No

Antibiotic, Carbapenem

Treatment of respiratory tract, urinary tract, intra-abdominal, gynecologic, bone and joint, skin structure, and polymicrobic infections as well as bacterial septicemia and endocarditis. Antibacterial activity includes resistant gram-negative bacilli ( Pseudomonas aeruginosa and Enterobacter sp), gram-positive bacteria (methicillin-sensitive Staphylococcus aureus and Streptococcus sp) and anaerobes.

C

Hypersensitivity to imipenem/cilastatin or any component

Dosage adjustment required in patients with impaired renal function; safety and efficacy in children <12 years of age have not yet been established; prolonged use may result in superinfection; use with caution in patients with a history of seizures or hypersensitivity to beta-lactams; elderly patients often require lower doses

1% to 10%:

Gastrointestinal: Nausea/diarrhea/vomiting (1% to 2%)

Local: Phlebitis (3%)

<1%: Hypotension, palpitations, seizures, rash, pseudomembranous colitis, neutropenia (including agranulocytosis), eosinophilia, anemia, (+) Coombs' test, thrombocytopenia, increased PT, increased LFTs, pain at injection site, increased BUN/creatine, abnormal urinalysis, emergence of resistant strains of P. aeruginosa

Symptoms of overdose include neuromuscular hypersensitivity, seizures

Hemodialysis may be helpful to aid in the removal of the drug from the blood; otherwise most treatment is supportive or symptom directed

Increased toxicity: Beta-lactam antibiotics, probenecid may increase toxic potential

Imipenem/cilastatin powder for injection should be stored at <30°C

Reconstituted solutions are stable 10 hours at room temperature and 48 hours at refrigeration (4°C) with NS

If reconstituted with 5% or 10% dextrose injection, 5% dextrose and sodium bicarbonate, 5% dextrose and 0.9% sodium chloride, is stable for 4 hours at room temperature and 24 hours when refrigerated

Imipenem/cilastatin is most stable at a pH of 6.5-7.5; imipenem is inactivated at acidic or alkaline pH

Standard diluent: 500 mg/100 mL NS; 1 g/250 mL NS

Comments: All IVPB should be prepared fresh; do not use dextrose as a diluent due to limited stability

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins (PBPs); which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Cilastatin prevents renal metabolism of imipenem by competitive inhibition of dehydropeptidase along the brush border of the renal tubules.

Absorption: I.M.: Imipenem: 60% to 75%; cilastatin: 95% to 100%

Distribution: Imipenem appears in breast milk; crosses the placenta; distributed rapidly and widely to most tissues and fluids including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations in cerebrospinal fluid

Metabolism: Imipenem is metabolized in the kidney by dehydropeptidase, this activity is blocked by cilastatin; cilastatin is partially metabolized in the kidneys

Half-life: Both: 60 minutes, extended with renal insufficiency

Elimination: Both: ~70% excreted unchanged in urine

Dosing based on imipenem component:

3 months to 3 years: 25 mg/kg every 6 hours; maximum: 2 g/day

greater than or equal to 3 years: 15 mg/kg/every 6 hours

Adults: I.V.:

Mild to moderate infection: 250-500 mg every 6-8 hours

Severe infections with only moderately susceptible organisms: 1 g every 6-8 hours

Mild to moderate infection only: I.M.: 500-750 mg every 12 hours ( Note: 750 mg is recommended for intra-abdominal and more severe respiratory, dermatologic, or gynecologic infections; total daily I.M. dosages >1500 mg are not recommended; deep I.M. injection should be carefully made into a large muscle mass only)

Dosing adjustment in renal impairment: Dosing based on creatinine clearance (mL/min/1.73 m²). Dose (mg) and frequency listed below:

Cl_cr 30-70: 500 mg q8h

Cl_cr 20-30: 500 mg q12h

Cl_cr 5-20: 250 mg q12h

Hemodialysis: Imipenem ( not cilastatin) is moderately dialyzable (20% to 50%); administer dose postdialysis

Peritoneal dialysis: Dose as for Cl_cr <10 mL/minute

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Dose as for Cl_cr 20-30 mL/minute; monitor for seizure activity; imipenem is well removed by CAVH but cilastatin is not; removes 20 mg of imipenem per liter of filtrate per day

Periodic renal, hepatic, and hematologic function tests; monitor for signs of anaphylaxis during first dose

