elimination: it is metabolised via Hepatic (extensively), plasma half-life is 2-8 hr, renal excretion is 70%.
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Indications
Ketoconazole is primarily indicated in conditions like Candidal chronic paronychia, Chronic vaginal candidosis, Cutaneous candidiasis, Fungal prophylaxis, Histoplasmosis, Liver transplant, Pityriasis capitis, Pityriasis versicolor, Recalcitrant cutaneous dermatophyte infection, Renal transplant, Seborrheic dermatitis, Serious chronic resistant mucocutaneous candidiasis, Serious git mycoses, Severe chronic mucocutaneous candidiasis, Social anxiety disorder, Systemic mycoses, Ventricular arrhythmias; Paroxysmal supraventricular tachyarrhythmias.
Ketoconazole is also indicated for secondary conditions like Prophylaxis of organ rejection in kidney allograft recipients.
Contraindications
Ketoconazole is contraindicated in conditions like Hypersensitivity.
Dosage
Ketoconazole's dosage details are as follows:
| Dose | Single Dose | Frequency | Route | Instructions |
|---|---|---|---|---|
| Adult Dosage | ||||
| 300 mg | 300 mg | Every 24h | PO | |
| 2 % | 2 % | Every 24h | Topical | For 5 Days |
| Paediatric Dosage (20kg) | ||||
| 3 mg/kg | 3 mg/kg | Every 24h | Oral | - |
| Neonatal Dosage (3kg) | ||||
| No data. | ||||
Drug Interactions
Always consult your physician for the change of dose regimen or an alternative drug of choice that may strictly be required.
Side Effects
Ketoconazole in overdosage may give rise to further complications which include Thrombocytopenia , Impotence , Papilloedema , Androgen suppression, Oligospermia , Gynecomastia.
Ketoconazole produces potentially life-threatening effects which include Anaphylaxis , Hepatitis . Careful monitoring is needed with proper medical management.
Ketoconazole is known to cause more or less tolerable side effects which are usually transient. These include Abdominal pain, Alopecia, Dermatitis, Diarrhea, Dizziness, Headache, Irritation, Itching, Local burning sensation, Nausea, Paresthesias, Photophobia , Pruritus , Sleepiness, Somnolence , Urticaria, Vomiting .
Warnings / Precautions
Interference in Pathology
Ketoconazole may interfere in the diagnosis of False Positive Levels of Triglycerides .
Available Brands
Storage Conditions
Drug Classification
- 1.6.3 — Antifungal drugs
- 2.13.1 — Antifungals, topical