Meropenem is available as a dry powder in 20- and 30-mL single-dose vials containing 500 mg and 1 g, respectively, of meropenem (as the trihydrate).3102 Vials also contain anhydrous sodium carbonate.3102
For intravenous bolus injection administration, the 500-mg and 1-g vials should be reconstituted with 10 and 20 mL, respectively, of sterile water for injection.3102 Vials should be shaken to dissolve the vial contents and allowed to stand until the solution is clear.3102 Each mL of the resultant solution contains approximately 50 mg of meropenem.3102
For intravenous infusion administration, vials may be reconstituted directly with a compatible infusion solution.3102 Alternatively, the appropriate dose of the reconstituted meropenem solution may be transferred to an intravenous container and further diluted with an appropriate infusion solution (e.g., sodium chloride 0.9%, dextrose 5%).3102
For intravenous infusion, meropenem also is available in dual-chamber single-dose flexible containers containing 500 mg or 1 g of meropenem (as the trihydrate) with sodium carbonate.3103 The diluent chamber contains 50 mL of sodium chloride 0.9%.3103 If meropenem doses less than the full dose supplied in the container are needed, the manufacturer states that these containers should not be used.3103 Specific product labeling should be consulted for instructions on reconstitution (activation) of the dual-chamber container.3103
pH
The freshly reconstituted solution has a pH ranging from 7.3 to 8.3.3102; 3103
Osmolality
Meropenem 500 mg or 1 g in dual-chamber single-dose flexible containers has an osmolality of approximately 356 or 417 mOsm/kg, respectively, when activated with the sodium chloride 0.9% diluent.3103
Sodium Content
Each gram of meropenem in single-dose vials provides 3.92 mEq (90.2 mg) of sodium from the sodium carbonate present in the formulation.3102
After reconstitution with the sodium chloride 0.9% diluent, each dual-chamber container of meropenem 500 mg or 1 g provides 10.7 mEq (245.1 mg) or 12.6 mEq (290.2 mg), respectively, of sodium.3103
Trade Name(s)
Merrem I.V.
Meropenem is administered by intravenous bolus injection of 5 to 20 mL over 3 to 5 minutes3102 or by intravenous infusion diluted in a compatible infusion solution over 15 to 30 minutes.3102; 3103
Extended infusion strategies for meropenem have been examined in the literature;2261; 2568; 3104; 3105; 3106 however, the poor stability of the drug, particularly at room temperature, typically limits the use of such strategies.2261; 3105
Intact vials of meropenem should be stored at a controlled room temperature of 20 to 25°C.3102 The drug is a white to pale yellow powder that yields a colorless to yellow solution depending on the concentration.3102
For intravenous bolus administration, the manufacturer indicates that solutions of meropenem reconstituted in vials with sterile water for injection at concentrations of up to 50 mg/mL are stable for up to 3 hours at temperatures of up to 25°C and for 13 hours at temperatures of up to 5°C.3102
For administration by intravenous infusion, meropenem solutions in sodium chloride 0.9% at a concentration of 1 to 20 mg/mL are stated to be stable for 1 hour at temperatures of up to 25°C or 15 hours at temperatures of up to 5°C.3102 Intravenous infusion solutions prepared in dextrose 5% at these concentrations should be used immediately.3102
Unactivated, dual-chamber meropenem containers should be stored at a controlled room temperature of 20 to 25°C.3103 Once the foil strip has been removed from the drug chamber, the product must be protected from light and used within 7 days or the labeled expiration date, whichever occurs first.3103 Once reconstituted (activated), the drug should be used within 1 hour if stored at room temperatures of up to 25°C or 15 hours if stored under refrigeration at temperatures of up to 5°C.3103
Meropenem 50 mg/mL reconstituted with sodium chloride 0.9% is reported to reach 10% loss in 4.8 hours at 25°C.2697
Meropenem (AstraZeneca) 1 g reconstituted with 20 mL of water for injection and diluted with 50 mL of sodium chloride 0.9% was stored in polyvinyl chloride (PVC) infusion bags.3517 Yellow discoloration was observed after 7 hours in solutions stored at 33°C and after 12 hours in solutions stored at 22°C.3517
Concentration Effects
