diphenylhydantoin

Action

Thought to limit seizure activity by promoting sodium efflux from neurons in motor cortex and reducing activity in brainstem centers responsible for tonic phase of tonic-clonic seizures

Availability

Capsules (prompt-release): 30 mg, 100 mg

Capsules (extended-release): 30 mg, 100 mg

Injection: 50 mg/ml in 2- and 5-ml ampules

Oral suspension: 30 mg/5 ml, 125 mg/5 ml

Tablets (chewable): 50 mg

Indications and dosages

➣ Status epilepticus

Adults: Loading dose of 10 to 15 mg/kg by slow I.V., then a maintenance dosage of 100 mg P.O. or I.V. q 6 to 8 hours

Neonates and children: Loading dose of 15 to 20 mg/kg I.V. in divided doses of 5 to 10 mg/kg

➣ Generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures

Adults: Loading dose of 1 g P.O. (extended-release) in three divided doses (400 mg, 300 mg, and 300 mg) at 2-hour intervals in hospitalized patients requiring rapid steady-state serum levels (when I.V. route isn't desired). Maintenance dosing usually starts 24 hours after loading dose. Patients who haven't had previous treatment usually start at 100 mg (125 mg suspension) P.O. t.i.d., adjusted as needed to a maximum of 600 mg (625 mg suspension) P.O. daily. Alternatively, if divided doses control seizures, one daily dose of 300 mg P.O. (extended-release phenytoin sodium).

Children: Initially, 5 mg/kg/day P.O. in two or three equally divided doses; maintenance dosage individualized and given in two to three divided doses (not to exceed 300 mg/day).

➣ To prevent seizures during neuro-surgery

Adults: 100 to 200 mg I.M. at 4-hour intervals

Off-label uses

• Arrhythmias

• Severe preeclampsia

• Trigeminal neuralgia

• Recessive dystrophic epidermolysis bullosa, junctional epidermolysis bullosa

Contraindications

• Hypersensitivity to drug

• Sinus bradycardia, sinoatrial block, second- or third-degree atrioventricular block, Adams-Stokes syndrome

Precautions

Use cautiously in:

• hepatic disease, diabetes mellitus, skin rash

• pregnant or breastfeeding patients (safety not established).

Administration

• Before I.V. use, check designated line for patency and flush with normal saline solution. Deliver no faster than 50 mg/minute for adults or 1 to 3 mg/kg/minute in children and neonates; then flush with normal saline solution. Avoid extravasation (can cause severe tissue damage).

☞ Don't administer I.V. into dorsal hand veins, because purple glove syndrome may occur.

• When giving oral solution through nasogastric tube, dilute dose with sterile water or normal saline solution; after administration, flush tube with at least 20 ml of diluent.

• Withhold enteral feedings for at least 1 hour before and 1 hour after oral administration.

• Give I.M. only as last resort (may cause pain and reduce drug absorption).

• Know that patients with history of renal or hepatic disease should not receive P.O. loading dose.

Adverse reactions

CNS: headache, fatigue, dizziness, drowsiness, weakness, depression, ataxia, slurred speech, confusion, agitation, dysarthria, dyskinesia, extrapyramidal symptoms, insomnia, irritability, twitching, nervousness, numbness, psychotic disturbances, tremor, CNS depression (with I.V. use), coma

CV: vasodilation, edema, chest pain, tachycardia, hypotension (increased with I.V. use), cardiovascular collapse (with I.V. use)

EENT: diplopia, amblyopia, nystagmus, visual field defect, eye pain, conjunctivitis, photophobia, mydriasis, hearing loss, tinnitus, ear pain, epistaxis, rhinitis, sinusitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, lip enlargement, dry mouth

GU: pink, red, or reddish-brown urine; gynecomastia; Peyronie's disease

Hepatic: jaundice, toxic hepatitis, hepatic damage

Hematologic: macrocytosis, simple anemia, megaloblastic anemia, monocytosis, leukocytosis, hemolytic anemia, thrombocytopenia, agranulocytosis, granulocytopenia, leukopenia, pancytopenia

Metabolic: hypocalcemia, diabetes insipidus, hyperglycemia

Musculoskeletal: back pain, pelvic pain, osteomalacia

Respiratory: dyspnea, increased cough and sputum, pneumonia, hyperventilation, hypoxia, hemoptysis, bronchitis, apnea, asthma, aspiration pneumonia, pulmonary fibrosis, atelectasis, pneumothorax

Skin: rash, pruritus, bruising, exfoliative dermatitis, hypertrichosis, hirsutism, alopecia, Stevens-Johnson syndrome

Other: gingival hyperplasia, altered taste, fever, lymphadenopathy, weight gain or loss, injection site reaction, coarsened facial features, lupus erythematosus syndrome, allergic reactions

Interactions

Drug-drug. Acetaminophen, amiodarone, carbamazepine, cardiac glycosides, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, hormonal contraceptives, methadone, metapyrone, mexiletine, quinidine, theophylline, valproic acid: increased metabolism and decreased effects of these drugs

Activated charcoal, antacids, sucralfate: decreased phenytoin absorption Allopurinol, amiodarone, benzodiaze-pines, chloramphenicol, chlorpheni-ramine, cimetidine, disulfiram, flucona-zole, ibuprofen, isoniazid, metronidazole, miconazole, omeprazole, phenacemide, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tricyclic antidepressants, trimethoprim, valproic acid: increased phenytoin effects Antineoplastics, barbiturates, carbamazepine, diazoxide, folic acid, influenza vaccine, loxapine, nitrofurantoin, pyridoxine, rifampin, theophylline: decreased phenytoin effects

Cyclosporine, dopamine, furosemide, levodopa, levonorgestrel, mebendazole, muscle relaxants, nondepolarizingphenothiazines, sulfonylureas: decreased effects of these drugs

Drug-diagnostic tests. Alkaline phosphatase, eosinophils, gamma-glutamyl-transferase, glucose: increased levels Dexamethasone (1-mg) suppression test, metyrapone test: interference with test results

Free thyroxine, serum thyroxine: decreased levels

Drug-food. Enteral tube feedings: decreased phenytoin absorption

Folic acid: decreased folic acid absorption

Drug-behaviors. Acute alcohol ingestion: increased phenytoin blood level

Chronic alcohol ingestion: decreased phenytoin blood level

Patient monitoring

• Assess blood pressure, ECG, and heart rate, especially during I.V. loading dose. Watch for adverse reactions.

• Monitor phenytoin blood level; therapeutic range is 10 to 20 mcg/ml.

• Evaluate CBC and kidney and liver function tests.

• Closely monitor prothrombin time and Internationalized Normal Ratio in patients receiving warfarin concurrently.

• Monitor drug efficacy.

Patient teaching

• Explain drug therapy, need for follow-up tests, and importance of taking drug exactly as prescribed.

• Caution patient not to stop therapy abruptly.

• Advise patient to avoid alcohol.

☞ Instruct patient to report rash immediately.

• Inform patient that drug may discolor urine.

• Tell female patient drug may make hormonal contraceptives ineffective.

• Instruct patient to practice good dental hygiene to minimize gingival hyperplasia.

• Encourage patient to seek medical advice before taking over-the-counter preparations.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.