Fosphenytoin side effects: what 2,553 FDA adverse event reports show
Drug class
Not stated in label
Label matched
Fosphenytoin Sodium (Fosphenytoin Sodium)
Who reports
2,553 reports · 88% serious · 354 with death outcome · 52% female
Used for
Fosphenytoin sodium injection is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Fosphenytoin sodium injection can also be substituted, short-term, for oral phenytoin.
What it is
Fosphenytoin Sodium Injection, USP is a prodrug intended for parenteral administration; its active metabolite is phenytoin. 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE).
Boxed warning
CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES The rate of intravenous fosphenytoin sodium injection administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias.
Causality screen of the 40 strongest signals
What the badges mean
- Labeled — boxed warning The term (or its clinical synonym) appears in the FDA boxed warning: causality is regulator-recognised and considered serious.
- Labeled adverse reaction The exact term appears in the label's warnings or adverse-reactions sections: a known, expected effect. The FAERS signal confirms the label rather than discovering anything.
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- 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. 78 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 |
|---|---|---|---|---|---|---|
| Status epilepticus | 169 | 124.5 107.5–144.2ROR 133.3 · χ² 20,284 / p <1e-300 | 121.0 EB05 106.4 · IC025 +6.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 80.0 · 98% clinician | no trial data cached |
| Respiratory depression | 36 | 24.2 17.5–33.5ROR 24.5 · χ² 775 / p 7e-171 | 23.8 EB05 18.0 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious PRR 16.2 · 100% clinician | no trial data cached |
| Stevens-johnson syndrome (severe blistering skin reaction) | 62 | 22.9 17.9–29.3ROR 23.5 · χ² 1,275 / p 1e-279 | 22.7 EB05 18.4 · IC025 +3.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 15.0 | no trial data cached |
| Toxic epidermal necrolysis (severe skin peeling reaction) | 35 | 19.1 13.7–26.6ROR 19.4 · χ² 582 / p 9e-129 | 18.9 EB05 14.1 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 12.4 | no trial data cached |
| Drug reaction with eosinophilia and systemic symptoms | 46 | 14.8 11.1–19.7ROR 15.1 · χ² 578 / p 4e-128 | 14.6 EB05 11.3 · IC025 +3.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.6 | no trial data cached |
| Drug eruption | 31 | 14.5 10.2–20.5ROR 14.6 · χ² 375 / p 8e-84 | 14.1 EB05 10.2 · IC025 +3.0 3/3 methods agree | Not in label — unassessed | serious PRR 10.1 | no trial data cached |
| Drug ineffective for unapproved indication | 98 | 14.5 11.9–17.6ROR 15.0 · χ² 1,216 / p 1e-266 | 14.4 EB05 12.1 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 17.4 · 99% clinician | no trial data cached |
| Generalised tonic-clonic seizure | 28 | 14.1 9.7–20.4ROR 14.2 · χ² 327 / p 2e-73 | 13.7 EB05 9.6 · IC025 +2.9 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 9.3 · 96% clinician | no trial data cached |
| Erythema multiforme | 15 | 13.2 8.0–21.9ROR 13.3 · χ² 157 / p 2e-36 | 12.1 EB05 7.1 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 8.9 | no trial data cached |
| Encephalopathy | 37 | 12.4 9.0–17.1ROR 12.6 · χ² 377 / p 3e-84 | 12.0 EB05 8.9 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.1 · 94% clinician | no trial data cached |
