Schedule H

Intravenous (IV)

• Injection: 50 mg/vial (lyophilized powder for reconstitution)

• Injection: 100 mg/vial (lyophilized powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Candidemia and Invasive Candidiasis (including peritonitis, abscesses, and disseminated infection)

Component Details

Starting dose 100 mg IV once daily

Titration May increase to 150 mg IV once daily based on clinical severity and response

Usual maintenance dose 100–150 mg IV once daily

Maximum dose 200 mg/day (under specialist supervision)

Clinical Notes:

• Administer as IV infusion over at least 60 minutes

• Duration: Minimum 14 days after last positive blood culture and resolution of clinical signs/symptoms

• Preferred in neutropenic patients and critically ill due to fungicidal activity against Candida species

• No loading dose required

1. Oesophageal Candidiasis

Component Details

Starting dose 150 mg IV once daily

Titration Not applicable

Usual maintenance dose 150 mg IV once daily

Maximum dose 150 mg/day

Clinical Notes:

• Duration: 14–21 days depending on clinical response

• Reserve for patients who cannot tolerate oral therapy (fluconazole preferred if oral route feasible)

• Administer as IV infusion over at least 60 minutes

1. Prophylaxis of Candida Infections in Haematopoietic Stem Cell Transplant (HSCT) Recipients

Component Details

Starting dose 50 mg IV once daily

Titration Not applicable

Usual maintenance dose 50 mg IV once daily

Maximum dose 50 mg/day

Clinical Notes:

• Duration: Throughout neutropenic period or as per institutional protocol

• Specialist use only; reserved for high-risk patients

• Continue until neutrophil recovery or per transplant team guidance

Secondary Indications – Adults (Off-label)

Indication Dose Duration Notes

Invasive Aspergillosis (salvage therapy) — OFF-LABEL 150 mg IV once daily Several weeks; based on clinical response Specialist only; for patients refractory or intolerant to primary therapy (voriconazole/amphotericin B)

Evidence basis: International case series and salvage therapy data; used in select Indian tertiary care centres for refractory cases

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Minimum age: 2 months (neonates <2 months: specialist supervision only, limited data)

1. Invasive Candidiasis (Children ≥2 months to <18 years)

Weight/Age Category Dose Maximum

<40 kg 2 mg/kg IV once daily (may increase to 4 mg/kg in severe infection) 100 mg/day

≥40 kg 100 mg IV once daily (may increase to 150 mg) 150 mg/day

Component Details

Starting dose 2 mg/kg IV once daily

Titration May increase to 4 mg/kg once daily in severe or refractory cases

Usual maintenance dose 2–4 mg/kg IV once daily

Maximum dose 100 mg/day (or 150 mg/day in children ≥40 kg)

1. Oesophageal Candidiasis (Children ≥4 months to <18 years)

Component Details

Starting dose 3 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 3 mg/kg IV once daily

Maximum dose 150 mg/day

1. Prophylaxis in HSCT (Children ≥2 years to <18 years)

Component Details

Starting dose 1 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 1 mg/kg IV once daily

Maximum dose 50 mg/day

Safety Monitoring:

• Liver function tests at baseline and weekly during treatment

• Complete blood count weekly

• Monitor for infusion-related reactions

• Weight-based dose recalculation with significant weight changes

Secondary Indications – Paediatrics (Off-label)

Indication Dose Duration Notes

Invasive Aspergillosis (salvage therapy) — OFF-LABEL 4–5 mg/kg IV once daily Minimum 2–4 weeks; based on clinical response Specialist only; for refractory disease

Evidence basis: Off-label salvage use supported by international paediatric series; used in select Indian tertiary centres

Age restriction: Not recommended below 2 months of age except under specialist supervision in exceptional circumstances with no alternative options.

• No dose adjustment required in any degree of renal impairment

• Micafungin is not significantly renally excreted (<1% unchanged in urine)

• Not removed by haemodialysis or peritoneal dialysis — no supplemental dosing required

• Mild impairment (Child-Pugh A): No dose adjustment required

• Moderate impairment (Child-Pugh B): Use with caution; monitor liver function tests closely

• Severe impairment (Child-Pugh C): Limited data; use with caution under specialist supervision; monitor hepatic enzymes frequently

• Known hypersensitivity to micafungin or any other echinocandin (caspofungin, anidulafungin)

• Prior anaphylactic reaction to micafungin or formulation components

• Pre-existing hepatic dysfunction — increased risk of hepatotoxicity; monitor LFTs

• Haematological malignancy — higher incidence of elevated hepatic enzymes reported

• History of allergic disorders — hypersensitivity reactions including anaphylaxis possible

• Prolonged therapy (>3 weeks) — hepatocellular tumours observed in animal studies with long-term use; clinical significance uncertain but avoid unnecessarily prolonged courses

