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The use of parenteral benzylpenicillins for the treatment of syphilis


UK Medicines Information summarises the evidence for this frequently asked question:

How are parenteral benzylpenicillins used in the treatment of syphilis?


Parenteral benzylpenicillin (also known as penicillin G) is the preferred drug treatment for all stages of syphilis. The long-acting forms of benzylpenicillin used to treat syphilis are procaine benzylpenicillin and benzathine benzylpenicillin, which are administered by deep intramuscular (IM)?injection (these medicines are not licensed in the UK, but are available from specials manufacturers or importers).

Usually, for the treatment of syphilis procaine benzylpenicillin is given once daily and benzathine benzylpenicillin is given once weekly or as a single dose. The recommended dose, duration and preparation varies according to the stage of disease and between guidelines.

For early syphilis, a single IM dose of benzathine benzylpenicillin (2.4 million units) is recommended. Alternatively, IM procaine benzylpenicillin can be given at a dose of 600,000 units daily for 10 days.

For late-latent, cardiovascular and gummatous syphilis, IM benzathine benzylpenicillin (2.4 million units) administered once weekly for three doses is recommended. Alternatively, IM procaine benzylpenicillin can be given (600,000 units) daily for 17 days.

For the treatment of neurosyphilis, UK guidance recommends the use of daily IM procaine benzylpenicillin (1.8–2.4 million units) plus oral probenecid (500mg four times a day) for 17 days. Alternatively, intravenous aqueous crystalline benzylpenicillin (3–4 million units) can be administered every four hours for 17 days.

The volume of benzathine benzylpenicillin that is required can be large and in such cases the dose can be split and given as two injections at separate sites.

Patients should be informed about possible adverse reactions, in particular the Jarisch-Herxheimer reaction — an acute febrile illness with headache, myalgia, chills and rigors that occurs most often after the first dose of therapy and usually resolves within 24 hours. However, if there is neurological or ophthalmic involvement the reaction can be fatal.   

Alternative oral antibiotics (eg, doxycycline) can be used for penicillin- allergic patients and for patients refusing parenteral therapy.

For patients with syphilis and HIV, late syphilis can develop more rapidly and the risk of neurological complications is increased. However, whether or not this should change the treatment approach is unclear.

This FAQ is adapted from a “Medicines Q&A” produced by UK Medicines Information.

The full document, including references, is available online (prepared July 2011).

Citation: Clinical Pharmacist URI: 11092777

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