Schedule H

Intravenous (IV)

Powder for Injection (Lyophilised):

• Imipenem 250 mg + Cilastatin 250 mg per vial

• Imipenem 500 mg + Cilastatin 500 mg per vial

• Imipenem 1 g + Cilastatin 1 g per vial

Note: Cilastatin is always in 1:1 ratio with imipenem. Cilastatin inhibits renal dehydropeptidase-I, preventing nephrotoxic metabolite formation and ensuring adequate urinary imipenem levels.

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Complicated Intra-abdominal Infections

Including peritonitis, intra-abdominal abscess, appendicitis with perforation

Parameter Dosing Details (Imipenem component)

Starting dose 500 mg IV every 6 hours

Titration Increase to 1 g every 6 hours for severe/life-threatening infection

Usual maintenance dose 500 mg–1 g IV every 6–8 hours

Maximum dose 4 g/day (1 g every 6 hours)

Key Clinical Notes:

• Administer as IV infusion over 20–30 minutes (doses ≤500 mg) or 40–60 minutes (doses >500 mg)

• Excellent coverage for polymicrobial infections including anaerobes

• Duration typically 5–14 days depending on source control

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

Parameter Dosing Details

Starting dose 500 mg IV every 6 hours

Titration Increase to 1 g every 6 hours for severe infection or suspected resistant organisms

Usual maintenance dose 500 mg–1 g IV every 6 hours

Maximum dose 4 g/day

Key Clinical Notes:

• Consider combination with aminoglycoside or fluoroquinolone for suspected Pseudomonas aeruginosa

• Duration: 7–14 days; may extend based on clinical response

• De-escalate based on culture sensitivity

1. Complicated Urinary Tract Infections / Pyelonephritis

Parameter Dosing Details

Starting dose 250–500 mg IV every 6–8 hours

Titration Not typically required; increase to 500 mg every 6 hours if severe

Usual maintenance dose 250–500 mg IV every 6–8 hours

Maximum dose 2 g/day for uncomplicated; up to 4 g/day for complicated cases

Key Clinical Notes:

• Lower doses often sufficient due to excellent urinary concentration

• Duration: 7–14 days

• Step-down to oral therapy once clinically stable

1. Septicaemia / Bloodstream Infections

Parameter Dosing Details

Starting dose 1 g IV every 6–8 hours

Titration Not applicable

Usual maintenance dose 1 g IV every 6–8 hours

Maximum dose 4 g/day

Key Clinical Notes:

• First dose should not be delayed for cultures

• Reassess at 48–72 hours based on culture results

• Duration: 7–14 days; longer for endocarditis or deep-seated infections

1. Skin and Soft Tissue Infections (Complicated)

Including necrotising fasciitis, diabetic foot infections with systemic involvement

Parameter Dosing Details

Starting dose 500 mg IV every 6 hours

Titration Increase to 1 g every 6 hours for necrotising infections

Usual maintenance dose 500 mg–1 g IV every 6–8 hours

Maximum dose 4 g/day

Key Clinical Notes:

• Surgical debridement essential for necrotising infections

• May require combination with clindamycin (for toxin inhibition) in necrotising fasciitis

1. Gynaecological Infections

Including endometritis, pelvic abscess, post-operative pelvic infections

Parameter Dosing Details

Starting dose 500 mg IV every 6–8 hours

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Same indications as adults: complicated intra-abdominal infections, pneumonia, UTI, septicaemia, skin/soft tissue infections

⚠️ NOT routinely recommended below 3 months of age (limited safety data)

Weight-Based Dosing (≥3 months):

Age/Weight Dose (Imipenem component) Frequency Maximum Daily Dose

3 months – 3 years 25 mg/kg IV Every 6 hours 2 g/day

3 years and <40 kg 15–25 mg/kg IV Every 6 hours 2–4 g/day depending on severity

≥40 kg Adult dosing Every 6–8 hours 4 g/day

Dosing by Infection Severity:

Severity Dose Notes

Mild-Moderate infections 15 mg/kg IV every 6 hours UTI, uncomplicated soft tissue

Severe/Life-threatening 25 mg/kg IV every 6 hours Sepsis, severe pneumonia

Key Clinical Notes:

• Administer as IV infusion over 30–60 minutes (longer infusion reduces seizure risk)

• Doses expressed as imipenem component (cilastatin is 1:1)

• Monitor renal function; adjust dose in renal impairment

• Increased seizure risk in children with CNS disorders or renal impairment

Secondary Indications — Paediatric (Off-label)

Indication Dose Duration Notes

MDR Gram-negative Infections (VAP, Severe Sepsis) (OFF-LABEL) 25 mg/kg IV every 6 hours (max 1 g/dose) Per clinical response Specialist/Paediatric ID only. Based on AIIMS/PGI paediatric ICU protocols.

