Phenytoin toxicity: signs, causes, blood levels and what to do

Phenytoin is an anti-epileptic medicine used to prevent seizures. Patient.info describes it as a medicine for epilepsy and trigeminal neuralgia that works by stabilising brain activity. Patient.info says it is taken exactly as prescribed, usually with or after food.

Toxicity means having too much of the medicine in the body, whether from a single large dose or from levels that build up gradually. Phenytoin is a medicine where the margin between a helpful and a harmful amount is relatively narrow, which is why the dose is adjusted carefully and why blood levels are sometimes measured.

The UK SmPC explains that there are marked variations among individuals in the serum levels at which toxicity may occur. In practice that means a level that is comfortable for one person can cause symptoms in another, and the symptoms themselves can be as important as the number.

This page is general information. If you or someone you look after takes phenytoin and you are concerned about toxicity, contact your prescriber, pharmacist or NHS 111 for advice, and use emergency services in an emergency.

The SmPC lists the initial symptoms of overdose as nystagmus, ataxia and dysarthria. It lists other signs as tremor, hyperreflexia, somnolence, drowsiness, lethargy, slurred speech, blurred vision, nausea and vomiting. In severe overdose the person can become comatose, with unresponsive pupils, low blood pressure and then breathing and circulatory depression.

Patient.info lists feeling confused, nervous, unsteady or shaky among the side effects to tell your doctor about if they become troublesome, and slurred speech, lack of concentration and difficulty sleeping in the same group. These overlap with the early signs of toxicity, which is why new unsteadiness, slurred speech or confusion should always be reported rather than assumed to be the epilepsy or tiredness.

• Involuntary jerking eye movements (nystagmus), sometimes with blurred or double vision.

• Unsteadiness or poor coordination (ataxia), including difficulty walking in a straight line.

• Slurred speech (dysarthria).

• Tremor, drowsiness or marked sleepiness.

• Nausea or vomiting.

• Confusion or lack of concentration.

• In severe cases, reduced consciousness and breathing difficulty, which are emergencies.

The SmPC describes how the signs relate to the serum concentration. It says nystagmus on lateral gaze usually appears at 20 mg/l, ataxia at 30 mg/l, and dysarthria and lethargy when the concentration is greater than 40 mg/l. It also notes that a concentration as high as 50 mg/l has been reported without evidence of toxicity, which underlines why the individual picture matters more than a single number.

The SmPC says that at the first sign of acute toxicity, serum drug level determinations are recommended, and that dose reduction is indicated if levels are excessive. It warns that interpreting total plasma concentrations needs caution in people with kidney or liver disease or low albumin, because the proportion of unbound drug is higher, and that unbound concentrations may be more useful in those patients.

Patient.info says that people taking phenytoin will need to have blood tests from time to time and should keep regular appointments so their doctor can check progress.

The SmPC mentions several situations that can change phenytoin levels. Acute alcohol intake may increase phenytoin serum levels, while chronic alcoholism may decrease them. Kidney or liver disease and low albumin change the proportion of unbound drug. Herbal preparations containing St John's wort should not be used while taking phenytoin because of the risk of decreased levels and reduced effect.

The SmPC also refers to interactions with other medicines in its interactions section. This is a reason to tell every prescriber and pharmacist that you take phenytoin and to check before starting or stopping any other medicine, including over-the-counter and herbal products.

If you notice new symptoms after a change in your medicines or after starting any new product, tell your prescriber.

Patient.info advises that if you suspect that you or someone else might have taken too much phenytoin, you should go to the accident and emergency department of your local hospital immediately, and take the container with you even if it is empty. The NHS poisoning advice says to call 999 or go to A&E if you think someone has swallowed something harmful, and to call NHS 111 if you are not sure whether something is harmful. Do not make the person sick.

The SmPC states that treatment of overdose is non-specific, since there is no known antidote. Management is supportive, and in severe cases may include support of the airway and breathing and monitoring of the heart and circulation. This is delivered in hospital.

For milder symptoms that you think could be due to your medicine, contact your GP, epilepsy specialist nurse or pharmacist the same day. Do not simply skip or reduce doses to try to correct things yourself.

It can be tempting to stop a medicine that seems to be causing side effects. The SmPC says that abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus, a prolonged seizure that is an emergency, and that dose reduction, discontinuation or substitution should be done gradually when the clinician judges it necessary. Patient.info likewise says not to stop taking phenytoin suddenly without medical advice.

The SmPC makes an exception for allergic or hypersensitivity reactions, where rapid substitution of alternative therapy may be necessary, and that decision is made by a clinician. Patient.info advises that a severe rash needs to be assessed by a doctor, and that you should contact your doctor straightaway if you develop a high temperature or other signs of blood or skin disorders.

The SmPC notes that levels sustained above the optimal range may produce confusional states described as delirium, psychosis or encephalopathy, and rarely irreversible cerebellar dysfunction or atrophy. It also notes that long-term use is associated with effects on bone health because of increased metabolism of vitamin D, and that a predominantly sensory peripheral polyneuropathy has been observed in long-term therapy.

Patient.info also advises reporting mood changes or thoughts of suicide straightaway, and says that people with epilepsy must stop driving at first and that the doctor will advise when it may be possible to drive again.

Do not change your treatment without speaking to a prescriber.