Penicillin G Benzathine side effects: what 1,343 FDA adverse event reports show
Drug class
Not stated in label
Brand names
Bicillin L-A
Who reports
1,343 reports · 36% serious · 39 with death outcome · 47% female
Used for
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Bicillin L-A and other antibacterial drugs, Bicillin L-A should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.
What it is
Description Bicillin L-A (penicillin G benzathine injectable suspension) is available for deep intramuscular injection. Penicillin G benzathine is prepared by the reaction of dibenzylethylene diamine with two molecules of penicillin G.
Boxed warning
NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH.
Causality screen of the 18 strongest signals
What the badges mean
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only and flags pairs whose reports are unusually skewed by sex or come mostly from consumers rather than clinicians. 10 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Syringe issue | 15 | 13.4 8.1–22.1ROR 13.5 · χ² 160 / p 7e-37 | 12.3 EB05 7.2 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Transfusion | 7 | 10.4 5.0–21.8ROR 10.4 · χ² 50 / p 6e-13 | 7.5 EB05 3.5 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 17.7 | no trial data cached |
| Premature baby | 18 | 9.3 5.9–14.7ROR 9.4 · χ² 125 / p 2e-29 | 8.1 EB05 5.2 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 15.3 | no trial data cached |
| Poor quality product administered | 6 | 9.2 4.1–20.4ROR 9.2 · χ² 36 / p 1e-9 | 6.2 EB05 2.9 · IC025 +1.1 3/3 methods agree | Not in label — unassessed | – | no trial data cached |
| Injection site nodule | 6 | 8.5 3.8–19.0ROR 8.6 · χ² 33 / p 5e-9 | 5.8 EB05 2.7 · IC025 +1.0 3/3 methods agree | Labeled (related wording) related wording | serious n=1 | no trial data cached |
| Economic problem | 8 | 8.1 4.1–16.2ROR 8.2 · χ² 43 / p 3e-11 | 6.0 EB05 3.1 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 12.5 | no trial data cached |
| Rash maculo-papular | 11 | 7.8 4.3–14.0ROR 7.8 · χ² 58 / p 1e-14 | 6.2 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 12.6 | no trial data cached |
| Needle issue | 13 | 7.1 4.1–12.2ROR 7.2 · χ² 62 / p 2e-15 | 5.9 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Agranulocytosis (severe loss of white cells) | 7 | 5.9 2.8–12.4ROR 5.9 · χ² 24 / p 5e-7 | 4.4 EB05 2.3 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Injection site warmth | 7 | 5.3 2.5–11.1ROR 5.3 · χ² 20 / p 3e-6 | 4.1 EB05 2.2 · IC025 +0.7 3/3 methods agree | Labeled (related wording) related wording | serious n=2 | no trial data cached |
| Anhedonia | 9 | 5.3 2.8–10.2ROR 5.3 · χ² 27 / p 9e-8 | 4.3 EB05 2.4 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Injection site swelling | 23 | 4.7 3.2–7.1ROR 4.8 · χ² 64 / p 5e-16 | 4.4 EB05 3.1 · IC025 +1.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.8 | no trial data cached |
| Device breakage | 10 | 4.0 2.1–7.4ROR 4.0 · χ² 19 / p 5e-6 | 3.4 EB05 2.0 · IC025 +0.7 3/3 methods agree | Reporting / coding artifact | serious PRR 1.4 | no trial data cached |
| Injury associated with device | 5 | 3.9 1.6–9.3ROR 3.9 · χ² 8 / p 0.002 | 3.0 EB05 1.5 · IC025 +0.1 | Not in label — unassessed | serious n=2 | no trial data cached |
| Foetal exposure during pregnancy | 19 | 3.7 2.3–5.7ROR 3.7 · χ² 34 / p 3e-9 | 3.4 EB05 2.3 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 6.0 | no trial data cached |
| Injection site mass | 8 | 3.4 1.7–6.8ROR 3.4 · χ² 11 / p 4e-4 | 2.9 EB05 1.6 · IC025 +0.4 | Labeled (related wording) related wording | serious PRR 3.6 | no trial data cached |
| Injection site pain (pain where injected) | 63 | 3.2 2.5–4.1ROR 3.4 · χ² 97 / p 4e-23 | 3.2 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.0 | no trial data cached |
| Bone density decreased | 6 | 3.0 1.3–6.6ROR 3.0 · χ² 6 / p 0.007 | 2.6 EB05 1.3 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Lab value / disease marker | serious PRR 5.0 | no trial data cached |
Trial evidence (ClinicalTrials.gov)
