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# Anticonvulsant toxicity (phenytoin, carbamazepine, valproate)

Poisoning from too much of a seizure medicine. Typical signs are unsteady walking, jerky eye movements and drowsiness; some cases affect the heart or liver.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/)
- [Liver](https://durgical.com/en/anatomy/liver/)
- [Pons](https://durgical.com/en/anatomy/pons/)
- [Midbrain](https://durgical.com/en/anatomy/midbrain/)
- [Medulla oblongata](https://durgical.com/en/anatomy/medulla-oblongata/)
- [Vestibulocochlear nerve (VIII)](https://durgical.com/en/anatomy/vestibulocochlear-nerve/)
- [Gums (gingiva)](https://durgical.com/en/anatomy/gums/)
- [Pancreas](https://durgical.com/en/anatomy/pancreas/)

## Why it happens

- [Ion channels and gating](https://durgical.com/en/physiology/ion-channels-and-gating/)
- [Functions of the cerebellum](https://durgical.com/en/physiology/functions-of-the-cerebellum/)
- [Enzyme kinetics (Michaelis–Menten and Lineweaver–Burk)](https://durgical.com/en/biochemistry/topics/enzyme-kinetics/)
- [Urea cycle](https://durgical.com/en/biochemistry/pathways/urea-cycle/)
- [Ammonia (ammonium)](https://durgical.com/en/biochemistry/molecules/ammonia/)

## What it is

Toxicity from overdose or excess blood levels of antiseizure medicines, mainly phenytoin, carbamazepine and valproate. It can follow a deliberate or accidental overdose or develop slowly in patients on long-term therapy because of dose changes, drug interactions, low albumin, liver disease or pregnancy. Each drug has its own pattern on top of a shared picture of cerebellar and brainstem depression.

## Who gets it

These drugs are widely used in Colombia for epilepsy, bipolar disorder and pain, and they appear among the medicines involved in intentional self-poisoning reported to INS surveillance. Chronic toxicity is common in older adults and in patients who start interacting drugs such as some antibiotics, antifungals or isoniazid.

## Causes

- Intentional overdose (self-harm)
- Accidental ingestion by a child
- Dose increase or dosing error
- Drug interactions that block metabolism (macrolides, azole antifungals, isoniazid, some anti-ulcer drugs)
- Low albumin, liver or [kidney](https://durgical.com/en/anatomy/kidney/) disease raising free drug level
- Rapid intravenous phenytoin infusion

## Risk factors

- Epilepsy or mood disorder with access to large supplies
- Depression and previous suicide attempts
- Older age and polypharmacy
- Hypoalbuminaemia, malnutrition, liver or kidney failure
- Genetic variants affecting metabolism or hypersensitivity (for example HLA-B*15:02 with carbamazepine)

## Pathophysiology

Phenytoin and carbamazepine block voltage-gated sodium channels; in excess this depresses the [cerebellum](https://durgical.com/en/anatomy/anterior-quadrangular-lobule/) and brainstem, causing nystagmus, ataxia and slurred speech, then coma. Phenytoin has saturable (zero-order) metabolism, so small dose increases cause large level rises; intravenous phenytoin and its propylene glycol diluent can cause hypotension and bradyarrhythmias. Carbamazepine is also anticholinergic, can widen the QRS and has erratic, delayed absorption with an active epoxide metabolite. Valproate disturbs mitochondrial fatty-acid oxidation and the urea cycle, causing hyperammonaemia, encephalopathy, metabolic acidosis and, rarely, liver failure and pancreatitis.

## Classification

- Acute overdose versus chronic (therapeutic) toxicity
- Phenytoin: neurological pattern; cardiovascular effects mainly with fast intravenous use
- Carbamazepine: neurological plus anticholinergic and sodium-channel cardiac effects
- Valproate: CNS depression, hyperammonaemia, metabolic effects and hepatotoxicity

## Symptoms and signs

- Horizontal nystagmus, unsteady gait and slurred speech
- Drowsiness, confusion and, in severe cases, coma
- Nausea and vomiting
- Paradoxical seizures in severe phenytoin or carbamazepine poisoning
- Carbamazepine: dry mouth, urinary retention, fast heart rate and dilated pupils
- Valproate: lethargy out of proportion, vomiting and confusion from high ammonia

## Red flags

- Coma or loss of airway protection
- Seizures in a patient with toxic levels
- Wide QRS, arrhythmia or hypotension
- Rising drug levels hours after ingestion (delayed absorption, bezoar)
- Valproate with high ammonia, acidosis, jaundice or severe abdominal pain

## Diagnosis

**Clinical**
History of drug, formulation (immediate or extended release), amount and time; examination for nystagmus, ataxia, mental status and anticholinergic signs; screen for co-ingestants.

