Syphilis treatment for adults and adolescents: Guidance in the event of shortage of benzathine penicillin G long-acting

Last partial content update: June 2026

The Public Health Agency of Canada previously published guidance titled “Interim syphilis treatment guidelines in the event of a benzathine penicillin G L-A shortage.” This guidance replaces it and has been partially updated based on expert advice from the National Advisory Committee on Sexually Transmitted and Blood-Borne Infections (NAC-STBBI).

• The contents of the page have been updated to replace references to the commercial drug “Bicillin® L-A” with the generic drug name “benzathine penicillin G long-acting (LA)”.
• The term “Penicillin G IV’ has been replaced with “short-acting aqueous penicillin G” for greater clarity.
• The outdated recommendations specific to persons living with HIV and for use of azithromycin have been removed.
• The suggestion to defer treatment of late latent syphilis if a shortage is expected to resolve quickly was removed, as shortage duration can be unpredictable and timely treatment is important to prevent complications.
• The recommendation to consider dual therapy with benzathine penicillin G-LA and doxycycline for some cases of latent syphilis of unknown duration was removed.

On this page

• Key information
• Treatment of syphilis during a benzathine penicillin G-LA shortage
  • Recommended treatment for pregnant individuals with syphilis during a benzathine penicillin G-LA shortage
  • Recommended treatment for non-pregnant individuals with syphilis during a benzathine penicillin G-LA shortage
  • Recommended epidemiological treatment for sexual contacts of syphilis during a benzathine penicillin G-LA shortage

Key information

Benzathine penicillin G long-acting (LA) is administered by intramuscular (IM) injection. Bicillin® L-A is an example of a benzathine penicillin G-LA formulation.

For the treatment of syphilis, short-acting aqueous penicillin G is administered by intravenous (IV) injection. Penicillin G Sodium for injection, USP is an example of a short-acting aqueous penicillin G formulation.

When considering epidemiological treatment for individuals who are sexual contacts of someone with syphilis, the syphilis stage of the index case and the recency of sexual contact are relevant. Generally, it is advised to consider epidemiological treatment with benzathine penicillin G-LA for individuals who had sexual contact with a person with infectious syphilis in the 90 days prior to the index case’s diagnosis. In this document, “recent contact” refers to a contact in the 90 days prior to the index case’s diagnosis.

To preserve existing stock when benzathine penicillin G-LA is in limited supply:

• Healthcare providers should consider prioritizing the use of benzathine penicillin G-LA for the treatment of syphilis in: (1) pregnant individuals; and (2) non-pregnant individuals who may not reliably adhere to treatment and follow-up.
• Oral doxycycline should be preferentially used for the treatment of syphilis in non-pregnant individuals in whom adherence to treatment and follow-up is expected.
• For epidemiological treatment of sexual contacts, use of benzathine penicillin G-LA should be prioritized for: (1) pregnant recent sexual contacts of someone with infectious syphilis; and (2) non-pregnant recent sexual contacts of someone with infectious syphilis when adherence with follow-up is uncertain.
• A course of oral doxycycline may be initiated as epidemiological treatment for other recent contacts of infectious syphilis while assessment and test results are pending.

When benzathine penicillin G-LA is unavailable:

• Pregnant individuals with syphilis should be treated with short-acting aqueous penicillin G, as there is no satisfactory alternative to penicillin for syphilis in pregnancy.
• Non-pregnant adolescents and adults with syphilis may be treated with oral doxycycline, IV short-acting aqueous penicillin G, or IM / IV ceftriaxone.
• Short-acting aqueous penicillin G can be initiated as epidemiological treatment for pregnant recent sexual contacts of someone with infectious syphilis.
• A course of oral doxycycline may be initiated as epidemiological treatment for non-pregnant recent sexual contacts of someone with infectious syphilis.

Close clinical and/or serologic follow-up of individuals with syphilis is especially important when non-penicillin regimens are used, to evaluate the treatment response. Refer to the treatment and follow-up section of the syphilis guide for details. Partner notification should also be considered, in alignment with provincial or territorial guidelines. For general information about partner notification, refer to the partner notification section in the STBBI prevention guide: STBBI management. For details about trace-back periods for syphilis, refer to the treatment and follow-up section of the syphilis guide.

The following treatment options are recommended in the absence of contraindications. Consult product monographs for contraindications and potential side effects.

Treatment of syphilis during a benzathine penicillin G-LA shortage

Recommended treatment for pregnant individuals with syphilis during a benzathine penicillin G-LA shortage

Syphilis stage	Treatment when benzathine penicillin G-LA is in limited supply	Treatment when benzathine penicillin G-LA is unavailable
Primary syphilis, secondary syphilis, early latent syphilisFootnote 1Footnote 2Footnote 3Footnote 4	Benzathine penicillin G-LA 2.4 million units IM as a single dose	Short-acting aqueous penicillin G 4 million units IV every 4 hours for 10 days
Latent syphilis of unknown duration, late latent syphilis, tertiary syphilisFootnote 1Footnote 2Footnote 3	Benzathine penicillin G-LA 2.4 million units IM once weekly for 3 doses
Neurosyphilis, including ocular syphilis and otosyphilis	Refer to a neurologist, infectious disease specialist, or experienced colleague
Notes: Footnote 1 Ideally, syphilis in pregnancy should be managed in consultation with an obstetric or maternal-fetal medicine specialist or an experienced colleague. Return to footnote 1 referrer Footnote 2 Since there is no satisfactory alternative to penicillin for syphilis in pregnancy, strongly consider penicillin desensitization followed by treatment with penicillin in pregnant individuals with a reported history of penicillin anaphylaxis. Return to footnote 2 referrer Footnote 3 Not involving the central nervous system, eye nor ear. Return to footnote 3 referrer Footnote 4 Given the complexity of accurately staging early syphilis, some experts recommend that primary, secondary and early latent cases in pregnancy be treated with two doses of benzathine penicillin G-LA 2.4 million units IM administered 1 week apart; the efficacy of this regimen in preventing congenital syphilis is not known. Return to footnote 4 referrer

Recommended treatment for non-pregnant individuals with syphilis during a benzathine penicillin G-LA shortage

Syphilis stage	Treatment when benzathine penicillin G-LA is in limited supply	Treatment when benzathine penicillin G-LA is unavailable
Uncertain adherence to treatment and follow-up
Primary syphilis, secondary syphilis, early latent syphilisFootnote 1	Benzathine penicillin G-LA 2.4 million units IM as a single dose	Doxycycline 100 mg orally twice a day for 14 days or Short-acting aqueous penicillin G 4 million units IV every 4 hours for 10 days or Ceftriaxone 1 g IV or IM every 24 hours for 10 days
Latent syphilis of unknown duration, late latent syphilis, or tertiary syphilisFootnote 1	Benzathine penicillin G-LA 2.4 million units IM weekly for 3 doses	Doxycycline 100 mg orally twice a day for 28 days or Short-acting aqueous penicillin G 4 million units IV every 4 hours for 10 days or Ceftriaxone 1 g IV or IM every 24 hours for 10 days
Adherence to treatment and follow-up is expected
Primary syphilis, secondary syphilis, early latent syphilisFootnote 1	Doxycycline 100 mg orally twice a day for 14 days
Latent syphilis of unknown duration, late latent syphilis or tertiary syphilisFootnote 1	Doxycycline 100 mg orally twice a day for 28 days
All patients
Neurosyphilis, including ocular syphilis and otosyphilis	Refer to a neurologist, infectious disease specialist, or experienced colleague
Notes: Footnote 1 Not involving the central nervous system, eye nor ear. Return to footnote 1 referrer

Recommended epidemiological treatment for sexual contacts of syphilis during a benzathine penicillin G-LA shortage

Situation	Epidemiological treatment when benzathine penicillin G-LA is in limited supply	Epidemiolocal treatment when benzathine penicillin G-LA is unavailable
Sexual contact with someone with infectious syphilis or latent syphilis of unknown duration in the 90 days prior to the index case’s diagnosis
Pregnant personFootnote 1Footnote 2	Benzathine penicillin G-LA 2.4 million units IM for a single dose	Short-acting aqueous penicillin G 4 million units IV every 4 hours for 10 days
Non-pregnant personFootnote 1Footnote 2	Doxycycline 100 mg orally twice daily for 14 days
Sexual contact with someone with syphilis of unknown stage, in the 90 days prior to the index case’s diagnosis
Pregnant personFootnote 1Footnote 2	Benzathine penicillin G-LA 2.4 million units IM for a single dose	Short-acting aqueous penicillin G 4 million units IV every 4 hours for 10 days
Non-pregnant personFootnote 1Footnote 2	Defer treatment pending confirmation of syphilis diagnosis in the patient
Sexual contact with someone with late latent or tertiary syphilis in the 90 days prior to the index case’s diagnosis
Pregnant or non-pregnant personFootnote 2Footnote 3	Defer treatment pending confirmation of syphilis diagnosis in the patient
Sexual contact with someone with syphilis (any stage) more than 90 days prior to the index case’s diagnosis
Pregnant or non-pregnant personFootnote 2Footnote 3	Defer treatment pending confirmation of syphilis diagnosis in the patient
Notes: Footnote 1 Generally, it is advised to consider epidemiological treatment with benzathine penicillin G-LA for individuals who had sexual contact with a person with infectious syphilis in the 90 days prior to the index case’s diagnosis. For recent sexual contacts of someone with syphilis where the index case was staged as latent syphilis of unknown duration, epidemiological treatment can be considered. For recent sexual contacts of someone with syphilis where staging information for the index case is unknown, epidemiological treatment can be considered for pregnant patients and may be deferred for non-pregnant patients pending assessment and diagnostic testing. Return to footnote 1 referrer Footnote 2 Clinicians may consider clinical findings and laboratory results in determining whether a syphilis treatment that was initiated for epidemiological reasons will be extended (i.e., to treat for latent syphilis of unknown duration or late latent syphilis). If the patient is found to have neurological signs or symptoms (including ocular or otic findings), they should be managed in consultation with a neurologist, infectious disease specialist, or experienced colleague. Return to footnote 2 referrer Footnote 3 In general, for asymptomatic sexual contacts of late latent and tertiary syphilis, initiation of treatment may be deferred until a diagnosis in the contact has been confirmed (i.e., via syphilis serologic results). When the contact is pregnant, initiation of epidemiological treatment may be considered. Return to footnote 3 referrer