Schedule H

Oral, Topical

• Tablets: 200 mg

• Cream: 2% w/w (10 g, 15 g, 30 g tubes)

• Shampoo: 2% w/v (50 mL, 100 mL bottles)

• Lotion: 2% w/v

• Soap: 2% w/w

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Seborrhoeic Dermatitis — Topical — Adults

Cream/Lotion:

Parameter Recommendation

Starting dose Apply 2% cream/lotion to affected area once or twice daily

Titration Not applicable

Usual maintenance dose Once daily application

Maximum dose Twice daily application

Duration: 2–4 weeks for initial treatment

Shampoo (Scalp Seborrhoeic Dermatitis/Dandruff):

Parameter Recommendation

Starting dose Apply 2% shampoo to wet scalp, leave for 3–5 minutes, rinse

Titration Not applicable

Usual maintenance dose Twice weekly for treatment; once weekly to fortnightly for prophylaxis

Maximum dose Twice weekly

Duration: 2–4 weeks for treatment; long-term prophylaxis as needed

1. Pityriasis Versicolor — Topical — Adults

Cream:

Parameter Recommendation

Starting dose Apply 2% cream to affected areas once daily

Titration Not applicable

Usual maintenance dose Once daily application

Maximum dose Twice daily

Duration: 2–3 weeks

Shampoo (for widespread disease):

Parameter Recommendation

Starting dose Apply 2% shampoo to affected body areas, leave for 5 minutes, rinse

Titration Not applicable

Usual maintenance dose Once daily for 5 days OR single application

Maximum dose Once daily for 5 days

1. Dermatophytoses (Tinea Corporis, Tinea Cruris, Tinea Pedis) — Topical — Adults

Parameter Recommendation

Starting dose Apply 2% cream to affected area once daily

Titration May increase to twice daily if response inadequate

Usual maintenance dose Once to twice daily

Maximum dose Twice daily application

Duration:

• Tinea corporis/cruris: 2–4 weeks

• Tinea pedis: 4–6 weeks

• Continue for 1–2 weeks after clinical clearance

1. Systemic Fungal Infections — Oral — Adults

(Restricted indication — use only when first-line agents unavailable, contraindicated, or failed)

Chronic Mucocutaneous Candidiasis:

Parameter Recommendation

Starting dose 200 mg orally once daily

Titration May increase to 400 mg once daily if no response after 1 week

Usual maintenance dose 200 mg once daily

Maximum dose 400 mg/day

Duration: Several months; guided by clinical response

Endemic Mycoses (Histoplasmosis, Blastomycosis, Paracoccidioidomycosis, Coccidioidomycosis):

Parameter Recommendation

Starting dose 200 mg orally once daily

Titration Increase to 400 mg once daily if no response after 1–2 weeks

Usual maintenance dose 200–400 mg once daily

Maximum dose 400 mg/day

Duration: 6–12 months depending on infection type and response

Clinical Notes:

• Oral ketoconazole is NOT first-line therapy due to hepatotoxicity — reserve for cases where itraconazole, fluconazole, or amphotericin B are unavailable, contraindicated, or failed

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Dermatophytoses and Seborrhoeic Dermatitis — Topical

≥6 months 2% Cream Apply once daily to affected area Safe for limited surface area

≥2 years 2% Shampoo Apply to affected area, leave 3–5 minutes, rinse — twice weekly For scalp seborrhoeic dermatitis

Duration: 2–4 weeks

Safety Monitoring:

• Monitor for local irritation

• Avoid application on large body surface areas

• No systemic monitoring required for topical use

1. Systemic Fungal Infections — Oral

(Restricted — only when safer alternatives unavailable)

Weight Dose Maximum Notes

15–30 kg 3.3–6.6 mg/kg once daily (typically 100 mg once daily) 200 mg/day Specialist supervision mandatory

30 kg 200 mg once daily 400 mg/day Adult dosing approach

Parameter Recommendation

Starting dose 3.3 mg/kg once daily (approximately 100 mg for 15–30 kg child)

Titration May increase to 6.6 mg/kg/day if no response

Usual maintenance dose 3.3–6.6 mg/kg once daily

Maximum dose 400 mg/day

Clinical Notes:

• Reserved for cases where itraconazole or fluconazole not suitable

• Baseline and weekly LFT monitoring mandatory

• Administer with food

Secondary Indications — Paediatric (Off-label)

Indication Dose Notes

Cushing's Syndrome 5–10 mg/kg/day in divided doses; titrate based on cortisol OFF-LABEL • Paediatric endocrinologist supervision mandatory • Very limited paediatric data

Age Restrictions:

• Topical: Not recommended below 6 months except under specialist dermatology supervision

• Oral: Not recommended below 2 years except under specialist supervision for life-threatening infections

