Gentamicin sulfate is available as a 40-mg/mL solution for injection in 2- and 20-mL vials.3943; 3945 Each mL contains the equivalent of gentamicin 40 mg as the sulfate with methylparaben 1.8 mg and propylparaben 0.2 mg as preservatives, edetate disodium 0.1 mg, and sodium metabisulfite in water for injection.3943; 3945 The solution may also contain sulfuric acid and/or sodium hydroxide for pH adjustment.3943; 3945
Gentamicin sulfate also is available as a 10-mg/mL (pediatric) preservative-free solution for intravenous or intramuscular injection in 2-mL single-dose vials.3944 Each mL contains the equivalent of gentamicin 10 mg as the sulfate in water for injection with sulfuric acid and/or sodium hydroxide for pH adjustment.3944
Gentamicin sulfate also is available as a premixed, ready-to-use solution for infusion in single-dose flexible plastic containers containing the equivalent of gentamicin 60, 80, 100, or 120 mg as the sulfate in sodium chloride 0.9%.3946 The solution may also contain sodium hydroxide and/or sulfuric acid for pH adjustment.3946
pH
The injection for intravenous or intramuscular administration has a pH of 3 to 5.5.3945 The premixed, ready-to-use solution has a pH of approximately 4.5.3946
Osmolality
Gentamicin sulfate (Wyeth) 40 mg/mL has an osmolality of 160 mOsm/kg.50 Gentamicin sulfate pediatric injection (Elkins-Sinn) 10 mg/mL has an osmolality of 116 mOsm/kg by freezing-point depression or 212 mOsm/kg by vapor pressure.1071
The osmolality of gentamicin sulfate 1 mg/mL was 262 mOsm/kg in dextrose 5% and 278 mOsm/kg in sodium chloride 0.9%. At a 2.5-mg/mL concentration, the osmolality was 278 mOsm/kg in dextrose 5% and 293 mOsm/kg in sodium chloride 0.9%.1375
The osmolality of gentamicin sulfate 80 mg was calculated for the following dilutions:1054
| Osmolality (mOsm/kg) | ||
|---|---|---|
| Diluent | 50 mL | 100 mL |
| Dextrose 5% | 293 | 285 |
| Sodium chloride 0.9% | 320 | 315 |
Osmolarity
The osmolarity of the premixed infusions in sodium chloride 0.9% is approximately 284 to 308 mOsm/L.4
Gentamicin sulfate is administered by intramuscular injection or intermittent intravenous infusion.3943; 3944 For intravenous administration in adults, dilution of the dose in 50 to 200 mL of sodium chloride 0.9% or dextrose 5% is recommended; smaller volumes should be used for pediatric patients.3943 The infusion is administered over 0.5 to 2 hours.3943; 3944
Intact vials should be stored at controlled room temperature.3943; 3944
The premixed, ready-to-use solution in intact containers should be stored at room temperature (25°C).3946 The manufacturer states that brief exposure up to 40°C does not adversely affect the product, but excessive heat should be avoided.3946
Freezing Solutions
Gentamicin sulfate (Schering) 50 mg in 50 mL of dextrose 5% and also sodium chloride 0.9% in polyvinyl chloride (PVC) containers frozen at -20°C was stable for 30 days.299
Gentamicin sulfate (Schering) 80 mg/100 mL of dextrose 5% in PVC bags was frozen at -20°C for 30 days and then thawed by exposure to ambient temperature or microwave radiation. No precipitation or color change was observed, and no drug loss occurred. Subsequent storage of the admixture at room temperature for 24 hours also yielded a physically compatible solution, exhibiting little or no drug loss.554
Gentamicin sulfate (Elkins-Sinn) 120 mg/50 mL lost 6% in dextrose 5% and 2% in sodium chloride 0.9% in 28 days when frozen at -20°C.981
The stability of gentamicin sulfate (Schering) 5.45 mg/mL in dextrose 5% frozen in an ambulatory pump reservoir was studied. The drug-filled reservoirs were stored at -20°C for 30 days and then thawed at 5°C for 4 days. This thawing was then followed by 2 days of drug delivery through the pump at 37°C. No visible changes and no loss occurred during storage and delivery. Furthermore, plasticizer diethylhexyl phthalate (DEHP) levels were insignificant.1490
Syringes