• Infusion-related reactions — administer slowly over ≥60 minutes

Aspect Details

Overall safety Limited human data; animal studies show fetal toxicity at high doses

Preferred alternatives Amphotericin B (lipid formulations) for life-threatening invasive fungal infections in pregnancy

When it may be used Only if potential benefit justifies risk and no safer alternative; specialist decision

Monitoring Maternal liver function tests; fetal growth and well-being

Aspect Details

Compatibility Unknown; not established in humans

Drug levels in milk Likely low (large peptide molecule with poor oral absorption)

Preferred alternatives Fluconazole for non-severe infections where oral therapy feasible

Infant monitoring Gastrointestinal disturbances, feeding difficulties, unusual symptoms

• Recommended starting dose: Same as younger adults (100 mg once daily for invasive candidiasis)

• Titration: No specific age-related titration; slower dose escalation may be appropriate in frail patients

• Extra risks:

• Monitor hepatic function closely (age-related decline in hepatic reserve)

• Assess for infusion-related reactions

• Watch for electrolyte disturbances (hypokalaemia)

• Consider comorbidities and polypharmacy

Interacting Drug Effect/Mechanism Recommendation

Sirolimus Increased sirolimus levels (CYP3A4 and P-gp inhibition) — risk of sirolimus toxicity Avoid combination or reduce sirolimus dose and monitor levels closely

Nifedipine Increased nifedipine exposure — risk of hypotension, oedema Monitor blood pressure; consider dose reduction of nifedipine

Itraconazole Increased itraconazole levels Monitor for itraconazole toxicity; check LFTs

Interacting Drug Effect/Mechanism Recommendation

Tacrolimus Slight increase in tacrolimus exposure Monitor tacrolimus trough levels and adjust dose as needed

Ciclosporin Minor increase in ciclosporin levels Monitor ciclosporin levels; routine adjustment usually not required

Amphotericin B No pharmacokinetic interaction but additive hepatotoxicity possible Monitor renal and hepatic function

Azole antifungals (fluconazole, voriconazole) Possible additive hepatotoxicity Monitor LFTs periodically

Warfarin Potential for altered INR Monitor INR during concurrent use

• Elevated transaminases (ALT, AST)

• Nausea and vomiting

• Hypokalaemia

• Headache

• Diarrhoea

• Rash

• Phlebitis at infusion site

• Infusion-related reactions (fever, chills, flushing)

• Anaphylaxis and severe hypersensitivity reactions — discontinue immediately; supportive management

• Severe hepatotoxicity — including hepatic failure; discontinue if significant elevation of liver enzymes with clinical symptoms

• Haemolytic anaemia — rare; requires discontinuation

• Thrombocytopenia — monitor platelet counts

• Stevens-Johnson Syndrome (SJS) — rare; requires immediate discontinuation

• Acute renal failure — rare

→ Serious adverse effects require immediate discontinuation and specialist consultation

Phase Parameters

Baseline Liver function tests (ALT, AST, bilirubin, ALP), serum creatinine, complete blood count with differential, serum potassium

During treatment LFTs at least weekly (more frequently if abnormal); serum potassium; signs of infusion reactions

Long-term (>2 weeks) Weekly LFTs; CBC; clinical assessment for hepatotoxicity

Paediatrics Weight-based dose verification; LFTs weekly; infusion monitoring

• Mycamine® (Astellas)

• Fungin® (Zydus Cadila)

• Micagard® (Mylan)

• Mica® (Hetero)

• Micaford® (Glenmark)

• NLEM status: Not included in NLEM 2022

• NPPA controlled: No

• Availability: Primarily at tertiary care centres, oncology hospitals, and transplant units; limited availability in smaller centres

• Preferred echinocandin in hepatic impairment compared to caspofungin — does not require dose adjustment for hepatic dysfunction

• Renal-safe antifungal — excellent choice when amphotericin B nephrotoxicity is a concern

• No loading dose required — simplifies dosing compared to some alternatives

• Administer over ≥60 minutes — rapid infusion increases risk of histamine-related reactions

• Weekly LFT monitoring essential — hepatotoxicity is the primary safety concern

• Cost consideration — significantly more expensive than fluconazole; reserve for invasive disease or azole-resistant Candida

Micafungin; antifungal; echinocandin; invasive candidiasis; oesophageal candidiasis; HSCT prophylaxis; candidemia; IV antifungal; renal-safe; hepatotoxicity-risk; specialist-use

RxIndia v1.1 — 18 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• API Textbook of Medicine (11th Edition) — Fungal Infections chapter

• AIIMS Antifungal Treatment Guidelines

• Harrison's Principles of Internal Medicine (21st Edition)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• ICMR Antimicrobial Resistance Surveillance and Research Network guidance (supportive)

• Indian tertiary hospital protocols (AIIMS, PGI Chandigarh) for invasive fungal infections