Clear Statement: NOT recommended below 3 months of age except under paediatric infectious disease specialist supervision with careful risk-benefit assessment.

Safety Monitoring in Children:

• Renal function (creatinine) at baseline and every 48–72 hours

• Seizure vigilance — especially with renal impairment or CNS pathology

• CBC if therapy >7 days

• Infusion site for phlebitis

Critical: Dose adjustment essential to prevent accumulation and neurotoxicity (seizures).

≥90 500 mg–1 g Every 6 hours Standard dosing

60–89 500 mg Every 6–8 hours Reduce frequency

30–59 500 mg Every 8–12 hours Maximum 1.5 g/day

15–29 250–500 mg Every 12 hours Maximum 1 g/day

<15 (not on dialysis) 250 mg Every 12–24 hours Maximum 500 mg/day

Haemodialysis 250–500 mg Post-dialysis; or every 12 hours on non-dialysis days Drug is dialysable (~70% removed)

CRRT (CVVH/CVVHDF) 250–500 mg Every 6–8 hours Adjust based on effluent rate; consult ID/pharmacy

Note: Seizure risk increases significantly with dose accumulation in renal impairment. Monitor closely.

• Known hypersensitivity to imipenem, cilastatin, or any carbapenem

• Severe hypersensitivity (anaphylaxis) to any beta-lactam antibiotic (penicillins, cephalosporins) — relative contraindication; use with extreme caution if no alternative

• Intrathecal or intraventricular administration (NOT approved; severe neurotoxicity)

• Concurrent use with valproic acid/divalproex (significant interaction — see Drug Interactions)

• History of seizures or CNS disorders (epilepsy, brain lesions, head trauma, stroke) — increased seizure risk

• Renal impairment — dose reduction mandatory; seizure risk increases with accumulation

• History of penicillin or cephalosporin allergy — cross-reactivity risk (~1–3%); assess prior reaction severity

• History of gastrointestinal disease, especially colitis — risk of Clostridioides difficile infection

• Elderly patients — reduced renal function common; increased seizure susceptibility

• Prolonged therapy — risk of superinfection with resistant organisms or fungi

• Rapid IV infusion — may precipitate nausea, vomiting, or hypotension

Parameter Details

Risk Category Limited human data; animal studies show no teratogenicity. Use only if clearly indicated.

Preferred alternatives Meropenem preferred if carbapenem required (more data in pregnancy, lower seizure risk)

When may be used Life-threatening infections where benefit clearly outweighs risk; specialist input recommended

Monitoring Fetal wellbeing; maternal renal function; seizure vigilance

Parameter Details

Compatibility Probably compatible; low levels expected in breast milk

Preferred alternatives Meropenem if long-term carbapenem therapy required

Drug levels in milk Low (minimal systemic absorption expected in infant)

Infant monitoring Monitor for diarrhoea, oral thrush, rash; theoretical disruption of gut flora

Parameter Recommendation

Starting dose Start at lower end of dosing range (e.g., 250–500 mg every 6–8 hours)

Titration Careful titration based on renal function; avoid maximum doses unless essential

Special risks Reduced renal reserve (serum creatinine may not reflect true GFR); increased seizure susceptibility; higher risk of C. difficile colitis; confusion/encephalopathy with dose accumulation

Monitoring Baseline and regular creatinine/eGFR; daily assessment for neurotoxicity; stool monitoring for diarrhoea

Interacting Drug Mechanism & Effect Management

Valproic acid / Divalproex Imipenem significantly reduces valproate serum concentrations (by 60–100%) → breakthrough seizures AVOID combination. Use alternative antibiotic or alternative antiepileptic (levetiracetam, phenytoin). If unavoidable, monitor valproate levels closely and increase valproate dose.

Ganciclovir / Valganciclovir Additive CNS toxicity; both drugs lower seizure threshold Avoid concurrent use if possible. If essential, ensure adequate renal dose adjustment for both; monitor closely for seizures.

Probenecid Inhibits tubular secretion of cilastatin; increases imipenem half-life Avoid combination; may increase toxicity.