• Oral use requires extreme caution due to hepatotoxicity — paediatric infectious diseases consultation recommended

Notes:

• Ketoconazole is primarily hepatically metabolised

• Not significantly removed by haemodialysis

• Topical formulations have negligible systemic absorption

Notes:

• Topical formulations may be used in hepatic impairment with caution (minimal systemic absorption)

• Oral ketoconazole has caused fatal hepatotoxicity — avoid in any significant liver disease

Oral Formulation:

• Known hypersensitivity to ketoconazole or other azole antifungals

• Acute or chronic liver disease (including elevated baseline transaminases)

• Co-administration with QT-prolonging drugs metabolised by CYP3A4:

• Cisapride, pimozide, quinidine, dofetilide, dronedarone

• Terfenadine, astemizole (if available)

• Co-administration with HMG-CoA reductase inhibitors metabolised by CYP3A4 (simvastatin, lovastatin)

• Co-administration with ergot alkaloids

• Co-administration with triazolam, oral midazolam

• Fungal meningitis (poor CNS penetration)

Topical Formulation:

• Known hypersensitivity to ketoconazole or formulation components

• History of hepatic disease — even if currently normal LFTs; strict monitoring if oral use essential

• Adrenal insufficiency risk with high-dose oral therapy (especially in Cushing's treatment)

• Concurrent proton pump inhibitors, H2 blockers, or antacids — reduce oral ketoconazole absorption

• Alcohol use — risk of disulfiram-like reaction; advise abstinence

• QT prolongation risk factors — obtain baseline ECG before oral therapy if concurrent medications

• Achlorhydria — reduced oral absorption

• Prolonged oral therapy (>2 weeks) — requires enhanced LFT monitoring

• Application to broken skin or mucous membranes (topical) — increased absorption risk

Route Safety Notes

Oral Contraindicated Teratogenic in animal studies; associated with skeletal abnormalities; avoid throughout pregnancy

Topical Use with caution Minimal systemic absorption; may use for limited duration on limited surface area if benefit outweighs risk

Parameter Information

Preferred Alternatives Topical: Clotrimazole, miconazole (better pregnancy data); Systemic: Amphotericin B if essential

When May Be Used Topical only for localised dermatophytoses when alternatives unsuitable

Monitoring Standard antenatal care if topical use; avoid oral use entirely

Route Safety Notes

Oral Avoid Excreted in breast milk; potential for infant hepatotoxicity

Topical Compatible with caution Avoid application to breast/nipple area

Parameter Information

Compatibility Topical: compatible; Oral: avoid

Expected Milk Levels Oral: moderate; Topical: negligible

Preferred Alternatives Topical clotrimazole or miconazole

Infant Monitoring If oral use unavoidable: monitor infant for jaundice, feeding difficulties

Parameter Recommendation

Starting dose Oral: 200 mg once daily (do not exceed); Topical: standard adult dosing

Titration Avoid dose escalation if possible

Special considerations Higher risk of hepatotoxicity; more likely to have concurrent hepatic impairment or polypharmacy

Extra monitoring Baseline and weekly LFTs for oral therapy; assess for drug interactions

Risk factors Multiple drug interactions due to CYP3A4 inhibition; age-related decline in hepatic function

Interacting Drug Effect & Mechanism Management

Cisapride, Pimozide, Quinidine, Dofetilide Increased QT prolongation → Torsades de pointes (CYP3A4 inhibition) CONTRAINDICATED

Simvastatin, Lovastatin Marked increase in statin levels → Rhabdomyolysis (CYP3A4 inhibition) CONTRAINDICATED — use pravastatin or rosuvastatin if statin needed

Triazolam, Oral Midazolam Profound sedation, respiratory depression (CYP3A4 inhibition) CONTRAINDICATED

Ergot alkaloids (ergotamine, dihydroergotamine) Ergotism — severe vasospasm (CYP3A4 inhibition) CONTRAINDICATED

Tacrolimus, Cyclosporine Markedly increased immunosuppressant levels → Nephrotoxicity (CYP3A4 inhibition) Monitor levels closely; reduce immunosuppressant dose by 50–75%

Warfarin Enhanced anticoagulation → Bleeding (CYP3A4/2C9 inhibition) Monitor INR frequently; reduce warfarin dose

Proton Pump Inhibitors (omeprazole, pantoprazole) Reduced ketoconazole absorption (requires gastric acidity) Administer ketoconazole 2 hours before PPI or with acidic beverage

Interacting Drug Effect Management

H2 blockers (ranitidine, famotidine), Antacids Reduced ketoconazole absorption Separate administration by 2 hours; give ketoconazole with cola or acidic drink

Rifampicin Markedly reduced ketoconazole levels (enzyme induction) Avoid combination; consider alternative antifungal

