Clinical beta

FMBM is currently in clinical beta. Content is for professional review/testing and must not replace local protocols, senior clinical judgment, or official prescribing references.

Drug Monograph

Imipenem-Cilastatin

Imipenem–cilastatin

Carbapenem (IV) + renal dehydropeptidase inhibitor

CarbapenemICUΞ²-lactam

Indication

Severe polymicrobial infection β€’ ESBL (selected) β€’ intra-abd β€’ HAP (susceptible)

At a glance

INDICATIONS (CORE USE)

Broad carbapenem β€” **higher seizure risk** vs meropenem; **always with cilastatin**; valproate interaction.

ADULT DOSE (STANDARD)

500 mg–1 g IV q6h (imipenem component); dose by imipenem mg

MAX DOSE

~4 g/day imipenem (adult) β€” renal adjustment critical

Route

IV, IM

PEDIATRIC DOSE

Pediatric dosing per weight q6h β€” NICU caution

Do not miss

Must-not-miss safety points

Major warning

- Ξ²-lactam anaphylaxis - **Seizure threshold** β€” higher risk than meropenem; worse with renal failure if not adjusted - **Valproate β€” avoid** (same class interaction) - Not first-line meningitis choice in many guidelines (meropenem preferred)

Indications

USE IF: Severe infections when carbapenem indicated and meropenem unavailable or protocol specifies. AVOID IF: On valproate; CNS infection first-line where meropenem standard; unadjusted renal failure.

Primary

  • Severe intra-abdominal infection combinations
  • Hospital-acquired infections when carbapenem-susceptible

Secondary

  • ESBL therapy where institution uses imipenem-based pathways

Other

  • Polymicrobial necrotizing infections as part of broad regimen

Dosing

STANDARD (ADULT PO)

500 mg–1 g IV q6h (imipenem dose; renal adjust)

ADULT DOSE

500 mg IV q6h moderate; 1 g IV q6h severe (imipenem dose) β€” reduce CrCl <70–90 per label

PEDIATRIC DOSE

Strict pediatric references β€” seizure caution.

MAX DOSE

~4 g/day imipenem adult ceiling in references β€” follow label.

Practical Note

Cilastatin prevents renal metabolism of imipenem β€” fixed combination product.

Warnings

Clinical warnings

  • **Ξ²-lactam allergy β€” immediate** (anaphylaxis, angioedema, bronchospasm, hypotension) β†’ **avoid** this agent; use non–β-lactam alternative
  • **Ξ²-lactam allergy β€” non-severe** (maculopapular rash without systemic anaphylaxis features) β†’ **caution**; risk/benefit + allergy/ID pathway; graded challenge or test dose **only** per protocol β€” do not dismiss automatically
  • **Neurotoxicity:** encephalopathy, confusion, myoclonus, seizures β€” **higher risk with CKD, elderly, dose accumulation** (notably cefepime, carbapenems, high-dose penicillins)
  • New CNS symptoms + renal impairment on IV Ξ²-lactam β†’ **hold dose**, check levels/exposure, rule out other causes
  • C. diff
  • CNS toxicity
  • Myoclonus β†’ seizure progression

Adverse effects

  • nausea
  • rash
  • diarrhea
  • seizures

Contraindications

  • Hypersensitivity to imipenem or cilastatin

Drug interactions

  • Valproate
  • Ganciclovir β€” seizure synergy reported
  • Probenecid

Special populations

Pediatrics

Pediatric dosing per weight q6h β€” NICU caution

Pregnancy

Use if severe maternal infection

Lactation

limited data β€” risk-benefit.

Renal impairment

Aggressive dose/interval reduction; dialysis redosing schedules. **CrCl scaffold (FMBM β€” titrate to FDA/SFDA label + institutional pharmacy nomogram):** - **CrCl β‰₯50** β†’ standard interval (per Adult dosing card) - **CrCl 10–50** β†’ extend interval and/or reduce dose (often q12–24h or ↓ dose β€” **product-specific**) - **CrCl <10** β†’ maximal interval extension / dose reduction; **HD: redose post-dialysis** per protocol; AKI β†’ re-estimate CrCl; **neuro signs** β†’ hold/adjust

Hepatic impairment

Combined severe hepatic + renal β€” extra caution.

