Phenytoin = PHT oral

Therapeutic action

Antiseizure (antiepileptic).

Indications

Epilepsy: generalised tonic-clonic seizures and focal (partial) seizures.

Forms and strengths

• 100 mg tablet.

Dose

Start with a low dose then increase gradually based on the patient's response and tolerance.

Due to the numerous and potentially severe adverse effects of PHT, patients should be kept under close surveillance.

Be cautious when increasing doses because the margin between therapeutic and toxic dose is narrow and pharmacokinetics are nonlinear.

• Child 1 month to 11 years: start with 1.5 to 2.5 mg/kg 2 times daily; increase the daily dose by 5 mg/kg every 3 to 4 weeks, up to 2.5 to 5 mg/kg 2 times daily if necessary, maximum 7.5 mg/kg 2 times daily or 300 mg daily.
• Child 12 years and over: start with 75 to 150 mg 2 times daily; increase the daily dose by 25 mg every 3 to 4 weeks, up to 150 to 200 mg 2 times daily if necessary, maximum 300 mg 2 times daily.
• Adult: start with 150 to 300 mg once daily or 75 to 150 mg 2 times daily; increase the daily dose by 50 mg every 3 to 4 weeks, up to 200 to 400 mg once daily or 100 to 250 mg 2 times daily if necessary, maximum 400 mg once daily or 300 mg 2 times daily.

Duration

As long as required. Do not stop treatment abruptly, even if changing treatment to another antiseizure medication.

Contra-indications, adverse effects, precautions

• Administer with caution to patients with hepatic impairment, heart failure, atrioventricular block, cardiac rhythm disorders, or hypotension.
• May cause drowsiness, dizziness, headache, behavioural disturbances, insomnia, gastrointestinal disturbances, vitamin D deficiency, osteoporosis, hepatotoxicity, gingival hypertrophy, and rarely haematologic disorders or severe hypersensitivity reactions including Stevens-Johnson, Lyell, and DRESS syndromes.
• Early symptoms such as fever, rash, mouth ulcers, and bleeding require immediate medical attention.
• If possible, perform at least a full blood count and liver enzymes at baseline and then regularly during treatment.
• Avoid or monitor the combination with rifampicin, mefloquine, sulfonamides, chloramphenicol, fluconazole, isoniazid, fluoxetine, omeprazole, alcohol-containing drugs, benzodiazepines, opioid analgesics, antipsychotics, first-generation antihistamines, antidepressants, and other antiseizure medications.
• PHT may reduce the effect of many drugs including diazepam, midazolam, digoxin, corticosteroids, antimicrobials, some antiretrovirals, itraconazole, and warfarin. Adjust dosage if necessary.
• For implants and oral contraceptives, use injectable medroxyprogesterone or an intrauterine device.
• Avoid alcohol during treatment.
• Pregnancy: avoid because of the risk of cardiac malformations. If PHT is the only option, use the lowest effective dose and administer folic acid 5 mg daily during the first trimester starting as early as possible.
• PHT plasma concentrations may decrease during pregnancy. Monitor clinical response, increase dose if needed, then resume the usual dose after delivery. Monitor the child for a few days.
• Breast-feeding: administer with caution and reduce the dose if it was increased during pregnancy.
• PHT is not recommended for myoclonic and absence seizures because symptoms may worsen.