imipenem/cilastatin/relebactam

REMS

Complicated urinary tract infections, including pyelonephritis (for patients with limited or no alternative treatment options).
Complicated intra-abdominal infections (for patients with limited or no alternative treatment options).
Hospital-acquired or ventilator-associated pneumonia.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity may occur with penicillins and cephalosporins).

Use Cautiously in:

Seizure disorders;
Renal impairment (↓ dose if CCr <90 mL/min);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be at ↑ risk for adverse reactions due to age-related renal impairment.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension

GI: ↑lipase, ↑liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, nausea, vomiting

Hemat: anemia

Local: phlebitis

Neuro: headache, SEIZURES

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

May ↓ valproate levels and ↑ risk of seizures.
↑risk of seizures with ganciclovir; avoid concurrent use.

Availability ⬆ ⬇

Powder for injection: imipenem 500 mg/cilastatin 500 mg/250 mg relebactam

Route/Dosage ⬆ ⬇

IV (Adults ): 1.25 g every 6 hr.

Renal Impairment

IV (Adults ): CCr 60–89 mL/min: 1 g every 6 hr; CCr 30–59 mL/min: 750 mg every 6 hr; CCr 15–29 mL/min: 500 mg every 6 hr; CCr <15 mL/min on hemodialysis: 500 mg every 6 hr (on dialysis days, administer doses after hemodialysis).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Imipenem binds to the bacterial cell wall, resulting in cell death. Cilastatin is a renal dehydropeptidase inhibitor that prevents renal inactivation of imipenem (does not have antibacterial properties). Relebactam inhibits beta-lactamase, which is an enzyme that can destroy beta-lactam antibiotics.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Spectrum is broad.
Active against many gram-negative aerobic bacteria:
- Acinetobacter calcoaceticus-baumannii complex,
- Citrobacter freundii,
- Enterobacter cloacae,
- Escherichia coli,
- Haemophilus influenzae,
- Klebsiella aerogenes,
- Klebsiella oxytoca,
- Klebsiella pneumoniae,
- Pseudomonas aeruginosa,
- Serratia marcescens.
Also active against the following gram-negative anaerobic bacteria:
- Bacteroides caccae,
- Bacteroides fragilis,
- Bacteroides ovatus,
- Bacteroides stercoris,
- Bacteroides thetaiotaomicron,
- Bacteroides uniformis,
- Bacteroides vulgatus,
- Fusobacterium nucleatum.

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives

Pharmacologic Classification: carbapenems, beta lactamase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Minimally metabolized. Primarily excreted unchanged by the kidneys (imipenem 63%, cilastatin 77%, relebactam >90%).

Half-Life: 1–1.2 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	6 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider for signs of superinfection (black, furry overgrowth on tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications, especially valproate.
Caution patient to notify health care provider if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care provider. May occur up to several weeks after discontinuation of medication.
Advise patient to notify health care provider for history of stroke, seizure, or valproic acid use prior to initiating therapy.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

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Indications ⬇