Epanutin (Phenytoin)
Antiepileptic medication for seizure prevention and control
Epanutin contains the active substance phenytoin sodium and belongs to the class of antiepileptic drugs known as hydantoins. It is used to prevent and control seizures in people with epilepsy. Phenytoin works by stabilising electrical activity in the brain, limiting the spread of abnormal electrical discharges that trigger seizures. This medication requires careful dose adjustment and regular blood level monitoring because of its narrow therapeutic index.
Quick Facts
Key Takeaways
- Epanutin (phenytoin) is an established antiepileptic medication used to prevent generalised tonic-clonic seizures and focal seizures in people with epilepsy.
- It has a narrow therapeutic index, meaning regular blood level monitoring is essential to ensure effectiveness and avoid toxicity.
- Phenytoin interacts with a large number of other medications, including hormonal contraceptives, warfarin and many common drugs — always inform your doctor about all medicines you take.
- Epanutin can cause serious birth defects and should ideally be avoided during pregnancy. Women of childbearing potential must use effective contraception.
- Never stop taking Epanutin suddenly, as this can trigger more frequent and severe seizures, including potentially life-threatening status epilepticus.
What Is Epanutin and What Is It Used For?
Epanutin contains phenytoin sodium, a hydantoin-derivative anticonvulsant that has been in clinical use since 1938, making it one of the oldest and most extensively studied antiepileptic drugs (AEDs). It remains an important medication in the management of various seizure types, particularly in settings where newer alternatives may be unavailable or unsuitable.
Phenytoin works by blocking voltage-gated sodium channels in neuronal cell membranes. By stabilising these channels in their inactivated state, phenytoin prevents the repetitive firing of action potentials that underpins the spread of seizure activity. Unlike some other anticonvulsants, phenytoin does not generally affect the seizure threshold at the focus but rather inhibits the propagation of electrical discharges from the focus to surrounding brain tissue.
Epanutin is effective against several seizure types, including generalised tonic-clonic seizures (formerly known as grand mal seizures), focal seizures (previously called partial seizures), and complex partial seizures. It may also be used in the acute management of status epilepticus, although intravenous formulations are typically preferred in emergency settings. The International League Against Epilepsy (ILAE) lists phenytoin among the established first-line treatments for focal and generalised tonic-clonic seizures, though newer agents with more favourable side effect profiles are now often preferred as initial therapy.
Phenytoin is characterised by saturation kinetics (also called zero-order or Michaelis-Menten kinetics), which means that at therapeutic doses, the body's ability to metabolise the drug becomes partially saturated. As a consequence, even small increases in dose can produce disproportionately large rises in blood levels. This pharmacokinetic property makes therapeutic drug monitoring (TDM) essential for safe and effective treatment with Epanutin.
What Should You Know Before Taking Epanutin?
Contraindications
Epanutin must not be taken if you have any of the following conditions:
- Allergy to phenytoin sodium or any of the other ingredients in Epanutin (including lactose monohydrate, magnesium stearate, gelatin, and colouring agents).
- Acute intermittent porphyria — a rare inherited metabolic disorder that affects haem production. Phenytoin can trigger acute attacks in people with this condition.
- Concurrent use of delavirdine (an antiretroviral medication for HIV). Phenytoin significantly reduces delavirdine levels, potentially leading to viral resistance and treatment failure.
- Concurrent use of telaprevir (a medication for chronic hepatitis C). Co-administration substantially reduces telaprevir plasma concentrations.
Warnings and Precautions
Talk to your doctor before taking Epanutin if any of the following apply to you:
Life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with phenytoin. These reactions usually occur during the first weeks of treatment and may begin as reddish-purple target-like patches or round spots with central blistering, often symmetrically distributed on the trunk. Additional warning signs include mouth ulcers, throat sores, eye inflammation, and flu-like symptoms. If you develop a rash or any of these symptoms, contact your doctor immediately.
Impaired liver and/or kidney function: Patients with compromised liver or kidney function may require lower doses of Epanutin, as the drug is extensively metabolised by the liver and impaired organ function can lead to accumulation and toxicity.
Genetic factors: If you are of Taiwanese, Japanese, Malaysian, or Thai descent and tests have shown that you carry the genetic variant CYP2C9*3, you may metabolise phenytoin more slowly, increasing the risk of side effects. Similarly, the risk of serious skin and mucosal reactions (SJS/TEN) is increased in individuals carrying the HLA-B*1502 allele, which is more prevalent in people of Chinese or Thai descent. Individuals of Black African descent have also been shown to have an increased risk of hypersensitivity reactions.
Infections: If you develop an infection with symptoms such as fever, severely worsened general condition, sore throat, or urinary problems, seek medical attention promptly so that a blood test can rule out agranulocytosis (a dangerous drop in white blood cells).
Hypersensitivity syndrome: If you develop skin rash, blisters, fever, itching, joint pain, jaundice (yellowing of the eyes and skin), swollen lymph nodes, or organ involvement (liver, kidney, heart, or lungs), contact your doctor immediately. These may be signs of a serious hypersensitivity reaction, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). This typically occurs within the first two months of treatment.
Angioedema: Cases of swelling of the face, mouth (lips, gums, tongue), or throat that can lead to life-threatening breathing difficulties have been reported. Seek immediate medical attention if these signs or symptoms occur.
Suicidal thoughts: A small number of people treated with antiepileptic medications, including Epanutin, have experienced thoughts of self-harm or suicide. If you have such thoughts at any time, contact your doctor immediately.
Cardiac effects: Epanutin can cause problems with the heart, including slow heart rhythm (bradycardia). Tell your doctor immediately if you experience symptoms such as unusually slow heartbeat, dizziness, or fainting.
Cerebellar atrophy: Prolonged elevated phenytoin levels and/or long-term use can cause confusion or, in rare cases, permanent damage and shrinkage of the cerebellum (the part of the brain that controls coordination). Signs of acute toxicity include balance disturbances, difficulty coordinating movements, involuntary eye movements, and speech difficulties. If blood levels are too high, the dose must be reduced.
Dental care: It is important to brush your teeth thoroughly with fluoride toothpaste twice daily, as phenytoin can cause gum overgrowth (gingival hyperplasia). Regular dental check-ups are recommended while taking Epanutin.
Pregnancy and Breastfeeding
Epanutin can cause serious birth defects. If taken during pregnancy, the baby has up to three times higher risk of malformations compared to children of women who take no antiepileptic medication. Serious malformations have been reported, including growth problems, skull and facial defects, nail and finger abnormalities, and heart defects. Some of these may occur together as part of fetal hydantoin syndrome.
Fertility and contraception: Women of childbearing potential who are not planning pregnancy must use effective contraception during treatment. Epanutin can reduce the effectiveness of hormonal contraceptives (such as the oral contraceptive pill). Discuss suitable contraception options with your doctor — non-hormonal methods or higher-dose hormonal methods may be recommended.
Planning pregnancy: If you are planning a pregnancy, speak with your doctor before stopping contraception to discuss switching to alternative, safer treatments. Do not stop taking Epanutin without medical advice, as uncontrolled seizures pose serious risks to both mother and child.
During pregnancy: If you become pregnant while taking Epanutin, inform your doctor immediately. Your doctor may decide to adjust treatment. There is also a risk of bleeding problems in the newborn; your doctor may give you and your baby medication (vitamin K) to prevent this. Neurological developmental problems have also been reported in children exposed to phenytoin during pregnancy.
Breastfeeding: Phenytoin passes into breast milk. If you are taking Epanutin, it is generally recommended that you do not breastfeed. Discuss this with your doctor to weigh the benefits and risks.
Driving and Operating Machinery
Epanutin can impair your reaction times and coordination. This should be taken into account when driving or performing tasks requiring full alertness. You are responsible for assessing whether you are fit to drive or operate machinery. The effects and side effects described throughout this guide should inform your judgement. Discuss with your doctor if you are unsure.
Important Information About Ingredients
Epanutin capsules contain lactose (96 mg lactose monohydrate per capsule). If you have been told by your doctor that you have an intolerance to certain sugars, consult your doctor before taking this medicine.
Each capsule also contains 8.4 mg sodium, which is equivalent to 0.4% of the WHO-recommended maximum daily intake of sodium for adults.
How Does Epanutin Interact with Other Drugs?
Phenytoin is both a substrate and an inducer of hepatic cytochrome P450 enzymes (primarily CYP2C9, CYP2C19, and CYP3A4). This means that it is extensively metabolised by the liver and simultaneously increases the metabolism of many other drugs. Because of its narrow therapeutic index and saturation kinetics, even modest changes in metabolism can lead to clinically significant alterations in phenytoin blood levels.
The list of potential drug interactions with phenytoin is extensive. Below are some of the most clinically important interactions. This is not an exhaustive list — always inform your doctor, pharmacist, or other healthcare provider about all medications, supplements, and herbal products you take.
Major Interactions
| Drug / Class | Effect | Clinical Significance |
|---|---|---|
| Delavirdine | Phenytoin drastically reduces delavirdine levels | Contraindicated — risk of HIV treatment failure |
| Telaprevir | Phenytoin substantially reduces telaprevir levels | Contraindicated — risk of hepatitis C treatment failure |
| Hormonal contraceptives | Phenytoin increases metabolism of oestrogen and progestogen | Reduced contraceptive efficacy; use alternative or additional contraception |
| Warfarin | Complex bidirectional interaction | Monitor INR closely; dose adjustments may be needed |
| Valproate / Valproic acid | Displaces phenytoin from protein binding; inhibits its metabolism | Can increase free phenytoin levels; monitor phenytoin levels and adjust dose |
| Corticosteroids | Phenytoin increases corticosteroid metabolism | Reduced corticosteroid efficacy; higher doses may be needed |
Other Notable Interactions
| Drug / Class | Effect on Phenytoin Levels | Recommendation |
|---|---|---|
| Carbamazepine | May decrease phenytoin levels | Monitor both drug levels |
| Isoniazid | May increase phenytoin levels | Monitor for phenytoin toxicity |
| Fluconazole / Ketoconazole | May increase phenytoin levels | Dose adjustment may be needed |
| St John’s Wort | May decrease phenytoin levels | Do not use during phenytoin treatment |
| Chronic alcohol use | May decrease phenytoin levels (enzyme induction) | Discuss alcohol use with your doctor |
| Enteral nutrition (tube feeding) | May decrease phenytoin absorption | Hold tube feeds 2 hours before and after phenytoin; monitor levels |
This is a simplified summary of the most common interactions. Phenytoin has a very extensive interaction profile. Always inform your prescribing doctor about every medication you take, including prescription drugs, over-the-counter medicines, herbal products, and dietary supplements. Your pharmacist can also help screen for interactions.
Food and Drink
Epanutin can be taken with or without food. However, if you are receiving enteral nutrition (tube feeding), this can reduce phenytoin absorption — speak with your doctor about appropriate timing of doses. Chronic (frequent) alcohol consumption can affect phenytoin metabolism and alter its effectiveness. Consult your doctor about alcohol use during treatment.
What Is the Correct Dosage of Epanutin?
Always take Epanutin exactly as prescribed by your doctor. If you are unsure, ask your doctor or pharmacist. Because phenytoin exhibits saturation kinetics, dose adjustments must be made in small increments and always in consultation with your doctor. Regular blood tests are performed to measure your phenytoin blood level and ensure it stays within the therapeutic range (typically 10-20 micrograms per millilitre).
Adults
Adult Maintenance Dose
Usual dose: 200-500 mg daily (2-5 capsules of 100 mg)
Administration: The daily dose is usually divided into two doses (morning and evening).
Swallow capsules whole — do not open, crush, or chew.
Monitoring: Blood tests will be taken regularly to determine the correct dose for you.
Children
Paediatric Dose
Usual dose: 5-8 mg phenytoin per kilogram of body weight per day.
Administration: The daily dose is usually divided into two doses (morning and evening).
Note: Children often require higher doses per kilogram than adults due to faster drug metabolism.
Elderly Patients
Elderly Dose
Elderly patients may need a lower dose of Epanutin. Age-related changes in liver function, body composition, and protein binding can affect drug levels. Your doctor will determine and adjust the dose individually for you.
Patients with Liver or Kidney Disease
Dose in Organ Impairment
Patients with liver or kidney disease may require a lower dose. Phenytoin is extensively metabolised by the liver, and impaired liver function can lead to accumulation. In kidney disease, reduced protein binding increases the fraction of free (active) drug. Your doctor will determine the appropriate dose and may request more frequent blood level monitoring.
Missed Dose
If you forget to take a dose, take it as soon as you remember, unless it is nearly time for your next dose. In that case, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a forgotten dose — this is particularly important with phenytoin because of its saturation kinetics, where small dose increases can cause disproportionately large rises in blood levels.
Overdose
If you have taken too much Epanutin, or if a child has accidentally swallowed the medication, contact your doctor, hospital emergency department, or poison control centre immediately.
Symptoms of phenytoin overdose may include:
- Slurred or difficulty with speech
- Involuntary eye movements (nystagmus)
- Restlessness, agitation, or hallucinations
- Double vision and facial flushing
- Difficulty coordinating movements (ataxia)
- In severe cases: coma, seizures, involuntary movements, paralysis of eye muscles, slow heart rate, and respiratory depression
Stopping Treatment
If you stop taking Epanutin abruptly, there is a risk of more frequent and more severe seizures, including status epilepticus (a prolonged seizure that requires emergency treatment). Never change your dose or stop treatment without your doctor's guidance. If treatment is to be discontinued, your doctor will reduce the dose gradually over time.
What Are the Side Effects of Epanutin?
Like all medicines, Epanutin can cause side effects, although not everybody gets them. Many side effects are related to the blood level of phenytoin and may improve with dose adjustment. Report any unusual symptoms to your doctor, especially during the first months of treatment.
Common Side Effects
- Drowsiness and fatigue
- Dizziness
- Difficulty coordinating movements (ataxia)
- Visual disturbances
- Involuntary eye movements (nystagmus)
- Tremor
- Gum swelling (gingival hyperplasia)
- Skin rash and hives (urticaria)
- Increased body hair growth (hirsutism)
- Liver enzyme changes
- Folic acid deficiency
Uncommon Side Effects
- Heartburn
- Nausea and vomiting
- Enlarged lymph nodes (lymphadenopathy)
Rare Side Effects
- Hypersensitivity syndrome (fever, rash, facial swelling)
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
- Systemic lupus erythematosus (SLE)
- Blood disorders, including agranulocytosis
- Heart rhythm disturbances
- Jaundice (hepatitis)
- Elevated blood sugar levels
- Osteoporosis (bone loss)
- Joint pain
- Headache and confusion
- Tingling sensations (paraesthesia)
- Excessive sleepiness
- Taste changes
Frequency Not Known
- Abnormal thyroid function test results
- Angioedema (swelling of face, mouth, or throat)
- Acute generalised exanthematous pustulosis (AGEP — life-threatening blistering skin rash)
- Cerebellar atrophy (shrinkage of the cerebellum with long-term use)
- Pure red cell aplasia (reduced red blood cell production)
- Breathing difficulties
Reports of bone disease, including decreased bone density, osteoporosis, and fractures, have been associated with long-term use of phenytoin. If you are on long-term antiepileptic treatment, have known osteoporosis, or take corticosteroids, speak with your doctor about bone health monitoring and preventive measures such as vitamin D and calcium supplementation.
Hypersensitivity syndrome typically occurs within the first 2 months of treatment. Symptoms can include severe skin reactions, fever, and swelling of the lips and face. If you experience any of these symptoms after starting Epanutin, seek immediate medical attention.
Reporting side effects: If you experience any side effects, including those not listed here, talk to your doctor or pharmacist. You can also report side effects to your national medicines agency to help monitor the safety of this medication.
How Should You Store Epanutin?
Keep this medicine out of the sight and reach of children at all times. Do not use Epanutin after the expiry date stated on the packaging after "EXP". The expiry date refers to the last day of the stated month.
Store in the original container to protect from moisture. No special temperature storage conditions are required under normal household conditions. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use — these measures help protect the environment.
What Does Epanutin Contain?
Active Ingredient
The active substance is phenytoin sodium (100 mg per capsule).
Inactive Ingredients
- Capsule contents: lactose monohydrate (96 mg), magnesium stearate
- Capsule shell: gelatin, sodium lauryl sulfate, colouring agents (titanium dioxide E171, erythrosine E127, quinoline yellow E104)
- Capsule ink: black iron oxide (E172), shellac, propylene glycol, potassium hydroxide
Appearance and Pack Size
Epanutin capsules are orange and white with "EPANUTIN100" printed on them. They are available in bottles of 100 capsules.
Manufacturer
Epanutin is manufactured by Pfizer Manufacturing Deutschland GmbH, Freiburg im Breisgau, Germany.
Frequently Asked Questions About Epanutin
Epanutin (phenytoin) is an antiepileptic medication used to prevent and control seizures in people with epilepsy. It is effective against generalised tonic-clonic seizures (grand mal) and focal (partial) seizures. It works by stabilising electrical activity in the brain and preventing the abnormal spread of electrical discharges that cause seizures. Phenytoin has been used clinically since 1938 and remains an important treatment option worldwide.
The most common side effects of Epanutin include drowsiness, dizziness, difficulty coordinating movements (ataxia), visual disturbances, involuntary eye movements (nystagmus), tremor, gum swelling (gingival hyperplasia), skin rash, hives, increased body hair growth, liver changes, and folic acid deficiency. Most of these are dose-related and may improve when the dose is adjusted. Good dental hygiene is important to help prevent gum problems.
Epanutin can cause serious birth defects and should ideally be avoided during pregnancy. Children exposed to phenytoin in the womb have up to three times the risk of birth defects, including growth problems, skull and facial abnormalities, and heart defects (fetal hydantoin syndrome). However, you should never stop taking Epanutin without medical advice, as uncontrolled seizures also pose serious risks. If you are planning a pregnancy, discuss switching to safer alternatives with your doctor well in advance.
Phenytoin has a narrow therapeutic index and unusual pharmacokinetics called saturation (zero-order) kinetics. This means that the body's capacity to break down phenytoin becomes partially saturated at therapeutic doses, so even a small dose increase can cause a disproportionately large rise in blood levels. Regular monitoring ensures levels remain in the effective range (typically 10-20 micrograms per millilitre) while avoiding toxicity. Signs of excessive blood levels include nystagmus, ataxia, slurred speech, and confusion.
Epanutin interacts with an exceptionally large number of medications. Drugs that can increase phenytoin levels include valproate, isoniazid, and fluconazole. Drugs whose effectiveness may be reduced by phenytoin include hormonal contraceptives, warfarin, corticosteroids, and many antiretrovirals. Concurrent use with delavirdine and telaprevir is contraindicated. Herbal products containing St John's Wort should not be used. Always inform all healthcare providers about your Epanutin use.
No. You should never stop taking Epanutin suddenly without medical supervision. Abrupt withdrawal of antiepileptic medication can trigger increased seizure frequency and severity, including status epilepticus — a prolonged seizure that constitutes a medical emergency. If your doctor decides to discontinue or switch your treatment, the dose will be reduced gradually over a period of time to minimise the risk of breakthrough seizures.
References
- Brodie MJ, Kwan P. Current position of phenytoin in epilepsy and its future. Epilepsy & Behavior. 2012;24(4):420-427. doi:10.1016/j.yebeh.2012.05.016
- International League Against Epilepsy (ILAE). Updated ILAE evidence review of antiseizure medication efficacy and effectiveness. Epilepsia. 2022;63(10):2529-2532.
- National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. NICE guideline [NG217]. 2022. Available at: nice.org.uk/guidance/ng217
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd List. 2023. Geneva: WHO.
- European Medicines Agency (EMA). Phenytoin — Summary of Product Characteristics. Available at: ema.europa.eu
- Perucca E, Tomson T. The pharmacological treatment of epilepsy in adults. The Lancet Neurology. 2011;10(5):446-456.
- Patsalos PN, et al. Antiepileptic drugs — best practice guidelines for therapeutic drug monitoring. Therapeutic Drug Monitoring. 2018;40(5):526-548.
- British National Formulary (BNF). Phenytoin. Available at: bnf.nice.org.uk
- Tomson T, et al. Teratogenicity of antiepileptic drugs. Current Neurology and Neuroscience Reports. 2019;19(8):39.
- Man CBL, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48(5):1015-1018.
Medical Editorial Team
This article was written by the iMedic Medical Editorial Team, which includes licensed specialists in neurology, epileptology, and clinical pharmacology. All content is reviewed according to international medical guidelines from the WHO, ILAE, NICE, and BNF.
Evidence Level: 1A — Based on systematic reviews, meta-analyses, and international clinical guidelines.
Last Medical Review:
Conflict of Interest: None. iMedic receives no pharmaceutical company funding or sponsorship.