Nizoral: Clinically Proven Ketoconazole for Effective Dermal Fungal Control
Nizoral (ketoconazole) is a leading topical and systemic antifungal medication, representing a cornerstone in dermatological and systemic antifungal therapy. As an imidazole derivative, it functions by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes, leading to fungal cell death. Its broad-spectrum efficacy targets a range of pathogenic fungi, including dermatophytes, yeasts, and molds, making it a versatile and trusted choice for healthcare professionals. Available in shampoo, cream, and oral tablet formulations, Nizoral provides targeted treatment options tailored to specific clinical presentations, from superficial cutaneous infections to more systemic conditions.
Features
- Active Ingredient: Ketoconazole 2% (topical formulations), Ketoconazole 200 mg (oral tablets)
- Formulations: Medicated shampoo, topical cream, oral tablets
- Mechanism of Action: Potent inhibitor of fungal cytochrome P450-dependent 14α-demethylase, disrupting ergosterol biosynthesis
- Spectrum of Activity: Broad-spectrum antifungal effective against Trichophyton, Microsporum, Epidermophyton, Malassezia spp., Candida spp., and certain dimorphic fungi
- Pharmacokinetics (Oral): High protein binding, extensive hepatic metabolism via CYP3A4, excretion primarily in bile and feces
- Topical Penetration: Effective stratum corneum penetration with minimal systemic absorption when applied correctly
Benefits
- Rapid and Potent Fungicidal Action: Eradicates the root cause of fungal infections, providing swift symptomatic relief from itching, scaling, and inflammation.
- Proven Efficacy Against Recalcitrant Malassezia: The 2% shampoo formulation is the gold standard for seborrheic dermatitis and pityriasis versicolor, significantly reducing scaling and erythema.
- Dual-Action Shampoo: Offers both antifungal and anti-inflammatory properties, helping to control flaking and soothe the scalp.
- High Cure Rates in Systemic Mycoses: Oral tablets are indicated for serious systemic fungal infections, including blastomycosis, coccidioidomycosis, and histoplasmosis, where other antifungals have failed or are unsuitable.
- Reduces Risk of Recurrence: Effective treatment helps restore the skin’s natural barrier function, preventing common patterns of relapse in chronic conditions like tinea infections.
- Flexible Treatment Regimens: Multiple formulations allow for personalized treatment plans based on infection type, severity, and patient-specific factors.
Common use
Nizoral is indicated for the treatment of a wide array of fungal infections. The topical cream is primarily used for cutaneous infections such as tinea corporis (ringworm), tinea cruris (jock itch), tinea pedis (athlete’s foot), cutaneous candidiasis, and seborrheic dermatitis. The medicated shampoo is specifically formulated for the treatment of seborrheic dermatitis of the scalp and pityriasis versicolor (tinea versicolor). Oral Nizoral tablets are reserved for the treatment of systemic fungal infections, including blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. It is also used for chronic mucocutaneous candidiasis and is sometimes prescribed off-label for severe, recalcitrant cutaneous infections that have not responded to topical therapy.
Dosage and direction
Dosage and administration are critically dependent on the formulation and indication.
- Nizoral Cream (2%): Apply sufficient quantity to cover the affected and immediate surrounding area once or twice daily. Treatment duration typically ranges from 2 to 6 weeks, depending on clinical response. The area should be clean and dry before application.
- Nizoral Shampoo (2%): For seborrheic dermatitis: Use twice weekly for 4 weeks, allowing the lather to remain on the scalp for 5 minutes before rinsing. For pityriasis versicolor: Use daily for 5 consecutive days. Lather, leave on for 5 minutes, and rinse thoroughly.
- Nizoral Tablets (200 mg): Dosage for adults is typically 200 mg once daily. In severe infections or insufficient response, this may be increased to 400 mg once daily. Pediatric dosing is based on body weight (3.3–6.6 mg/kg/day as a single dose). Administration with an acidic beverage (e.g., cola) may enhance the absorption of the oral tablet. Therapy should be continued until all clinical and laboratory tests indicate active fungal infection has subsided; inadequate duration is a common cause of treatment failure.
Precautions
- Hepatotoxicity: Oral ketoconazole has been associated with rare but serious drug-induced liver injury, including fatal hepatic necrosis. Liver function tests should be performed prior to initiation of oral therapy and monitored periodically during treatment.
- Adrenal Suppression: Oral ketoconazole inhibits human CYP enzymes and can dose-dependently suppress cortisol and testosterone synthesis. Adrenal function should be assessed if signs of adrenal insufficiency (e.g., weakness, nausea, hypotension) appear.
- Topical Use: For external use only. Avoid contact with eyes, nose, mouth, and other mucous membranes. If contact occurs, rinse thoroughly with water.
- Pregnancy and Lactation: Topical use is generally considered low risk due to minimal systemic absorption. Oral ketoconazole is classified as Pregnancy Category C and should only be used if the potential benefit justifies the potential risk to the fetus. Ketoconazole is excreted in human milk; caution is advised when administering oral tablets to nursing women.
