How to Dilute Penicillin
For intravenous penicillin G potassium, use Sterile Water for Injection or Sterile Isotonic Sodium Chloride Solution for reconstitution, following the specific concentration table provided in the FDA labeling, and avoid carbohydrate-containing solutions which rapidly inactivate penicillins at alkaline pH. 1
Reconstitution Technique
The proper technique for reconstituting penicillin powder involves three critical steps 1:
- Loosen the powder in the vial first
- Hold the vial horizontally and rotate it while slowly directing the diluent stream against the vial wall (not directly onto the powder)
- Shake vigorously after all diluent has been added
Diluent Selection
Use only Sterile Water for Injection, USP or Sterile Isotonic Sodium Chloride Solution for Parenteral Use 1.
Critical caveat: Never use carbohydrate solutions (dextrose-containing solutions) at alkaline pH, as penicillins are rapidly inactivated under these conditions 1. However, research data shows that penicillin G diluted in 5% dextrose injection remains stable for 21 days when stored at 5°C 2, suggesting this restriction primarily applies to alkaline conditions rather than all dextrose solutions.
Concentration Table for IV Penicillin G
The FDA label provides specific dilution volumes 1:
| Desired Concentration (units/mL) | Volume for 1,000 units | Solvent for 5,000 unit vial | Solvent for 20,000 unit vial |
|---|---|---|---|
| 50,000 units/mL | 20 mL | - | - |
| 100,000 units/mL | 10 mL | - | - |
| 250,000 units/mL | 4 mL | 18.2 mL | 75 mL |
| 500,000 units/mL | 1.8 mL | 8.2 mL | 33 mL |
| 750,000 units/mL | - | 4.8 mL | - |
| 1,000 units/mL | - | 3.2 mL | 11.5 mL |
Route-Specific Considerations
Intramuscular Administration
- Preferred concentration: Up to 100,000 units/mL provides minimum discomfort 1
- Higher concentrations are physically possible but may increase injection pain
- For benzathine penicillin G (IM): Dilution with 1% lidocaine hydrochloride significantly reduces injection pain without altering serum penicillin concentrations 3, 4. Use 3.2 mL of 1% lidocaine as diluent, or 0.5 mL of 1% mepivacaine 3
Intravenous Administration
- For continuous IV drip: Add the total daily dose to the patient's 24-hour fluid requirement and adjust infusion rate accordingly 1
- Example: For 10 million units daily in a patient requiring 2 liters over 24 hours, add 5 million units to each liter and infuse each liter over 12 hours 1
- The 20,000 unit dosage may ONLY be administered by IV infusion, never IM 1
Large Volume Dilution
When the required diluent volume exceeds vial capacity 1:
- Inject only a portion of diluent into the vial
- Withdraw the resulting solution
- Combine with the remaining diluent in a larger sterile container
Storage and Stability
- Refrigerate all reconstituted solutions 1
- Penicillin solutions remain stable for 7 days when refrigerated without significant potency loss 1
- Research confirms 21-day stability at 5°C for solutions of 2,500 or 50,000 units/mL in both 0.9% sodium chloride and 5% dextrose when stored in PVC bags or elastomeric pumps 2