imipenem and cilastatin sodium
Primaxin I.M., Primaxin I.V.

Available forms
Available by prescription only
Injection: 250-mg, 500-mg vials, ADD-Vantage, and infusion bottles
Powder (for I.M. injection): 500-mg, 750-mg vial

Indications and dosages
 Mild to moderate lower respiratory tract, skin and skin-structure, or gynecologic infections. Adults who weigh at least 70 kg (154 lb): 500 to 750 mg I.M. q 12 hours.
 Mild to moderate intra-abdominal infections. Adults who weigh at least 70 kg (154 lb): 750 mg I.M. q 12 hours.
 Serious respiratory and urinary tract infections; intra-abdominal, gynecologic, bone, joint, or skin infections; bacterial septicemia; endocarditis. Adults who weigh at least 70 kg (154 lb): 250 mg to 1 g by I.V. infusion q 6 to 8 hours. Maximum daily dose is 50 mg/kg or 4 g, whichever is less.
Children: 15 to 25 mg/kg q 6 hours.
≡ Dosage adjustment. For patients with renal impairment and creatinine clearance of 6 to 20 ml/ minute, 125 to 250 mg I.V. q 12 hours for most pathogens. There may be an increased risk of seizures when doses of 500 mg q 12 hours are administered to these patients. When creatinine clearance is 5 ml/minute or less, imipenem shouldn’t be given unless hemodialysis is instituted within 48 hours. Note: In patients who weigh less than 70 kg (154 lb) or those with impaired renal function, dosages vary. Check current literature for recommended protocol.

Pharmacodynamics
Antibacterial action: A bactericidal drug, imipenem inhibits bacterial cell wall synthesis. Its spectrum of antimicrobial activity includes many gram-positive, gram-negative, and anaerobic bacteria, including Escherichia coli; Pseudomonas aeruginosa;Bacteroides species, including B. fragilis; and Staphylococcus, Streptococcus, Klebsiella, Proteus, and Enterobacter species. Resistant bacteria include methicillin-resistant staphylococci, Clostridium difficile, and other Pseudomonas species.
 Cilastatin inhibits the enzymatic breakdown of imipenem in the kidneys, making it effective in treating urinary tract infections.

Pharmacokinetics
Absorption: Given I.V. and I.M.
Distribution: Distributed rapidly and widely. About 20% of imipenem is protein-bound; 40% of cilastatin is protein-bound.
Metabolism: Imipenem is metabolized by kidney dehydropeptidase I, resulting in low urine levels. Cilastatin inhibits this enzyme, thereby reducing metabolism of imipenem.
Excretion: About 70% of imipenem and cilastatin dose is excreted unchanged by the kidneys (when imipenem is combined with cilastatin) by tubular secretion and glomerular filtration. Imipenem is cleared by hemodialysis; therefore, a supplemental dose is required after this procedure. Half-life of drug is about 1 hour after I.V. administration. The prolonged absorption that occurs after I.M. administration results in a longer half-life (2 to 3 hours).

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Imipenem and cilastatin sodium reconstituted with lidocaine hydrochloride for I.M. injection is contraindicated in patients hypersensitive to local anesthetics of the amide type and in patients with severe shock or heart block.
  Use cautiously in patients with impaired renal function, seizure disorders, or allergy to penicillins or cephalosporins.

Interactions
Drug-drug. Chloramphenicol: May impede bactericidal effects of imipenem. Give chloramphenicol a few hours after imipenem and cilastatin.
Ganciclovir: Generalized seizures have occurred in several patients during combined imipenem and cilastatin and ganciclovir therapy. Monitor patient closely.
Probenecid: May prevent tubular secretion of cilastatin (but not imipenem) and prolong plasma cilastatin half-life. Use together cautiously.

Adverse reactions
CNS: seizures, dizziness, somnolence, fever.
CV: thrombophlebitis, hypotension.
GI: nausea, vomiting, diarrhea, PSEUDOMEMBRANOUS COLITIS.
Hematologic: agranulocytosis, thrombocytosis.
Skin: rash, urticaria, pruritus, pain at injection site.
Other: hypersensitivity reactions (anaphylaxis).

Effects on lab test results
• May increase BUN, creatinine, ALT, AST, alkaline phosphatase, bilirubin, and LDH levels.
• May increase eosinophil count. May decrease WBC and platelet counts.

Overdose and treatment
If overdose occurs, discontinue drug, treat symptomatically, and institute supportive measures as required. Although imipenem and cilastatin sodium are hemodialyzable, use of hemodialysis in treating drug overdose is questionable.

Special considerations
• Culture and sensitivity tests should be done before starting therapy.
• Drug may be physically incompatible with aminoglycosides; avoid mixing together.
• Don’t administer drug by direct I.V. bolus injection. Infuse 250- or 500-mg dose over 20 to 30 minutes; infuse 1-g dose over 40 to 60 minutes. If nausea occurs, slow infusion.
• Drug has broadest antibacterial spectrum of any available antibiotic. It’s most valuable for empiric treatment of unidentified infections and for mixed infections that would otherwise require combination of antibiotics, possibly including an aminoglycoside.
• Interferes with urinary glucose determinations using the cupric sulfate method.
• Continue use of anticonvulsants in patients with seizure disorders. Patients who exhibit CNS toxicity should receive phenytoin or benzodiazepines. Reduce dosage or discontinue drug if CNS toxicity continues.
• Prolonged use may result in overgrowth of nonsusceptible organisms. In addition, use of imipenem and cilastatin as a sole course of therapy has resulted in resistance during therapy.
Pregnant patients
• Use I.V. form during pregnancy only if potential benefits outweigh potential risk to the fetus.
Breast-feeding patients
• It’s unknown whether drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children younger than age 12 haven’t been established; however, drug has been used in children ages 3 months to 13 years. Dosage range is 15 to 25 mg/kg every 6 hours.
Geriatric patients
• Administer cautiously to elderly patients because they may also have renal dysfunction.

Patient education
• Advise patient of potential adverse reactions.
• Instruct patient to immediately report serious adverse drug effects.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use