**Tests**
Serial serum drug levels until clearly falling (free phenytoin if albumin is low); ECG and cardiac monitoring; glucose, electrolytes, blood gas; ammonia, [liver](https://durgical.com/en/anatomy/liver/) enzymes, lipase and blood count with valproate; acetaminophen and salicylate levels in any intentional overdose.

**Imaging**
Usually none; head CT if there is trauma, focal signs or another cause of coma is possible.

## Differential diagnosis

- Alcohol, benzodiazepine or other sedative intoxication
- Tricyclic antidepressant overdose (wide QRS, anticholinergic signs)
- Posterior circulation stroke or cerebellar haemorrhage
- Postictal state or non-convulsive status epilepticus
- Wernicke encephalopathy

## Goal of treatment

Protect the airway and circulation, limit absorption, speed elimination when levels are dangerous and correct drug-specific problems such as hyperammonaemia.

## Treatment

**Acute**
Airway, breathing and circulation; intubation for coma; benzodiazepines for seizures. Activated charcoal when the airway is protected and the ingestion is recent; repeated doses can help with carbamazepine.

**Medical**
Sodium bicarbonate for QRS widening from carbamazepine. For valproate with hyperammonaemia or hepatotoxicity, L-carnitine is used. Hold the drug in chronic toxicity and review interactions.

**Procedure**
Haemodialysis (high-flux) for severe carbamazepine or valproate poisoning with very high levels, coma, shock or severe acidosis.

**Follow-up**
Continuous ECG, neurological checks and serial levels. Nursing: fall precautions for ataxia, aspiration precautions, seizure precautions and check the intravenous site with phenytoin (purple glove syndrome).

**Conservative**
After recovery, psychiatric assessment for intentional overdose and a safe plan to restart antiseizure therapy to avoid breakthrough seizures.

## Complications

- Aspiration pneumonia from coma
- Arrhythmias and hypotension
- Status epilepticus after drug withdrawal or in severe toxicity
- Hyperammonaemic encephalopathy, liver failure and pancreatitis (valproate)
- Soft-tissue injury from intravenous phenytoin extravasation

## Prognosis

Most patients recover fully with supportive care. Severe outcomes cluster in large carbamazepine and valproate overdoses with coma, cardiac toxicity or delayed peak levels, and in patients with co-ingestants.

## Prevention

- Level monitoring when doses change or interacting drugs start, careful prescribing in older adults, limited supplies for people at risk of self-harm, and child-resistant storage

## Test yourself

Think of the answer, then tap the question to see it.

## What is the classic triad of phenytoin toxicity?

Nystagmus, ataxia and slurred speech (dysarthria), with drowsiness as levels rise.

## Why can a small phenytoin dose increase cause toxicity?

Its metabolism is saturable (zero-order), so near saturation blood levels rise disproportionately.

## Which ECG finding suggests severe carbamazepine poisoning and how is it treated?

QRS widening from sodium-channel blockade; treated with sodium bicarbonate.

## Which laboratory test is key in valproate toxicity with lethargy?

Serum ammonia, because valproate causes hyperammonaemic encephalopathy; L-carnitine is used.

## Why are repeated drug levels needed after carbamazepine overdose?

Absorption is erratic and can be delayed (and the tablets can form bezoars), so levels may peak many hours later.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/anticonvulsant-toxicity/)

## Related conditions

- [Epilepsy and seizures](https://durgical.com/en/conditions/epilepsy-and-seizures/)
- [Status epilepticus](https://durgical.com/en/conditions/status-epilepticus/)
- [Hyperammonaemia](https://durgical.com/en/conditions/hyperammonaemia/)
- [Acute liver failure](https://durgical.com/en/conditions/acute-liver-failure/)
- [Acute pancreatitis](https://durgical.com/en/conditions/acute-pancreatitis/)
- [Stevens–Johnson syndrome and toxic epidermal necrolysis](https://durgical.com/en/conditions/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis/)
- [Cutaneous drug reactions and DRESS](https://durgical.com/en/conditions/cutaneous-drug-reactions-and-dress/)
- [Aplastic anaemia](https://durgical.com/en/conditions/aplastic-anaemia/)
- [Tricyclic antidepressant overdose](https://durgical.com/en/conditions/tricyclic-antidepressant-overdose/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Phenytoin overdose](https://medlineplus.gov/ency/article/002533.htm) (MedlinePlus, US National Library of Medicine, 2026); [Therapeutic drug levels](https://medlineplus.gov/ency/article/003430.htm) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/conditions/anticonvulsant-toxicity/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/anticonvulsant-toxicity/