Phenytoin, Carbamazepine, Phenobarbital Reduced ketoconazole levels; also ketoconazole may increase anticonvulsant levels Monitor anticonvulsant levels; consider alternative antifungal

Isoniazid Reduced ketoconazole levels; potential additive hepatotoxicity Monitor LFTs closely; consider alternative antifungal

Alcohol Disulfiram-like reaction (flushing, nausea, headache) Advise abstinence from alcohol during oral therapy

Calcium channel blockers (amlodipine, nifedipine) Increased CCB levels Monitor blood pressure; consider dose reduction

Corticosteroids (prednisolone, methylprednisolone) Increased steroid levels Monitor for steroid side effects

Sildenafil, Tadalafil Increased PDE5 inhibitor levels Reduce sildenafil to 25 mg; tadalafil to 10 mg

Oral Use:

• Nausea, vomiting

• Abdominal pain

• Elevated hepatic transaminases (dose-related)

• Headache

• Dizziness

• Pruritus

• Gynecomastia, breast tenderness (with prolonged use)

• Menstrual irregularities

Topical Use:

• Local irritation, burning, stinging

• Pruritus

• Contact dermatitis

• Dryness (shampoo — hair/scalp)

• Oiliness or dryness changes in hair texture (shampoo)

Adverse Effect Clinical Action

Hepatotoxicity (elevated transaminases, cholestatic hepatitis, acute liver failure) Immediate discontinuation; hepatology referral; can be fatal — reported even with short courses

Adrenal insufficiency (high-dose oral therapy) Discontinue or reduce dose; cortisol replacement; endocrinology consultation

QT prolongation / Torsades de pointes Discontinue immediately; cardiology referral; avoid in combination with other QT-prolonging drugs

Anaphylaxis / Severe hypersensitivity Immediate discontinuation; emergency management

Gynaecomastia (prolonged oral use) Reversible on discontinuation; consider alternative antifungal

Note: Hepatotoxicity has occurred even with short-term oral use — strict LFT monitoring mandatory.

Oral Use:

After initiation LFTs weekly for first month

During maintenance LFTs every 2–4 weeks for duration of therapy

Clinical monitoring Symptoms of hepatotoxicity (nausea, fatigue, anorexia, jaundice, dark urine); adrenal insufficiency symptoms (fatigue, hypotension)

Discontinuation threshold Stop if ALT >3× ULN or any symptoms of hepatotoxicity

Topical Use:

• No routine laboratory monitoring required

• Clinical monitoring for local irritation or allergic reaction

Oral:

• Nizral (Johnson & Johnson)

• Ketoconazole (Generic — multiple manufacturers)

• Fungoral (Cadila)

• Ketovate (Intas)

Topical:

• Nizral Cream/Shampoo (Johnson & Johnson)

• Keto (Torrent)

• Extop (Glenmark)

• Keraglo AD Shampoo (IPCA)

• Scalpe (Glenmark)

• Arcolane Shampoo (Systopic)

• Ketomac (Zee Labs)

• Dandrazol (Lupin)

Note: Multiple generic and branded topical formulations available; oral tablets less commonly stocked due to restricted use.

Note: Ketoconazole 2% topical formulations included in NLEM 2022 — may be NPPA price-controlled. Oral tablets not in NLEM due to safety concerns.

• Oral ketoconazole is no longer first-line for systemic fungal infections — reserve for cases where itraconazole, fluconazole, or amphotericin B are unavailable, contraindicated, or have failed; hepatotoxicity risk is significant

• Gastric acidity is essential for oral absorption — avoid PPIs/antacids; if unavoidable, administer ketoconazole with acidic beverage (cola, orange juice) at least 2 hours before acid suppressants

• LFT monitoring is mandatory for oral use — baseline and weekly for first month; discontinue immediately if ALT >3× ULN or any hepatotoxicity symptoms

• Topical ketoconazole remains first-line for seborrhoeic dermatitis and pityriasis versicolor — effective, safe, and minimal systemic absorption

• Major CYP3A4 inhibitor — oral ketoconazole has extensive drug interactions; review all concurrent medications carefully before prescribing

• For Cushing's syndrome, ketoconazole is one of the most effective medical therapies — but requires specialist supervision and intensive monitoring for hepatotoxicity and adrenal insufficiency

Ketoconazole; antifungal; azole; imidazole; topical antifungal; seborrhoeic dermatitis; pityriasis versicolor; hepatotoxic; CYP3A4 inhibitor; Cushing's syndrome; dermatophytosis; NLEM India (topical); pregnancy-contraindicated (oral)

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022

• API Textbook of Medicine, 11th Edition

• AIIMS Drug Formulary

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine, 21st Edition

• Endocrine Society of India Guidelines (Cushing's syndrome — off-label use)

• WHO Model List of Essential Medicines

• Manufacturer Product Inserts (Johnson & Johnson, Glenmark)