Benzathine Penicillin

• Approved Indications:
• Treatment of streptococcal pharyngitis and tonsillitis caused by Streptococcus pyogenes.
• Prevention of recurrent rheumatic fever and associated heart disease.
• Treatment of syphilis, including primary, secondary, and early latent stages.
• Management of yaws and other treponemal infections.
• Treatment of susceptible infections caused by Streptococcus species and certain susceptible Staphylococcus strains.
• Off-label and Clinically Accepted Uses:
• Prophylaxis of bacterial endocarditis in high-risk patients undergoing dental or surgical procedures (where indicated).
• Adjunctive therapy in other susceptible bacterial infections requiring prolonged low-level penicillin exposure.

• Route: Intramuscular (IM) injection only; not for intravenous or oral use.
• Adults:
• Streptococcal infections: 1.2 million units as a single IM dose.
• Rheumatic fever prophylaxis: 1.2 million units IM every 3 to 4 weeks.
• Syphilis (early stages): 2.4 million units IM as a single dose.
• Late latent syphilis or tertiary syphilis: 2.4 million units IM once weekly for 3 consecutive weeks (total 7.2 million units).
• Yaws: 1.2 million units IM as a single dose.
• Pediatrics:
• Dose adjusted by weight (generally 50,000 units/kg, max 1.2 million units) administered IM.
• Rheumatic fever prophylaxis doses similar to adults, adjusted for weight.
• Elderly:
• Dose adjustments usually not required; administer with caution considering comorbidities.
• Special Populations:
• Use cautiously in patients with renal impairment; no specific dose adjustment but monitor renal function.
• Avoid use in patients with known penicillin allergy.
• Administration Notes:
• Deep intramuscular injection is essential (preferably into the gluteal muscle) to minimize pain and ensure slow absorption.
• Do not administer intravenously due to risk of severe reactions.

Benzathine penicillin is a long-acting, depot formulation of penicillin G. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), which interferes with the final transpeptidation step of peptidoglycan cross-linking in the bacterial cell wall. This leads to cell lysis and death in actively dividing, susceptible gram-positive bacteria such as Streptococcus species and Treponema pallidum. The benzathine salt form allows slow release from the injection site, maintaining bactericidal concentrations over prolonged periods.

• Absorption:
  After IM injection, benzathine penicillin is slowly absorbed, providing low but sustained plasma concentrations lasting 2 to 4 weeks.
• Distribution:
  Widely distributed in body tissues and fluids, but poorly penetrates the cerebrospinal fluid unless meninges are inflamed.
• Metabolism:
  Minimal metabolism; penicillin is primarily excreted unchanged.
• Elimination:
  Excreted mainly by the kidneys via glomerular filtration and tubular secretion.
• Half-life:
  Prolonged due to depot formulation; serum penicillin levels remain bactericidal for up to 4 weeks.

• Pregnancy:
  Classified as FDA Category B. Animal studies have shown no risk, and clinical use in pregnancy is considered safe and often necessary, especially for syphilis treatment.
• Lactation:
  Penicillin is excreted into breast milk in small amounts but considered safe for breastfeeding mothers.

• Primary Therapeutic Class: Antibiotic
• Subclass: Beta-lactam, Penicillin, Long-acting depot formulation

• Known hypersensitivity or allergic reactions to penicillins or beta-lactam antibiotics.
• History of severe allergic reaction (e.g., anaphylaxis) to any penicillin.
• Do not administer intravenously due to risk of severe reactions.

• Perform skin testing if penicillin allergy is suspected.
• Use cautiously in patients with a history of asthma or other allergic conditions.
• Monitor for signs of hypersensitivity reactions including rash, anaphylaxis, or serum sickness-like reactions.
• Rare cases of neurotoxicity reported in high doses or impaired renal function.
• Avoid use in patients with known severe renal impairment without careful monitoring.
• Appropriate facilities for managing anaphylaxis must be available when administering.

• Common:
• Pain, swelling, or inflammation at the injection site.
• Mild gastrointestinal upset (nausea, diarrhea).
• Serious but Rare:
• Hypersensitivity reactions: urticaria, angioedema, anaphylaxis.
• Serum sickness-like reactions: fever, rash, arthralgia.
• Hematologic effects: hemolytic anemia, neutropenia, thrombocytopenia.
• Neurotoxicity in overdose or renal impairment.

• May reduce effectiveness of oral contraceptives (rare).
• Probenecid prolongs penicillin plasma levels by inhibiting renal tubular secretion.
• Concurrent use with aminoglycosides can be synergistic but requires careful monitoring.
• Potential interaction with methotrexate increasing toxicity.
• No significant involvement of CYP450 enzyme systems.

• Benzathine penicillin remains the gold standard for syphilis treatment and rheumatic fever prophylaxis per WHO, CDC, and international guidelines.
• Updated guidelines emphasize ensuring proper dosing intervals for rheumatic fever prevention to avoid breakthrough infections.
• Ongoing monitoring for penicillin allergy prevalence and management protocols.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from freezing and excessive heat.
• Keep the vial tightly closed and protected from light.
• Do not use if suspension is discolored or contains particulate matter after reconstitution.
• Use immediately after reconstitution; discard any unused portion.