Interferes with urinary glucose determination using Clinitest®

Reports of encephalopathy

May rarely cause neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Report warmth, swelling, irritation at infusion or injection site. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake) and nutrition. Report unresolved nausea or vomiting (small, frequent meals may help). Diabetics must use serum glucose testing rather than Clinitest®. Report feelings of excessive dizziness, palpitations, visual disturbances, and CNS changes. Report chills, or unusual discharge, or foul-smelling urine. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Administer by I.V. intermittent infusion; final concentration for administration should not exceed 5 mg/mL; in fluid-restricted patients, a final concentration of 7 mg/mL has been administered; infuse over 20-60 minutes; if nausea and/or vomiting occur during administration, decrease the rate of I.V. infusion

Powder for injection:

Imipenem 500 mg and cilastatin 500 mg

Imipenem 750 mg and cilastatin 750 mg

I.V.:

Imipenem 250 mg and cilastatin 250 mg

Imipenem 500 mg and cilastatin 500 mg

Ahonkhai VI, Cyhan GM, Wilson SE, et al, "Imipenem-Cilastatin in Pediatric Patients: An Overview of Safety and Efficacy in Studies Conducted in the United States," Pediatr Infect Dis J, 1989, 8(11):740-4.

Balfour JA, Bryson HM, and Brogden RN, "Imipenem/Cilastatin: An Update of Its Antibacterial Activity, Pharmacokinetics, and Therapeutic Efficacy in the Treatment of Serious Infections," Drugs, 1996, 51(1):99-136.

Barza M, "Imipenem: First of a New Class of Beta-Lactam Antibiotics," Ann Intern Med, 1985, 103(4):552-60.

Bomback T, Sesin GP, and Mucciardi N, "Possible Imipenem/Cilastatin-Induced Aplastic Anemia," Pharm Therapeut, 1995, 20(5):293-302.

Donowitz GR and Mandell GL, "Beta-Lactam Antibiotics," N Engl J Med, 1988, 318(7):419-26 and 318(8):490-500.

Finch RG, Craddock C, Kelly J, et al, "Pharmacokinetic Studies of Imipenem/Cilastatin in Elderly Patients," J Antimicrob Chemother, 1986, 18(Suppl E):103-7.

Hellinger WC and Brewer NS, "Carbapenems and Monobactams: Imipenem, Meropenem, and Aztreonam," Mayo Clin Proc, 1999, 74(4):420-34.

Leo RJ and Ballow CH, "Seizure Activity Associated With Imipenem Use: Clinical Case Reports and Review of the Literature," DICP, 1991, 25(4):351-4.

Norrby SR, "Carbapenems," Med Clin North Am, 1995, 79(4):745-59.

O'Donovan CA, White ML, Cheung A, et al, "Seizure Incidence With Imipenem Use at VA Hospital," Hosp Formul, 1995, 30:172-5.

O'Riordan J, Jared M, Hutchinson M, et al, "Worsening of Myasthenia Gravis on Treatment With Imipenem/Cilastatin," J Neurol Neurosurg Psychiatry, 1994, 57(3):383.

Overturf GD, "Use of Imipenem-Cilastatin in Pediatrics," Pediatr Infect Dis J, 1989, 8(11):792-4.

Park SY and Parker RH, "Review of Imipenem," Infect Control, 1986, 7(6):333-7.

Somani P, Freimer EH, Gross ML, et al, "Pharmacokinetics of Imipenem-Cilastatin in Patients With Renal Insufficiency Undergoing Continuous Ambulatory Peritoneal Dialysis," Antimicrob Agents Chemother, 1988, 32(4):530-4.

Tegeder I, Bremer F, Oelkers R, et al, "Pharmacokinetics of Imipenem-Cilastatin in Critically Ill Patients Undergoing continuous Veno-Venous Hemofiltration," Antimicrob Agents Chemother, 1997, 41(12):2640-5.

Toon S, Hopkins KJ, Garstang FM, et al, "Pharmacokinetics of Imipenem and Cilastatin After Their Simultaneous Administration to the Elderly," Br J Clin Pharmacol, 1987, 23(2):143-9.

Wong VK, Wright HT Jr, Ross LA, et al, "Imipenem/Cilastatin Treatment of Bacterial Meningitis in Children," Pediatr Infect Dis J, 1991, 10(2):122-5.

Yoshikawa TT, "Antimicrobial Therapy for the Elderly Patient," J Am Geriatr Soc, 1990, 38(12):1353-72.