Schedule H

Intravenous (IV)

Form Strengths

Powder for injection (lyophilized) 500 mg, 1 g per vial

Pre-mixed IV infusion (limited availability) 500 mg/50 mL, 1 g/100 mL

Combination formulations:

• Meropenem + Sulbactam: Limited FDCs available (not widely standardised)

• Meropenem + Vaborbactam: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Complicated Intra-abdominal Infections

Parameter Details

Starting dose 1 g IV every 8 hours

Titration Not routinely required; may increase to 2 g q8h in severely ill patients

Usual maintenance dose 1 g IV every 8 hours

Maximum dose 6 g/day (2 g every 8 hours)

Duration 5–14 days depending on source control and clinical response

Clinical Notes:

• Infuse over 15–30 minutes (standard infusion)

• Extended infusion (3–4 hours) may be considered in critically ill patients — off-label but practised in Indian ICUs

• Source control (surgical/drainage) is essential alongside antibiotic therapy

1. Complicated Urinary Tract Infections (including Pyelonephritis)

Parameter Details

Starting dose 500 mg–1 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 1 g IV every 8 hours

Maximum dose 6 g/day

Duration 7–14 days

Clinical Notes:

• Reserve for resistant gram-negative organisms or treatment failure with other agents

• Step-down to oral therapy based on culture sensitivity when feasible

1. Hospital-Acquired Pneumonia (HAP) / Ventilator-Associated Pneumonia (VAP)

Parameter Details

Starting dose 1 g IV every 8 hours

Titration Increase to 2 g IV every 8 hours in critically ill or suspected resistant organisms

Usual maintenance dose 1–2 g IV every 8 hours

Maximum dose 6 g/day

Duration 7–14 days

Clinical Notes:

• Combination with aminoglycoside or fluoroquinolone may be considered initially for suspected Pseudomonas or MDR organisms

• De-escalate based on culture results

• Extended infusion strategy improves pharmacodynamic target attainment in severe infections

1. Bacterial Meningitis (Adults)

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours

Maximum dose 6 g/day

Duration 10–21 days depending on pathogen

Clinical Notes:

• High dose required for adequate CSF penetration

• Preferred carbapenem for CNS infections (imipenem has higher seizure risk)

• Monitor for neurotoxicity, especially in renal impairment

1. Febrile Neutropenia (Empiric Therapy)

Parameter Details

Starting dose 1 g IV every 8 hours

Titration Escalate to 2 g q8h if inadequate response or suspected resistant organism

Usual maintenance dose 1 g IV every 8 hours

Maximum dose 6 g/day

Duration Until afebrile for 48 hours and ANC recovery (typically 7–14 days)

Clinical Notes:

• Specialist (haematology/oncology) supervision recommended

• Consider combination therapy if fungal infection or resistant gram-positive suspected

• Reassess at 72 hours based on clinical response and microbiological data

Secondary Indications — Adults (Off-label, if any)

Indication Dose Duration Notes

Severe MDR Gram-negative Infections (ESBL, AmpC producers) — OFF-LABEL 2 g IV every 8 hours via extended infusion (3–4 hours) 10–14 days or as guided by clinical response Specialist only. Evidence: Indian ICU protocols; pharmacodynamic modelling supports extended infusion for organisms with elevated MICs.

CNS Shunt Infections (resistant to third-generation cephalosporins) — OFF-LABEL 2 g IV every 8 hours 10–21 days Specialist only (Neurosurgery/Infectious Diseases). Evidence: Case series and Indian tertiary centre practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Severe Bacterial Infections (Intra-abdominal, UTI, Sepsis)

Neonates:

Age/Weight Dose Frequency Maximum Dose

≤7 days AND ≤2 kg 20 mg/kg IV Every 12 hours 40 mg/kg/day

≤7 days AND >2 kg 20 mg/kg IV Every 12 hours 40 mg/kg/day

8–28 days AND ≤2 kg 20 mg/kg IV Every 12 hours 40 mg/kg/day

8–28 days AND >2 kg 20 mg/kg IV Every 8 hours 60 mg/kg/day

Infants and Children (≥3 months to 12 years):

Indication Dose Frequency Maximum Dose

Standard infections 20 mg/kg IV Every 8 hours 1 g per dose (3 g/day)

Severe infections / HAP / VAP 40 mg/kg IV Every 8 hours 2 g per dose (6 g/day)

1. Bacterial Meningitis

Age ≥3 months:

Parameter Details

Starting dose 40 mg/kg IV every 8 hours

Titration Not applicable

Usual maintenance dose 40 mg/kg IV every 8 hours

Maximum dose 2 g per dose (6 g/day)

Duration 10–21 days depending on pathogen

Clinical Notes:

• Infuse over 15–30 minutes

• High dose essential for adequate CSF penetration

• Monitor for seizures, especially in neonates and those with renal impairment

Secondary Indications — Paediatrics (Off-label, if any)

Indication Age Dose Duration Notes

Febrile Neutropenia (Empiric) — OFF-LABEL ≥3 months 20–40 mg/kg IV every 8 hours (max 2 g/dose) Until afebrile + ANC recovery Specialist only (Paediatric oncology). Evidence: Indian paediatric oncology protocols.

