Schedule H

Oral, Intravenous

Formulation Salt Form Strength

Granules for oral solution (sachet) Fosfomycin trometamol 3 g per sachet

Injection (vial) Fosfomycin disodium 1 g, 2 g, 4 g vials

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Acute Uncomplicated Cystitis in Women (Oral)

Single-dose therapy for lower urinary tract infection in non-pregnant adult women.

Parameter Recommendation

Starting dose 3 g orally as a single dose

Titration Not applicable (single-dose regimen)

Usual maintenance dose Not applicable

Maximum dose 3 g single dose; may repeat once after 48–72 hours if symptoms persist

Clinical Notes:

• Dissolve sachet contents in half glass of water; take on empty stomach (2–3 hours before or after meals)

• Preferably administer at bedtime after emptying bladder

• Not suitable for complicated UTI, pyelonephritis, or prostatitis when given orally

• Obtain urine culture before treatment in recurrent cases

1. Complicated Urinary Tract Infections / Pyelonephritis (IV)

Hospital-based therapy for complicated or resistant urinary infections.

Parameter Recommendation

Starting dose 4 g IV every 8–12 hours

Titration Based on clinical response and susceptibility; may increase to q8h dosing

Usual maintenance dose 12–16 g/day IV in 2–3 divided doses

Maximum dose 16 g/day

Clinical Notes:

• Duration: 7–14 days depending on clinical response

• Administer each dose as slow IV infusion over 15–30 minutes

• Obtain cultures and sensitivities; adjust based on MIC

• Prefer combination therapy for MDR organisms

1. Multidrug-Resistant Gram-Negative Infections (IV)

For ESBL-producers, carbapenem-resistant Enterobacteriaceae (CRE), or MDR Pseudomonas (combination therapy mandatory).

Parameter Recommendation

Starting dose 4 g IV every 8 hours

Titration Adjust based on MIC and clinical/microbiological response

Usual maintenance dose 12–16 g/day IV in divided doses (q8h)

Maximum dose 16 g/day; higher doses under specialist guidance only

Clinical Notes:

• Never use as monotherapy — rapid resistance emergence when used alone

• Combine with aminoglycosides, colistin, carbapenems, or tigecycline based on susceptibility

• Duration determined by infection site and response (typically 10–21 days)

• Mandatory: culture-guided therapy with confirmed in-vitro susceptibility

Secondary Indications – Adults (Off-label)

Indication Dose Duration Notes

Osteomyelitis (MDR pathogens, ESBL-GNB) 8–12 g/day IV in 2–3 divided doses 4–6 weeks or longer OFF-LABEL; Specialist only; Always in combination; Evidence: European RCTs, Indian tertiary centre protocols

Nosocomial pneumonia (MDR-GNB) 8–12 g/day IV in 2–3 divided doses 10–21 days OFF-LABEL; Specialist only; Must combine with colistin, aminoglycoside, or carbapenem; Evidence: Observational cohorts, Indian ICU practice

Prosthetic joint infections (biofilm-forming organisms) 4 g IV every 8 hours 6 weeks (with surgery) OFF-LABEL; Orthopaedic/ID specialist; Combined with rifampicin or fluoroquinolone

PAEDIATRIC DOSING (Specialist Only)

⚠️ Oral fosfomycin: Safety in children below 12 years not established — avoid unless specialist indication.

⚠️ IV fosfomycin: Reserved for serious infections under paediatric infectious diseases supervision.

