benzathine benzylpenicillin
Long-acting penicillin antibiotic· Brands: Bicillin L-A, Penidure, Retarpen, PermapenIM
Mechanism of action
Benzathine benzylpenicillin is a long-acting penicillin antibiotic. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) on the bacterial cell membrane, thereby preventing cross-linking of peptidoglycan chains. This action leads to cell wall weakening and lysis in susceptible organisms. The benzathine salt forms a depot at the injection site, releasing penicillin slowly over time, allowing sustained plasma concentrations.
Pharmacokinetics
The terminal half-life is long, typically about 3 to 7 days, with detectable serum concentrations persisting for 2 to 4 weeks, allowing for infrequent dosing, often once every 2 to 4 weeks for prophylaxis.
Indications & dosing
Primary and secondary syphilis
Also used for early latent syphilis (<1 year). Give as a single deep IM injection. Treat all sexual contacts.
- adult · IM: 2.4 million units single dose · Also used for early latent syphilis (<1 year). Give as a single deep IM injection. Treat all sexual contacts.
Late latent syphilis (or unknown duration)
Administered once weekly for 3 consecutive weeks. Refer to local STI guidelines for follow-up.
- adult · IM: 2.4 million units weekly for 3 weeks · Administered once weekly for 3 consecutive weeks. Refer to local STI guidelines for follow-up.
Rheumatic fever prophylaxis
For prevention of recurrent rheumatic fever. Consider every 3 weeks in high-risk patients. Continue per local guidelines.
- adult · IM: 1.2 million units every 4 weeks · For prevention of recurrent rheumatic fever. Consider every 3 weeks in high-risk patients. Continue per local guidelines.
Rheumatic fever prophylaxis
For children weighing <27 kg. For children >=27 kg, give 1.2 million units.
- pediatric · IM: 0.6 million units every 4 weeks · For children weighing <27 kg. For children >=27 kg, give 1.2 million units.
Group A streptococcal pharyngitis
Used when oral therapy is not feasible or adherence is a concern. Oral penicillin V is a preferred alternative.
- adult · IM: 1.2 million units single dose · Used when oral therapy is not feasible or adherence is a concern. Oral penicillin V is a preferred alternative.
Group A streptococcal pharyngitis
For children weighing <27 kg. For children >=27 kg, use 1.2 million units.
- pediatric · IM: 0.6 million units single dose · For children weighing <27 kg. For children >=27 kg, use 1.2 million units.
Congenital syphilis
For asymptomatic congenital syphilis. If CSF abnormalities or symptomatic, use aqueous penicillin G for 10 days.
- neonatal · IM: 50000 units/kg single dose · For asymptomatic congenital syphilis. If CSF abnormalities or symptomatic, use aqueous penicillin G for 10 days.
Contraindications & precautions
- Hypersensitivity to benzathine benzylpenicillin, other penicillins, or any component of the formulation
- History of severe immediate hypersensitivity reaction (e.g., anaphylaxis) to beta-lactam antibiotics
- Intravenous or intra-arterial administration · For IM use only; these routes may cause severe complications
- Confirm absence of penicillin allergy before administration; ask about previous allergic reactions
- Use with caution in renal impairment; consider dose adjustment with prolonged high-dose therapy
- Administer by deep intramuscular injection into the upper outer quadrant of the buttock; do not give intravenously or subcutaneously
- Monitor for Jarisch-Herxheimer reaction when treating syphilis; warn patients about expected symptoms
- Be alert to superinfection with prolonged use, particularly candida and Clostridium difficile
- Keep resuscitation equipment and adrenaline (epinephrine) available for anaphylaxis
Adverse effects
- Injection site pain and inflammation
- Allergic skin reactions (rash, pruritus, urticaria)
- Jarisch-Herxheimer reaction (fever, chills, myalgia)serious
- Anaphylaxisserious
- Convulsions (especially with high doses or in renal impairment)serious
- Blood dyscrasias (e.g., neutropenia, thrombocytopenia)serious
- Severe cutaneous reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)serious
- Pseudomembranous colitis (Clostridium difficile infection)serious
Renal & hepatic adjustment
- eGFR 30+: No dose adjustment required.
- eGFR 10–29: Use with caution; consider increasing the dosing interval.
- eGFR 0–9: Avoid in severe renal impairment; consider alternative therapy. (avoid)
Monitoring, pregnancy & toxicity
- Signs of hypersensitivity or anaphylaxis · During and after each injection
- Injection site reaction · At each injection
- Renal function · In prolonged therapy
- Serologic response · For syphilis treatment, at 6 and 12 months after treatment
- Pregnancy: Benzathine benzylpenicillin is the treatment of choice for syphilis in pregnancy. It is considered safe and is recommended for treating pregnant women with syphilis to prevent congenital transmission.
- Toxicity: Hypersensitivity reactions, including anaphylaxis · Stop drug, give epinephrine, oxygen, IV fluids; consider antihistamines and corticosteroids.
- Toxicity: Neurotoxicity (e.g., seizures, confusion) with very high doses or in renal impairment · Discontinue drug; supportive care; consider haemodialysis.
- Toxicity: Jarisch-Herxheimer reaction (when treating syphilis) · Explain to patient; treat symptomatically with paracetamol; usually self-limiting.
Clinical notes
Benzathine benzylpenicillin is indicated for the treatment of syphilis, particularly primary, secondary, and early latent syphilis, and for prophylaxis of rheumatic fever. It is also used for the treatment of other penicillin-sensitive infections where sustained concentrations are required. The recommended dose for primary and secondary syphilis is 2.4 million units IM as a single dose, per local guidelines. For rheumatic fever prophylaxis, 1.2 million units IM every 3 to 4 weeks is commonly used. Ensure proper IM injection technique into the upper outer quadrant of the gluteus maximus; do not give intravenously or subcutaneously. Monitor for local pain, induration, and signs of hypersensitivity, including anaphylaxis. Contraindicated in patients with a history of penicillin allergy. Use with caution in patients with renal impairment.
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BNF; local formulary