Nizoral: Clinically Proven Ketoconazole for Effective Dermal Fungal Control
Nizoral (ketoconazole) is a broad-spectrum imidazole antifungal agent, representing a cornerstone in the therapeutic management of superficial fungal infections. Its primary mechanism of action involves the inhibition of ergosterol synthesis, a critical component of fungal cell membranes, leading to increased cellular permeability and eventual cell death. Available in both topical (shampoo, cream) and oral (tablet) formulations, its efficacy is well-documented across a range of dermatological conditions. This monograph provides a comprehensive, evidence-based overview for healthcare professionals to guide its appropriate clinical application.
Features
- Active Ingredient: Ketoconazole 2% (topical formulations), Ketoconazole 200 mg (oral tablets).
- Pharmacological Class: Synthetic imidazole broad-spectrum antifungal agent.
- Formulations: Medicated shampoo (100 mL), topical cream (15g, 30g, 60g tubes), oral tablets.
- Mechanism of Action: Inhibits the cytochrome P-450 dependent synthesis of ergosterol, a key sterol in the fungal cell membrane.
- Spectrum of Activity: Demonstrates potent in vitro activity against Malassezia spp. (e.g., M. furfur, M. globosa), Trichophyton spp., Microsporum spp., Candida spp., and Epidermophyton floccosum.
Benefits
- Targeted Fungicidal Action: Eradicates the root cause of infection by disrupting fungal cell integrity, providing a curative rather than merely suppressive effect for many conditions.
- Anti-inflammatory and Sebostatic Properties: Particularly effective against Malassezia-driven conditions like seborrheic dermatitis and pityriasis versicolor, reducing associated scaling, itching, and erythema.
- Proven Efficacy in Recalcitrant Cases: Serves as a first-line or second-line treatment for dermal mycoses that are unresponsive to other topical antifungals, including some cases of tinea corporis and cruris.
- Multiple Formulations for Flexible Treatment: Allows for tailored therapeutic strategies—shampoo for scalp involvement, cream for localized skin lesions, and oral tablets for extensive or systemic infections.
- Reduces Recurrence Rates: Regular prophylactic use of the shampoo, as maintenance therapy, can significantly delay the recurrence of dandruff and seborrheic dermatitis.
- Rapid Symptomatic Relief: Patients often report a noticeable reduction in pruritus and scaling within the first week of initiating proper treatment.
Common use
Nizoral is indicated for the treatment of a variety of superficial fungal infections caused by susceptible organisms.
- Topical Cream/Shampoo: Tinea corporis (ringworm), tinea cruris (jock itch), tinea pedis (athlete’s foot), cutaneous candidiasis, seborrheic dermatitis of the scalp and body, and pityriasis versicolor.
- Oral Tablets: Systemic fungal infections including candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Also indicated for severe recalcitrant cutaneous dermatophyte infections not responsive to topical therapy or oral griseofulvin.
Dosage and direction
Administration is route-specific and must be tailored to the indication.
- Nizoral Shampoo (2%):
- For seborrheic dermatitis/dandruff: Apply to wet hair, lather, and leave in place for 3-5 minutes before rinsing. Use twice weekly for 2-4 weeks, spacing washes by at least 3 days. For maintenance, use once every 1-2 weeks.
- For pityriasis versicolor: Apply to affected areas on the body, lather, and leave on for 5 minutes. Rinse thoroughly. Use once daily for up to 5 consecutive days.
- Nizoral Cream (2%): Apply a sufficient amount to cover the affected and immediate surrounding area once or twice daily. Treatment duration typically ranges from 2 to 6 weeks, depending on the infection’s nature and response.
- Nizoral Tablets (200 mg):
- Adults: The standard dose is 200 mg once daily. In severe infections or insufficient response, this may be increased to 400 mg once daily.
- Children: Dosing is weight-based (3.3 - 6.6 mg/kg/day as a single dose). Use in children is typically reserved for serious systemic infections under strict specialist supervision.
- Duration of therapy varies widely by infection, from a few days for oral thrush to many months for deep mycoses.
Precautions
- Topical Use: For external use only. Avoid contact with eyes, mucous membranes, and open wounds. If contact occurs, rinse thoroughly with water.
- Oral Use: Nizoral tablets have been associated with serious hepatotoxicity, including fatal liver failure. Liver function tests should be performed prior to initiation of treatment and at regular intervals during treatment. Discontinue immediately if signs of liver injury (e.g., unusual fatigue, nausea, vomiting, jaundice, dark urine, pale stools) appear.
- Adrenal Function: Ketoconazole is a potent inhibitor of steroidogenesis. Oral therapy can suppress cortisol and testosterone serum levels. Monitor for signs of adrenal insufficiency.
- QT Prolongation: Oral ketoconazole has been shown to prolong the QT interval. Avoid use in patients with known QT prolongation or those taking other drugs that prolong the QT interval.
