Shortage of Penicillin G Benzathine (Bicillin L-A)


Dear Colleague:

The FDA listed a shortage of Penicillin G benzathine injectable suspension products (Bicillin L-A®) on April 26, 2023, due to increased demand. Pfizer provided an availability update on June 12, 2023, with an expected recovery in the second quarter of 2024. There are no emergency stockpiles of this medication, and product is being allocated with limited inventory released, resulting in the supply not meeting demand. Providers should work with their supplier or Pfizer directly regarding product availability.

Virginia has observed an increasing incidence of syphilis among adults and congenital syphilis.  Reported cases of syphilis during the first four months of 2023 were 22% higher than during the same timeframe in 2022, and six cases of congenital syphilis have been reported so far this year.  The number of syphilis cases with ocular, otic, or neurological manifestations has increased 118% from 2022 compared to the first four months of 2023. Many syphilis diagnoses are occurring among persons who inject or otherwise use drugs. Successful disease intervention efforts by health counselors in local health departments have also led to increased utilization of Bicillin L-A to treat patients infected with syphilis and their exposed partners.

Bicillin L-A is the only CDC-recommended treatment for some patients, including pregnant people infected with or exposed to syphilis, and babies with congenital syphilis. Although Bicillin L-A remains the treatment of choice for patients with syphilis, CDC has recommended that healthcare providers prioritize the use of Bicillin L-A to treat pregnant people and babies with congenital syphilis. If warranted due to the drug shortage, doxycycline is an alternative therapy for non-pregnant patients diagnosed with or exposed to syphilis; however, doxycycline is an FDA Pregnancy Category D medication, and is not recommended as an alternative treatment for pregnant individuals. Pregnant individuals should be treated with the recommended penicillin regimen for their stage of infection.

The Virginia Department of Health (VDH) advises health care providers to consider the following recommendations, in order to conserve Bicillin L-A for use with patients for whom it is the sole recommended treatment against syphilis.

VDH Recommendations for Alternative Treatment Options

  • If a drug shortage of Bicillin L-A warrants alternative therapy, consider using doxycycline to treat syphilis for adult patients who are not pregnant or allergic to doxycycline. This will help ensure Bicillin L-A doses are available for use for the priority populations below:
    • Pregnant people and their sexual partners
    • Infants and neonates with congenital syphilis
    • People of reproductive age who can get pregnant and their sexual partners
    • Patients with doxycycline allergy
    • Patients who have already begun a course of treatment with either 1.2MU or 2.4MU doses of Bicillin L-A.
  • Educate patients receiving doxycycline on the importance of adherence
  • Consider alternatives to Bicillin L-A to treat other infectious diseases (such as streptococcal pharyngitis) when other treatment options are available
  • Should Bicillin L-A 2.4MU doses be unavailable, providers may consider administration of two (2) doses of 1.2MU per dose interval.
  • Use of other intramuscular formulations of penicillin, including Bicillin C-R, are not acceptable alternatives for the treatment of syphilis.

Below are the CDC-recommended courses of treatment using doxycycline for patients diagnosed with probable syphilis.

  • Early syphilis (primary, secondary, or early latent): doxycycline 100mg by mouth twice daily for 14 days.
  • Late syphilis (late latent or unknown duration): doxycycline 100mg by mouth twice daily for 28 days.

Additional CDC Recommendations

  • Thorough clinical and serologic follow-up of persons receiving doxycycline or another alternative therapy for syphilis is essential to ensure treatment is successful. Patients should be followed to ensure that a fourfold RPR titer decrease is achieved within six to 12 months of completing treatment.
  • Patients who are coinfected with HIV can be treated as described for patients who do not have HIV. However, consider additional follow-up to ensure adherence and successful fourfold RPR titer reduction.
  • Sexual partners of patients diagnosed with primary, secondary, or early latent syphilis who were exposed more than 90 days before the diagnosis should be treated presumptively for early syphilis, even if serologic tests are negative. These partners should also be treated presumptively if serologic tests are not immediately available and opportunity for follow-up is uncertain.
  • Clinicians with questions about syphilis clinical management may contact the National Network on STD Prevention Training Centers (NNPTC) STD Clinical Consultation Network.

Additional Resources and Reference Materials for Clinicians

Thank you for partnering with us for disease treatment and prevention as we strive to reduce syphilis and especially to reduce congenital syphilis in Virginians.


Karen Shelton, MD
State Health Commissioner