About Benzathine Penicillin

What is benzathine penicillin?

Benzathine penicillin is long-acting form of penicillin. It is an antibiotic medication (type: beta-lactam antibiotic) useful for the treatment of several bacterial infections. Specifically, it is used to treat streptococcus (strep throat), diphtheria, syphilis, and yaws. It is also used to prevent rheumatic fever.

At present, benzathine penicillin is the only recommended treatment for syphilis in pregnant women. It not only treats the pregnant woman, but also crosses the placental barrier which prevents congenital syphilis. Other medications to treat syphilis, such as erythromycin and azithromycin, do not cross the placental barrier completely and as a result the fetus is not treated.

How is benzathine penicillin also known?

The international nonproprietary name (INN) of benzathine penicillin is benzathine benzylpenicillin. It is also commonly known as benzathine penicillin G (abbreviation: “BPG”), or penicillin G benzathine. Trade names include Bicillin L-A®, Benzetacil®, Penadure LA® among others. An extensive list is available here.

Note that benzathine penicillin should not be confused with other natural penicillin forms, such as penicillin G sodium, penicillin G potassium, or procaine penicillin.

In what doses and forms is benzathine benzylpenicillin available on the market?

Benzathine penicillin is available in the market in three doses: 2.4, 1.2 and 0.6 million international units (MIU). This is equivalent to approximately 1,800 mg, 900 mg and 450 mg of penicillin. Before administering, it is important to confirm the dosage.

Benzathine penicillin is usually supplied as a vial of sterile powder to be reconstituted or as a suspension for injection. Some suppliers offer prefilled syringes, which need to be stored between 2-8⁰C. Please check manufacturer instructions for appropriate storage conditions.

What dose of benzathine penicillin is required to treat a pregnant woman with syphilis?

In 2017, the World Health Organization launched a Guideline on Syphilis screening and treatment for pregnant women. Link to this Guideline here.

The fetus can be easily cured with benzathine penicillin 2.4 MIU once intramuscularly. Additional doses of benzathine penicillin may be required to also treat the pregnant women.

In pregnant women with unknown stage of syphilis or late syphilis (more than two years’ duration), the WHO STI Guideline recommends benzathine penicillin 2.4 MIU intramuscularly once weekly for three consecutive weeks. The interval between consecutive doses of benzathine penicillin should not exceed 14 days.

In pregnant women with early syphilis (less than 2 years duration), the WHO STI Guideline recommends benzathine penicillin 2.4 MIU once intramuscularly.

How should benzathine penicillin be administered?

Benzathine penicillin should be administered by deep intramuscular injection into the upper, outer quadrant of the gluteus maximus (buttocks).

Before administering, you must carefully read the warnings, adverse reactions, dosage, expiry date and administration labelling. To help you administer the injection correctly, the World Health Organization recommends five steps:

  • Interviewing the patient,
  • Preparing the injection,
  • Identifying the injection site and positioning the patient,
  • Administering the injection, and
  • Post-care.

An instruction video can be found here. Take care to avoid injection into blood vessels. Always have an emergency anaphylaxis kit ready at the injection room, prior to giving a penicillin injection.

Is benzathine penicillin contraindicated for any patients?

Benzathine penicillin is contraindicated for patients with severe life-threatening hypersensitivity (anaphylaxis) to penicillin or to another beta-lactam agent. While penicillin allergy (skin rash) is commonly self-reported, it occurs in only one per 10,000 injections. Anaphylaxis, which is a serious, life-threatening allergic reaction, is very rare, occurring in 0 to 3 per 100,000 injections.

To find out whether a patient has a history of severe life-threatening hypersensitivity, ask them if they have had any immediate adverse reactions to penicillin, or other penicillin-based drugs in the past. More details on penicillin allergy and how to manage it are available here.

Patients who have an advanced or unstable cardiac condition are at risk of severe reactions to penicillin treatment. If patient has a pre-existing cardiac condition, you will need to ensure the patient has eaten and is adequately hydrated, and then take extra care when injecting them.

What treatment is recommended for pregnant women when penicillin cannot be used?

When benzathine or procaine penicillin cannot be used (e.g., due to a severe life-threatening hypersensitivity to penicillin and where penicillin desensitization is not possible) or are not available (e.g., due to stockouts), the WHO STI Guideline suggests using, with caution, erythromycin 500 mg orally four times daily for 30 days. Although erythromycin treats the pregnant women, it does not cross the placental barrier completely and as a result the fetus is not treated. It is therefore necessary to treat the newborn infant with penicillin soon after delivery. Alternative options include ceftriaxone 1 g injection daily for 14 days or azithromycin 2 g orally once.

What is the recommended treatment option for infants with confirmed or suspected syphilis?

In infants with confirmed congenital syphilis or infants who are clinically normal, but whose mothers had untreated syphilis, inadequately treated syphilis (including treatment within 30 days of delivery) or syphilis that was treated with non-penicillin regimens, the WHO STI guideline suggests aqueous benzyl penicillin or procaine penicillin.

The dosage would either be aqueous benzylpenicillin (100 000–150 000 U/kg/day) intravenously for 10–15 days or procaine penicillin (50 000 U/kg/day single dose) intramuscularly for 10–15 days. Aqueous benzylpenicillin may be preferred instead of intramuscular injections of procaine penicillin, however this is only if an experienced venipuncturist is available.

Is there a WHO prequalified benzathine penicillin supplier?

No, there is no WHO prequalified supplier at the moment. Several suppliers have received market authorization from Stringent Regulatory Authorities (SRA). Buyers should confirm the approval status directly with the manufacturers or identified partners. In addition, buyers should purchase, whenever possible, quality assured (SRA approved or WHO prequalified) product to ensure product safety and effectiveness.

Are there global shortages of benzathine penicillin?

No, many countries did report shortages of benzathine penicillin in 2016 but the supply has now been restored. WHO is monitoring the market and if you have any questions of concerns, you may report these via this website.

About Benzathine Penicillin:

RHD Action – Benzathine Penicillin G
Médecins Sans Frontières Essential Drugs – Benzathine Benzylpenicillin Injectable

Indications for Benzathine Penicillin:


Centers for Disease Control and Prevention – Syphilis Fact Sheet
World Health Organization Sexually Transmitted Infections (STIs) Fact Sheet

Congenital Syphilis

World Health Organization – WHO Publishes New Estimates on Congenital Syphilis

Rheumatic Heart Disease

World Health Organization Rheumatic Heart Disease – Fact Sheet

Group A Streptococcal Infection

Centers for Disease Control and Prevention Diseases Caused by Group A Streptococcal


World Health Organization Yaws Fact Sheet