Imipenem and cilastatin

Dosage in Adult Patients with Renal Impairment Patients with creatinine clearance less than 90 mL/min require dosage reduction of Imipenem and Cilastatin for Injection as indicated in Table 3. The serum creatinine should represent a steady state of renal function. Use the Cockcroft-Gault method described below to calculate the creatinine clearance: [See table below.] [See table below.] Dosage of Imipenem and Cilastatin for Injection If the infection is suspected or proven to be due to bacterial species with intermediate susceptibility [see Microbiology] 1000 mg every 6 hours 750 mg every 8 hours 500 mg every 6 hours 500 mg every 12 hours In patients with creatinine clearances of less than 30 to greater than or equal to 15 mL/min, there may be an increased risk of seizures [see Warnings and Precautions and Use in Specific Populations] .

Patients with creatinine clearance less than 15 mL/min should not receive Imipenem and Cilastatin for Injection unless hemodialysis is instituted within 48 hours. There is inadequate information to recommend usage of Imipenem and Cilastatin for Injection for patients undergoing peritoneal dialysis.

Dosage in Hemodialysis Patients When treating patients with creatinine clearances of less than 15 mL/min who are undergoing hemodialysis , use the dosage recommendations for patients with creatinine clearances of less than 30 to greater than or equal to 15 mL/min in Table 3 above [see Dosage and Administration ]. Both imipenem and cilastatin are cleared from the circulation during hemodialysis.

The patient should receive Imipenem and Cilastatin for Injection after hemodialysis and at intervals timed from the end of that hemodialysis session. Dialysis patients, especially those with background CNS disease, should be carefully monitored; for patients on hemodialysis, Imipenem and Cilastatin for Injection is recommended only when the benefit outweighs the potential risk of seizures. [See Warnings and Precautions ].

Reconstitution and Preparation of Imipenem and Cilastatin for Injection Solution for Intravenous Administration Imipenem and Cilastatin for Injection Vials

Do not use diluents containing benzyl alcohol to reconstitute Imipenem and Cilastatin for Injection for administration to neonates 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 the appropriate diluent to the vial. List of appropriate diluents are as follows : o 0.9% Sodium Chloride Injection o 5% Dextrose Injection o 5% Dextrose and 0.9% Sodium Chloride Injection o 5% Dextrose Injection with 0.225% or 0.45% saline solution

Reconstituted Solutions of Imipenem and Cilastatin for Injection 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 an appropriate infusion solution 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.

Discard unused portion of the infusion solution where applicable.

Storage of Reconstituted Solutions Vials (After Reconstitution)

Imipenem and Cilastatin for Injection, as supplied in single dose vials and reconstituted with the appropriate diluents [see Dosage and Administration ] , maintains satisfactory potency for 4 hours at room temperature or for 24 hours under refrigeration (5°C). Do not freeze solutions of Imipenem and Cilastatin for Injection.

Incompatibility and Compatibility of Imipenem and Cilastatin for Injection with Other Antibacterial Drugs

Do not mix Imipenem and Cilastatin for Injection with, or physically add to, other antibacterial drugs.

Imipenem and Cilastatin for Injection may be administered concomitantly with other antibacterial drugs, such as aminoglycosides.