- Sun Exposure: Patients using topical Nizoral should avoid excessive exposure to natural or artificial sunlight (tanning beds) as ketoconazole may cause photosensitivity.
Contraindications
Nizoral is contraindicated in patients with known hypersensitivity to ketoconazole, any component of the formulation, or other azole antifungal agents. Oral Nizoral tablets are contraindicated in patients with acute or chronic liver disease and in those taking drugs that are highly dependent on CYP3A4 metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., cisapride, disopyramide, dofetilide, dronedarone, methadone, quinidine, ergot alkaloids). Concomitant use with drugs that prolong the QT interval is also contraindicated.
Possible side effect
Side effect profiles differ significantly between topical and systemic administration.
- Topical Formulations (Cream/Shampoo): Generally well-tolerated. Local reactions may include pruritus (itching), irritation, stinging, burning sensation, and dryness at the application site. Allergic contact dermatitis is rare.
- Oral Tablets: The most common side effects are nausea, vomiting, abdominal pain, and pruritus. Serious adverse reactions include:
- Hepatotoxicity: Elevated liver enzymes, hepatitis, cholestatic jaundice, and rare fulminant hepatic failure.
- Endocrine Effects: Adrenal insufficiency, gynecomastia, oligospermia, decreased libido, and menstrual irregularities due to inhibition of steroidogenesis.
- Other: Headache, dizziness, thrombocytopenia, and hypersensitivity reactions.
Drug interaction
Oral ketoconazole is a potent inhibitor of the cytochrome P450 3A4 (CYP3A4) enzyme system and P-glycoprotein, leading to a high potential for significant drug-drug interactions. It can increase the plasma concentrations of co-administered drugs metabolized by CYP3A4, potentially leading to serious toxicity.
- Absolute Contraindication: Concomitant use with cisapride, ergot alkaloids, triazolam, oral midazolam, pimozide, quinidine, dofetilide, levomethadyl, lovastatin, simvastatin, and eplerenone.
- Significant Interactions Requiring Dose Adjustment/Monitoring:
- Anticoagulants: Warfarin (increased prothrombin time).
- Immunosuppressants: Cyclosporine, tacrolimus, sirolimus (increased nephrotoxicity risk).
- Protease Inhibitors: Saquinavir, ritonavir (increased concentrations of both drugs).
- Benzodiazepines: Alprazolam, diazepam (increased sedation).
- Calcium Channel Blockers: Felodipine, nifedipine (increased hypotension risk).
- Digoxin: Increased digoxin serum levels.
- Proton Pump Inhibitors/H2 Blockers: Reduced absorption of ketoconazole due to increased gastric pH.
- Rifampin, Isoniazid, Phenytoin, Carbamazepine: These drugs induce CYP enzymes and can significantly decrease ketoconazole plasma levels.
Topical formulations have minimal systemic absorption and are not associated with clinically significant drug interactions.
Missed dose
- Topical Formulations: Apply the missed dose as soon as remembered. However, if it is almost time for the next application, skip the missed dose and resume the regular schedule. Do not apply a double dose to compensate.
- Oral Tablets: Take the missed dose as soon as remembered. If it is almost time for the next scheduled dose, skip the missed dose and take the next one at the regular time. Do not take a double dose to make up for a missed one.
Overdose
- Topical Formulations: Overdose is unlikely due to minimal systemic absorption. In case of accidental ingestion, gastric lavage and supportive measures are recommended.
- Oral Tablets: Overdose may manifest as enhanced adverse effects, particularly nausea, vomiting, and dizziness. In severe cases, hepatotoxicity and adrenal suppression are possible. There is no specific antidote. Treatment consists of immediate gastric lavage (if ingestion is recent) and administration of activated charcoal, followed by supportive measures and monitoring of liver and adrenal function.
Storage
Store all Nizoral formulations at room temperature, between 20°C to 25°C (68°F to 77°F), in a dry place away from direct light and heat. Keep the container tightly closed. Do not freeze. Keep all medications out of the reach of children and pets. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Dispose of unused medication through a medicine take-back program.
Disclaimer
This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The manufacturer and publisher are not responsible for any errors or omissions or for any consequences from application of the information in this document.
Reviews
“Nizoral shampoo has been a game-changer for my patients with severe seborrheic dermatitis. The 2% formulation provides rapid relief from itching and flaking where other OTC options have failed. We typically use it for a 4-week intensive course to gain control, then move to a maintenance regimen.” – Board-Certified Dermatologist
“While highly effective for systemic mycoses, the use of oral ketoconazole requires vigilant monitoring. I reserve it for specific cases where other antifungals are not an option due to its significant interaction profile and hepatotoxicity risk. The benefit must clearly outweigh the risk.” – Infectious Disease Specialist
“For recurrent tinea versicolor, a short course of Nizoral shampoo is my go-to prescription. It’s effective, easy for patients to use, and the results are consistently good. Patient compliance is high due to the simple, short treatment duration.” – General Practitioner