imipenem/cilastatin

REMS

Treatment of:
- Lower respiratory tract infections,
- Urinary tract infections,
- Abdominal infections,
- Gynecologic infections,
- Skin and skin structure infections,
- Bone and joint infections,
- Bacteremia,
- Endocarditis,
- Polymicrobic infections.

Action ⬆ ⬇

Imipenem binds to the bacterial cell wall, resulting in cell death.
Combination with cilastatin prevents renal inactivation of imipenem, resulting in high urinary concentrations.
Imipenem resists the actions of many enzymes that degrade most other penicillins and penicillin-like anti-infectives.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Spectrum is broad.
Active against most gram-positive aerobic cocci:
- Streptococcus pneumoniae,
- Group A beta-hemolytic streptococci,
- Enterococcus,
- Staphylococcus aureus.
Active against many gram-negative bacillary organisms:
- Escherichia coli,
- Klebsiella,
- Acinetobacter,
- Proteus,
- Serratia,
- Pseudomonas aeruginosa.
Also displays activity against:
- Salmonella,
- Shigella,
- Neisseria gonorrhoeae,
- Numerous anaerobes.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: 70% excreted unchanged by the kidneys.

Half-Life: 1 hr (↑ in renal impairment).

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	6–8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Cross-sensitivity may occur with penicillins and cephalosporins.

Use Cautiously in:

Previous history of multiple hypersensitivity reactions;
Seizure disorders;
Renal impairment (dose ↓ required if CCr ≤90 mL/min);
OB: Safety not established in pregnancy;
Lactation: Use during breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Children with CNS infections ( risk of seizures) or children 30 kg with renal impairment (safety and effectiveness not established);
Geri: Older adults may be at risk for adverse reactions due to age-related in renal function.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

Derm: rash, pruritus, sweating, urticaria

GI: diarrhea, nausea, vomiting, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD)

Hemat: eosinophilia

Local: phlebitis at IV site

Neuro: dizziness, SEIZURES, somnolence

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), superinfection

Interactions ⬆ ⬇

Drug-drug:

Do not admix with aminoglycosides; inactivation may occur.
Probenecid↓ renal excretion and ↑ levels.
↑risk of seizures with ganciclovir or cyclosporine; avoid concurrent use with ganciclovir.
May ↓ serum valproate levels and ↑ risk of seizures.

Route/Dosage ⬆ ⬇

IV (Adults ): If infection is suspected or proven to be due to a susceptible bacterial species: 500 mg every 6 hr or 1 g every 8 hr; If infection is suspected or proven to be due to bacterial species with intermediate susceptibility : 1 g every 6 hr.
IV (Children ≥3 mo): 15–25 mg/kg every 6 hr; higher doses have been used in older children with cystic fibrosis.
IV (Children 4 wk–3 mo): 25 mg/kg every 6 hr.
IV (Children 1–4 wk): 25 mg/kg every 8 hr.
IV (Children <1 wk): 25 mg/kg every 12 hr.

Renal Impairment

IV (Adults ):
If infection is suspected or proven to be due to a susceptible bacterial species:
CCr 60–89 mL/min: 400 mg every 6 hr or 500 mg every 6 hr; CCr 30–59 mL/min: 300 mg every 6 hr or 500 mg every 8 hr; CCr 15–29 mL/min: 200 mg every 6 hr or 500 mg every 12 hr; CCr <15 mL/min receiving hemodialysis: 200 mg every 6 hr or 500 mg every 12 hr;
If infection is suspected or proven to be due to bacterial species with intermediate susceptibility:
CCr 60–89 mL/min: 750 mg every 8 hr; CCr 30–59 mL/min: 500 mg every 6 hr; CCr 15–29 mL/min: 500 mg every 12 hr; CCr <15 mL/min receiving hemodialysis: 500 mg every 12 hr.

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout 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.

Lab Test Considerations:

BUN, AST, ALT, LDH, serum alkaline phosphatase, bilirubin, and creatinine may be transiently ↑.
- Hemoglobin and hematocrit concentrations may be ↓.
- May cause positive direct Coombs’ test.

Implementation ⬆ ⬇

IV Administration:

Intermittent Infusion: Reconstitute each 250- or 500-mg vial with 10 mL of D5W, D5/0.9% NaCl, 0.9% NaCl, or D5/0.45% NaCl and shake well. Diluent: Further dilute in 100 mL of D5W or 0.9% NaCl. Solution may range from clear to yellow in color. Infusion is stable for 4 hr at room temperature and 24 hr if refrigerated.Concentration: 2.5 mg/mL (with 250-mg vial); 5 mg/mL (with 500-mg vial).
Rate: Infuse doses ≤500 mg over 20–30 min. Infuse doses ≥750 mg over 40–60 min. Pedi: Infuse doses 500 mg over 15–30 min. Infuse doses >500 mg over 40–60 min.
- Rapid infusion may cause nausea and vomiting. If these symptoms develop, slow infusion.

Patient/Family Teaching ⬆ ⬇

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.
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 ⬆ ⬇