Ventilator-Associated Pneumonia — OFF-LABEL ≥3 months 40 mg/kg IV every 8 hours (max 2 g/dose) 7–14 days Specialist only. Evidence: PICU protocols at tertiary Indian centres.

Age Restriction:

Not recommended in infants below 3 months of age except under paediatric infectious diseases or neonatology specialist supervision. Neonatal dosing requires careful assessment of gestational age, postnatal age, and renal function.

Safety Monitoring (All Paediatric Patients):

• Baseline and periodic renal function assessment

• Monitor for seizures (especially at high doses or in CNS infections)

• Observe for hypersensitivity reactions and GI disturbances

• Infuse over 15–30 minutes minimum

50 No adjustment required

26–50 1 g every 12 hours (or 500 mg q8h for moderate infections)

10–25 500 mg every 12 hours

<10 500 mg every 24 hours

Dialysis Modality Recommendation

Intermittent Haemodialysis (IHD) 500 mg after each dialysis session

Continuous Renal Replacement Therapy (CRRT) 1 g every 12 hours (individualise based on effluent flow rate)

Peritoneal Dialysis 500 mg every 24 hours

• Known hypersensitivity to meropenem or any other carbapenem antibiotic

• History of severe immediate-type (Type I) hypersensitivity reaction to any β-lactam antibiotic (penicillins, cephalosporins)

• Intrathecal or intraventricular administration (not approved — risk of severe neurotoxicity)

• History of seizures or CNS disorders — carbapenems may lower seizure threshold, particularly at high doses or in renal impairment

• Elderly patients with reduced renal reserve — increased risk of neurotoxicity

• Concurrent use with valproic acid — risk of subtherapeutic valproate levels leading to breakthrough seizures

• History of non-immediate β-lactam allergy — use with caution; cross-reactivity is low but monitor for hypersensitivity

• Prolonged use may lead to superinfection with resistant organisms or fungi

• Clostridioides difficile-associated diarrhoea risk with prolonged or broad-spectrum antibiotic use

Parameter Details

Overall safety Limited human data; animal studies have not shown teratogenic effects

Risk category Generally considered acceptable when clinically indicated (former FDA Category B equivalent)

Preferred alternatives Ceftriaxone (for non-Pseudomonal infections), Piperacillin-tazobactam (if susceptible organism) — when appropriate

When to use May be used when benefit clearly outweighs risk (e.g., life-threatening sepsis, meningitis, MDR gram-negative infections); specialist input advised

Monitoring Maternal renal function; complete blood count; fetal monitoring in severe sepsis

Parameter Details

Compatibility Compatible with breastfeeding

Milk levels Low — minimal excretion into breast milk

Preferred alternatives Ceftriaxone, amoxicillin (if organism susceptibility allows and clinical situation permits)

Infant monitoring Observe for diarrhoea, oral thrush (candidiasis), feeding difficulties (all rare)

Parameter Recommendation

Starting dose No change if renal function is normal

Titration Adjust dose based on renal function (eGFR); more frequent monitoring required

Special considerations Increased risk of CNS adverse effects (confusion, myoclonus, seizures). Regularly assess renal function. Elderly often have reduced renal reserve even with "normal" serum creatinine — use eGFR for dosing decisions.

Interacting Drug Mechanism / Effect Recommendation

Valproic Acid / Sodium Valproate Meropenem drastically reduces valproate serum levels (by 60–90%) within 24–48 hours via unknown mechanism Avoid combination — high risk of breakthrough seizures. If meropenem essential, switch to alternative antiepileptic (levetiracetam, phenytoin).

