Benzathine Penicillin G Dilution
Benzathine penicillin G (Bicillin) is administered intramuscularly without dilution as supplied by the manufacturer, but dilution with 1% lidocaine or mepivacaine significantly reduces injection pain without affecting drug efficacy. 1, 2
Standard Administration
- Benzathine penicillin G is given as an intramuscular injection in the undiluted form as packaged, typically as a pre-mixed suspension requiring no preparation. 3, 4
- The standard adult dose for early syphilis is 2.4 million units IM as a single injection. 3, 4
- For late latent syphilis, three doses of 2.4 million units IM are given at weekly intervals (total 7.2 million units). 3, 4
Pain Reduction Through Dilution
- Diluting benzathine penicillin G with 0.5 mL of 1% mepivacaine significantly reduces immediate injection pain (mean pain intensity 2.92-3.36 with anesthesia vs. 5.06-5.56 without anesthesia on a 0-10 scale, p<0.001). 1
- Dilution with 1% lidocaine hydrochloride (3.2 mL) does not alter serum penicillin concentrations and maintains therapeutic efficacy while significantly reducing pain scores. 2
- Peak serum penicillin concentrations at 24 hours were identical whether diluted with sterile water (0.100 μg/mL) or lidocaine (0.102 μg/mL). 2
Practical Dilution Technique
- When diluting for pain reduction, use 1% lidocaine or 1% mepivacaine as the diluent rather than sterile water alone. 1, 2
- The volume of local anesthetic used ranges from 0.5 mL to 3.2 mL depending on the protocol. 1, 2
- Needle gauge (19G vs 21G) does not affect pain intensity, so dilution with anesthetic is the key intervention. 1
Alternative Dosing Strategy for Tolerability
- For the 2.4 million unit dose, the injection can be split into two 1.2 million unit injections (one in each buttock) without compromising efficacy, and this approach is equally well tolerated as a single 2.4 million unit injection. 5
- Patients show no preference between single-dose and divided-dose techniques when given the choice. 5
Critical Caveats
- Never dilute or modify benzathine penicillin G for neurosyphilis—it should never be used for CNS disease regardless of preparation; aqueous crystalline penicillin G IV is required instead. 3, 4
- Dilution with local anesthetics is an off-label practice supported by research evidence but not explicitly mentioned in CDC treatment guidelines. 1, 2
- The primary concern is ensuring adequate treponemicidal levels, which are maintained with proper dilution techniques. 2