Schedule H

Oral, Intravenous

• Oral suspension: 40 mg/mL (105 mL bottle)

• Delayed-release tablets: 100 mg

• Intravenous solution: 300 mg per vial (lyophilised powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Prophylaxis of Invasive Aspergillus and Candida Infections in High-Risk Patients — Adults

(Haematological malignancy with prolonged neutropenia, HSCT recipients)

Delayed-Release Tablets or IV (Preferred):

Parameter Recommendation

Starting dose 300 mg twice daily on Day 1

Titration Not applicable

Usual maintenance dose 300 mg once daily from Day 2 onwards

Maximum dose 300 mg once daily

Oral Suspension (Alternative — less reliable absorption):

Parameter Recommendation

Starting dose 200 mg (5 mL) three times daily with food

Titration Not applicable

Usual maintenance dose 200 mg three times daily

Maximum dose 800 mg/day

Duration: Throughout the period of neutropenia or immunosuppression

Clinical Notes:

• Delayed-release tablets and IV formulation preferred over oral suspension due to superior bioavailability

• Oral suspension must be administered with full meal or nutritional supplement

• Consider therapeutic drug monitoring if compliance or absorption concerns exist

1. Oropharyngeal Candidiasis (Fluconazole-Refractory or Resistant) — Adults

Oral Suspension:

Parameter Recommendation

Starting dose 100 mg (2.5 mL) twice daily on Day 1

Titration Not applicable

Usual maintenance dose 100 mg once daily from Day 2

Maximum dose 400 mg/day in refractory cases

Duration: 7–14 days; may extend based on clinical response in severe/refractory cases

Clinical Notes:

• Administer each dose with full meal to maximise absorption

• Reserved for azole-resistant oropharyngeal candidiasis or fluconazole treatment failure

1. Invasive Fungal Infections (Mucormycosis, Invasive Aspergillosis) — Adults

(When other antifungals are unsuitable or as step-down/salvage therapy)

Delayed-Release Tablets or IV:

Parameter Recommendation

Starting dose 300 mg twice daily on Day 1 (loading)

Titration Not applicable

Usual maintenance dose 300 mg once daily from Day 2

Maximum dose 300 mg once daily (higher doses not established)

Duration: Minimum 6–12 weeks; guided by clinical, radiological, and mycological response and immune reconstitution

Clinical Notes:

• For mucormycosis: specialist input mandatory; posaconazole typically used as step-down after initial amphotericin B therapy

• Therapeutic drug monitoring strongly recommended — target trough >1 µg/mL (treatment) or >0.7 µg/mL (prophylaxis)

• IV-to-oral switch permissible once patient is clinically stable and tolerating oral intake

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Chronic Refractory Fusariosis 300 mg BD Day 1, then 300 mg OD Prolonged; guided by response OFF-LABEL • Specialist only • Indian tertiary centre practice; case series evidence

Scedosporiosis (salvage therapy) 300 mg BD Day 1, then 300 mg OD Prolonged course OFF-LABEL • Specialist only • Limited efficacy data

Coccidioidomycosis / Histoplasmosis (refractory) 300 mg BD Day 1, then 300 mg OD Long-term maintenance OFF-LABEL • Specialist only • International guidelines supportive

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Prophylaxis of Invasive Fungal Infections

Age ≥13 Years (Delayed-Release Tablets or IV):

Parameter Recommendation

Starting dose 300 mg twice daily on Day 1

Titration Not applicable

Usual maintenance dose 300 mg once daily from Day 2

Maximum dose 300 mg once daily

Age 2–12 Years (Oral Suspension Only):

Parameter Recommendation

Starting dose 4–6 mg/kg/dose three times daily with food

Titration Not applicable

Usual maintenance dose 4–6 mg/kg/dose three times daily

Maximum dose 200 mg per dose (600 mg/day)

1. Treatment of Invasive Fungal Infections (Salvage/Step-Down)

Age ≥13 Years:

• Use adult dosing (300 mg BD Day 1, then 300 mg OD)

Age 2–12 Years (Oral Suspension Only):

Parameter Recommendation

Starting dose 6–9 mg/kg/dose three times daily with full meal

Titration Not applicable

Usual maintenance dose 6–9 mg/kg/dose three times daily

Maximum dose 200 mg per dose

Duration: Guided by clinical and mycological response

Safety Monitoring:

• Baseline and periodic LFTs (weekly for first month)

• Electrolytes (potassium, magnesium)

• Therapeutic drug monitoring if available (target trough >0.7 µg/mL for prophylaxis; >1 µg/mL for treatment)

• ECG if concurrent QT-prolonging medications

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

Chronic Granulomatous Disease (CGD) — antifungal prophylaxis Prophylactic dosing as above Long-term OFF-LABEL • Specialist only • Paediatric immunology practice

Primary Immunodeficiency — invasive aspergillosis prophylaxis Prophylactic dosing as above During high-risk periods OFF-LABEL • Specialist only

Age Restrictions:

• Not recommended in children <2 years except under specialist paediatric infectious diseases/haematology supervision

• Delayed-release tablets and IV: limited paediatric data below 13 years — oral suspension preferred in younger children

Formulation CrCl ≥50 mL/min CrCl <50 mL/min

Oral (tablets and suspension) No adjustment required No adjustment required

Intravenous No adjustment required Avoid — cyclodextrin (SBECD) vehicle accumulates; switch to oral formulation

Dialysis: Posaconazole not significantly dialysable; no supplemental dosing required. Avoid IV formulation in dialysis-dependent patients.

• Known hypersensitivity to posaconazole or other azole antifungals

• Co-administration with:

• Ergot alkaloids (ergotamine, dihydroergotamine) — risk of ergotism

• Sirolimus — marked increase in sirolimus levels; contraindicated

• Pimozide, quinidine, halofantrine — risk of QT prolongation/torsades de pointes

• CYP3A4 substrates with narrow therapeutic index: terfenadine, astemizole, cisapride

• Atorvastatin >20 mg/day, simvastatin, lovastatin — risk of rhabdomyolysis

• IV formulation in CrCl <50 mL/min (due to cyclodextrin accumulation)

• Pre-existing hepatic disease — monitor LFTs closely; discontinue if significant elevation

• QT prolongation or concurrent use of QT-prolonging agents — baseline and periodic ECG recommended

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia) — correct before initiating therapy

• Variable absorption with oral suspension — ensure administration with high-fat meal; consider TDM

• Prolonged therapy — risk of breakthrough fungal infections; reassess if clinical deterioration

• Cardiac arrhythmias or structural heart disease

• Concurrent immunosuppressant therapy requiring dose adjustment

Parameter Information

Risk Category Presumed teratogenic (based on azole class data); inadequate human studies

Overall Safety Avoid during pregnancy unless life-threatening infection with no suitable alternative

Preferred Alternatives Liposomal amphotericin B

When May Be Used Only if potential benefit clearly justifies fetal risk; specialist decision with informed consent

Monitoring Fetal anomaly scan if exposure in first trimester; maternal hepatic function

Parameter Information

Compatibility Not recommended — insufficient human data

Expected Milk Levels Likely moderate-high (lipophilic compound with long half-life)

Preferred Alternatives Liposomal amphotericin B for systemic infections

Decision Avoid breastfeeding during therapy; if unavoidable, monitor infant

Infant Monitoring GI disturbance, feeding difficulties, weight gain

Parameter Recommendation

Starting dose Same as adult dosing; no age-based reduction required

Titration Not applicable

Special considerations Lower threshold for hepatic and renal function monitoring

Extra monitoring LFTs, electrolytes, ECG (higher prevalence of cardiac comorbidities)

Risk factors Polypharmacy increasing drug interaction risk; age-related hepatic decline

Interacting Drug Effect & Mechanism Management

Sirolimus Marked increase in sirolimus levels (CYP3A4 inhibition) CONTRAINDICATED

Tacrolimus 2–4 fold increase in tacrolimus levels Reduce tacrolimus dose by ~66%; monitor trough levels closely

Cyclosporine Increased cyclosporine levels ~1.4 fold Reduce cyclosporine dose by ~25%; monitor levels

Simvastatin, Lovastatin, Atorvastatin (high dose) Rhabdomyolysis risk (CYP3A4 inhibition) Avoid simvastatin/lovastatin; limit atorvastatin to ≤20 mg

Ergot alkaloids Risk of ergotism (vasoconstriction) CONTRAINDICATED

Pimozide, Quinidine QT prolongation; torsades de pointes risk CONTRAINDICATED

Midazolam, Triazolam (oral) Prolonged/excessive sedation Avoid or reduce benzodiazepine dose significantly

