Causality assessment · Expected pharmacological effect

Fosphenytoin and Hypotension: is the FAERS signal real?

n=114 co-reports · PRR 4.7 · ROR 4.8

A written Bradford Hill assessment of one drug–event pair. The grade is a judgement about the signal, not a statement that this drug causes this event in any one person; FAERS counts are reports, not rates.

Expected pharmacological effect

Fosphenytoin ↔ Hypotension

n=114 co-reports · PRR 4.7 · ROR 4.8

Fosphenytoin is a prodrug of phenytoin given intravenously; rapid infusion causes hypotension and arrhythmias, so the label mandates a maximum infusion rate and monitoring (114 co-reports, PRR 4.7). The effect is rate-related rather than a fixed property of the drug, and is worse in patients with cardiac disease or pre-existing hypotension.

Regulatory basis: fosphenytoin (Cerebyx) prescribing information — hypotension and arrhythmias; maximum infusion-rate guidance.

Bradford Hill viewpoint	Status	Note
Temporality (necessary)	met	Hypotension during rapid infusion
Strength	met	PRR 4.7, modest
Consistency	met	Consistent across infusion series
Specificity	partial	Shared with intravenous phenytoin
Biological gradient	met	Rate-related
Plausibility	met	Vasodilation and cardiac depression
Coherence	met	Fits the pharmacology
Experiment	met	Infusion-rate studies quantify it
Analogy	met	Analogous to intravenous phenytoin hypotension

This table is this page's own qualitative read of the literature cited above, not an automated or citation-gated assessment — see the note at the bottom of this page.

✓ Trial evidence found — Established Status Epilepticus Treatment Trial (NCT01960075)

Adverse event	Fosphenytoin (FOS) (n=125) · Valproic Acid (n=125) · Levetiracetam (n=150)
Hypotension	7/125	6/125	4/150

Post-marketing signal terms appear in this trial's posted adverse-event tables; per-arm counts shown as affected/at-risk. View on ClinicalTrials.gov →