- Pregnancy and Lactation: Topical use is generally considered low risk. Oral ketoconazole is contraindicated in pregnancy due to animal data showing teratogenicity and because treatment of systemic fungal infections often requires prolonged high-dose therapy. It is excreted in human milk; a decision should be made to discontinue nursing or discontinue the drug.
Contraindications
- Hypersensitivity to ketoconazole, any component of the formulation, or other azole antifungals.
- Oral formulation is contraindicated: in patients with acute or chronic liver disease; in patients who have shown hypersensitivity to the drug; with co-administration of drugs that are highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., quinidine, dofetilide, pimozide, triazolam, oral midazolam, eplerenone, cisapride, ergot alkaloids, HMG-CoA reductase inhibitors like lovastatin and simvastatin); and in pregnancy.
Possible side effect
- Topical Formulations: Generally well-tolerated. Localized irritation, stinging, burning, pruritus, and dryness at the application site are possible. Allergic contact dermatitis is rare.
- Oral Tablets:
- Common: Nausea, vomiting, abdominal pain, pruritus, headache.
- Serious: Hepatotoxicity (may be fatal), adrenal insufficiency, QT prolongation, thrombocytopenia, leukopenia, severe dermatologic reactions (e.g., Stevens-Johnson syndrome), anaphylaxis.
Drug interaction
Oral ketoconazole is a potent inhibitor of the hepatic cytochrome P-450 3A4 enzyme system. Co-administration can lead to significantly increased plasma concentrations of other drugs, resulting in potentially serious adverse effects.
- Contraindicated Interactions: Cisapride, pimozide, quinidine, dofetilide, ergot derivatives, triazolam, oral midazolam, eplerenone, lovastatin, simvastatin.
- Significant Interactions Requiring Dose Adjustment/Monitoring/Alternative Therapy: Warfarin (increased INR), phenytoin, cyclosporine, tacrolimus, sirolimus, methylprednisolone, budesonide, certain calcium channel blockers (e.g., felodipine), certain HIV protease inhibitors, tricyclic antidepressants, carbamazepine, buspirone, alfentanil, fentanyl, sildenafil, and many others.
- Drugs that decrease ketoconazole absorption: Antacids, H2-receptor antagonists, proton pump inhibitors, sucralfate. Administer ketoconazole at least 2 hours after these agents.
- Drugs that induce metabolism: Rifampin, rifabutin, isoniazid, phenytoin, carbamazepine. These may decrease ketoconazole plasma levels.
Missed dose
- Topical: Apply the next dose at the regularly scheduled time. Do not double the dose to make up for the missed application.
- Oral: Take the missed dose as soon as remembered. If it is almost time for the next dose, skip the missed dose and resume the normal dosing schedule. Do not take a double dose.
Overdose
- Topical: Overdose is unlikely due to minimal systemic absorption. In case of accidental ingestion, gastric lavage and supportive measures are advised.
- Oral: Symptoms may include nausea, vomiting, and dizziness. In cases of severe overdose, liver toxicity is a paramount concern. Treatment is nonspecific and supportive. Gastric lavage may be indicated if performed soon after ingestion. There is no specific antidote.
Storage
- Store at room temperature (15-30°C or 59-86°F) in a dry place.
- Protect from light and moisture. Do not freeze.
- Keep all medications out of the reach of children and pets.
Disclaimer
This information is for educational and professional medical reference purposes only and is not a substitute for the professional judgment of a qualified healthcare practitioner in diagnosing and treating patients. The information does not cover all possible uses, directions, precautions, interactions, or adverse effects. The prescriber or user should consult the full manufacturer’s prescribing information for complete details and exercise independent clinical judgment in determining the appropriate therapy for a given patient. The author and publisher disclaim any liability, loss, or risk incurred as a consequence, directly or indirectly, of the use and application of any of the contents of this document.
Reviews
- “As a dermatologist, Nizoral shampoo remains a first-line, indispensable tool in my arsenal against seborrheic dermatitis. Its anti-fungal and anti-inflammatory efficacy is consistently reliable for achieving rapid clearance of scale and erythema.” – Board-Certified Dermatologist, 15 years experience
- “The 2% cream formulation is highly effective for localized tinea infections that have proven resistant to clotrimazole or miconazole. I appreciate its targeted action and the low incidence of local side effects.” – Infectious Disease Specialist
- “While the oral formulation’s efficacy is undeniable for systemic mycoses, the risk of hepatotoxicity and significant drug interactions mandates extreme caution. It requires vigilant patient selection and intensive monitoring, limiting its use to situations where the benefit clearly outweighs the risk.” – Clinical Pharmacologist
- “Patient adherence is generally high with the shampoo due to its cosmetically elegant feel and clear instructions. The twice-weekly dosing schedule for active treatment is manageable for most.” – Dermatology Nurse Practitioner