The stability of gentamicin sulfate (Schering) repackaged in plastic syringes (Monoject) was significantly less than in glass syringes (Glaspak, Becton Dickinson) at both 4 and 25°C. The commercial concentrations were tested in the following amounts: 40 mg/mL—1, 0.75, 0.5, and 0.25 mL; and 10 mg/mL—1.5, 1, and 0.5 mL. Storage in plastic syringes resulted in an average loss of 16% in 30 days and in the formation of a brown precipitate. In glass syringes, the average loss was 7% at 30 days. The brown precipitate did not appear after 30 days but was present at 60 days. It appeared in the cannula of the needle in both glass and plastic syringes. For the 40-mg/mL concentration, the volume of the sample also affected stability. Significantly less loss was noted in the smaller volumes (0.25 and 0.5 mL) than in the larger volumes (0.5 and 1 mL). This volume-related phenomenon was not demonstrated in the 10-mg/mL pediatric concentration. Storage temperature had no effect on stability over 90 days.297
The manufacturer also expressed concern about plastic packaging of gentamicin, noting a possibly inadequate oxygen and moisture barrier both through the tip and the walls of the syringe. It was indicated that gentamicin is oxygen sensitive and that depletion of the antioxidant present could result in instability. Further, loss of moisture at the tip could result in occlusion by the dried product.403
Gentamicin sulfate 40 mg/1 mL was packaged in polypropylene syringes (Plastipak, Becton Dickinson). No significant change in concentration occurred over 30 days at 4 or 25°C.401
Gentamicin sulfate (Elkins-Sinn) 120 mg, diluted with 1 mL of sodium chloride 0.9% to a final volume of 4 mL, was stable (less than 10% loss) when stored in polypropylene syringes (Becton Dickinson) for 48 hours at 23°C under fluorescent light.1159
The stability of gentamicin sulfate (Elkins-Sinn) diluted to 10 mg/mL with sodium chloride 0.9% and stored in glass syringes (Becton Dickinson) at 4°C was studied. No loss of gentamicin sulfate was found during 12 weeks of storage.1265
Sorption
Gentamicin sulfate was shown not to exhibit sorption to PVC bags and tubing, polyethylene bags and tubing, multilayer bags of polyethylene, polyamide, and polypropylene, Silastic tubing, polypropylene syringes, and elastomeric reservoirs.536; 606; 2014; 2269
Filtration
The effect of several filters on the delivered concentration of gentamicin sulfate (Roussel) from simulated pediatric infusions was studied. A syringe containing dextrose 10% on a syringe pump set at 8.26 mL/hr was connected by intravenous tubing to a 0.5-µm air-blocking filter set (Travenol), a 0.22-µm air-eliminating filter set (Travenol), and a 0.2-µm air-eliminating filter set (Pall). Gentamicin doses of 2.5 and 7.5 mg were injected antegrade to the filter. The effluents were sampled at 1, 1.5, 2, and 4 hours. No significant drug sorption to the plastic tubing or inline filters occurred. However, because of the difference in specific gravity of the drug (1.010) and intravenous solution (1.032), variations in delivered gentamicin did occur due to filter design and position. With the Travenol filters, gentamicin delivery was more rapid with ascending flow in both horizontal and vertical positions. Drug delivery was significantly delayed with descending flow in both positions. The Pall filter delivered gentamicin more rapidly in the horizontal position with either ascending or descending flow. The vertical filter position significantly delayed drug delivery in both flow directions.804
However, in another study, gentamicin sulfate 60 mg/15 mL was injected as a bolus through a 0.2-µm nylon air-eliminating filter (Ultipor, Pall) to evaluate the effect of filtration on simulated intravenous push delivery. About 38% of the drug was delivered through the filter after flushing with 10 mL of sodium chloride 0.9%.809
Gentamicin sulfate 5 and 10 mg/55 mL of dextrose 5% and sodium chloride 0.9% was filtered over 20 minutes through a 0.22-µm cellulose ester filter set (Ivex-2, Millipore). Virtually all of the drug was delivered through the filter.1003
