Imipenem/Cilastatin Actavis (Cilastatin Sodium, Imipenem Monohydrate)

Imipenem/Cilastatin is a broad‑spectrum carbapenem used to treat serious bacterial infections in the hospital setting.

• Complicated intra‑abdominal infections: provides effective bacterial eradication in severe abdominal sepsis.
• Complicated urinary tract infections: clears resistant uropathogens causing pyelonephritis and cystitis.
• Hospital‑acquired and ventilator‑associated pneumonia: combats multidrug‑resistant organisms in lower respiratory infections.
• Skin and soft‑tissue infections: treats deep or necrotizing infections caused by Gram‑negative and Gram‑positive bacteria.
• Febrile neutropenia: offers rapid coverage against potential bloodstream pathogens in immunocompromised patients.

• Imipenem binds to multiple penicillin‑binding proteins, inhibiting the final stages of bacterial cell‑wall peptidoglycan synthesis, which leads to cell lysis. Cilastatin, co‑formulated with imipenem, inhibits renal dehydropeptidase I, preventing enzymatic degradation of imipenem and thereby increasing its urinary concentration and systemic exposure.

Adverse reactions may occur with imipenem/cilastatin therapy.

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Vomiting: occasional emesis following infusion.
• Diarrhea: may range from loose stools to mild colitis.
• Headache: transient cranial discomfort.
• Rash: skin erythema or pruritus.
• Elevated liver enzymes: transient increase in transaminases.

Serious or Rare Side Effects

• Seizures: risk increases with high doses or renal impairment.
• Anaphylaxis: severe hypersensitivity reaction requiring immediate medical attention.
• Clostridioides difficile‑associated diarrhea: possible severe colitis.
• Stevens‑Johnson syndrome/toxic epidermal necrolysis: rare but life‑threatening skin reactions.
• Severe neutropenia or thrombocytopenia: marked reduction in blood cell counts.
• Acute renal failure: abrupt loss of kidney function, especially in predisposed patients.

Use imipenem/cilastatin with careful clinical monitoring.

• Renal impairment: adjust dose based on creatinine clearance to avoid accumulation.
• Hypersensitivity: discontinue immediately if signs of allergic reaction appear.
• Seizure risk: avoid in patients with a history of epilepsy or CNS disorders unless benefits outweigh risks.
• Pregnancy and lactation: prescribe only if potential benefit justifies potential risk to fetus or infant.
• Concomitant valproic acid: monitor for reduced valproate levels and possible seizure breakthrough.
• Store at ambient temperature: keep in original container, protect from moisture and light.

Imipenem/cilastatin may interact with several medications.

Major Interactions (Avoid)

• Valproic acid: reduces serum valproate concentrations, increasing seizure risk.
• Other carbapenems: concurrent use may lead to additive toxicity without added benefit.
• Nephrotoxic agents (e.g., aminoglycosides): heightened risk of renal injury.

Moderate Interactions (Monitor Closely)

• Diuretics: may affect renal clearance, requiring dose adjustment.
• Anticoagulants (warfarin): monitor INR for potential alteration.
• Oral contraceptives: possible reduction in efficacy, advise alternative contraception.
• NSAIDs: increased risk of renal dysfunction, especially in dehydrated patients.
• Phenytoin: may lower phenytoin levels, necessitate therapeutic drug monitoring.