Phenytoin oral liquids
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral liquid containing phenytoin
Epilepsy - combination of both partial and tonic-clonic seizures
Epilepsy - partial seizures
Epilepsy - tonic-clonic seizures
Seizure prevention & treatment during/after neurosurgery &/or head injury
Control of tonic-clonic seizures (grand mal epilepsy), partial seizures (focal including temporal lobe) or a combination of these.
Prevention of seizures occurring during or following neurosurgery and/or severe head injury.
Treatment of trigeminal neuralgia, as a second line treatment if carbamazepine is unsuitable.
Treatment with phenytoin should be tailored to the individual patient as there is wide inter-patient variability in phenytoin serum levels with equivalent dosage.
Maintenance of treatment should be the lowest dose of anticonvulsant consistent with the control of seizures.
Initial dose: 3mg/kg to 4mg/kg daily. Adjust dose as necessary.
Maintenance dose: 200mg to 500mg daily in single or divided doses.
Exceptionally, a daily dose outside this range may be indicated.
Dosage should normally adjusted according to serum levels where assay facilities exist.
Total serum phenytoin levels should not exceed 20micrograms/ml in Trigeminal Neuralgia.
Phenytoin clearance may be decreased in elderly patients and therefore, lower or less frequent dosing may be required (See Dosage; Adult).
Initial dose: 5mg/kg daily in two divided doses. Adjust dose as necessary.
Maintenance dose: Usually 4mg/kg to 8mg/kg.
Maximum dose: 300mg daily
The following alternative dosing schedule may be suitable:
Focal seizure; Tonic-clonic seizures
Children aged 12 to 18 years
Initial dose: 75mg to 150mg twice daily. Titrate according to response and plasma-phenytoin concentration.
Maintenance dose: Up to 150mg to 200mg twice daily.
Maximum dose: 300g daily.
Children aged 1 month to 12 years
Initial dose: 1.5mg/kg to 2.5 mg/kg twice daily. Titrate according to response and plasma-phenytoin concentration.
Maintenance dose: Up to 2.5mg/kg to 5mg/kg twice daily.
Maximum dose: 7.5mg/kg twice daily or 300mg daily.
Prophylaxis and treatment of seizures during or following neurosurgery or severe head injury
Initial dose: 2.5mg/kg twice daily. Titrate according to response.
Maintenance dose: Up to 4mg/kg to 8mg/kg daily. Titrate according to response and plasma-phenytoin concentration.
Maximum dose: 300g daily.
The absorption of phenytoin following oral administration in neonates is unpredictable and the metabolism of phenytoin may be depressed. It is therefore especially important to monitor serum levels in the neonate.
Loading dose by slow intravenous infusion: 18mg/kg.
Maintenance dose by mouth: 2.5mg/kg to 5mg/kg twice daily. Titrate according to response and plasma-phenytoin concentration.
Maximum dose: 7.5mg/kg twice daily.
Patients with Hepatic Impairment
Phenytoin is highly protein bound and extensively metabolised by the liver. Therefore, consider reducing dose inpatients with hepatic impairment to prevent accumulation and toxicity.
Where protein binding is reduced, as in uraemia, total serum phenytoin levels will be reduced accordingly. However, the pharmacologically active free drug concentration is unlikely to be altered. Under these circumstances, therapeutic control may be achieved with total phenytoin levels below the normal range of 10micrograms/ml to 20micrograms/ml (40micromoles/l to 80micromoles/l).
Additional Dosage Information
Phenytoin has non-linear kinetics and a low therapeutic index. Frequent serum phenytoin level measurements may be required. Genetically patients may either be fast or slow metabolisers of phenytoin. Dosage should be individualised, as there will be wide inter-patient variability in phenytoin serum levels with equivalent dosage. Introduce phenytoin in small dosages with gradual increments until control is achieved or until toxic effects appear. Serum levels must be measured after initiating therapy.
The clinically effective level is usually in the range of 10mcg/l to 20mcg/l (40micromoles/litre to 80micromoles/litre). In some cases tonic clonic seizures may be controlled with lower serum levels of phenytoin. Plasma half-life is usually in the range of 20 to 40 hours. With recommended dosage, a period of ten days may be required to achieve steady state serum levels. Changes in dosage should not be carried out at intervals shorter than ten days.
Bioavailability of phenytoin sodium and phenytoin.
Tablets and capsules usually contain phenytoin sodium.
Suspension and paediatric tablets contain phenytoin.
Theoretically 100mg of phenytoin sodium is equivalent to 92mg of phenytoin on a molecular weight basis. These molecular equivalents are not necessarily biologically equivalent. Physicians should exercise care in those situations where it is necessary to change patients between different dosage forms and monitoring is advised.
The interpretation of total plasma phenytoin concentrations should be made with caution in patients with renal or hepatic disease, or in those with hypoalbuminemia, due to an increased fraction of unbound phenytoin. Unbound concentration of phenytoin may be elevated in patients with hyperbilirubinemia. Unbound phenytoin concentrations may be more useful in these patient populations.
