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.

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.

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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

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

Use Cautiously in:

Seizure disorders;
Renal impairment (dose ↓ required 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 ↓ serum valproate levels and ↑ risk of seizures.
↑risk of seizures with ganciclovir; avoid concurrent use.

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).

Availability ⬆ ⬇

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

Assessment ⬆ ⬇

Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Obtain a history before initiating therapy to determine previous use of and reactions to penicillins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify the physician immediately if these occur. Have epinephrine, an antihistamine, and resuscitative equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.

Implementation ⬆ ⬇

dexmedetomidine
dopamine
epinephrine
fentanyl
heparin
midazolam
norepinephrine
phenylephrine

Intermittent Infusion: Reconstitution: Reconstitute with 0.9% NaCl, D5W, D5/0.9% NaCl, D5/0.45% NaCl, or D5/0.225% NaCl.Diluent: Step 1: For diluents available in 100-mL prefilled infusion bags, proceed to step 2. Step 2: For diluents not available in 100-mL prefilled infusion bags, withdraw 100 mL of desired diluent and transfer it to an empty infusion bag, then proceed to step 2. Withdraw 20 mL (as two 10-mL aliquots) of diluent from appropriate infusion bag and constitute vial with one 10-mL aliquot of the diluent. Constituted suspension is for intravenous infusion only after dilution in an appropriate infusion solution. Step 3: After constitution, shake vial well and transfer suspension into remaining 80 mL of infusion bag. Step 4: Add second 10-mL aliquot of infusion diluent to vial and shake well to ensure complete transfer of vial contents; repeat transfer of resulting suspension to infusion solution before administering. Agitate the resulting mixture until clear. Solution is colorless to yellow; do not use solutions that are discolored or contain particulate matter. Stable for 2 hr at room temperature or 24 hr if refrigerated; do not freeze.
Rate: Infuse over 30 min.
Y-Site Incompatibility: propofol.

Patient/Family Teaching ⬆ ⬇

Explain purpose of medication to patient, that it is only for bacterial infections, and that skipping or missing doses can increase risk or resistance to medication.
Instruct patient to notify health care professional immediately if signs and symptoms of allergic reactions occur.
Advise patient to report the signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy. Consult health care professional before treating with antidiarrheals.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially valproate.
Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several wk after discontinuation of medication.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