Phenytoin sodium capsules (all strengths) and 100mg tablets
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations containing phenytoin sodium.
Epilepsy - partial and/or 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 and treatment 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 of 3mg/kg to 4mg/kg a day. Doses should be adjusted based on each individual patient response.
Alternatively, an initial dose of 150mg to 300mg a day, given as a single dose or in divided doses.
The usual maintenance dose is 200mg to 500mg as a single dose, or in divided doses.
Initial dose of 5mg/kg a day, given in 2 divided doses. Doses should be adjusted based on each individual patient response.
Maintenance dose of 4mg/kg to 8mg/kg. Maximum daily dose should not exceed 300mg.
The following alternate dosing schedule may be suitable:
Prevention and treatment of seizures following a head injury
Initial dose of 2.5mg/kg twice a day. Doses should be adjusted based on each individual patient response.
Maintenance dose of 4mg/kg to 8mg/kg a day. Maximum daily dose should not exceed 300mg.
Tonic clonic and focal seizures
Children aged 12 to 18 years
Initial dose of 75mg to 150mg twice a day. Doses should be adjusted based on each individual patient response.
Maintenance dose of 150mg to 200mg twice a day. Maximum daily dose should not exceed 600mg.
Children aged 1 month to 12 years
Initial dose of 1.5mg/kg to 2.5mg/kg twice a day.Doses should be adjusted based on each individual patient response.
Maintenance dose of 2.5mg/kg to 5mg/kg twice a day. Maximum of 7.5mg/kg per dose. Maximum daily dose should not exceed 300mg.
Patients with Hepatic Impairment
Phenytoin is highly protein bound and extensively metabolised by the liver. Reduce dosage to prevent accumulation and toxicity in patients with impaired liver function.
Where protein binding levels are reduced, total serum phenytoin levels will be reduced accordingly. But the pharmacologically active free drug concentration is unlikely to be altered. Therefore, under these circumstances therapeutic control may be achieved with total phenytoin levels below the normal range of 10 to 20mg/litre (40 to 80micromoles/litre).
Patients with impaired liver function, elderly patients or those who are gravely ill may show early signs of toxicity.
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.
The clinically effective level is usually in the range of 10 -20mg/l (40-80micromoles/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 10 days may be required to achieve steady state serum levels. Changes in dosage should not be carried out at intervals shorter than 10 days.
Bioavailability of phenytoin sodium and phenytoin.
Capsules and tablets 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.
Precautions and Warnings
Females of childbearing potential
Elevated serum bilirubin
Glucose-galactose malabsorption syndrome
Patients at risk of suicide should be closely supervised
Patients with diabetes may experience fluctuations in blood glucose
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
Some formulations contain lactose
Caution in changing formulations containing phenytoin and phenytoin sodium
Monitor blood counts regularly
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
Advise patient to seek immediate medical advice if rash occurs
Advise patients/carers to seek medical advice if suicidal intent develops
Consult Dr.at once if rash, sore throat, mouth ulcers, bruising,fever occur
May affect results of some laboratory tests
Do not withdraw this drug suddenly
Discontinue if hypersensitivity reactions occur
Discontinue treatment if rash 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
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.
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.
Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present together, combined drug therapy is needed.
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.
Phenytoin may cause lowered serum levels of calcium and folic acid - it is recommended that serum folate levels be measured at least every six months, and folic acid supplements given if necessary. Serum levels of phenytoin above the optimal range may produce confusional states. Determine serum drug levels at first sign of acute toxicity.
Use in Porphyria
Contraindicated in porphyria
Pregnancy and Lactation
Use phenytoin sodium with caution during pregnancy.
The manufacturer advises caution if phenytoin sodium is used during pregnancy. Extensive studies have shown teratogenic effects including malformations, orofacial clefts, cardiac defects and growth abnormalities following the use of phenytoin sodium during pregnancy.
Use phenytoin sodium with caution during breastfeeding.
The manufacturer does not recommend breastfeeding whilst taking phenytoin sodium. Available data indicates phenytoin sodium is expressed in human breast milk, but the quantity is unknown. Effects on exposed infants are unknown.
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: January 2020
Summary of Product Characteristics: Phenytoin Sodium Flynn hard capsules. Flynn Pharma Ltd. Revised January 2019.
Summary of Product Characteristics: Phenytoin 100mg film-coated tablets. Wockhardt. Revised November 2018.
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 January 2020
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