The fixed combination of imipenem-cilastatin sodium is available as a powder in single-dose vials containing the equivalents of imipenem 250 mg (as the monohydrate) and cilastatin 250 mg (as the sodium salt) with sodium bicarbonate 10 mg as a buffer, or imipenem 500 mg (as the monohydrate) and cilastatin 500 mg (as the sodium salt) with sodium bicarbonate 20 mg as a buffer.3928; 3929
The powder must be reconstituted and diluted with an appropriate solution prior to administration.3928; 3929 The contents of each vial should be reconstituted with approximately 10 mL of a compatible diluent (sodium chloride 0.9%; dextrose 5%; or dextrose 5% in sodium chloride 0.225, 0.45, or 0.9%) and shaken well to form a suspension.3928; 3929 The reconstituted suspension must not be administered intravenously.3928; 3929 The reconstituted suspension should be shaken well and transferred to 100 mL of an appropriate infusion solution.3928; 3929 To ensure all of the vial contents are transferred, a second 10-mL aliquot of diluent should be added to the vial, shaken well, and transferred to the infusion bag.3928; 3929 Agitate the infusion bag until the solution is clear.3928; 3929
Diluents containing benzyl alcohol should not be used to reconstitute the drug for use in neonates.3928; 3929
pH
The formulation is buffered to provide solutions with pH ranging from 6.5 to 8.5.3928; 3929
Sodium Content
Each vial containing imipenem 250 mg and cilastatin 250 mg contains 18.8 mg (0.8 mEq) of sodium.3929 Each vial containing imipenem 500 mg and cilastatin 500 mg contains 37.5 mg (1.6 mEq) of sodium.3928; 3929
Trade Name(s)
Primaxin I.V.
Imipenem-cilastatin sodium is administered by intravenous infusion only after reconstitution and dilution.3928; 3929 Doses of 500 mg (of imipenem) are administered over 20 to 30 minutes.3928; 3929 Doses of 1000 mg (of imipenem) are administered over 40 to 60 minutes.3928; 3929
Intact vials should be stored below 25°C3928 or at controlled room temperature.3929
Reconstituted solutions range in color from colorless to yellow; variations of color within this range do not affect the potency of the drug.3928; 3929 Solutions reconstituted with appropriate diluents are stable for 4 hours at room temperature or 24 hours under refrigeration (5°C).3928; 3929 Do not freeze solutions.3928; 3929
Imipenem degradation kinetics were determined for a 2.5-mg/mL solution in sodium chloride 0.9%. The degradation rates were temperature dependent, with a half-life of over 44 hours at 2°C dropping to 6 hours at 25°C and to 2 hours at 37°C. The decomposition was consistent with hydrolysis, and the loss of antimicrobial activity suggests cleavage of the ß-lactam ring.1272
Concentration Effects
In one study, solutions of imipenem-cilastatin in sterile water for injection at concentrations exceeding 8 g/L (not specified whether concentration refers to single component or combined components) resulted in precipitation.3105
pH Effects
Imipenem is inactivated at acidic or alkaline pH but is more stable at neutral pH.4 The pH range of maximum stability appears to be 6.5 to 7.5, with increasing rates of decomposition occurring as the pH moves away from this range.1273 At a pH of about 4, the half-life of imipenem is about 35 minutes.2166
Freezing Solutions
Reconstituted imipenem-cilastatin solutions should not be frozen.3928; 3929 At concentrations of 250 and 500 mg/100 mL in sodium chloride 0.9%, imipenem losses of around 15% occurred in 1 week when frozen at -20 and -10°C.1141 Freezing solutions at temperatures above -70°C offers no stability advantage over refrigerated storage1141 and results in decomposition of imipenem in a manner similar to ampicillin.4
Effects of Solution Components
Dextrose exerts an adverse effect on the stability of imipenem. Dextrose 5 and 10% reduced the time to 10% decomposition by about one-half compared to sterile water. Sodium chloride content increases imipenem stability because of a positive kinetic salt effect similar to other ß-lactam antibiotics. Both lactate and bicarbonate anions attack the ß-lactam ring and decrease imipenem stability.1141
Elastomeric Reservoir Pumps
Imipenem-cilastatin sodium (Merck) 5 mg/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). Less than 1% binding was found after storage for 2 weeks at 35°C with gentle agitation.2014
Central Venous Catheter
Imipenem-cilastatin (MSD) 2 mg/mL in sodium chloride 0.9% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
For a list of references cited in the text of this monograph, search the monograph titled References.