Penicillin G potassium is available as a powder in vials containing 5 million or 20 million units of penicillin G as the potassium salt with sodium citrate and citric acid as buffers.3892; 3893 Depending on the intended route of administration, reconstitute the vials with sterile water for injection or sodium chloride 0.9%.3892; 3893 The recommended reconstitution volumes may vary slightly between manufacturers; the amount of diluent indicated in the specific product labeling should be used for reconstitution.3892; 3893 To reconstitute the drug, loosen the powder in the vial.3893 While holding the vial horizontally, rotate it and add the diluent slowly, directing the stream against the wall of the vial.3893 Shake the vial vigorously.3893 When the required volume of solvent is greater than the capacity of the vial, a portion of the total volume of diluent may be added to the vial first to dissolve the drug.3892; 3893 The resulting solution should then be withdrawn and mixed with the remainder of the needed diluent in a larger container.3892; 3893
Penicillin G potassium is also available as a frozen premixed infusion solution in single-dose Galaxy plastic containers containing the equivalent of 1, 2, and 3 million units of penicillin G in 50-mL bags with dextrose 2 g, 1.2 g, and 350 mg, respectively, in water with sodium citrate buffer.3894 Hydrochloric acid and/or sodium hydroxide may have been used to adjust the pH during manufacture.3894
pH
Reconstituted solutions have a pH of 6 to 8.5.3892; 3893 The frozen premixed infusion solutions have a pH of 5.5 to 8.3894
Osmolality
The frozen premixed penicillin G potassium infusion solutions are iso-osmotic.3894
The osmolality of penicillin G potassium (Pfizer) 250,000 units/mL in sterile water for injection was determined to be 776 mOsm/kg by freezing-point depression and 767 mOsm/kg by vapor pressure.1071 Another report cited the osmolality of this concentration as 749 mOsm/kg.50
The osmolality of penicillin G potassium 50,000 units/mL was 402 mOsm/kg in dextrose 5% and 414 mOsm/kg in sodium chloride 0.9%. At 100,000 units/mL, the osmolality was 535 mOsm/kg in dextrose 5% and 554 mOsm/kg in sodium chloride 0.9%.1375
The osmolality of penicillin G potassium was calculated for the following dilutions:1054
| Osmolality (mOsm/kg) | ||
|---|---|---|
| Penicillin G in Diluent | 50 mL | 100 mL |
| 3 million units in Dextrose 5% | 411 | 340 |
| 3 million units in Sodium chloride 0.9% | 437 | 367 |
| 5 million units in Dextrose 5% | 501 | 394 |
| 5 million units in Sodium chloride 0.9% | 527 | 420 |
The following maximum penicillin G potassium concentrations were recommended to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients:1180
| Diluent | Maximum Concentration (units/mL) | Osmolality (mOsm/kg) |
|---|---|---|
| Dextrose 5% | 81,568 | 566 |
| Sodium chloride 0.9% | 73,455 | 545 |
| Sterile water for injection | 147,205 | 513 |
Sodium and Potassium Content
Penicillin G potassium contains, in each million units, 65.6 mg (1.7 mEq) of potassium and 7.9 mg (0.3 mEq) of sodium.3892
Trade Name(s)
Buffered Pfizerpen
NOTE: Do not confuse other forms of penicillin G with penicillin G potassium.
Penicillin G potassium is administered by intramuscular injection or intravenous infusion.3892; 3893 The drug may also be administered by intrathecal, intra-articular, or intrapleural injection and other local instillations.3892; 3893 Vials containing 20 million units are intended for intravenous infusion only.3892; 3893 For intramuscular injection, concentrations of up to 100,000 units/mL will cause minimal discomfort; however, higher concentrations may be used when needed.3892; 3893
Intravenous infusion of high doses (i.e., over 10 million units) should be administered slowly to avoid electrolyte imbalance from the potassium content.3892; 3893
Penicillin G potassium is a white to almost white powder that forms a colorless solution upon reconstitution.3893 Intact vials of penicillin G potassium powder should be stored at controlled room temperature3893 or below 30°C.3892 The reconstituted solution is stated to be stable for 7 days under refrigeration.3892; 3893
However, penicillin G potassium 500,000 units/mL was stored at room temperature and 4°C. After 24 hours at room temperature, a new compound formed, which increased by 72 hours. Storage at 4°C substantially reduced the rate of formation. Although the activity of penicillin G potassium was retained over the time period, its potential as an antigen may change due to formation of polymers or conjugation products that may cause allergic reactions. It was recommended that the drug be freshly prepared before use or refrigerated during storage.785
Another study found increased formation of specific antipenicillin antibodies in patients administered aged penicillin solutions, not only at room temperature, but also 4°C. The causative antigens were degradation or transformation products of penicillin G. Freshly prepared solutions did not seem to be immunogenic.946
