Antiepileptic, hydantoin derivative (sodium channel blocker)
ATC code: N03AB02 (Phenytoin)
Brand names
Dilantin, Phenytek
Blocks fast sodium channels in cardiomyocytes and neurons in the activated state, stabilising the membrane and preventing repetitive firing. Metabolised by hepatic CYP2C9 and CYP2C19 with non-linear (saturable) kinetics: a 30% dose increase can double the blood level. Phenytoin itself is a strong inducer of CYP3A4, CYP2C9, CYP2C19, UGT and P-glycoprotein, accelerating metabolism of most co-administered drugs.
Second line
Phenytoin is a second-line antiepileptic for focal and generalised tonic-clonic seizures in adults when levetiracetam, lamotrigine or oxcarbazepine fail. The narrow therapeutic window (10–20 mcg/mL) and non-linear kinetics require blood level monitoring. ILAE 2017 and SEN moved phenytoin off first-line because of gingival hyperplasia, hirsutism, long-term osteopenia and drug hypersensitivity syndrome.
9 pairs found. Sorted from critical to minor.
Mechanism
Phenytoin is a strong CYP3A4 + P-gp inducer. Apixaban level falls 50–75% with loss of anticoagulation and risk of stroke or VTE recurrence. Eliquis Section 7.
Symptoms
Ischemic stroke in atrial fibrillation patient or recurrent venous thrombosis.
Management
Combination contraindicated. Alternative anticoagulant: warfarin (INR 2.0–3.0 in AF). Alternative anticonvulsant: levetiracetam (no induction).
Mechanism
Strong CYP3A4 induction.
Symptoms
Mycosis progression.
Management
Combination contraindicated.
Mechanism
Same as apixaban: CYP3A4 + P-gp induction by phenytoin drops rivaroxaban by 50%. Xarelto does not recommend the combination.
Symptoms
Stroke or recurrent venous thrombosis.
Management
Combination contraindicated. Warfarin or levetiracetam as alternative.
Mechanism
Disulfiram inhibits CYP2C9 and CYP2C19. Phenytoin rises 2-3 fold – toxicity (nystagmus, ataxia).
Symptoms
Nystagmus, ataxia, dizziness within 5-7 days.
Management
Check phenytoin level at 5 and 14 days. Reduce dose 30-50%.
Mechanism
5-FU inhibits CYP2C9 – phenytoin rises 2-fold. Toxicity with ataxia, nystagmus.
Symptoms
Nystagmus, ataxia, drowsiness after 7-14 days.
Management
Check phenytoin level on day 7. Reduce dose 25-50%.
Mechanism
Phenytoin induces UGT1A4. Lamotrigine falls 50%.
Symptoms
Seizure breakthrough.
Management
Double lamotrigine dose.
Mechanism
Phenytoin induces CYP3A4. Simvastatin level falls 60%, lipid-lowering effect is lost. cholesterol returns to baseline, cardiovascular risk rises.
Symptoms
returns to baseline over 4–6 weeks.
Management
Alternative statin: pravastatin or rosuvastatin (not CYP3A4-metabolised). Alternative anticonvulsant: levetiracetam.
Mechanism
Phenytoin induces CYP3A4. Tacrolimus level falls 2–3 fold with transplant rejection risk.
Symptoms
Tacrolimus trough below target, laboratory signs of rejection.
Management
For post-transplant epilepsy: levetiracetam or lacosamide as alternative. If phenytoin is needed, increase tacrolimus 2–3 fold with frequent monitoring.
Mechanism
Phenytoin induces CYP1A2. Theophylline falls 30-50%.
Symptoms
Return of obstructive symptoms.
Management
Theophylline level monitoring with dose adjustment.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Teratogen: raises the risk of facial malformations (fetal hydantoin syndrome), cleft palate and cardiac defects. EMA recommends pre-conception planning and, when possible, switching to levetiracetam or lamotrigine. While on therapy, folic acid 5 mg/day is required.
Passes into breast milk in small amounts. AEMPS allows breastfeeding with infant monitoring for drowsiness and poor sucking.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Phenytoin is evaluated for the following indications with varying evidence strength: Epilepsy (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Phenytoin (≥ 1 in 100): Nystagmus, ataxia, dizziness with supratherapeutic levels, Gingival hyperplasia, Hirsutism and coarsening of facial features on long-term use, Drowsiness, Rash, Laboratory liver enzyme rise. See the Safety section for uncommon and serious reactions.
FDA category D. Teratogen: raises the risk of facial malformations (fetal hydantoin syndrome), cleft palate and cardiac defects. EMA recommends pre-conception planning and, when possible, switching to levetiracetam or lamotrigine. While on therapy, folic acid 5 mg/day is required.
Passes into breast milk in small amounts. AEMPS allows breastfeeding with infant monitoring for drowsiness and poor sucking.
Phenytoin is contraindicated in: Second- or third-degree AV block and sinus bradycardia (for IV use); Combination with delavirdine – risk of ARV resistance; Known hydantoin hypersensitivity or prior DRESS; Acute porphyria. Full list in the Safety section.