Is Penicillin V (Pen VK) administered intramuscularly (IM) an acceptable treatment for syphilis?

Penicillin V (Pen VK) is NOT acceptable for syphilis treatment

Penicillin V administered by any route, including intramuscular injection, is explicitly contraindicated for syphilis treatment and should never be used. 1

Why Pen VK Cannot Be Used

• Oral penicillin preparations are completely ineffective for syphilis treatment, as clearly stated in CDC guidelines 1
• The only acceptable penicillin formulations are:
  • Benzathine penicillin G (BPG) for early and late latent syphilis 2, 1
  • Aqueous crystalline penicillin G for neurosyphilis 2, 1
  • Procaine penicillin G (with probenecid) as an alternative for neurosyphilis 3

Correct Treatment Regimens

For Early Syphilis (Primary, Secondary, Early Latent)

• Benzathine penicillin G 2.4 million units IM as a single dose is the only recommended first-line treatment 2, 1
• This applies regardless of HIV status 2

For Late Latent Syphilis

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 2, 1

For Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units IV daily for 10-14 days (administered as 3-4 million units every 4 hours or continuous infusion) 3, 2
• Procaine penicillin 2.4 million units IM daily plus probenecid 500 mg orally four times daily for 10-14 days is an alternative, but procaine penicillin alone without probenecid does not achieve adequate CSF levels 3

Alternatives for Penicillin-Allergic Patients

• Doxycycline 100 mg orally twice daily for 14 days for early syphilis 2, 1
• Doxycycline 100 mg orally twice daily for 28 days for late latent syphilis 2, 1
• Ceftriaxone 1 gram IM/IV daily for 10 days may be considered based on randomized trial data showing comparable efficacy to benzathine penicillin 3
• Tetracycline 500 mg orally four times daily is another option, though compliance is better with doxycycline due to less frequent dosing 2

Critical Pitfalls to Avoid

• Never substitute oral penicillin formulations (including Penicillin V) for parenteral benzathine penicillin G 1
• Pregnant patients with penicillin allergy must undergo desensitization and receive penicillin, as no alternative reliably prevents congenital syphilis 2, 1, 4
• Do not use azithromycin in the United States due to widespread macrolide resistance and documented treatment failures 3, 1
• Procaine penicillin without probenecid is inadequate for neurosyphilis treatment 3