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Phenytoin paediatric tablets

Updated 2 Feb 2023 | Neuropathic pain Phenytoin

Presentation

Paediatric tablets containing phenytoin

Drugs List

  • EPANUTIN 50mg INFATAB
  • phenytoin 50mg chewable tablet
  • Therapeutic Indications

    Uses

    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
    Trigeminal neuralgia

    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.

    Dosage

    Treatment with phenytoin should be tailored to the individual patient as there is wide inter-patient variability in phenytoin serum levels with equivalent dosage.
    Treatment should be initiated in small dosages with gradual increments until control is achieved or unacceptable adverse reactions occur. With the recommended dosage, a period of seven to ten days may be required to achieve steady state serum levels. Changes in dosage should not be carried out at intervals shorter than seven to ten days.
    Maintenance of treatment should be the lowest dose of anticonvulsant consistent with control of seizures.

    Adults

    Seizures
    Initial dose: 3mg/kg to 4mg/kg daily. Adjust dose if necessary.
    Maintenance dose: 200mg to 500mg daily in single or divided doses.
    Occasionally a daily dose outside this range may be indicated. Dosage should normally adjusted according to serum levels where assay facilities exist.

    Trigeminal Neuralgia
    300mg to 500mg daily, given in divided doses has been reported in the literature.
    Dosing should be adjusted based on clinical response and monitoring of serum phenytoin levels is recommended.
    Total phenytoin level should not exceed 20micrograms/ml.

    Children

    Initial dose: 5mg/kg daily, given in two divided doses. Adjust dose if necessary.
    Maintenance dose: 4mg/kg to 8mg/kg
    Maximum dose: 300mg daily.

    The following alternative dosing schedule may be suitable:

    Focal seizures; Tonic-clonic seizures
    Dose should be adjusted to serum-phenytoin concentrations.
    Children aged 12 to 18 years
    Initial dose: 75mg to 150mg twice a day. Titrate to response.
    Maintenance dose: 150mg to 200mg twice a day.
    Maximum dose: 300mg twice a day.

    Children aged 1 month to 12 years
    Initial dose: 1.5mg/kg to 2.5mg/kg twice a day. Titrate to response.
    Maintenance dose: 2.5mg/kg to 5mg/kg twice a day.
    Maximum dose: 7.5mg/kg twice a day or 300mg per day.

    Treatment or prevention and of seizures during or following neurosurgery or severe head injury
    Initial dose: 2.5mg/kg twice a day. Titrate to response.
    Maintenance dose: 4mg/kg to 8mg/kg daily.
    Maximum dose: 300mg per day.

    Neonates

    The absorption of phenytoin following oral administration in neonates is unpredictable. Furthermore, the metabolism of phenytoin may be depressed. It is therefore especially important to monitor serum levels in the neonate.

    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 interpatient 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.

    Bioavailability of phenytoin sodium and phenytoin.
    Tablets and capsules usually contain phenytoin sodium.
    Suspension and paediatric tablets contain phenytoin.

    Theoretically 100 mg of phenytoin sodium is equivalent to 92 mg 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.

    Contraindications

    Glucose-galactose malabsorption syndrome
    Hereditary fructose intolerance
    Porphyria
    Sucrase-isomaltase insufficiency

    Precautions and Warnings

    Chronic illness
    Debilitation
    East Asian ancestry
    Elderly
    Hypoalbuminaemia
    Neonates
    Suicidal ideation
    Breastfeeding
    Diabetes mellitus
    Elevated serum bilirubin
    Hepatic impairment
    Pregnancy

    Patients at risk of suicide should be closely supervised
    Patients with diabetes may experience fluctuations in blood glucose
    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
    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
    Preparation contains sucrose
    Caution in changing formulations containing phenytoin and phenytoin sodium
    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
    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

    Pregnancy

    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 ).

    Lactation

    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

    Counselling

    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.

    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.

    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 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.

    Side Effects

    Acne
    Agranulocytosis
    Angioedema
    Anorexia
    Aplastic anaemia
    Arthralgia
    Asterixis
    Ataxia
    Benign lymph node hyperplasia
    Bone marrow depression
    Bullous eruption
    Cerebellar dysfunction (irreversible)
    Chorea
    Coarse facial features
    Confusion
    Constipation
    Decrease in bone mineral density
    Dermatitis
    Disturbed vitamin D metabolism
    Dizziness
    Drowsiness
    Dupuytren's contracture
    Dyskinesia
    Dystonia
    Eosinophilia
    Exfoliative rash
    Fever
    Fractures
    Gingival hypertrophy and tenderness
    Granulocytopenia
    Headache
    Hepatitis
    Hepatotoxicity
    Hirsutism
    Hodgkin's disease
    Hypersensitivity reactions
    Hypertrichosis
    Hypocalcaemia
    Hypophosphataemia
    Immunoglobulin abnormalities
    Impaired co-ordination
    Insomnia
    Interstitial nephritis
    Leucopenia
    Lip enlargement
    Liver damage
    Lupus erythematosus
    Lymphadenopathy
    Lymphoma
    Macrocytic anaemia
    Megaloblastic anaemia
    Morbilliform eruption
    Nausea
    Nervousness
    Nystagmus
    Osteopenia
    Osteoporosis
    Pancytopenia
    Paraesthesia
    Peripheral neuropathy
    Peyronie's disease
    Pneumonitis
    Polyarteritis nodosa
    Polyarthropathy
    Pseudolymphoma
    Purpuric dermatitis
    Scarlatiniform rash
    Serum sickness
    Slurred speech
    Somnolence
    Stevens-Johnson syndrome
    Suicidal tendencies
    Taste disturbances
    Thrombocytopenia
    Toxic epidermal necrolysis
    Tremor
    Twitching
    Vertigo
    Vomiting

    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.

    Overdosage

    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 ).

    Further Information

    Last Full Review Date: October 2015

    Reference Sources

    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 Infatabs. 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: 07 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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