Interacting Drug Effect Management

Cyclosporine Possible additive nephrotoxicity; both drugs have CNS effects Monitor renal function and cyclosporine levels; watch for neurotoxicity

Aminoglycosides (concurrent) Potential additive nephrotoxicity Monitor renal function daily; avoid prolonged combination if possible

Warfarin / Acenocoumarol Rare potentiation of anticoagulant effect (mechanism unclear) Monitor INR closely; adjust anticoagulant if needed

Live vaccines (BCG, typhoid oral) Antibiotics may reduce vaccine efficacy Avoid live vaccines during treatment

Other beta-lactams Potential antagonism; confounds culture interpretation Avoid concurrent use unless specifically indicated

• Nausea, vomiting (especially with rapid infusion)

• Diarrhoea

• Injection site reactions (phlebitis, pain, erythema)

• Rash (maculopapular)

• Elevated hepatic transaminases (AST/ALT — usually transient)

• Headache

• Eosinophilia

Adverse Effect Clinical Notes

Seizures Dose-related; risk factors: renal impairment, CNS disease, high doses, rapid infusion. Discontinue immediately if seizures occur; initiate anticonvulsant therapy; consider switch to meropenem.

Anaphylaxis / Severe Hypersensitivity Cross-reactivity with beta-lactams. Discontinue immediately; emergency management with adrenaline.

Clostridioides difficile Colitis Can occur during or weeks after therapy. Discontinue if severe diarrhoea develops; confirm with stool testing; treat appropriately.

Stevens-Johnson Syndrome / TEN Rare; requires immediate discontinuation and dermatology consultation

Blood Dyscrasias Thrombocytopenia, leukopenia, agranulocytosis (rare); monitor CBC in prolonged therapy

Encephalopathy / Myoclonus Especially in renal impairment with dose accumulation; discontinue and allow drug clearance

Acute Renal Failure Rare; interstitial nephritis reported

During treatment (ICU/severe infections) Renal function daily or every 48 hours; daily clinical assessment for seizures, encephalopathy; monitor for diarrhoea

Prolonged therapy (>7 days) CBC, LFTs, renal function twice weekly; assess for superinfection (oral thrush, new fever)

Culture-directed monitoring Review cultures at 48–72 hours for de-escalation opportunity

Originator:

• Tienam® (MSD)

Generic/Other Brands:

• Imicin® (Cipla)

• Cilanem® (Sun Pharma)

• Lastinem® (Lupin)

• Ipenem® (Alkem)

• Zynim® (Zydus)

• Cilaspan® (Glenmark)

• Iminem® (Abbott)

• Clapenam® (Ranbaxy/Sun)

• Impel® (Intas)

Note: All available as lyophilised powder for reconstitution in vials.

Note: Imipenem + Cilastatin is NOT listed in NLEM 2022. Not under NPPA price ceiling. Prices vary significantly between brands. Government supply available at concessional rates in tertiary care hospitals.

1. Renal dosing is critical — overdose in renal impairment leads to seizures. Always calculate eGFR and adjust dose before initiating therapy. When in doubt, start with lower dose.

1. Avoid in CNS infections — imipenem has higher seizure propensity than meropenem. For bacterial meningitis or brain abscess requiring carbapenem, meropenem is preferred.

1. Valproate interaction is clinically significant — imipenem dramatically reduces valproate levels, risking breakthrough seizures. Switch to alternative antiepileptic or use meropenem instead.

1. No activity against key pathogens — imipenem does NOT cover MRSA, Enterococcus faecium (VRE), Stenotrophomonas maltophilia, or carbapenem-resistant Enterobacteriaceae (CRE). Do not rely on empiric carbapenem monotherapy for these.

1. Infusion rate matters — administer over 30–60 minutes. Rapid infusion increases nausea, vomiting, and potentially seizure risk.

1. Extended infusion for severe infections — in critically ill patients with suspected MDR organisms, extended infusion (3–4 hours) may optimise pharmacodynamics. Consult ID or clinical pharmacist.

1. Reconstituted stability — use within 4 hours at room temperature or 24 hours if refrigerated. Do not freeze reconstituted solution.

carbapenem; ICU-antibiotic; MDR-gram-negative; ESBL; sepsis; nosocomial-pneumonia; renal-dose-adjust; seizure-risk; Schedule-H; reserve-antibiotic; Imipenem + Cilastatin

RxIndia v1.0 — 06 Jun 2025

• CDSCO Drug Database

• Indian Pharmacopoeia 2022

• National Formulary of India (NFI) 2021

• API Textbook of Medicine (11th Edition)

• ICMR Treatment Guidelines for Antimicrobial Use in Common Syndromes (2019)

• ICMR-AMR Surveillance Guidelines

• AIIMS Antibiotic Policy (2023)

• PGI Chandigarh ICU Antibiotic Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th Edition)

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

• Product package inserts (Tienam®, Imicin®)