| Grand mal convulsion | 14 | 12.3 7.3–20.7ROR 12.4 · χ² 134 / p 3e-31 | 10.9 EB05 6.3 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.5 | no trial data cached |
| Epilepsy | 45 | 12.1 9.1–16.2ROR 12.3 · χ² 448 / p 8e-100 | 11.8 EB05 9.0 · IC025 +2.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.6 · 91% clinician | no trial data cached |
| Ventricular tachycardia | 24 | 11.9 8.0–17.7ROR 12.0 · χ² 229 / p 5e-52 | 11.2 EB05 7.6 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.8 · ♀ 81% (drug 52%) · 100% clinician | no trial data cached |
| Cardiac arrest (heart stopping) | 119 | 11.8 9.9–14.1ROR 12.3 · χ² 1,170 / p 1e-256 | 11.7 EB05 10.0 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.7 · 96% clinician | no trial data cached |
| Vitamin d deficiency | 13 | 11.0 6.4–18.9ROR 11.0 · χ² 108 / p 1e-25 | 9.4 EB05 5.3 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 8.6 | no trial data cached |
| Seizure | 151 | 10.8 9.3–12.6ROR 11.4 · χ² 1,341 / p 5e-294 | 10.7 EB05 9.3 · IC025 +3.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 7.2 | no trial data cached |
| Electrolyte imbalance | 15 | 10.7 6.5–17.8ROR 10.8 · χ² 123 / p 9e-29 | 9.3 EB05 5.6 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 7.2 | no trial data cached |
| Brain oedema | 16 | 10.4 6.4–17.0ROR 10.5 · χ² 127 / p 1e-29 | 9.1 EB05 5.6 · IC025 +2.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.8 | no trial data cached |
| Hyperbilirubinaemia | 13 | 10.4 6.0–17.8ROR 10.4 · χ² 101 / p 5e-24 | 8.8 EB05 5.0 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.9 | no trial data cached |
| Neuroleptic malignant syndrome | 15 | 10.4 6.3–17.2ROR 10.4 · χ² 118 / p 1e-27 | 9.0 EB05 5.4 · IC025 +2.1 3/3 methods agree | Not in label — unassessed | serious PRR 6.8 | no trial data cached |
| Posterior reversible encephalopathy syndrome | 12 | 10.4 5.9–18.2ROR 10.4 · χ² 92 / p 4e-22 | 8.6 EB05 4.8 · IC025 +1.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.7 | no trial data cached |
| Rhabdomyolysis (muscle breakdown) | 52 | 10.3 7.8–13.4ROR 10.5 · χ² 426 / p 5e-95 | 9.9 EB05 7.7 · IC025 +2.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.7 · ♀ 24% (drug 52%) · 92% clinician | no trial data cached |
| Altered state of consciousness | 26 | 9.9 6.8–14.5ROR 10.0 · χ² 200 / p 1e-45 | 9.1 EB05 6.3 · IC025 +2.4 3/3 methods agree | Not in label — unassessed | serious PRR 6.5 · 100% clinician | no trial data cached |
| Drug level decreased | 12 | 9.6 5.5–17.0ROR 9.7 · χ² 84 / p 2e-20 | 7.9 EB05 4.5 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 7.1 | no trial data cached |
| Bradycardia (slow heart rate) | 60 | 9.3 7.2–11.9ROR 9.5 · χ² 436 / p 4e-97 | 8.9 EB05 7.1 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.2 · 96% clinician | no trial data cached |
| Cardiogenic shock | 16 | 9.2 5.7–15.0ROR 9.3 · χ² 109 / p 8e-26 | 7.9 EB05 4.9 · IC025 +2.0 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | no trial data cached |
| Bacteraemia | 13 | 9.1 5.3–15.6ROR 9.1 · χ² 86 / p 1e-20 | 7.5 EB05 4.4 · IC025 +1.9 3/3 methods agree | Not in label — unassessed | serious PRR 6.0 | no trial data cached |
| Myoclonus | 13 | 9.0 5.2–15.4ROR 9.0 · χ² 84 / p 2e-20 | 7.4 EB05 4.4 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.2 | no trial data cached |
