Long-Acting Penicillin — Syphilis / Rheumatic Fever Prophylaxis Pregnancy: Safe — benzathine penicillin is the ONLY treatment for syphilis in pregnancy; doxycycline and azithromycin have insufficient evidence for prevention of congenital syphilis

Benzathine Benzylpenicillin

Brand names: Bicillin L-A, Penidure LA

Adult dose

Dose: Primary/secondary syphilis: 2.4 million units IM single dose; Latent syphilis (>1 year duration): 2.4 million units IM weekly × 3 doses; Rheumatic fever prophylaxis: 1.2 million units IM every 3–4 weeks

Route: Deep intramuscular injection (gluteal — never IV)

Frequency: Single dose (early syphilis) or monthly (prophylaxis)

Max: 2.4 million units per dose

Depot penicillin — slow absorption gives sustained low-level penicillin concentrations for 2–4 weeks. NEVER give IV — risk of cardiorespiratory arrest (Hoigne syndrome). Warm to room temperature before injection. Inject into upper outer quadrant of gluteal muscle using a large-bore needle — viscous preparation. Allergy: desensitisation protocol for penicillin-allergic syphilis patients if doxycycline fails.

Paediatric dose

Route:

Children: 37,500–50,000 units/kg IM (weight-based); neonatal congenital syphilis — different regimen (aqueous penicillin G preferred); seek specialist guidance

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Clinical pearls

Jarisch-Herxheimer reaction: occurs 2–8 hours after first dose — fever, headache, myalgia from cytokine release as spirochetes die; warn patient — antipyretics manage symptoms; do not re-treat or stop treatment
Hoigne syndrome: extremely rare — occurs if accidentally enters vein; transient neurological and cardiovascular symptoms (anxiety, visual disturbance, dizziness) from microemboli of procaine or penicillin crystals — resolves spontaneously but terrifying for patient
NEVER use IV — the viscous preparation causes cardiorespiratory arrest if given IV; use only IM route with aspiration before injection
Neurosyphilis: aqueous penicillin G IV (18–24 million units/day) required — benzathine penicillin has poor CNS penetration; lumbar puncture to rule out neurosyphilis before treating latent syphilis

Contraindications

Penicillin hypersensitivity/anaphylaxis
IV administration (absolute — fatal)
Use in neonates as primary congenital syphilis treatment (aqueous penicillin G preferred for CNS penetration)

Side effects

Injection site pain (significant)
Jarisch-Herxheimer reaction (fever, rigors 2–8 hours post-treatment — especially in secondary syphilis — warn patient)
Hoigne syndrome (inadvertent IV — immediately: anxiety, fear of death, visual disturbance, tinnitus, confusion — transient)
Anaphylaxis
Sterile abscess

Interactions

Probenecid — increases penicillin levels (used therapeutically)
Methotrexate — increased methotrexate toxicity

Monitoring

Syphilis serology (RPR/VDRL) at 3, 6, 12, 24 months post-treatment — 4× decline in titre confirms cure
CSF examination if neurosyphilis suspected (neurological symptoms, late latent syphilis)
Jarisch-Herxheimer reaction warning and temperature monitoring
HIV status (syphilis a risk factor — test if not known)

Reference: BNFc; BNF 90; BASHH Syphilis Guidelines 2019; NICE STI Guidelines; WHO Syphilis Treatment Guidelines 2016. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways