Cilanem IV Injection

This 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
• Endocarditis

This is a combined preparation of Imipenem and Cilastatin. Imipenem is a penem antibacterial drug. Cilastatin sodium is a renal dehydropeptidase inhibitor that limits the renal metabolism of imipenem. 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 betalactamases from certain Gram-negative bacteria which are inherently resistant to most beta-lactam antibacterials, e.g., Pseudomonas aeruginosa, Serratia spp., and Enterobacter spp.

The dosage in adult patients: This 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 1000 mg every 8 hours OR 1000 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 this combination unless hemodialysis is instituted within 48 hours.

Reconstitute this vial with appropriate diluent and dilute the reconstituted suspension with an appropriate infusion solution before administering by intravenous infusion.

Recommended Dosage in Pediatric Patients for Non-CNS Infections:

Greater than or equal to 3 Months of Age: 15-25 mg/kg in every 6 hours

Less than or equal to 3 months of age (Greater than or equal to 1,500 g body weight):

• 4 weeks to 3 months of age: 25 mg/kg in every 6 hours
• 1 to 4 weeks of age: 25 mg/kg in every 8 hours
• Less than 1 week of age: 25 mg/kg in every 12 hours

Doses less than or equal to 500 mg should be given by intravenous infusion over 20 to 30 minutes. Doses greater than 500 mg should be given by intravenous infusion over 40 to 60 minutes Recommend that the maximum total daily dosage not exceed 4g/day.

Concurrent admin with probenecid may increase the half-life of cilastatin. Increased risk of generalised seizures when used concurrently with ganciclovir.

Hypersensitivity to any component of this combination.

• Phlebitis
• Nausea, diarrhea, vomiting
• Rash, pruritus, urticaria
• Pain injection site, erythema
• at injection site, vein induration
• Fever
• Hypotension
• Seizures, dizziness, somnolence

Pregnancy Category C. There are no adequate and well-controlled studies of this combination in pregnant women. This combination should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and fetus. It is not known whether Imipenem-Cilastatin sodium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when this combination is administered to a nursing woman.

Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. If an allergic reaction to Cilanem 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 Cilanem. If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of Cilanem re-examined to determine whether it should be decreased or the antibacterial drug discontinued.

Other beta-lactam Antibiotics

Reconstitution and Preparation of Cilanem Solution for Intravenous Administration:

• Do not use diluents containing benzyl alcohol to reconstitute Cilanem for administration tovneonates because it has been associated with toxicity in neonates. While toxicity has not been demonstrated in pediatric patients greater than three months of age, small pediatric patients in this age range may also be at risk for benzyl alcohol toxicity.
• Contents of the vials must be reconstituted by adding approximately 10 mL of 0.9% Sodium Chloride Injection (supplied).
• Reconstituted Solutions of Cilanem range from colorless to yellow. Variations of color within this range do not affect the potency of the product.
• The reconstituted suspension must not be administered by direct Intravenous Infusion
• After reconstitution, shake vial well and transfer the resulting suspension to 100 mL of 0.9% Sodium Chloride infusion solution (supplied) before administering by intravenous infusion.
• Repeat transfer of the resulting suspension with an additional 10 mL of infusion solution to ensure complete transfer of vial contents to the infusion solution. Agitate the resulting mixture until clear.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Storage of Reconstituted Solutions: Cilanem, as supplied in single dose vials and reconstituted with the supplied 0.9% Sodium Chloride Injection maintains satisfactory potency for 4 hours at room temperature or for 24 hours under refrigeration (5°C). Do not freeze solutions of Cilanem.

Store at or below 25° C temperature. Keep away from light and wet place. Keep out of reach of children.