| Convulsion (seizure) | 61 | 8.6 6.7–11.1ROR 8.8 · χ² 406 / p 2e-90 | 8.3 EB05 6.6 · IC025 +2.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 5.7 · 93% clinician | no trial data cached |
| Unresponsive to stimuli | 27 | 8.6 5.9–12.6ROR 8.7 · χ² 175 / p 4e-40 | 7.9 EB05 5.5 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious PRR 5.7 | no trial data cached |
| Acute respiratory failure | 20 | 8.6 5.5–13.3ROR 8.6 · χ² 127 / p 1e-29 | 7.6 EB05 5.0 · IC025 +2.1 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.6 | no trial data cached |
| Blood creatine phosphokinase increased | 30 | 8.4 5.9–12.0ROR 8.5 · χ² 189 / p 2e-43 | 7.7 EB05 5.6 · IC025 +2.3 3/3 methods agree | Lab value / disease marker | serious PRR 6.1 · ♀ 14% (drug 52%) · 100% clinician | no trial data cached |
| Hepatic function abnormal | 38 | 8.4 6.1–11.6ROR 8.5 · χ² 242 / p 9e-55 | 7.9 EB05 5.9 · IC025 +2.4 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.9 · 97% clinician | no trial data cached |
| Metabolic acidosis | 32 | 8.3 5.9–11.7ROR 8.4 · χ² 199 / p 2e-45 | 7.7 EB05 5.6 · IC025 +2.3 3/3 methods agree | Labeled (related wording) related wording | serious PRR 5.4 · 100% clinician | no trial data cached |
| Ataxia | 12 | 8.3 4.7–14.6ROR 8.3 · χ² 70 / p 4e-17 | 6.7 EB05 3.9 · IC025 +1.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.4 | no trial data cached |
| Circulatory collapse | 16 | 7.7 4.7–12.5ROR 7.7 · χ² 87 / p 7e-21 | 6.5 EB05 4.2 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 5.0 | no trial data cached |
| Multi-organ failure | 16 | 7.5 4.6–12.2ROR 7.5 · χ² 84 / p 3e-20 | 6.4 EB05 4.1 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.9 | no trial data cached |
| Drug level increased | 15 | 7.4 4.5–12.3ROR 7.5 · χ² 77 / p 7e-19 | 6.3 EB05 4.0 · IC025 +1.8 3/3 methods agree | Reporting / coding artifact | serious PRR 4.6 | no trial data cached |
| Hypocalcaemia (low calcium) | 17 | 7.4 4.6–11.9ROR 7.4 · χ² 88 / p 4e-21 | 6.4 EB05 4.1 · IC025 +1.8 3/3 methods agree | Not in label — unassessed | serious PRR 4.8 | no trial data cached |
| Hemiparesis | 15 | 7.2 4.4–12.0ROR 7.3 · χ² 74 / p 3e-18 | 6.1 EB05 3.9 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 5.1 | 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 |
|---|---|---|---|---|---|---|
| Drug ineffective (drug did not work) | 536 | 3.3 3.1–3.6ROR 4.0 · χ² 937 / p 4e-206 | 3.3 EB05 3.1 · IC025 +1.6 3/3 methods agree | Reporting / coding artifact | serious PRR 5.9 · 99% clinician | no trial data cached |
| Status epilepticus | 169 | 124.5 107.5–144.2ROR 133.3 · χ² 20,284 / p <1e-300 | 121.0 EB05 106.4 · IC025 +6.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 80.0 · 98% clinician | no trial data cached |
| Seizure | 151 | 10.8 9.3–12.6ROR 11.4 · χ² 1,341 / p 5e-294 | 10.7 EB05 9.3 · IC025 +3.1 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 7.2 | no trial data cached |
| Cardiac arrest (heart stopping) | 119 | 11.8 9.9–14.1ROR 12.3 · χ² 1,170 / p 1e-256 | 11.7 EB05 10.0 · IC025 +3.2 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.7 · 96% clinician | no trial data cached |
| Hypotension (low blood pressure) | 114 | 4.7 3.9–5.6ROR 4.8 · χ² 329 / p 9e-74 | 4.6 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 3.2 · 97% clinician | no trial data cached |