Elderly

Renal dosing; seizure precautions.

Administration

IV infusion; IM rarely.

Monitoring

  • Monitor: - ICU or CKD β†’ **creatinine daily** β†’ mandatory dose reduction; maladjustment β†’ **neurotoxicity** - **Valproate co-therapy** β†’ avoid overlap; if unavoidable β†’ VPA level + neurology (seizure breakthrough) - CRE / MDR context β†’ infection control + stewardship documentation - Neurologic checks in CKD / seizure threshold patients
  • Recheck: - No clinical improvement at 48–72h β†’ reassess diagnosis, resistance, source control, and drug interactions - If targets not met after reassessment of dose, organ function, and interactions β†’ escalate per protocol (DO NOT continue blindly)

Overdose / toxicity

Clinical Picture

**Life-threatening (first):** **CNS toxicity** β€” seizures, encephalopathy, agitation, myoclonus, coma (**↑ CKD, elderly, accumulation**; cefepime, carbapenems, high-dose penicillins). **Allergic:** anaphylaxis / angioedema (separate pathway). **Secondary:** nausea/vomiting/diarrhea mainly with acute massive **oral** co-ingestion or local infusion reaction.

Immediate Actions

Stop Ξ²-lactam β†’ ABCs β†’ **seizure precautions**; benzos if seizures; check renal function / dose vs CrCl; anaphylaxis β†’ epinephrine + ACLS

Antidote

No specific antidote; treat complications (e.g. anaphylaxis β†’ epinephrine per ACLS)

Decontamination

Stop infusion; recent large PO load β†’ charcoal if protected airway + early presentation

Escalation

Status epilepticus, coma, refractory seizures β†’ **ICU**; **severe CNS toxicity or AKI with accumulation β†’ consider hemodialysis** for dialyzable agents β€” nephrology + pharmacy; persistent anaphylaxis β†’ ICU

Clinical pearls

Common mistakes, resistance logic, and bedside traps

High-Yield Summary

Classic carbapenem β€” **more seizureogenic** than meropenem. **Cilastatin** is mandatory. **Valproate** clash.

Clinical pearls

Prefer meropenem when both stocked for CNS infection / seizure risk. Stewardship: narrow after cultures. *Stewardship (all antimicrobials):* Empiric choice β†’ syndrome severity + **local antibiogram**; shortest effective course.

Stewardship & safety

  • Seizure risk
  • Valproate
  • Renal dose

Pharmacokinetics

Renal elimination; CNS penetration less favored than meropenem for meningitis in many protocols.

Mechanism of action

Carbapenem Ξ²-lactam + cilastatin blocks renal dipeptidase inactivation.

Common brand names

Saudi Arabia

Tienam, Primaxin

Global

(placeholder β€” verify local formulary)

Common trade names are curated examples only β€” formulations and availability vary. Verify the exact product name with your local pharmacy and national regulator before prescribing or dispensing.

Country practice notes

  • Empiric choice β†’ tie to syndrome, severity, and local antibiogram β€” not habit.
  • IV β†’ PO step-down when oral bioavailability and susceptibility allow.
  • Do not use antibiotics for uncomplicated viral illness β€” stewardship.

References

Saudi Arabia

  • SFDA (Saudi Food & Drug Authority)
  • Saudi National Formulary / MOH (where available)

International

  • WHO Model List of Essential Medicines (verify current edition)
  • US FDA or EU EMA product information (when national SmPC is unavailable)
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling
  • Sanford Guide
  • IDSA / ESCMID (indication-specific)
  • Local antimicrobial stewardship / hospital formulary
  • FDA / SFDA / regional product labeling

Do not miss

  • Uncomplicated viral URI/bronchitis β†’ antibiotics rarely indicated
  • Narrow or stop when susceptibilities + clinical stability allow
  • Renal maladjustment β†’ myoclonus.
  • Meningitis: compare to meropenem guideline.
  • Seizure risk
  • Valproate
  • Renal dose