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# Benzathine benzylpenicillin

An intramuscular depot of penicillin G that releases the drug for weeks: the mainstay for syphilis and for preventing rheumatic fever.

Updated 2026-11-01

- Class: [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/)
- Enzyme: Penicillin-binding proteins (bacterial DD-transpeptidases)
- ATC code: J01CE08
- WHO Model List of Essential Medicines

Also called: benzathine penicillin G, penicillin G benzathine

✂**Penicillin-binding proteins (bacterial DD-transpeptidases)**Benzathine benzylpenicillin

ⓘ The figure shows the DD-peptidase of Streptomyces R61, the classic PBP model, acylated by penicillin G (the active molecule the benzathine salt releases).

**Target in 3D:** Penicillin-binding proteins (bacterial DD-transpeptidases). PDB structure 1PWC (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/1PWC) · Drag to rotate · pinch to zoom

## Mechanism of action

It is a poorly soluble salt of penicillin G. Injected into muscle it forms a depot that dissolves slowly and keeps low but long-lasting penicillin G levels, which acylate the PBPs and stop wall synthesis. Treponema pallidum and group A streptococcus remain susceptible, and the long action avoids relying on many doses.

- The intramuscular injection forms a crystal depot
- The depot releases penicillin G slowly for weeks
- Penicillin G acylates the PBPs of Treponema and streptococci
- Dividing bacteria lose their wall and die

## Pharmacokinetics

**Absorption**
Very slow absorption from muscle; low, sustained levels.

**Elimination**
The released penicillin is eliminated by the kidney.

**Onset and duration**
Slow; not suitable when high levels are needed quickly, as in neurosyphilis or meningitis.

## Indications

- Primary, secondary and latent syphilis, including syphilis in pregnancy to prevent congenital syphilis. [Syphilis →](https://durgical.com/en/conditions/syphilis/)
- Long-term secondary prophylaxis of rheumatic fever and rheumatic heart disease. [Rheumatic heart disease →](https://durgical.com/en/conditions/rheumatic-heart-disease/)
- Group A streptococcal pharyngitis, with a single injection. [Streptococcal pharyngitis →](https://durgical.com/en/conditions/streptococcal-pharyngitis/)

## Adverse effects

### Common

- Pain, hardening or a lump at the injection site
- Jarisch–Herxheimer reaction (fever, chills, headache, myalgia) in the first hours when treating early syphilis

### Serious (rare, important)

- Anaphylaxis
- Cardiorespiratory arrest and death if injected into a vein by mistake
- Nerve or vascular injury or necrosis from injection near nerves or arteries, especially in children

## Contraindications

- History of a hypersensitivity reaction to any penicillin (in pregnancy with syphilis the patient is desensitised rather than switched)
- Intravenous use: it is forbidden

## Key interactions

**Probenecid**
Reduces tubular secretion: higher and longer-lasting β-lactam levels.

**Tetracyclines and other bacteriostatic drugs**
May reduce penicillin's bactericidal effect.

## What is monitored

- In syphilis, serial non-treponemal tests to confirm the response
- Observe the patient after the injection for allergic reaction

## Administration and safety

- Deep intramuscular only, into a large muscle (gluteal in adults, lateral thigh in small children). Never intravenous.
- Aspirate before injecting and stop if blood or severe immediate pain appears.
- Do not confuse it with procaine benzylpenicillin or the benzathine–procaine mix: they are not interchangeable in syphilis.
- It is a thick suspension: injected slowly and steadily.

## Nursing care

- Before the first dose: ask about allergy to penicillins, cephalosporins and other β-lactams, and what the reaction was.
- Keep the patient under observation after the injection with anaphylaxis equipment ready.
- Warn that fever and malaise may come a few hours later (Jarisch–Herxheimer); in pregnancy it can trigger contractions, but treatment is not delayed.
- In rheumatic fever prophylaxis, schedule and remind each injection: adherence is what protects.
- In syphilis, offer testing and treatment to sexual partners.

## Pregnancy and breastfeeding

Parenteral penicillin G is the only treatment with documented efficacy for syphilis in pregnancy and prevents congenital syphilis; if there is allergy, the patient is desensitised.

## Memory aid

'Benzathine = bank': penicillin is deposited in the muscle and withdrawn slowly for weeks. You never rob a bank through the vein: never intravenous.

## Test yourself

Think of the answer, then tap the question to see it.

## Why is benzathine penicillin not used for neurosyphilis?

Because it releases low penicillin levels that do not reach adequate concentrations in the cerebrospinal fluid; neurosyphilis needs intravenous penicillin G.

## What is done for a pregnant woman with syphilis and penicillin allergy?

She is desensitised and treated with penicillin, because it is the only treatment with documented efficacy to prevent congenital syphilis.

## Hours after treatment for secondary syphilis, the patient has fever, chills and myalgia. What is it?

Most likely a Jarisch–Herxheimer reaction, from products released by dying treponemes; it is not a penicillin allergy.

## What is the most dangerous administration error with this drug?

Injecting it into a vein: it can cause cardiorespiratory arrest and death. It is given by deep intramuscular injection only.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/benzathine-benzylpenicillin/)

## Related drugs

- [Benzylpenicillin (penicillin G)](https://durgical.com/en/pharmacology/benzylpenicillin/)
- [Procaine benzylpenicillin](https://durgical.com/en/pharmacology/procaine-benzylpenicillin/)
- [Phenoxymethylpenicillin (penicillin V)](https://durgical.com/en/pharmacology/phenoxymethylpenicillin/)

## Related conditions

- [Syphilis](https://durgical.com/en/conditions/syphilis/)
- [Rheumatic heart disease](https://durgical.com/en/conditions/rheumatic-heart-disease/)
- [Streptococcal pharyngitis](https://durgical.com/en/conditions/streptococcal-pharyngitis/)

[← Back to the class: Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Penicillin G Benzathine Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a615051.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Syphilis - STI Treatment Guidelines](https://www.cdc.gov/std/treatment-guidelines/syphilis.htm) (Centers for Disease Control and Prevention (CDC), 2021); [Rheumatic heart disease](https://www.who.int/news-room/fact-sheets/detail/rheumatic-heart-disease) (World Health Organization, 2024); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025).

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Representative model, for educational purposes only.

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