Fosphenytoin

An injectable prodrug of phenytoin, FDA-approved for status epilepticus, seizures during neurosurgery and short-term replacement of oral phenytoin.

psilodex.org/m/fosphenytoin · data v2026.10.05

Clinical contraindication: None listed; No label contraindication covering psilocybin was found. This is not a finding that the combination has been shown to be without risk.
Psilocybin evidence: No psilocybin data
Half-life: ~15 min; Approximate, in adults. Source under Interaction below.

Named in state rules?

Not namedColorado Condition rules (3)

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Fosphenytoin”, v2026.10.05. psilodex.org/m/fosphenytoin

Clinical data and state rules are separate facts. Both are shown; neither is a decision.

What it is used for

FDA status

FDA-approved

Availability

Injection given in hospital or emergency settings

FDA-approved for

Generalized tonic-clonic status epilepticus
Prevention and treatment of seizures during neurosurgery
Short-term substitute for oral phenytoin

Sources [1]

Other safety

Boxed warning: rapid intravenous infusion carries a risk of severe low blood pressure and cardiac arrhythmias.

About the medication itself, separate from any interaction with psilocybin.

Sources [1]

01 Interaction with psilocybin

It may lower psilocybin levels by speeding how the body clears psilocybin (untested). Also, rapid infusion can cause severe low blood pressure.

Detail There are no psilocybin data. Fosphenytoin is an injectable prodrug (precursor) of phenytoin, which strongly induces (speeds up) liver drug-processing enzymes. So psilocin levels may fall; this is untested. Also, rapid infusion can cause severe low blood pressure and arrhythmias (irregular heartbeats). High phenytoin levels can cause confusion or psychosis. Abrupt withdrawal can trigger status epilepticus (nonstop seizures). Sources [1][2]

Human data with psilocybin: No psilocybin data; based on how it works and its label
Half-life: ~15 min (conversion to phenytoin); phenytoin 12–29 h (FDA label, checked 2026-10-04) Phenytoin half-life is longer at higher plasma concentrations.

Evidence types on this record

No psilocybin dataNo psilocybin data: no human data with psilocybin or another classic psychedelic; the text draws on the medication's own pharmacology and its label or reference facts

02 Pharmacology relevant to psilocybin

6 listed · counted on reports

Withdrawal or rebound if stopped abruptly: Stopping suddenly can cause withdrawal or a rebound of symptoms. Sources [1]
Speeds up drug metabolism: Increases the liver enzymes that break down many medicines, lowering their levels. When it is stopped, levels of other medicines can rise over the following weeks. Sources [1]
Liver injury: The label or source warns of liver injury, from raised liver enzymes to liver failure. Liver disease also affects how the body clears psilocin. Sources [1]
Lowers blood pressure or causes orthostasis: Lowers blood pressure, or causes a drop on standing (orthostasis) that can bring dizziness or fainting. Sources [1]
Psychiatric reactions: The label or source warns of psychiatric effects such as psychosis, mania, hallucinations, suicidal thoughts or severe mood or behavior changes. Psilocybin can also bring up strong emotions, so these warnings are relevant to screening. Sources [1]
QT-prolonging: Lengthens the QT interval on an ECG, a measure of the heart’s electrical recovery between beats. A long QT raises the risk of a dangerous heart rhythm, more so with other QT-prolonging drugs or low potassium or magnesium. Sources [1]

03 State rules

Plain-language summary · official text governs

CO4 CCR 755-1

Not namedCondition rules (3)

No provision names this medication or its class.

Colorado · checked 2026-10-04

OROAR 333-333

Not named

No provision names this medication or its class.

Oregon · checked 2026-10-04

NM7.35.3 NMAC (proposed)

Pending

New Mexico's clinical rules (proposed 7.35.3 NMAC) are not final. No provision naming this medication has been found.

New Mexico · checked 2026-10-04

04 Conditions to ask about

Screening items in state rules

This medication is usually taken for a condition. State rules screen for some conditions directly, so the medication is a prompt to ask about them. Confirm with the participant; never assume a condition from the medication.

Seizure disorder (usual indication)
- CO 2.5(A)(2) · Clinical Facilitator licensees
- CO 6.16(F)(2)(a) · Facilitators without a clinical facilitator license
- CO 6.16(F)(1) · All licensees

05 Sources

CEREBYX (fosphenytoin sodium) injection · FDA label (DailyMed) — revised 2025-08 | Lowers blood pressure or causes orthostasis: 5.2 Cardiovascular Risk Associated with Rapid Infusion "Rapid intravenous administration of CEREBYX increases the risk of adverse cardiovascular reactions, including severe hypotension and cardiac arrhythmias." | QT-prolonging: 5.2 Cardiovascular Risk Associated with Rapid Infusion "Cardiac arrhythmias have included bradycardia, heart block, QT interval prolongation, ventricular tachycardia, and ventricular fibrillation" | Withdrawal or rebound if stopped abruptly: 5.3 Withdrawal Precipitated Seizure, Status Epilepticus "Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure frequency, including status epilepticus." | Liver injury: 5.8 Hepatic Injury "Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with phenytoin (the active metabolite of CEREBYX)." | Psychiatric reactions: 5.17 Serum Phenytoin Levels above Therapeutic Range "Serum levels of phenytoin (the active metabolite of CEREBYX) sustained above the therapeutic range may produce confusional states referred to as "delirium," "psychosis," or "encephalopathy,"" | Speeds up drug metabolism: 7 Drug Interactions "Phenytoin or CEREBYX is a potent inducer of hepatic drug-metabolizing enzymes." | BOXED WARNING "because of the risk of severe hypotension and cardiac arrhythmias" | 12.3 Pharmacokinetics "The conversion half-life of fosphenytoin to phenytoin is approximately 15 minutes."
Thomann J, Kolaczynska KE, Stoeckmann OV, et al. In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin. Front Pharmacol 2024;15:1391689. — Lab studies: MAO-A, CYP2D6 and CYP3A4 metabolized psilocin; glucuronidation and conversion to 4-HIAA are the main routes.

Record history

v2026.10.02First published.
2026-10-04Last reviewed against its sources.

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