Degradation of meropenem is concentration dependent.3104; 3106; 3298 Meropenem has demonstrated improved stability in solution at concentrations of 40 g/L or lower.3104; 3106
In one study, reconstituting meropenem with sterile water for injection to concentrations exceeding 64 g/L resulted in unacceptably viscous solutions that impeded flow from elastomeric pumps to less than 75% of the nominal flow rate.3105
Temperature Effects
Degradation of meropenem also is temperature dependent.3104; 3105; 3106 Meropenem has demonstrated improved stability in solution at temperatures less than or equal to 25°C.3104; 3105; 3106 Meropenem (AstraZeneca) 5 mg/mL in sodium chloride 0.9% exceeded 10% drug loss by 12, 8, and 6 hours at temperatures of 30, 35, and 40°C, respectively.3109
Freezing Solutions
Manufacturers state that solutions of meropenem should not be frozen.3102; 3103
Meropenem (Ranbaxy Australia) 6, 12, 20, and 25 mg/mL in sodium chloride 0.9% in glass vials was frozen at -19°C for 144 hours.4001 Upon thawing, a precipitate was present in all samples and attempts to dissolve the precipitate were unsuccessful.4001
Syringes
Meropenem (AstraZeneca; Fresenius Kabi; Hospira; Sandoz) was diluted to concentrations of 10, 20, and 40 mg/mL in sodium chloride 0.9% and stored in polypropylene syringes (Becton Dickinson).3298 Solutions containing meropenem 10 and 20 mg/mL were stable for 12 hours at 25°C; solutions containing meropenem 40 mg/mL were stable for 8 hours at 25°C.3298
Elastomeric Reservoir Pumps
Meropenem (Ranbaxy Australia) 6, 12, 20, and 25 mg/mL in sodium chloride 0.9% (Baxter Australia) was evaluated for stability in 250-mL elastomeric reservoirs (Baxter LV10).4001 For optimal stability, hydrochloric acid was added to the solutions to adjust the pH to 6.5.4001 The solutions were stored refrigerated at 6.7°C for up to 6 days or at 22.5°C for 24 hours following a period of refrigerated storage to simulate ambient temperature infusion over 24 hours.4001 Under refrigeration, the 6-mg/mL solution was stable for up to 6 days (7.5% loss), the 12- and 20-mg/mL solutions were stable for up to 72 hours (5.2 and 7.6% loss, respectively), and the 25-mg/mL solution was stable up to 48 hours (8.6% loss).4001 The solutions we less stable when exposed to ambient temperature.4001 The 6-mg/mL solution stored for 48 hours refrigerated followed by 24 hours at 22.5°C had a loss of 7.4% over the total 72-hour period.4001 The 12-mg/mL solution stored for 24 hours refrigerated followed by 24 hours at 22.5°C had a loss of 9.6% over the total 48-hour period.4001 The 20-mg/mL solution stored for 24 hours refrigerated followed by 24 hours at 22.5°C had losses exceeding 10%, but when immediately stored at 22.5°C for 24 hours (without prior refrigerated storage) the loss was 9.3%.4001 Therefore, the investigators stated immediate administration would be necessary for 20-mg/mL solutions exposed to 22.5°C for 24 hours.4001 At a concentration of 25 mg/mL, meropenem loss exceeded 10% in 24 hours at 22.5°C and was not considered stable for ambient-temperature administration over 24 hours.4001
Meropenem (Aurovitas), reconstituted with and diluted in sodium chloride 0.9% (Baxter Spain) to concentrations of 2 and 25 mg/mL, was evaluated for stability with a final volume of 250 mL in 300-mL Accufuser elastomeric reservoirs (Grifols).4038 The solutions were stored at 2 to 8, 25, or 32°C.4038 The 2-mg/mL solution was physically and chemically stable for up to 24 hours at 2 to 8°C (4.2% loss) or 25°C (8.4% loss) with significant degradation observed after 24 hours.4038 At 32°C, the 2-mg/mL solution was stable up to 8 hours (3.2% loss) with losses exceeding 16% in 24 hours.4038 The 25-mg/mL solution was physically and chemically stable up to 24 hours at 2 to 8°C (8% loss).4038 At 25 or 32°C, the 25-mg/mL solution was stable for up to 8 hours (5.5 or 8.5% loss, respectively).4038 Losses exceeded 19 or 32% in 24 hours at 25 or 32°C, respectively, with unacceptable percentages of degradation products.4038
Central Venous Catheter
Meropenem (Zeneca) 5 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
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Peritoneal Dialysis Solutions
Meropenem (AstraZeneca) 1 g in 2 L of Dianeal PD-4 with dextrose 2.5% (Baxter) exhibited 6% drug loss over 6 hours at 37°C.3108
For a list of references cited in the text of this monograph, search the monograph titled References.