Primary Indications (Approved/Standard Use in India)

Complicated UTI / Pyelonephritis (IV) — Inpatient Setting

Weight/Age Dose Frequency Maximum

Infants <12 kg (approx. <2 years) 100 mg/kg/day Divided into 2–3 doses Single dose: 2 g; Daily: 4 g

Children ≥12 kg to <40 kg 100–200 mg/kg/day Divided every 8 hours 12 g/day

Children ≥40 kg / Adolescents Adult dosing Every 8–12 hours 16 g/day

Clinical Notes:

• Reserve for culture-confirmed resistant organisms or treatment failures

• Starting dose: 100 mg/kg/day; titrate upward for severe infections

• Duration: 7–14 days based on clinical response

• Infuse slowly to avoid hyperosmolarity-related effects

Safety Monitoring:

• Baseline and periodic: serum creatinine, electrolytes (Na⁺, K⁺)

• Monitor fluid balance (high sodium load)

• Renal function assessment every 48–72 hours during therapy

Secondary Indications – Paediatrics (Off-label)

Indication Dose Duration Notes

MDR Gram-negative sepsis 100–200 mg/kg/day IV divided q8h 7–14 days OFF-LABEL; Specialist only (paediatric ID/NICU); Combine with second active agent; Limited observational data from Indian tertiary NICUs

Age Restrictions:

• Neonates (<28 days): Not routinely recommended; use only under neonatologist/microbiologist guidance when no alternatives exist

• Oral fosfomycin: Not recommended below 12 years of age

Intravenous Fosfomycin

80 No adjustment required

50–80 Extend interval to every 12 hours

10–50 4 g every 24–48 hours; adjust based on severity and response

<10 (non-dialysis) 4 g every 48 hours; specialist guidance recommended

Haemodialysis 4 g after each dialysis session (thrice weekly); coordinate with nephrology

CAPD Limited data; 4 g every 48–72 hours with close monitoring

Oral Fosfomycin (Single-Dose Cystitis)

• Single 3 g dose: No adjustment required for mild-moderate renal impairment

• Severe impairment (eGFR <10): Avoid or use with caution; efficacy uncertain

• Known hypersensitivity to fosfomycin or any excipient

• Anuria (IV formulation)

• Severe renal failure (eGFR <10) without dialysis support (IV formulation)

• Monotherapy in systemic infections: Rapid resistance development — always use in combination for non-UTI indications

• High sodium content (IV): Each gram of fosfomycin disodium contains approximately 0.32 g sodium; exercise caution in:

• Congestive heart failure

• Uncontrolled hypertension

• Fluid-overload states

• Sodium-restricted patients

• Electrolyte disturbances: Risk of hypokalaemia and hypernatraemia with high-dose IV therapy

• Clostridioides difficile-associated diarrhoea: Monitor for antibiotic-associated colitis

• Renal impairment: Accumulation risk; dose adjustment mandatory

• Concurrent nephrotoxic agents: Increased risk of renal injury

Parameter Recommendation

Overall Safety Generally considered safe; one of the preferred agents for UTI in pregnancy

Oral (single-dose cystitis) Safe in all trimesters; commonly used for uncomplicated UTI

IV formulation Limited data in first trimester; use if benefit outweighs risk

Preferred Alternatives Nitrofurantoin (avoid near term), cephalexin, amoxicillin-clavulanate

Monitoring Maternal renal function; serum sodium if IV administered

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug Levels in Milk Low; minimal transfer observed

Preferred Alternatives None required; fosfomycin is acceptable

Infant Monitoring Observe for loose stools or feeding changes; generally well-tolerated

Parameter Recommendation

Starting Dose (Oral) 3 g single dose — no adjustment for cystitis if renal function normal

Starting Dose (IV) Start at lower end (4 g every 12 hours); titrate based on renal function

Titration Slower titration; assess renal function before dose escalation

Special Risks Higher susceptibility to fluid overload (sodium load), hypokalaemia, renal impairment

Monitoring Creatinine, electrolytes (Na⁺, K⁺), fluid balance; fall risk if electrolyte-depleted

Interacting Drug Effect/Mechanism Management

Metoclopramide Accelerates GI transit → reduces oral fosfomycin absorption significantly Avoid concurrent use; if essential, space by ≥2–3 hours

IV Aminoglycosides Additive nephrotoxicity Monitor renal function closely; avoid if possible or use with caution

IV Loop diuretics (furosemide) Potential additive nephrotoxicity; electrolyte depletion Monitor renal function and electrolytes; avoid high-dose combinations