Hereditary fructose intolerance
Precautions and Warnings
East Asian ancestry
Restricted sodium intake
Elevated serum bilirubin
Glucose-galactose malabsorption syndrome
Patients at risk of suicide should be closely supervised
Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Confirm HLA-B 1502 status in Han Chinese & Thai patients before initiating
Contains sodium benzoate: may increase risk of jaundice in neonates
Folic acid 5mg daily required pre-conception to end of 1st trimester
Increased risk of osteomalacia; consider vitamin D supplement
May precipitate or aggravate absence and myoclonic seizures
Prescribe by manufacturer's product to ensure seizure control maintenance
Contains sunset yellow (E110) - may cause allergic reaction
Preparation contains sucrose
Caution in changing formulations containing phenytoin and phenytoin sodium
Diabetic control may need adjustment
Monitor blood counts regularly
Monitor for Antiepileptic Hypersensitivity Syndrome
Monitor serum folate levels - add supplements if necessary
Monitor serum folate levels at least every six months
Plasma level monitoring may be useful: refer to local guidelines
Refer women considering pregnancy for specialist advice and monitoring
Consult Dr.at once if rash, sore throat, mouth ulcers, bruising,fever occur
Discontinue treatment if DRESS is suspected
May affect results of some laboratory tests
Do not withdraw this drug suddenly
Discontinue if hypersensitivity reactions occur
Discontinue immediately if angioedema involves face/oropharynx/larynx
Discontinue treatment if rash occurs
Discontinue immediately if Antiepileptic Hypersensitivity Syndrome occurs
Maintain treatment at the lowest effective dose
Reduce dose and/or alter dose interval in elderly patients
Advise patient not to take St John's wort concurrently
Neonate exposed in utero: Administer vitamin K at birth
Pregnancy: Administer vitamin K in the last few weeks of pregnancy
Advise patient of need for high oral hygiene standards
Antiepileptic treatment is associated with a small increased risk of suicidal thoughts and behaviour; available data suggest that the increased risk applies to all antiepileptics and is seen as early as 1 week after staring treatment.
Patients should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment. They should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary.
The available evidence does not define whether the risk of suicidal thoughts and behaviour differs between antiepileptics. Patients should not stop or switch treatment on the basis of this information and without speaking to a healthcare professional.
Phenytoin is not suitable for the treatment of seizures caused by hypoglycaemia or other metabolic causes, nor absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present together, combined drug therapy is needed.
Antiepileptic drug hypersensitivity syndrome is a rare but potentially fatal syndrome associated with some antiepileptic drugs. Patients usually present with fever, rash, lymphadenopathy and other organ system involvement. Other possible symptoms include liver dysfunction, haematological, renal and pulmonary abnormalities, vasculitis and multi-organ failure. If signs or symptoms of hypersensitivity syndrome occur, the drug should be withdrawn immediately and expert advice sought.
Discontinue permanently if serious rash occurs (i.e. exfoliative, purpuric or bullous, or suspected lupus erythematosus, Stevens-Johnson syndrome or toxic epidermal necrolysis).
Milder rash (e.g. scarlatiniform) - consider resuming therapy once rash has completely disappeared.
Published literature suggests an increased (although still rare) risk of hypersensitivity reactions in black patients.
Patients should be aware of the risks of developing Hypersensitivity Syndrome (HSS) or Drug Reaction with Eosinophilia Systemic Symptoms (DRESS). If alternative diagnosis for the signs and symptoms of HSS and DRESS cannot be determined, treatment should be discontinued. Patients at increased risk of HSS/DRESS include black patients, patients with a personal or family history, and immuno-suppressed patients.
Obtain serum drug levels at the first sign of toxicity. Plasma levels of phenytoin above the optimal range may produce confusional states such as delirium, psychosis or encephalopathy. Reduce dose if serum levels are excessive and if symptoms persist consider discontinuing treatment.
The presence of the HLAB* 1502 allele may be associated with an increased risk of developing Stevens Johnson Syndrome in patients of Thai and Han Chinese origin when treated with phenytoin. Use only if the benefits outweigh the risks in patients known to be positive for this allele. The frequency of HLAB*1502 is extremely low in the Caucasian and Japanese population, therefore it is not possible to conclude on risk association, and adequate information about risk association in other ethnicities is currently not available.
Long-term treatment with phenytoin is associated with decreased bone mineral density, resulting in an increased risk of developing osteopenia, osteoporosis, osteomalacia, hypocalcaemia, hypophosphataemia and bone fractures in at-risk patients (those immobilised for long periods or who have inadequate sun exposure or dietary calcium intake). Consider vitamin D supplementation for all at-risk patients on long-term treatment.
Pregnancy and Lactation
Use phenytoin with caution in pregnancy.
The use of phenytoin during pregnancy involves significant risk to the foetus in terms of major and minor congenital abnormalities and haemorrhage at birth. Distinct facial abnormalities in infants exposed to phenytoin include craniofacial, limbic, impaired growth and congenital heart defects. Adverse effects on neurodevelopment have also been reported.