Probenecid Inhibits renal tubular secretion of meropenem, increasing plasma levels and half-life Avoid concurrent use; if unavoidable, consider dose reduction and enhanced monitoring

Ganciclovir / Valganciclovir Additive risk of CNS toxicity including seizures Avoid combination if possible; if essential, monitor closely for neurotoxicity

Live Oral Typhoid Vaccine (Ty21a) Antibiotics may reduce vaccine efficacy Avoid concurrent use; complete antibiotic course at least 3 days before administering live vaccine

Interacting Drug Effect Recommendation

Aminoglycosides (amikacin, gentamicin) Additive nephrotoxicity; synergistic antibacterial activity May be used together for serious infections but monitor renal function closely

Loop Diuretics (furosemide) Potential increased risk of nephrotoxicity Monitor renal function and hydration status

Warfarin Antibiotic-induced alteration of gut flora may affect vitamin K metabolism and alter INR Monitor INR when starting or stopping meropenem; adjust warfarin dose as needed

Cyclosporine Possible additive nephrotoxicity Monitor renal function and cyclosporine levels

• Diarrhoea

• Nausea, vomiting

• Headache

• Injection site reactions (phlebitis, pain, inflammation)

• Rash (maculopapular)

• Elevated hepatic transaminases (transient)

Adverse Effect Clinical Notes

Seizures Risk increased with high doses, renal impairment, CNS pathology. Reduce dose if renal dysfunction; consider alternative in seizure-prone patients.

Anaphylaxis / severe hypersensitivity Discontinue immediately; emergency management required

Clostridioides difficile-associated diarrhoea (CDAD) Suspect if severe or persistent diarrhoea; discontinue and treat appropriately

Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) Rare; immediate discontinuation and hospitalisation required

Haematological toxicity Neutropenia, thrombocytopenia, agranulocytosis (rare); monitor CBC in prolonged therapy

Hepatotoxicity Elevated LFTs, cholestatic jaundice (rare); monitor in prolonged courses

Baseline:

• Serum creatinine and eGFR

• Liver function tests (AST, ALT, bilirubin)

• Complete blood count

• Allergy history (β-lactam antibiotics)

During therapy:

• Renal function: Every 2–3 days in critically ill or elderly patients

• Neurological status: Monitor for confusion, myoclonus, or seizures — particularly if dose >2 g every 8 hours or in renal impairment

• Clinical response: Assess fever, inflammatory markers, source control

Prolonged therapy (>7 days):

• Weekly complete blood count

• Weekly liver function tests

• Monitor for signs of superinfection (candidiasis, resistant organisms)

• Reassess need for continued therapy and potential de-escalation

Brand Name Manufacturer

Meronem Pfizer

Merocrit Cipla

Merofast Aristo

Merotrol FDC Ltd

Merocide Alkem

Merowin Mankind

Merosure Lupin

Ronem Ranbaxy/Sun Pharma

Multiple generic formulations available from various Indian manufacturers.

Regulatory status: Meropenem is included in NLEM 2022. Available through Jan Aushadhi stores at subsidised rates. Private market prices vary by brand.

1. Antimicrobial stewardship essential — Reserve meropenem for confirmed or strongly suspected resistant gram-negative infections (ESBL, AmpC producers). Avoid empiric use for mild-to-moderate infections to prevent carbapenem resistance emergence.

1. Extended infusion improves outcomes — For critically ill patients or infections caused by organisms with elevated MICs, consider 3–4 hour extended infusion (off-label but widely practised in Indian ICUs) to optimise pharmacodynamic target attainment.

1. Preferred carbapenem for CNS infections — Meropenem has lower seizure potential compared to imipenem; use high-dose (2 g q8h) for meningitis to ensure adequate CSF penetration.

1. Valproate interaction is critical — Never use meropenem with valproic acid without switching antiepileptic. Valproate levels drop dramatically, leading to seizure breakthrough within 24–48 hours.

1. Renal dosing is crucial — Most meropenem toxicity (particularly neurotoxicity) occurs in patients with unrecognised or under-dosed renal impairment. Use eGFR-based dosing consistently.

1. Nephrotoxicity is minimal as monotherapy — Meropenem has low intrinsic nephrotoxicity, but risk increases significantly when combined with aminoglycosides or other nephrotoxins.

meropenem; carbapenem; beta-lactam; HAP; VAP; meningitis; ESBL; MDR gram-negative; renal-adjustment; ICU antibiotic; febrile neutropenia; antimicrobial stewardship; NLEM India

RxIndia v1.0 — 25 Apr 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• NLEM 2022

• API Textbook of Medicine, 11th Edition

• AIIMS Antimicrobial Policy 2023

• ICMR Antimicrobial Resistance Guidelines

• IAP Guidelines (Paediatric Infectious Diseases)

• MoHFW National Treatment Guidelines

• Harrison's Principles of Internal Medicine (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (pharmacology reference)

• Published pharmacodynamic studies on extended infusion protocols (supporting off-label infusion strategy)