Interacting Drug Effect Management

Calcium/Magnesium/Aluminium antacids Chelation reduces oral fosfomycin absorption Separate administration by at least 2 hours

Potassium-depleting agents (thiazides, corticosteroids) Additive hypokalaemia with high-dose IV fosfomycin Monitor potassium; supplement if needed

Vancomycin Possible synergistic nephrotoxicity Monitor renal function; combination generally safe with monitoring

Warfarin/Anticoagulants Hypokalaemia from IV fosfomycin may increase arrhythmia risk Monitor INR and potassium

• Diarrhoea (most common)

• Nausea and vomiting

• Headache

• Dizziness

• Abdominal discomfort

• Vulvovaginitis (oral)

• Injection site phlebitis (IV)

• Transient dysuria

• Hypokalaemia (IV, especially high doses)

Adverse Effect Clinical Action

Anaphylaxis/severe hypersensitivity Immediate discontinuation; standard anaphylaxis management

Clostridioides difficile-associated diarrhoea (CDAD) Stop fosfomycin; initiate oral vancomycin or fidaxomicin

Severe hypokalaemia with cardiac arrhythmias Discontinue or reduce dose; potassium replacement; cardiac monitoring

Seizures Usually in renal failure with drug accumulation; stop therapy; supportive care

Hypernatraemia / acute fluid overload Risk with IV in elderly/cardiac patients; dose reduction; diuretics if needed

During IV therapy (48–72 hours) Renal function, serum electrolytes, fluid balance assessment

Weekly (prolonged IV courses) Renal function panel, electrolytes, clinical response, repeat cultures if indicated

Oral single-dose No routine monitoring; follow-up culture if symptoms persist beyond 72 hours

MDR infections Mandatory: pre-treatment susceptibility testing; therapeutic drug monitoring where available

Oral (3 g sachet):

• MONUROL® (Zambon/Cipla)

• FOSFOMYCIN® (Various)

• MONURAL® (Generic)

Intravenous:

• FOSMICIN® (Meiji)

• FOSCICLIN® (Cipla)

• FOSFO-IV® (Generic)

• PHOSPHOMYCIN® (Various generics — 1 g, 2 g, 4 g)

Note: Fixed-dose combinations are not commonly available; monotherapy formulations preferred.

Regulatory Notes:

• Not included in NLEM 2022

• Not under NPPA price control

• Government supply limited; primarily available in private sector and tertiary care centres

1. Single-dose efficacy: Oral fosfomycin 3 g is among the most convenient treatments for uncomplicated cystitis — high cure rates with excellent compliance; ideal for young women and pregnant patients.

1. Never monotherapy for systemic infections: IV fosfomycin develops resistance rapidly when used alone; always combine with a second active agent (aminoglycoside, colistin, carbapenem, or tigecycline) for MDR infections.

1. Oral form limitations: Not effective for upper tract infections (pyelonephritis), prostatitis, or complicated UTI — reserve for simple cystitis only.

1. Sodium load awareness: IV preparations contain significant sodium (~0.32 g per gram of drug); calculate total sodium intake in cardiac, hypertensive, or fluid-overloaded patients.

1. Timing matters for oral dose: Administer on empty stomach, preferably at bedtime after voiding, to maximize urinary concentrations and contact time.

1. Culture before treatment: For recurrent or complicated infections, always obtain pre-treatment urine culture; local resistance patterns vary significantly across India.

fosfomycin; UTI; acute cystitis; MDR gram-negative; ESBL; CRE; single-dose antibiotic; phosphonic acid; pregnancy-safe; intravenous antibiotic; combination therapy

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Product Information (India)

• Indian Pharmacopoeia

• AIIMS Antimicrobial Stewardship Guidelines

• API Textbook of Medicine (UTI Chapter)

• NCDC: Hospital Infection Control Guidelines

• ICMR: Treatment Guidelines for Antimicrobial Use in Common Syndromes

• Indian Association of Clinical Microbiologists — MDR Pathogen Protocols

• International RCTs/meta-analyses (referenced for off-label indications only)