Imipenem

in PRIMAXIN

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Pronunciation: i-mi-PEN-em

Imipenem ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Imipenem ballicule

What it isCarbapenem given with cilastatin; severe and resistant infection.

Why this oneBroad cover including Pseudomonas and enterococci, with the widest spectrum of the carbapenems.

What limits itThe highest seizure risk of the carbapenems, so meropenem is preferred in meningitis. Cilastatin is required to block renal degradation.

Imipenem molecular structure (skeletal formula) — Molecular structure: Imipenem

FDA-approved for

serious infections (1985)

FDA label

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FDA dosing	Population	Start	Target	Max
Serious infections by susceptible bacteria: lower respiratory tract, UTI, intra-abdominal, gynecologic, bacterial septicemia, bone/joint, skin and skin structure, endocarditis	Adults, CLcr ≥90 mL/min	500 mg IV q6h OR 1 g IV q8h (imipenem component)	1 g IV q6h if pathogen of intermediate susceptibility	4 g/day
Same, non-CNS infections	Peds ≥3 months	15–25 mg/kg IV q6h	Per susceptibility	4 g/day
Same, non-CNS infections	Peds ≤3 months, ≥1,500 g	25 mg/kg IV: <1 wk q12h; 1–4 wk q8h; 4 wk–3 mo q6h	Per susceptibility	4 g/day

Renal CLcr <90 mL/min requires dose reduction (e.g. susceptible-pathogen regimen: CLcr 60–<90 → 400 mg q6h or 500 mg q6h; 30–<60 → 300 mg q6h or 500 mg q8h; 15–<30 → 200 mg q6h or 500 mg q12h; see label Table 3). CLcr <15: do not give unless hemodialysis is instituted within 48 h — dose after dialysis sessions. Seizure risk ↑ at CLcr ≤30. Peds <30 kg with renal impairment: not recommended (no data).

Hepatic Undefined

All doses expressed as the imipenem component; an equivalent amount of cilastatin is co-administered.

Instructions

For intravenous infusion only: doses ≤500 mg over 20–30 min; doses >500 mg over 40–60 min; slow the infusion if nausea develops.
Reconstitute vial and dilute in an appropriate infusion solution before administration.
Do not use diluents containing benzyl alcohol for neonates.
Not indicated in meningitis; not recommended in pediatric CNS infections (seizure risk).

Available strengths

inj 250/250, 500/500 mg

Cautions

Serious, occasionally fatal hypersensitivity (anaphylactic) reactions with beta-lactams; inquire about prior penicillin/cephalosporin/beta-lactam allergy; discontinue immediately if allergic reaction occurs.
Seizures and CNS adverse reactions (confusional states, myoclonus) — most common with CNS disorders (brain lesions, seizure history) and/or renal impairment or when doses exceeded; continue anticonvulsants in known seizure disorders; if focal tremors/myoclonus/seizures occur, evaluate neurologically, start anticonvulsants, decrease or discontinue.
Valproic acid/divalproex interaction — carbapenems reduce valproate levels below therapeutic range (breakthrough-seizure risk); concomitant use generally not recommended.
Clostridioides difficile–associated diarrhea, mild to fatal colitis — evaluate if diarrhea occurs.
Prescribing without proven/suspected bacterial infection risks drug-resistant bacteria.

Adverse reactions

Adults (≥0.2%): phlebitis, nausea, diarrhea, vomiting, rash, injection-site pain, fever, hypotension, seizures, injection-site erythema, dizziness, pruritus, vein induration, urticaria, somnolence.
Peds ≥3 months (>1%): diarrhea, rash, phlebitis, gastroenteritis, vomiting, IV-site irritation, urine discoloration.
Neonates to 3 months (>1%): convulsions, diarrhea, oliguria/anuria, oral candidiasis, rash, tachycardia.

Pregnancy Insufficient human data. Animal studies (mice, rats, rabbits, monkeys, 0.4–2.9× RHD) showed no drug-induced fetal malformations; embryonic loss increased in cynomolgus monkeys at doses similar to the RHD.

Lactation Insufficient data on presence in human milk, effects on the breastfed child, or milk production; weigh benefits of breastfeeding against clinical need and potential adverse effects.

Cost

Imipenem (IN PRIMAXIN)

Strength		#/mo	generic $/unit	CostPlus
250/250 mg	inj	per unit		not offered
500/500 mg	inj	per unit		not offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Imipenem is administered under clinical supervision and dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

NO BOXED WARNINGS

Principal riskThe highest seizure risk of the carbapenems

Classes and tags

Clinical profile

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Defining liabilitySeizures with excessive exposure, especially renal impairment

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