| Drug ineffective for unapproved indication | 98 | 14.5 11.9–17.6ROR 15.0 · χ² 1,216 / p 1e-266 | 14.4 EB05 12.1 · IC025 +3.4 3/3 methods agree | Reporting / coding artifact | serious PRR 17.4 · 99% clinician | no trial data cached |
| Drug interaction | 93 | 4.8 3.9–5.9ROR 5.0 · χ² 279 / p 5e-63 | 4.7 EB05 4.0 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 3.4 · 97% clinician | no trial data cached |
| Toxicity to various agents | 84 | 4.1 3.3–5.1ROR 4.2 · χ² 196 / p 7e-45 | 4.0 EB05 3.4 · IC025 +1.7 3/3 methods agree | Not in label — unassessed | serious PRR 2.6 · 98% clinician | no trial data cached |
| Stevens-johnson syndrome (severe blistering skin reaction) | 62 | 22.9 17.9–29.3ROR 23.5 · χ² 1,275 / p 1e-279 | 22.7 EB05 18.4 · IC025 +3.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 15.0 | no trial data cached |
| Convulsion (seizure) | 61 | 8.6 6.7–11.1ROR 8.8 · χ² 406 / p 2e-90 | 8.3 EB05 6.6 · IC025 +2.6 3/3 methods agree | Labeled — boxed warning synonym match | serious PRR 5.7 · 93% clinician | no trial data cached |
| Bradycardia (slow heart rate) | 60 | 9.3 7.2–11.9ROR 9.5 · χ² 436 / p 4e-97 | 8.9 EB05 7.1 · IC025 +2.7 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.2 · 96% clinician | no trial data cached |
| Treatment failure | 54 | 5.4 4.2–7.0ROR 5.5 · χ² 190 / p 1e-43 | 5.2 EB05 4.1 · IC025 +1.9 3/3 methods agree | Reporting / coding artifact | serious PRR 6.5 · ♀ 78% (drug 52%) · 94% clinician | no trial data cached |
| Rhabdomyolysis (muscle breakdown) | 52 | 10.3 7.8–13.4ROR 10.5 · χ² 426 / p 5e-95 | 9.9 EB05 7.7 · IC025 +2.8 3/3 methods agree | Labeled (related wording) related wording | serious PRR 6.7 · ♀ 24% (drug 52%) · 92% clinician | no trial data cached |
| Respiratory failure | 47 | 5.3 4.0–7.0ROR 5.4 · χ² 160 / p 6e-37 | 5.0 EB05 3.9 · IC025 +1.9 3/3 methods agree | Labeled (related wording) related wording | serious PRR 3.5 · ♀ 75% (drug 52%) · 98% clinician | no trial data cached |
| Drug reaction with eosinophilia and systemic symptoms | 46 | 14.8 11.1–19.7ROR 15.1 · χ² 578 / p 4e-128 | 14.6 EB05 11.3 · IC025 +3.2 3/3 methods agree | Labeled — boxed warning exact term | serious PRR 9.6 | no trial data cached |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Drug eruption — n=31, PRR 14.5
- Altered state of consciousness — n=26, PRR 9.9
- Unresponsive to stimuli — n=27, PRR 8.6
✓ A hand-written Bradford Hill causality assessment exists for this drug: Fosphenytoin ↔ Hypotension.
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 Fosphenytoin?
In FDA FAERS, the most frequently co-reported reaction terms for Fosphenytoin are status epilepticus, seizure, cardiac arrest, hypotension, toxicity to various agents, stevens-johnson syndrome. 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 Fosphenytoin have an FDA boxed warning?
Yes. The current FDA label carries a boxed warning: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES The rate of intravenous fosphenytoin sodium injection administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias.
Do FAERS signals prove that Fosphenytoin 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 519a44e3-8a93-456c-b71c-894513810d45, effective 20240410; matched on
openfda.generic_name.exact:"FOSPHENYTOIN SODIUM") - 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, 118 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.