The binding of gentamicin sulfate to the filter of a set used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Gentamicin sulfate 60 mg/2 L in Dianeal 137 with dextrose 4.25 and 1.5% was filtered through a Peridex CAPD filter set (Millipore); this set has a surface area 27 times larger than an inline intravenous filter. About 25% binding occurred from the solution containing dextrose 4.25%, but only 7.5% was bound with the 1.5% solution.1112
Gentamicin sulfate (Unicet-Unilabo) 0.32 mg/mL in dextrose 5% and sodium chloride 0.9% was filtered through a 0.22-µm cellulose ester membrane filter (Ivex-HP, Millipore) over 6 hours. No significant drug loss due to binding to the filter was noted.1034
Central Venous Catheter
Gentamicin sulfate (Fujisawa) 1 mg/mL in dextrose 5% 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
The activity of gentamicin 10 mg/L was evaluated in peritoneal dialysis fluids containing 1.5 or 4.25% dextrose (Dianeal 137, Travenol). Storage at 25°C resulted in no loss of antimicrobial activity in 24 hours.515
Gentamicin sulfate (Schering) 3 and 10 mg/L in peritoneal dialysis concentrate with 50% dextrose retained about 90% of initial activity in 7 hours and about 50 to 70% in 24 hours at room temperature.1044
The stability of gentamicin sulfate 8 mg/L, alone and with cefazolin sodium 75 and 150 mg/L, was evaluated in a peritoneal dialysis solution of dextrose 1.5% with heparin sodium 1000 units/L. Gentamicin activity was retained for 48 hours at both 4 and 26°C, alone and with both concentrations of cefazolin. Cefazolin activity was also retained over the study period. At 37°C, gentamicin losses ranged from 4 to 8% and cefazolin losses ranged from 10 to 12% in 48 hours.1029
In another study, the stability of gentamicin sulfate (Schering) was evaluated in peritoneal dialysate concentrates containing dextrose 30 and 50% (Dianeal) as well as in a diluted solution containing dextrose 2.5%. The gentamicin sulfate concentrations were 100 and 160 mg/L in the peritoneal dialysate concentrates and 5 and 8 mg/L in the diluted solutions. Gentamicin sulfate was found to be stable in all of these solutions for at least 24 hours at 23°C.1229
Gentamicin 4 mcg/mL was evaluated in Dianeal PDS with dextrose 1.5 and 4.25% (Travenol) with cefazolin 125 mcg/mL, heparin 500 units, and albumin human 80 mg in 2-L bags. The gentamicin content was retained for 72 hours.1413
The retention of antimicrobial activity of gentamicin sulfate (SoloPak) 120 mg/L alone and with vancomycin hydrochloride (Lilly) 1 g/L was evaluated in Dianeal PD-2 (Travenol) with dextrose 1.5%. Little or no loss of either antibiotic occurred in 8 hours at 37°C. Gentamicin sulfate alone retained activity for at least 48 hours at 4 and 25°C. In combination with vancomycin hydrochloride, antimicrobial activity of both antibiotics was retained for up to 48 hours. However, the authors recommended refrigeration at 4°C for storage periods greater than 24 hours.1414
Gentamicin sulfate (Schering) 25 mcg/mL combined separately with the cephalosporins cefazolin sodium (Lilly) and cefoxitin (MSD) at a concentration of 125 mcg/mL in peritoneal dialysis solution (Dianeal 1.5%) exhibited enhanced rates of lethality to Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa compared to any of the drugs alone.1623
Gentamicin sulfate (American Pharmaceutical Partners) 8 mcg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) is stable with little or no loss occurring in 14 days refrigerated and at room temperature.2573
Gentamicin sulfate (American Pharmaceutical Partners) 8 mcg/mL with vancomycin hydrochloride (Lederle) 25 mcg/mL in Delflex peritoneal dialysis solution bags with 2.5% dextrose (Fresenius) is stable with little or no loss of either drug occurring in 14 days refrigerated and at room temperature.2573