Frozen premixed solutions in single-dose Galaxy containers should be stored at -20°C.3894 Solutions should be thawed at room temperature (25°C) or under refrigeration (5°C); solutions should not be force thawed by immersion in water baths or microwaving.3894 Thawed solutions are stable for 24 hours at room temperature or 14 days at 5°C.3894 Thawed solutions should not be refrozen.3894 The manufacturer states that precipitation may occur in the frozen solution which will dissolve with little or no agitation upon reaching room temperature.3894 The container should be agitated upon reaching room temperature.3894 Discard the solution if it is cloudy or precipitate is present.3894
pH Effects
The stability of penicillin G potassium 500,000 units/mL is greatest at pH 7.160 Penicillin G activity rapidly declines at pH 5.5 and below and at pH values above 8.47
Penicillin G potassium is both an acid- and alkali-labile drug. It should not be mixed with drugs that may result in a final pH outside of its stability range of pH 5.5 to 8.47 Unfortunately, the citrate buffer is of little value in the presence of strongly acidic or alkaline drugs.48
The times to 10% decomposition of combinations of penicillin G potassium buffered with multivitamin infusion concentrate in dextrose 5% and sodium chloride 0.9% have been calculated on the basis of the final pH of the admixture:304
| Penicillin G Potassium | Multivitamin Infusion Concentrate | pH | Time to 10% Decomposition |
|---|---|---|---|
| 1 million units/L | 1 mL/L | 5.1 | 6.51 hr |
| 1 million units/L | 5 mL/L | 4.9 | 4.56 hr |
| 3 million units/L | 1 mL/L | 5.4 | 13.54 hr |
| 3 million units/L | 5 mL/L | 5 | 6.38 hr |
| 5 million units/L | 1 mL/L | 5.7 | 22.01 hr |
| 5 million units/L | 5 mL/L | 5.1 | 6.51 hr |
| 10 million units/L | 1 mL/L | 5.9 | over 24 hr |
| 10 million units/L | 5 mL/L | 5.4 | 13.54 hr |
Freezing Solutions
Penicillin G potassium 1 million units/100 mL of dextrose 5% in polyvinyl chloride (PVC) bags was frozen at -20°C for 30 days and then thawed by exposure to ambient temperature or microwave radiation. No evidence of precipitation or color change was observed, and a 3 to 4% loss was reported. The thawed solution at room temperature was physically compatible and exhibited no further loss over 24 hours.554
A fivefold increase in particles of 2 to 60 µm was produced by freezing and thawing penicillin G potassium (Squibb) 2 million units/100 mL of dextrose 5% (Travenol). The constituted drug was filtered through a 0.45-µm filter into PVC bags of solution and frozen for 7 days at -20°C. Thawing was performed at 29°C for 12 hours. Although the total number of particles increased significantly, no particles greater than 60 µm were observed; the solutions complied with USP standards for particle sizes and numbers in large volume parenteral solutions.822
Penicillin G potassium 1 million units/50 mL of dextrose 5% lost 5% in 16 days and 7% in 25 days when frozen at -7°C. However, samples of the same solution stored at 4°C showed similar results, indicating a lack of advantage for frozen storage.1035
Ambulatory Pumps
The stability of penicillin G potassium 100,000 and 200,000 units/mL in sterile water for injection was evaluated in PVC portable pump reservoirs (Pharmacia Deltec). A 6% loss occurred in 3 days at 25°C. The 200,000-unit/mL concentration was also tested stored at 5°C. A 3% loss occurred in 14 days.2080
Elastomeric Reservoir Pumps
Penicillin G potassium (Pfizer) 40,000 units/mL in both dextrose 5% and sodium chloride 0.9% was evaluated for binding potential to natural rubber elastomeric reservoirs (Baxter). No binding was found after storage for 2 weeks at 35°C with gentle agitation.2014
Filtration
Filtering penicillin G potassium (Pfizer) through 5-µm stainless steel and 0.22-µm cellulose ester inline filters resulted in no significant reduction in activity under conditions of varying doses, temperatures, flow rates, and administration methods.167
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Peritoneal Dialysis Solutions
The activity of penicillin G 6 mg/L was evaluated in peritoneal dialysis fluids containing dextrose 1.5 and 4.25% (Dianeal 137, Travenol). Storage at 25°C resulted in about a 25% loss of antimicrobial activity in 24 hours. The loss of activity was attributed to the pH (5.2) of the dialysis fluids.515
However, penicillin G potassium (Parke-Davis) 500,000 units/L in peritoneal dialysis concentrate (Travenol) containing dextrose 30% with and without heparin sodium 2500 units/L underwent substantial reduction in activity within as little as 10 minutes.273
For a list of references cited in the text of this monograph, search the monograph titled References.