mephenytoin
Mesantoin

Available forms
Available by prescription only
Tablets: 100 mg

Indications and dosages
 Generalized tonic-clonic or complex-partial seizures. Adults: 50 to 100 mg P.O. daily; may increase by 50 to 100 mg at weekly intervals. Usual maintenance dosage is 200 to 600 mg daily in three equally divided doses. Doses up to 800 mg daily may be required.
Children: Initial dose is 50 to 100 mg P.O. daily. May increase slowly by 50 to 100 mg at weekly intervals. Dosage must be adjusted individually. Usual maintenance dosage is 100 to 400 mg daily (or 3 to 15 mg/kg daily or 100 to 450 mg/m²/day) in three equally divided doses.

Pharmacodynamics
Anticonvulsant action: Like other hydantoin derivatives, mephenytoin stabilizes the neuronal membranes and limits seizure activity either by increasing efflux or by decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. Like phenytoin, mephenytoin appears to have antiarrhythmic effects.
 Mephenytoin is used for prophylaxis of tonic-clonic (grand mal), psychomotor, focal, and jacksonian-type partial seizures in patients refractory to less toxic agents. It’s usually combined with phenytoin, phenobarbital, or primidone; phenytoin is preferred because it causes less sedation than barbiturates. Mephenytoin also is used with succinimides to control combined absence and tonic-clonic disorders; combined use with oxazolidinediones, paramethadione, or trimethadione isn’t recommended because of the increased hazard of blood dyscrasias.

Pharmacokinetics
Absorption: Absorbed from the GI tract.
Distribution: Distributed widely throughout the body; good seizure control without toxicity occurs when serum levels of drug and major metabolite reach 25 to 40 mcg/ml.
Metabolism: Metabolized by the liver.
Excretion: Excreted in urine.

Contraindications and precautions
Contraindicated in patients with hydantoin hypersensitivity.

Interactions
Drug-drug. Antihistamines, chloramphenicol, cimetidine, diazepam, diazoxide, disulfiram, isoniazid, oral anticoagulants, phenylbutazone, salicylates, sulfamethizole, valproate: May increase therapeutic effects and mephenytoin toxicity. Monitor patient closely.
Folic acid: May decrease therapeutic effects of mephenytoin. Use together cautiously.
Hormonal contraceptives: Decreases contraceptive effect. Recommend alternative means of contraception.
Drug-lifestyle. Alcohol use: May reduce therapeutic effects of drug. Discourage alcohol use.

Adverse reactions
CNS: ataxia, drowsiness, fatigue, irritability, choreiform movements, depression, tremor, insomnia, dizziness.
CV: edema.
EENT: conjunctivitis, diplopia, nystagmus, gingival hyperplasia.
GI: nausea and vomiting.
Hematologic: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, eosinophilia, leukocytosis.
Musculoskeletal: polyarthropathy.
Respiratory: pulmonary fibrosis.
Skin: rash, exfoliative dermatitis, Stevens-Johnson syndrome, fatal dermatitides.
Other: lymphadenopathy.

Effects on lab test results
• May increase liver function test values and eosinophil count. May decrease neutrophil, granulocyte, and platelet counts. May increase or decrease WBC count.

Overdose and treatment
Signs and symptoms of acute mephenytoin toxicity may include restlessness, dizziness, drowsiness, nausea, vomiting, nystagmus, ataxia, dysarthria, tremor, and slurred speech. Hypotension, respiratory depression, and coma may follow. Death may result from respiratory and circulatory depression.
 Treat overdose with gastric lavage or emesis and follow up with supportive treatment. Carefully monitor vital signs and fluid and electrolyte balance. Forced diuresis is of little or no value. Hemodialysis or peritoneal dialysis may be helpful.

Special considerations
• Decreased alertness and coordination are most pronounced at start of treatment. Patient may need help with walking and other activities for first few days.
• Don’t discontinue drug abruptly. Transition from mephenytoin to other anticonvulsant should progress over 6 weeks.
• When patient is receiving phenobarbital, continue phenobarbital until the transition to the other anticonvulsant is completed. Then attempt a gradual withdrawal of phenobarbital.
• Obtain CBC and platelet counts before therapy, after 2 weeks of initial therapy, and after 2 weeks on maintenance dosage; then every month for 1 year and, subsequently, at 3-month intervals. If neutrophil count declines to 1,600 to 2,500/mm³, obtain CBC every 2 weeks.
• Discontinue drug if neutrophil count is less than 1,600/mm³.
Pregnant patients
• Safe use of mephenytoin during pregnancy hasn’t been established. Use drug during pregnancy only when clearly needed.
Breast-feeding patients
• Safe use in breast-feeding women hasn’t been established. An alternative to breast-feeding is recommended.
Pediatric patients
• Children usually require from 100 to 400 mg/day.

Patient education
• Tell patient never to discontinue drug or change dosage except as prescribed and to avoid alcohol, which decreases effectiveness of drug and increases sedative effects.
• Explain that follow-up laboratory tests are essential for safe use.
• Instruct patient to report unusual changes immediately (cutaneous reaction, sore throat, glandular swelling, fever, mucous membrane swelling).

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use