Drug name
Last update: May 2026Benzathine benzylpenicillin
Developer(s)
Drug information
Benzathine benzylpenicillin, Penicillin G benzathine anhydrous, Benzathine benzylpenicillin anhydrous,
BICILLIN® L-A; EXTENCILLINE; BICILLIN-5; BICILLIN-3
Small molecule
First Generation Penicillin - Bacterial Cell Wall Synthesis Inhibitor (narrow spectrum)
Penicillin G inhibits the final stage of bacterial cell wall synthesis by binding to select penicillin‑binding proteins (PBPs) located within the bacterial cell wall. It demonstrates in‑vitro activity against a range of aerobic and anaerobic, gram‑positive and gram‑negative organisms. Following intramuscular administration of benzathine penicillin G (BPG), penicillin G is absorbed slowly, with a median time to maximum concentration (t_max) of 48 hours. After reaching maximum concentration, plasma levels decline in a monophasic manner, with a mean apparent terminal half‑life of 189 hours. The geometric mean values for AUC_inf and C_max were 50,770 ng·h/mL and 259 ng/mL, respectively. The median duration during which concentrations exceeded the established therapeutic threshold for syphilis.
Benzathine benzylpenicillin LAI is approved in 55 countries including United States, Asian countries, European countries, Australia and New Zealand, Africa, and Latin America as branded and generic versions. In the US, some alternative brands are authorised only for temporary import or shortage mitigation rather than full approval. It has received approval for syphilis, congential syphilis and upper-respiratory tract infections.
Benzathine benzylpenicillin 0.6 M IU; 1.2 M IU; 2.4 M IU has received approval from US FDA, TGA, RFDA, ARCSA, EDA, DNM, FDA, DoH HK, CDSCO, BADAN POM, EMA/BASG, EMA/FAHMP, EMA/MoH, EMA/CBG, PMDA, MOHW, MFDS, LMHRA, NPRA, NMRC, Medsafe, NAFDAC, Minzdrav, CCMPA, NMPA, SSSHCS, AMMDC, SFDA, HSA, MOHHS, NHRA, NMRA, COFEPRIS, Swissmedic, TFDA, Thailand FDA, ZAMRA, ADPI, EMA/AEMPS, EMA/JAZMP, EMA/ANMDMR, EMA/INFARMED, EMA/URPL, EMA/AIFA, MHRA, RCETH, DCGA, BoMRA, ANVISA, HC, INVIMA, and DDF. EXNTENCILLIN and LENTOCILLIN has been made available temporarily in USA by USFDA due to shortage of BICILLIN.
Therapeutic area(s)
- Other(s) : "Syphilis and Congential Syphilis; upper-respiratory tract due to susceptible streptococci; yaws, bejel, pinta and rheumatic fever"
- Syphilis
- Treatment
- Prevention
Administration route
Intramuscular
Associated long-acting platforms
Aqueous drug particle suspension
Use of drug
- Administered by a community health worker
- Administered by a nurse
- Administered by a specialty health worker
- Weekly
- Monthly
- Every 2 weeks
Not provided
Dosage
600000 units/1mL; 1,200,000 units/2 mL; 240000 units/4 mL prefilled syringes
240000 units/4 mL
1) Upper Respiratory Infections (for example, pharyngitis): Adults—1,200,000 units bolus; older pediatric patients—900,000 units bolus; infants and pediatric patients (under 27 kg)—300,000 to 600,000 units. 2) Syphilis (Primary, secondary, and latent)—2,400,000 units bolus. (i) Late (tertiary and neurosyphilis)— 2,400,000 units weekly for three weeks. (ii) Congenital (<2 years of age)— 50,000 units/kg/body weight; ages 2 to 12 years: adjust dosage based on adult dosage schedule. 3) Treatment of Yaws, Bejel, and Pinta—1,200,000 units bolus 4) Prophylaxis for rheumatic fever and glomerulonephritis. Following an acute attack, penicillin G benzathine 1,200,000 units Q1M (or) 600,000 units Q2W.
Not provided
Associated technologies
Not provided
Comment & Information
Developer(s)
Pfizer Inc
Pfizer Inc. is an American multinational pharmaceutical and biotechnology company headquartered in Manhattan, New York City. Established in 1849 by two German entrepreneurs, the company has contributed to the development of several widely used medicines, including sildenafil (Viagra), sertraline (Zoloft), and atorvastatin (Lipitor). The organization has played a notable role in advancing treatment
Drug structure
Scale-up and manufacturing prospects
The cost of Bicillin L- A is USD $80–$150 per vial. There is a shortage of benzathine benzylpenicillin which has been extended until 30 November 2026.
1) Round bottom flask - Multi-neck; Ca-Cl₂ drying tube fitted 2) Dropping funnel (500 mL capacity) 3) Hydrogenation apparatus - H2 absorbed at 45 min; 175 mm Hg 4) Vaccum fractionator (Distils 160–175°C / 0.5 mm Hg; n=1.5621) 5) Crystallination vessel ( 95% ethanol; recryst. hot alcohol; M.P. 110–112°C) 6) Suction filter (Vacuum applied; white needle crystals collected) 7) Jacketed mixing vessel 8) Mechanical stirrer 9) Suction filter 10) Spread-layer dryer
1) ISO Class 5 (Grade A) for aseptic filling, ISO Class 7 (Grade B) as background for aseptic processing, and ISO Class 8 (Grade C/D) for pharmaceutical manufacturing support areas 2) Manufacturing process includes: Step 1 — Prepare the Diamine salt (DBED Diacetate) in 95% EtOH Step 2 — React with sodium penicillin G in cold water (0-4 celsius) Step 3 — Filter, wash, and dry Step 4 — Add excipeints and formulate pre-filled syringe
1) Refractometer 2) FTIR spectrometer 3) H-NMR spectrometer 4) RP-HPLC system 5) Laser diffraction 6) Light microscope 7) SEM 8) DSC 9) X-ray diffratometer 10) Viscometer 11) Karl Fischer titrator
Excipients
Not provided
1) Methyl hydroxybenzoate 2) Propyl hydroxybenzoate. 3) Lecithin 4) Polysorbate 80 5) Carmellose sodium 6) Sodium citrate, anhydrous 7) Povidone
Not provided
Delivery device(s)
Not provided
There are either no relevant patents or these were not yet submitted to LAPaL
Publications
Gartlan WA, Rahman S, Pellegrini MV, et al. Benzathine Penicillin. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507723/
This activity delves into the multifaceted clinical applications of benzathine penicillin, a potent antibiotic derived from the reaction between penicillin G molecules and diphenylethylene diamine. With broad-spectrum activity against gram-positive bacteria, benzathine penicillin emerges as a formidable agent, effectively combating diverse strains such as β-hemolytic streptococci (groups A, B, C, G, H, L, and M). Its exceptional efficacy against Treponema pallidum and T. carateum positions benzathine penicillin as a cornerstone in treating syphilis and yaws. Importantly, its unparalleled record is underscored by the absence of reported resistance in Streptococcus pyogenes, solidifying its status as a reliable therapeutic tool for specific infections.
This educational initiative offers an in-depth exploration of benzathine penicillin, providing healthcare professionals with comprehensive insights into its indications, dosing regimens, administration modalities, potential adverse effects, and specific contraindications. By unraveling the robust mechanism of action against various bacterial species, this CME activity aims to empower healthcare professionals with an enhanced understanding of the clinical utility of benzathine penicillin. The goal is to foster informed decision-making and optimize therapeutic strategies, ensuring the effective management of bacterial infections susceptible to this antibiotic. Participants will gain valuable knowledge to navigate the nuances of benzathine penicillin therapy, ultimately contributing to improved patient outcomes.
Pharmacokinetics and Safety of Intramuscular Injectable Benzathine Penicillin G in Japanese Healthy Participants, Yinhua Li PhD, Akifumi Okayama MS, Toshiaki Hagi MS, Chieko Muto PhD, Susan Raber PharmD, MPH, Masahito Nagashima BS. 12 May 2024. https://doi.org/10.1002/jcph.2454
An intramuscular (IM) suspension of benzathine penicillin G (BPG) has been used as first-line therapy for the treatment of syphilis worldwide since its approval in the 1950s. However, there are limited reports about the pharmacokinetics of BPG. A Phase 1 study was conducted on eight Japanese healthy participants to investigate the pharmacokinetics (samples collected predose to 648 h post-dose) and safety of 2.4 million units of BPG after a single IM injection. Following administration, penicillin G, the active moiety of BPG, was absorbed slowly from the injection site with a median time to Cmax (tmax) of 48 h post-dose. After the achievement of Cmax, concentrations of penicillin G declined slowly in a monophasic fashion with a mean apparent terminal half-life of 189 h. Geometric mean AUCinf and Cmax were 50770 ng•h/mL and 259 ng/mL, respectively. Median time (range) above the well-accepted therapeutic concentration (18 ng/mL) for syphilis treatment was 561 h (439-608 h [18-25 days]), which reached and exceeded the necessary duration of 7-10 days for syphilis treatment. Two participants were underdosed with residual drug left in the syringe due to the high viscosity of the drug product. Only one (12.5%) participant reported a mild adverse event of nasopharyngitis, which was considered not related to the study treatment. The study results supported BPG approval in Japan as an option for syphilis treatment.
Additional documents
Useful links
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