The concentration of phenytoin in the blood may change during pregnancy so plasma-drug concentration must be monitored and doses adjusted accordingly. Phenytoin accumulates in fat tissues and plasma concentrations are lower in pregnant than non-pregnant women, which may account for higher seizure tendency during pregnancy. Combination therapy may further reduce efficacy, and hence monotherapy should be the goal.
Due to the teratogenic effects of phenytoin, Briggs states that the epileptic pregnant women taking phenytoin, either alone or in combination with other anticonvulsants, has a 2 to 3 times greater risk for delivering a child with congenital defects over the general population. It is unclear whether the increased risk is caused by antiepileptic drugs, the disease itself, genetic factors or a combination of these. However, if phenytoin is stopped, the risk to the mother of uncontrolled seizures is great. Briggs concludes that the risk: benefit ratio in this case favours the continued use of phenytoin during pregnancy, and Schaefer agrees that therapy should be continued if epilepsy is well controlled with phenytoin.
Treatment with phenytoin is not an indication for termination, but an expanded prenatal diagnosis should be considered, including anatomical ultrasound diagnosis to rule out major disturbances of structural development. The lowest possible level required to prevent seizures should be used in order to lessen the likelihood of foetal anomalies. To decrease the risk of coagulation disturbances in the neonate, administer 1 mg of vitamin K (preferably intramuscular) at birth and 1 mg orally every 3 days during the first 2 weeks of life.
Evaluate the benefits and risks of continuing anti-epileptic therapy throughout pregnancy. Adjusting or stopping any anti-epileptic medication during pregnancy should not be done without specialist advice, and the relative benefits and risks should be discussed carefully first. The risk of harm to the mother and unborn child from seizures outweighs any teratogenic risk. Pregnancy in epileptic women is associated with a higher risk of congenital abnormalities, which are mainly associated with the use of anti-epileptic drugs rather than the disease itself. This risk is increased when multiple drugs are used. Routine monitoring of antiepileptic drugs is not recommended, but may be useful in cases where seizures have increased or are likely to, in order to plan the extent of dose adjustment needed. The Clinical Knowledge Summaries recommend that folic acid 5 mg daily should be prescribed to all women with epilepsy who are taking antiepileptic drugs, prior to conception and continued until the 12th week of pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Use phenytoin with caution in breastfeeding.
Phenytoin is excreted into breast milk, but Briggs concludes that there is little risk to the nursing infant if maternal levels are kept in the therapeutic range. Studies have shown that an infant may be exposed to a maximum of 10% of the maternal weight-related dose via the mother's milk, which is normally less than 5% of a paediatric phenytoin dose.
At the time of writing, swallowing difficulties, methemoglobinemia, drowsiness and decreased sucking activity have been reported in one infant, but no other reports of adverse effects with the use of phenytoin during lactation have been located.
Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions, and the use of multiple anticonvulsants is not routinely recommended due to a lack of data or clinical experience. Mothers on anti-epileptic drugs are encouraged to breastfeed, except in rare circumstances, as it is generally considered safe. The risk of injury to the infant caused by a maternal seizure is low.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Advise patients of the potential risk to the foetus if this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug. Patients should be advised to consult their physician if they are considering pregnancy and consider taking folic acid 5mg daily before conception.
Advise women of childbearing potential on the use of adequate conception.
Patients or their carers should be told how to recognise signs of blood or skin disorders, and advised to seek immediate medical attention if symptoms such as fever, sore throat, rash, mouth ulcers, bruising or bleeding develop. Leucopenia which is severe, progressive or associated with clinical symptoms requires withdrawal (if necessary under cover of suitable alternative).
Advise patient not to use products containing St John's wort with phenytoin.
Patients and caregivers should be aware of the need to monitor for the emergence of suicidal thoughts and behaviour, and the need to seek medical advice immediately if they present.
Advise patients that treatment with phenytoin may lead to adverse effects such as dizziness and drowsiness, and so impair their ability to perform skilled tasks such as driving and operating machinery.
Benign lymph node hyperplasia
Bone marrow depression
Cerebellar dysfunction (irreversible)
Coarse facial features
Decrease in bone mineral density
Disturbed vitamin D metabolism
Gingival hypertrophy and tenderness
Toxic epidermal necrolysis
Effects on Laboratory Tests
Phenytoin may cause decreased serum levels of protein-bound iodine (PBI). It may also produce lower than normal values for dexamethasone or metapyrone tests.
Phenytoin may cause raised serum levels of glucose, alkaline phosphatase, gamma glutamyl transpeptidase and lowered serum levels of calcium and folic acid.
Phenytoin may affect blood sugar metabolism tests.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: October 2015
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Epanutin 30mg/5ml oral suspension. Pfizer Ltd. Revised September 2020.
MHRA Drug Safety Update Vol 2, Issue 9, April 2009
Antiepileptics: adverse effects on bone
Available at: www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/index.htm
Last accessed: April 23, 2009
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 11 September 2017
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Phenytoin Last revised: 04 September 2014
Last accessed: 07 October 2015
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