Gentamicin sulfate (Pfizer) 20 mg/L in Extraneal with icodextrin 7.5% (Baxter) peritoneal dialysis solution bags exhibited less than 10% loss in 14 days at 37, 25, and 4°C.3537 Gentamicin sulfate (Pfizer) 20 mg/L with vancomycin hydrochloride (Hospira) 1 g/L in Extraneal with icodextrin 7.5% (Baxter) peritoneal dialysis solution bags exhibited less than 10% loss of either drug in 14 days at 25 and 4°C and 3% loss of gentamicin and 7% loss of vancomycin in 4 days at 37°C.3537 Gentamicin sulfate (Pfizer) 20 mg/L and cefazolin sodium (Hospira) 500 mg/L in Extraneal with icodextrin 7.5% (Baxter) peritoneal dialysis solution bags exhibited less than 10% loss of either drug in 14 days at 4°C, no loss of gentamicin and 7% loss of cefazolin in 4 days at 25°C, and 1% loss of gentamicin and 5% loss of cefazolin in 1 day at 37°C.3537
ß-Lactam Antibiotics
In common with other aminoglycoside antibiotics, gentamicin activity may be impaired by ß-lactam antibiotics. The inactivation is dependent on concentration, temperature, and time of exposure.68; 219; 504; 574; 575; 654; 667; 740; 792; 816; 824; 973; 1052; 1382
The clinical significance of these interactions in patients appears to be primarily confined to those with renal failure.218; 334; 361; 364; 616; 737; 816; 847 Literature reports of greatly reduced aminoglycoside levels in such patients have appeared frequently.363; 365; 366; 367; 614; 666; 962 In addition, the interaction may be clinically important if assays for aminoglycoside levels in serum are sufficiently delayed.576; 618; 735; 832; 847; 1052; 1382
Most authors believe that in vitro mixing of penicillins with aminoglycoside antibiotics should be avoided but that clinical use of the drugs in combination can be of great value. It is generally recommended that the drugs be given separately in such combined therapy.157; 218; 222; 224; 361; 364; 368; 369; 370
Local Anesthetics
Gentamicin sulfate 80 mg (2 mL) was physically compatible with 1 mL of each of the following local anesthetics and did not show significant loss in 24 hours at room temperature or under refrigeration:227
Heparin
Addition of gentamicin sulfate (Roussel) 80 mg to the tubing of an infusion solution of sodium chloride 0.9% containing heparin resulted in immediate precipitation.528
Gentamicin sulfate 10 mg/L with heparin sodium 1000 units/L in Dianeal with dextrose 5% peritoneal dialysis solution was reported to be conditionally compatible. No significant reduction in gentamicin sulfate concentration occurred in 4 to 6 hours.228 However, a marked reduction in the anticoagulant activity of heparin sodium occurred if opalescence or a precipitate formed (which results if the undiluted drugs are combined), even if the precipitate redissolved. Heparin activity was retained if one drug was added to a dilute solution of the other and no precipitate formed.295
The incompatibility of heparin sodium with gentamicin sulfate is said to result from coprecipitation.230
A white precipitate may result from the administration of gentamicin sulfate through a heparinized intravenous cannula.976 Flushing heparin locks with sodium chloride 0.9% before and after administering drugs incompatible with heparin has been recommended.4
Sodium Citrate
The physical stability of gentamicin sulfate (Schering) 1, 2, and 5 mg/mL in sodium citrate 4% anticoagulant solution (Baxter) was evaluated. The combination has been used in preventing hemodialysis catheter-related infections. The gentamicin dilutions were packaged in 3-mL syringes and were stored at 4 and 23°C. The solutions remained clear and colorless for 35 days at both temperatures. The pH was found to be near 5.1 initially and did not change throughout the study. Although the gentamicin content was not measured, the authors pointed out that other studies had reported that the drug in solutions within the pH range of 4 to 7 was stable for up to 90 days. Furthermore, in another study, sodium citrate also had been documented to be stable for 28 days at room temperature.2631
Gentamicin sulfate (Sandoz) 2.5 mg/mL in sodium citrate 4% (Cytasol) was found to be physically and chemically stable for 112 days at 24°C packaged in polyethylene plastic syringes sealed with tip caps.2824
For a list of references cited in the text of this monograph, search the monograph titled References.