Mechanism of Action
Imipenem and Cilastatin for Injection (I.V.) is a combination of imipenem and cilastatin. The bactericidal activity of imipenem results from the inhibition of cell wall synthesis. Its greatest affinity is for penicillin binding proteins (PBPs) 1A, 1B, 2, 4, 5 and 6 of Escherichia coli, and 1A, 1B, 2, 4 and 5 of Pseudomonas aeruginosa. The lethal effect is related to binding to PBP 2 and PBP 1B.
Imipenem has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases produced by Gram-negative and Gram-positive bacteria. It is a potent inhibitor of beta-lactamases from certain Gram-negative bacteria which are inherently resistant to most beta-lactam antibacterials, e.g., Pseudomonas aeruginosa, Serratia spp., and Enterobacter spp.
Cilastatin sodium is a renal dehydropeptidase inhibitor that limits the renal metabolism of imipenem.
Drug Label Information | Brands:
Brands of Imipenem / Cilastatin available in Kenya
Bacqure®, Sun Pharmaceutical Industries Limited
Cispenam®, Incepta Pharmaceutical Ltd
Imbac, Popular Pharmaceuticals Ltd.
Imicil®, Swiss Parenterals (Pvt.) Ltd
Inno-Cila®, Innocia Lifesciences Pvt. Ltd.
Lastinem®, Venus Remedies Limited
Mitin® , Laso Healthcare Pvt. Ltd.
Pantin®, M.J. Biopharm Pvt. Limited
Pelastin®, PT Sanbe Farma
Tienam®,MSD (Pty) Ltd
Imipenem and Cilastatin for Injection, USP for intravenous use is a combination of imipenem, a penem antibacterial, and cilastatin, a renal dehydropeptidase inhibitor, indicated for the treatment of the following serious infections caused by designated susceptible bacteria:
- Lower respiratory tract infections.
- Urinary tract infections.
- Intra-abdominal infections.
- Gynecologic infections.
- Bacterial septicemia.
- Bone and joint infections.
- Skin and skin structure infections.
DOSAGE AND ADMINISTRATION
The dosage of Imipenem and Cilastatin for Injection (I.V.) in adult patients should be based on suspected or confirmed pathogen susceptibility .
- For adult patients with normal renal function (creatinine clearance of greater than or equal to 90 mL/min), the recommended dosage regimens are: 500 mg every 6 hours OR 1,000 mg every 8 hours OR 1,000 mg every 6 hours .
- A reduction in dose must be made for a patient with a creatinine clearance of less than 90 mL/min .
- Patients with creatinine clearances of less than 15 mL/min should not receive Imipenem and Cilastatin for Injection (I.V.) unless hemodialysis is instituted within 48 hours .
- Reconstitute Imipenem and Cilastatin for Injection, USP (I.V.) vial with appropriate diluent and dilute the reconstituted suspension with an appropriate infusion solution before administering by intravenous infusion
- Known hypersensitivity to any component of Imipenem and Cilastatin for Injection (I.V.)
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. If an allergic reaction to Imipenem and Cilastatin for Injection (I.V.) occurs, discontinue the drug immediately.
Seizure Potential: Seizures and other CNS adverse reactions, such as confusional states and myoclonic activity, have been reported during treatment with Imipenem and Cilastatin for Injection (I.V.). If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of Imipenem and Cilastatin for Injection (I.V.) re-examined to determine whether it should be decreased or the antibacterial drug discontinued .
Increased Seizure Potential Due to Interaction with Valproic Acid:
Co-administration of Imipenem and Cilastatin for Injection (I.V.), to patients receiving valproic acid or divalproex sodium results in a reduction in valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. The concomitant use of Imipenem and Cilastatin for Injection (I.V.) and valproic acid/divalproex sodium is generally not recommended
Clostridium difficile-Associated Diarrhea (CDAD): has been reported with use of Imipenem and Cilastatin for Injection (I.V.) and may range in severity from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs (
The most frequently occurring adverse reactions (≥ 0.2%) in adults were phlebitis, nausea, diarrhea, vomiting, rash, pain injection site, fever, hypotension, seizures, erythema at injection site, dizziness, pruritus, vein induration, urticaria, somnolence .
The most frequently occurring adverse reactions (> 1%) in pediatric patients greater than or equal to 3 months of age were diarrhea, rash, phlebitis, gastroenteritis, vomiting, IV site irritation, urine discoloration .
The most frequently occurring adverse reactions (> 1%) in neonates to 3 months of age were convulsions, diarrhea, oliguria/anuria, oral candidiasis, rash, tachycardia
Ganciclovir: Generalized seizures have been reported in patients who received ganciclovir. Do not co-administer unless benefit outweighs risk
Probenecid: Concomitant administration of Imipenem and Cilastatin for Injection (I.V.) and probenecid results in increases in the plasma level and half-life of imipenem. Concomitant administration is not recommended .
Valproic acid/divalproex sodium: Concomitant use with Imipenem and Cilastatin for Injection (I.V.) is generally not recommended. Consider other antibacterial drugs to treat infections in patients whose seizures are well-controlled on valproic acid or divalproex sodium
USE IN SPECIFIC POPULATIONS
Renal Impairment: Dosage adjustment is necessary in patients with renal impairment .
Adult patients with creatinine clearances of less than or equal to 30 mL/min, whether or not undergoing hemodialysis, had a higher risk of seizure activity than those without impairment of renal function .
Therefore, close adherence to the dosing guidelines and regular monitoring of creatinine clearance for these patients is recommended