Vincristine, Vinblastine Increased vinca alkaloid toxicity (neurotoxicity) Monitor closely; consider dose reduction

Rifampicin Reduces posaconazole levels by ~75% Avoid combination

Phenytoin Bidirectional interaction; reduced posaconazole, increased phenytoin Avoid if possible; if essential, increase posaconazole and monitor phenytoin levels

Efavirenz Reduces posaconazole levels significantly Avoid combination if possible

Interacting Drug Effect Management

Carbamazepine Reduces posaconazole levels (CYP induction) Avoid if possible; consider alternative antiepileptic

Rifabutin Reduces posaconazole levels; increased rifabutin toxicity Avoid unless essential; monitor for uveitis

Proton pump inhibitors May reduce oral suspension absorption Use delayed-release tablets (unaffected); if using suspension, separate dosing

H2-receptor antagonists May reduce oral suspension absorption Prefer tablet formulation

Metoclopramide May reduce oral suspension absorption Consider timing adjustments

Digoxin Possible increased digoxin levels Monitor serum digoxin concentration

Sulfonylureas (glibenclamide) Hypoglycaemia risk Monitor blood glucose closely

Calcium channel blockers Increased CCB levels Monitor for hypotension, oedema; consider dose reduction

Warfarin May increase INR Monitor INR frequently

Fentanyl Increased fentanyl exposure Monitor for respiratory depression

• Nausea, vomiting

• Diarrhoea

• Headache

• Elevated hepatic transaminases

• Rash

• Hypokalaemia

• Abdominal pain

• Fatigue

• Fever

Adverse Effect Clinical Action

Hepatotoxicity (severe transaminase elevation, cholestatic hepatitis, fulminant hepatic failure) Discontinue immediately; hepatology consultation

QT prolongation / Torsades de pointes Discontinue; ECG monitoring; correct electrolytes; cardiology input

Anaphylaxis / Severe hypersensitivity Immediate discontinuation; supportive care

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Immediate discontinuation; dermatology/ICU referral

Haemolytic uraemic syndrome (rare) Discontinue; haematology and nephrology input

Adrenal insufficiency (with prolonged use) Consider cortisol assessment; endocrinology referral

After initiation LFTs weekly for first 4 weeks

During therapy Therapeutic drug monitoring (target trough: prophylaxis >0.7 µg/mL, treatment >1 µg/mL); electrolytes; immunosuppressant levels if applicable

Long-term Monthly LFTs; periodic ECG if QT risk; reassess for breakthrough infection

• Posoxil (Cipla)

• Posacad (Cadila/Zydus)

• Posatral (MSN Laboratories)

• Posantin (Natco)

• Noxafil (MSD) — originator brand

• Posanox (Dr. Reddy's)

• Posaone (Hetero)

FDCs: Not commonly available

Note: Included in NLEM 2022 for specific indications; check NPPA ceiling prices for capped formulations. Significant price variation between brands and procurement channels.

• Delayed-release tablets are now standard for neutropenic prophylaxis due to consistent bioavailability — avoid oral suspension if tablets or IV available

• Oral suspension has erratic absorption — must be administered with full high-fat meal; consider TDM to confirm adequate levels

• In renal impairment (CrCl <50 mL/min), IV formulation is contraindicated due to cyclodextrin accumulation — switch to oral

• Therapeutic drug monitoring is critical in invasive infections (especially mucormycosis) — target trough >1 µg/mL for treatment

• Suspect subtherapeutic levels early if breakthrough fungal infection occurs despite therapy — check compliance, food intake, and drug interactions

• When used with calcineurin inhibitors (tacrolimus, cyclosporine), anticipate 50–75% dose reduction and monitor levels within 3–5 days of initiation

Posaconazole; antifungal; triazole; mucormycosis; invasive aspergillosis; neutropenic prophylaxis; HSCT; haematology; hepatotoxicity; QT prolongation; TDM recommended; CYP3A4 inhibitor

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM India 2022

• AIIMS Antifungal Treatment Protocols

• API Textbook of Medicine, 11th Edition

• ICMR Guidelines for Management of Invasive Fungal Infections (Mycoses Guidelines 2022)

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Manufacturer Product Inserts (India-licensed)

• Indian tertiary care antifungal protocols