Natural long-acting penicillin (benzylpenicillin, IM)
Treatment of infections due to penicillin G-sensitive microorganisms requiring prolonged serum levels, including syphilis (all stages), prophylaxis of rheumatic fever, scarlet fever, erysipelas and streptococcal pharyngitis.
Also known as: Benzetacil, Penicilina G benzatínica
DailyMed approved label (Bicillin L-A, Pfizer; setID 012d46f1-d0a0-4676-a879-cd320297ab16).
DailyMed approved label (Bicillin L-A, Pfizer; setID 012d46f1-d0a0-4676-a879-cd320297ab16).
Penicillin G benzathine (a β-lactam antibiotic) may alter the INR in patients anticoagulated with warfarin, with a bleeding risk during antibiotic therapy.
The warfarin label identifies antibiotics, including penicillins, as drugs that can alter INR in anticoagulated patients. The mechanism is multiple: reduction of vitamin K-producing gut flora, metabolic inhibition, and the infectious disease itself altering the coagulation state. With benzathine benzylpenicillin (long-acting IM injection, e.g., rheumatic fever prophylaxis), the effect on INR may be less predictable and more delayed. Monitor INR during and after the antibiotic course, watch for bleeding signs and adjust the warfarin dose according to the values.
Warfarin + benzylpenicillin: antibiotics may alter INR (gut flora and enzymes). Monitor INR.
There have been reports of changes in INR in patients taking warfarin and antibiotics; pharmacokinetic studies have not shown consistent effects on plasma warfarin concentrations, so the mechanism is multifactorial (possible reduction of vitamin-K-producing gut flora and altered haemostasis).
INR, signs of bleeding (gums, bruising, melena, haematuria).
Unexplained bleeding, haematuria, melena, INR above the therapeutic range.
Closely monitor the INR when starting and stopping the antibiotic; adjust the warfarin dose as needed during antibiotic therapy.
DailyMed/FDA (NIH/NLM) — approved Warfarin label (section 7.4 Antibiotics and Antifungals): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 ; approved Bicillin L-A label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Penicillin G benzathine may increase plasma methotrexate concentrations, with an increased risk of toxicity (myelosuppression, hepatotoxicity).
The methotrexate label identifies penicillins among the drugs that can increase plasma methotrexate concentrations: penicillins inhibit the renal tubular secretion of methotrexate, reducing its clearance and raising levels, with risk of toxicity (myelosuppression, mucositis, hepatotoxicity, nephrotoxicity) — especially with high-dose methotrexate or in patients with impaired renal function and dehydration. In patients receiving methotrexate and benzathine benzylpenicillin, monitor renal function and signs of methotrexate toxicity, and consider measuring serum levels when clinically indicated.
Benzylpenicillin + methotrexate: penicillins reduce renal methotrexate clearance — risk of toxicity.
Oral or intravenous penicillins are listed in the methotrexate label among drugs that may increase methotrexate exposure (possible reduced renal tubular secretion of methotrexate and protein-binding displacement).
Blood count (myelosuppression), liver and renal function, signs of mucositis, stomatitis or bleeding.
Haematological or hepatic toxicity, pancytopenia, severe mucositis.
Monitor closely for methotrexate toxicity when coadministration cannot be avoided; consider methotrexate dose adjustment.
DailyMed/FDA (NIH/NLM) — approved Methotrexate label (section 7.1 Effects of Other Drugs on Methotrexate): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04a95db9-a124-4b97-bd71-1c37a6b3b0c8 ; approved Bicillin L-A label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Benzathine benzylpenicillin is given intramuscularly; food does not affect its pharmacokinetics.
May be administered regardless of meals.
DailyMed/FDA (NIH/NLM) — approved Bicillin L-A label (Pfizer): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
No relevant pharmacokinetic interaction; usual moderation during treatment.
Moderate alcohol intake.
DailyMed/FDA (NIH/NLM) — approved Bicillin L-A label (Pfizer): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Benzathine benzylpenicillin is contraindicated in patients with documented penicillin allergy (risk of anaphylaxis).
Confirm allergy history before administering; consider an alternative class.
DailyMed/FDA (NIH/NLM) — approved Bicillin L-A label (Pfizer): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Penicillin G elimination is reduced in renal impairment, with a risk of neurotoxicity at high doses.
Adjust the dosing interval in severe renal impairment.
DailyMed/FDA (NIH/NLM) — approved Bicillin L-A label (Pfizer): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Penicillins are considered safe in pregnancy; benzathine benzylpenicillin is the treatment of choice for syphilis in pregnancy.
May be used in any trimester when indicated (e.g., syphilis).
Present in breast milk in small amounts; compatible with breastfeeding.
No specific contraception required.
DailyMed/FDA (NIH/NLM) — approved Bicillin L-A label (Pfizer): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=012d46f1-d0a0-4676-a879-cd320297ab16
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal antibiotic with prolonged action: the low solubility of the benzathine salt ensures slow release from the intramuscular depot, maintaining low but effective serum levels for days to weeks, allowing long-interval regimens (e.g. syphilis).
Inhibits bacterial cell-wall synthesis during active multiplication. Hydrolysis of the benzathine salt releases penicillin G slowly and continuously, maintaining prolonged serum levels.
Slow release from the IM injection site: 300,000 U maintain levels of 0.03–0.05 U/mL for 4–5 days; 1,200,000 U maintain detectable levels for up to 4 weeks.
Hydrolyzed to penicillin G; approximately 60% of penicillin G is serum-protein bound. Widely distributed in tissues, with highest levels in kidney, liver, skin and intestines; poor CSF penetration with normal meninges.
Effective elimination half-life of days to weeks, dose dependent (detectable levels up to 4 weeks after 1.2 million units).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