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Injection site pain (pain where injected) | 63 | 3.2 2.5–4.1ROR 3.4 · χ² 97 / p 4e-23 | 3.2 EB05 2.6 · IC025 +1.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 8.0 | no trial data cached |
| Injection site swelling | 23 | 4.7 3.2–7.1ROR 4.8 · χ² 64 / p 5e-16 | 4.4 EB05 3.1 · IC025 +1.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 10.8 | no trial data cached |
| Foetal exposure during pregnancy | 19 | 3.7 2.3–5.7ROR 3.7 · χ² 34 / p 3e-9 | 3.4 EB05 2.3 · IC025 +1.0 3/3 methods agree | Reporting / coding artifact | serious PRR 6.0 | no trial data cached |
| Premature baby | 18 | 9.3 5.9–14.7ROR 9.4 · χ² 125 / p 2e-29 | 8.1 EB05 5.2 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 15.3 | no trial data cached |
| Syringe issue | 15 | 13.4 8.1–22.1ROR 13.5 · χ² 160 / p 7e-37 | 12.3 EB05 7.2 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Needle issue | 13 | 7.1 4.1–12.2ROR 7.2 · χ² 62 / p 2e-15 | 5.9 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious n=1 | no trial data cached |
| Rash maculo-papular | 11 | 7.8 4.3–14.0ROR 7.8 · χ² 58 / p 1e-14 | 6.2 EB05 3.6 · IC025 +1.6 3/3 methods agree | Not in label — unassessed | serious PRR 12.6 | no trial data cached |
| Device breakage | 10 | 4.0 2.1–7.4ROR 4.0 · χ² 19 / p 5e-6 | 3.4 EB05 2.0 · IC025 +0.7 3/3 methods agree | Reporting / coding artifact | serious PRR 1.4 | no trial data cached |
| Anhedonia | 9 | 5.3 2.8–10.2ROR 5.3 · χ² 27 / p 9e-8 | 4.3 EB05 2.4 · IC025 +1.0 3/3 methods agree | Not in label — unassessed | serious PRR 8.4 | no trial data cached |
| Injection site mass | 8 | 3.4 1.7–6.8ROR 3.4 · χ² 11 / p 4e-4 | 2.9 EB05 1.6 · IC025 +0.4 | Labeled (related wording) related wording | serious PRR 3.6 | no trial data cached |
| Economic problem | 8 | 8.1 4.1–16.2ROR 8.2 · χ² 43 / p 3e-11 | 6.0 EB05 3.1 · IC025 +1.3 3/3 methods agree | Reporting / coding artifact | serious PRR 12.5 | no trial data cached |
| Injection site warmth | 7 | 5.3 2.5–11.1ROR 5.3 · χ² 20 / p 3e-6 | 4.1 EB05 2.2 · IC025 +0.7 3/3 methods agree | Labeled (related wording) related wording | serious n=2 | no trial data cached |
| Agranulocytosis (severe loss of white cells) | 7 | 5.9 2.8–12.4ROR 5.9 · χ² 24 / p 5e-7 | 4.4 EB05 2.3 · IC025 +0.9 3/3 methods agree | Not in label — unassessed | serious PRR 9.6 | no trial data cached |
| Transfusion | 7 | 10.4 5.0–21.8ROR 10.4 · χ² 50 / p 6e-13 | 7.5 EB05 3.5 · IC025 +1.4 3/3 methods agree | Not in label — unassessed | serious PRR 17.7 | no trial data cached |
| Bone density decreased | 6 | 3.0 1.3–6.6ROR 3.0 · χ² 6 / p 0.007 | 2.6 EB05 1.3 · IC025 -0.1 PRR-only: not supported by EBGM or IC | Lab value / disease marker | serious PRR 5.0 | no trial data cached |
Unlabeled candidate signals
Every screened signal with n ≥ 20 was either labeled, an indication term, or an artifact pattern — no unlabeled candidate stood out in the top signals.
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Penicillin G Benzathine?
In FDA FAERS, the most frequently co-reported reaction terms for Penicillin G Benzathine are injection site pain, injection site swelling, premature baby, syringe issue, needle issue, rash maculo-papular. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Penicillin G Benzathine have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: NOT FOR INTRAVENOUS USE. DO NOT INJECT INTRAVENOUSLY OR ADMIX WITH OTHER INTRAVENOUS SOLUTIONS. THERE HAVE BEEN REPORTS OF INADVERTENT INTRAVENOUS ADMINISTRATION OF PENICILLIN G BENZATHINE WHICH HAS BEEN ASSOCIATED WITH CARDIORESPIRATORY ARREST AND DEATH.
Do FAERS signals prove that Penicillin G Benzathine causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 012d46f1-d0a0-4676-a879-cd320297ab16, effective 20260721; matched on
openfda.generic_name.exact:"PENICILLIN G BENZATHINE") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 28 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath
Page generated 2026-10-08. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.