Phenytoin | Epilepsy clinician handbook

In intravenous form, phenytoin is used in status epilepsy, with efficacy similar to levetiracetam and sodium valproate.
As maintenance therapy, phenytoin may be used where a sodium channel blocker has known efficacy (for example in certain genetic epilepsies).
General usage is now restricted to situations where other first and second line drugs have failed for generalized tonic clonic seizures, focal seizures or combinations.
Adverse effects and complicated pharmacokinetics can hinder usage of phenytoin, however it can be very effective.
Phenytoin has a role in neonatal seizures in some situations.
It is contraindicated for absences, myoclonic seizures and maintenance therapy in Dravet syndrome.

Possible side effects

Rare but potentially life-threatening side effects:

Rash: DRESS Syndrome, Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)
Lymphadenopathy: a variety of causes.
Haematological abnormalities: leucopenia, anaemia, pancytopenia with or without bone marrow suppression.
Hepatotoxicity, rare cases may be fatal.

Other notable side effects:

Peripheral neuropathy
Choreiform movements
Cerebellar atrophy
Systemic Lupus Erythematosus
All anti-seizure medications are potentially teratogenic and this is often dose related

Carrying the HLA-B 1502 allele is a risk factor for SJS and TEN. Asian ancestry (especially Han Chinese, Thai, and Malay) are more likely to carry the HLA-B 1502 allele, which significantly increases the risk of severe skin reactions.
There is a cross-reactivity of hypersensitivity drug reactions with carbamazepine and phenytoin. Symptoms of rash should be medically evaluated immediately.
Good dental care should be maintained to prevent phenytoin from causing enlarged gums.
Folic acid supplementation may be necessary as phenytoin lowers folic acid blood levels-.
Phenytoin is contraindicated in Porphyria
Phenytoin is a potential teratogen. It should not be used in women of childbearing potential without trial of other options and without full consent of the patient regarding risk to the foetus.
Phenytoin may cause congenital malformations and impaired growth in the foetus (e.g. craniofacial dysmorphism, digital and nail hypoplasia, orofacial clefts).
Extravasation of intravenous preparation can cause “Purple glove syndrome”.

Interactions:

Phenytoin is associated with significant pharmacokinetic interactions and is an inducer of hepatic metabolism (See MIMS for a complete list, particularly non-antiepileptic medications).
Phenytoin may increase the metabolism of levothyroxine, hence levothyroxine doses may need to be increased.
Acetazolamide, brivaracetam, carbamazepine, clobazam and clonazepam, felbamate, oxcarbazepine, phenobarbital, rufinamide, stiripentol, sulthiame and topiramate can decrease the clearance of phenytoin and increase phenytoin plasma levels (certain interactions are complex and the same drug may either increase or decrease phenytoin levels, e.g. phenobarbitone).
Phenytoin can decrease plasma levels of brivaracetam, carbamazepine, clobazam, clonazepam, ethosuximide, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, rufinamide, stiripentol, topiramate, valproic acid and zonisamide.
Phenytoin can increase plasma levels of phenobarbital.
Phenytoin enhances the metabolism of oral contraceptives and may lead to contraception failure.
Valproate can increase the free fraction of phenytoin and also inhibit its clearance.
Hyperammonaemia may occur with the combination of phenytoin and valproate.

Pharmacodynamic interactions: