Phenytoin

phenytoin (diphenylhydantoin, phenytoin sodium) (fen' i toe in) Dilantin-125, Dilantin Infatab, Dilantin Injection, Dilantin Kapseals, Phenytek, Phenytex (CAN) Pregnancy Category D Drug classes

Antiepileptic Hydantoin Therapeutic actions

Has antiepileptic activity without causing general CNS depression; stabilizes neuronal membranes and prevents hyperexcitability caused by excessive stimulation; limits the spread of seizure activity from an active focus; also effective in treating cardiac arrhythmias, especially those induced by digitalis; antiarrhythmic properties are very similar to those of lidocaine; both are class IB antiarrhythmics. Indications

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Control of grand mal (tonic-clonic) and psychomotor seizures Prevention and treatment of seizures occurring during or following neurosurgery Parenteral administration: Control of status epilepticus of the grand mal type Unlabeled uses: Antiarrhythmic, particularly in digitalis-induced arrhythmias (IV preparations); treatment of trigeminal neuralgia (tic douloureux)

Contraindications and cautions

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Contraindicated with hypersensitivity to hydantoins, sinus bradycardia, sinoatrial block, Stokes-Adams syndrome, pregnancy (data suggest an association between antiepileptic use and an elevated incidence of birth defects; however, do not discontinue antiepileptic therapy in pregnant women who are receiving such therapy to prevent major seizures; this is likely to precipitate status epilepticus, with attendant hypoxia and risk to both mother and fetus), lactation. Use cautiously with acute intermittent porphyria, hypotension, severe myocardial insufficiency, diabetes mellitus, hyperglycemia.

Available forms

Chewable tablets—50 mg; oral suspension—125 mg/5 mL; capsules—30, 100 mg; ER capsules—200, 300 mg; injection—50 mg/mL Dosages ADULTS Phenytoin sodium, parenteral

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Status epilepticus: 10–15 mg/kg by slow IV. For maintenance, 100 mg PO or IV q 6–8 hr. Higher doses may be required. Do not exceed an infusion rate of 50 mg/min. Follow each IV injection with an injection of sterile saline through the

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same needle or IV catheter to avoid local venous irritation by the alkaline solution. Continuous IV infusion is not recommended. Neurosurgery (prophylaxis): 100–200 mg IM q 4 hr during surgery and the postoperative period (IM route is not recommended because of erratic absorption, pain and muscle damage at the injection site). IM therapy in a patient previously stabilized on oral dosage: Increase dosage by 50% over oral dosage. When returning to oral dosage, decrease dose by 50% of the original oral dose for 1 wk to prevent excessive plasma levels due to continued absorption from IM tissue sites. Avoid IM route of administration if possible due to erratic absorption and pain and muscle damage at injection site.

Phenytoin and phenytoin sodium, oral

Individualize dosage. Determine serum levels for optimal dosage adjustments. The clinically effective serum level is usually between 10 and 20 mcg/mL. • Loading dose (hospitalized patients without renal or liver disease): Initially, 1 g of phenytoin capsules (phenytoin sodium, prompt) is divided into 3 doses (400 mg, 300 mg, 300 mg) and given q 2 hr. Normal maintenance dosage is then instituted 24 hr after the loading dose with frequent serum determinations. • No previous treatment: Start with 100 mg tid PO. Satisfactory maintenance dosage is usually 300–400 mg/day. An increase to 600 mg/day may be necessary. • Single daily dosage (phenytoin sodium, extended): If seizure control is established with divided doses of three 100-mg extended phenytoin sodium capsules per day, once-a-day dosage with 300 mg PO may be considered. PEDIATRIC PATIENTS Phenytoin sodium, parenteral

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Status epilepticus: Administer phenytoin IV. Determine dosage according to weight in proportion to dose for a 150-lb (70-kg) adult (see adult dosage above; see Appendix Calculating Pediatric Doses). Pediatric dosage may be calculated on the basis of 250 mg/m2. Dosage for infants and children also may be calculated on the basis of 10–15 mg/kg, given in divided doses of 5–10 mg/kg. For neonates, 15–20 mg/kg in divided doses of 5–10 mg/kg is recommended.

Phenytoin and phenytoin sodium, oral

Children not previously treated: Initially, 5 mg/kg/day in 2–3 equally divided doses. Subsequent dosage should be individualized to a maximum of 300 mg/day. Daily maintenance dosage is 4–8 mg/kg. Children > 6 yr may require the minimum adult dose of 300 mg/day. GERIATRIC PATIENTS AND PATIENTS WITH HEPATIC IMPAIRMENT

Use caution and monitor for early signs of toxicity; phenytoin is metabolized in the liver. Pharmacokinetics Route Oral IV

Onset Slow 1–2 hr

Peak 2–12 hr Rapid

Duration 6–12 hr 12–24 hr

Metabolism: Hepatic; T1/2: 6–24 hr Distribution: Crosses placenta; enters breast milk Excretion: Urine

IV facts

Preparation: Administration by IV infusion is not recommended because of low solubility of drug and likelihood of precipitation; however, this may be feasible if proper precautions are observed. Use suitable vehicle of 0.9% sodium chloride or lactated Ringer's injection, appropriate concentration; prepare immediately before administration, and use an in-line filter. Infusion: Infuse slowly in small increments, each 25–50 mg over 1–5 min; infuse flush immediately after drug to reduce the risk of damage to vein and tissues. Incompatibilities: Do not combine with other medications in solution. Y-site incompatibilities: Do not give with potassium chloride. Adverse effects

Some adverse effects are related to plasma concentrations, as follows: Plasma Concentration 5–10 mcg/mL 10–20 mcg/mL > 20 mcg/mL > 30 mcg/mL > 40 mcg/mL

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Adverse Effects Some therapeutic effects Usual therapeutic range Far-lateral nystagmus risk Ataxia is usually seen Significantly diminished mental capacity

CNS: Nystagmus, ataxia, dysarthria, slurred speech, mental confusion, dizziness, drowsiness, insomnia, transient nervousness, motor twitchings, fatigue, irritability, depression, numbness, tremor, headache, photophobia, diplopia, conjunctivitis CV: CV collapse, hypotension (when administered rapidly IV; not to exceed 50 mg/min) Dermatologic: Dermatologic reactions, scarlatiniform, morbilliform, maculopapular, urticarial and nonspecific rashes; serious and sometimes fatal dermatologic reactions—bullous, exfoliative, or purpuric dermatitis, lupus erythematosus, and Stevens-Johnson syndrome, toxic epidermal necrolysis, hirsutism, alopecia, coarsening of the facial features, enlargement of the lips, Peyronie's disease GI: Nausea, vomiting, diarrhea, constipation, gingival hyperplasia, toxic hepatitis, liver damage, sometimes fatal; hypersensitivity reactions with hepatic involvement, including hepatocellular degeneration and fatal hepatocellular necrosis GU: Nephrosis Hematologic: Hematopoietic complications, sometimes fatal: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia; macrocytosis and megaloblastic anemia that usually respond to folic acid therapy; eosinophilia, monocytosis, leukocytosis, simple anemia, hemolytic anemia, aplastic anemia, hyperglycemia IV use complications: Hypotension, transient hyperkinesia, drowsiness, nystagmus, circumoral tingling, vertigo, nausea, cardiovascular collapse, CNS depression Respiratory: Pulmonary fibrosis, acute pneumonitis

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Other: Lymph node hyperplasia, sometimes progressing to frank malignant lymphoma, monoclonal gammopathy and multiple myeloma (prolonged therapy), polyarthropathy, osteomalacia, weight gain, chest pain, periarteritis nodosa

Interactions

Drug-drug • Increased pharmacologic effects with chloramphenicol, cimetidine, disulfiram, isoniazid, phenacemide, phenylbutazone, sulfonamides, trimethoprim • Complex interactions and effects when phenytoin and valproic acid are given together; phenytoin toxicity with apparently normal serum phenytoin levels; decreased plasma levels of valproic acid; breakthrough seizures when the two drugs are given together • Decreased pharmacologic effects with antineoplastics, diazoxide, folic acid, sucralfate, rifampin, theophylline (applies only to oral hydantoins, absorption of which is decreased) • Increased pharmacologic effects and toxicity with primidone, oxyphenbutazone, amiodarone, chloramphenicol, fluconazole, isoniazid • Increased hepatotoxicity with acetaminophen • Decreased pharmacologic effects of the following: Corticosteroids, cyclosporine, disopyramide, doxycycline, estrogens, furosemide, levodopa, methadone, metyrapone, mexiletine, hormonal contraceptives, quinidine, atracurium, gallamine triethiodide, pancuronium, tubocurarine, vecuronium, carbamazepine, diazoxide • Severe hypotension and bradycardia when IV phenytoin is given with dopamine Drug-lab test • Interference with the metyrapone and the 1-mg dexamethasone tests for at least 7 days Nursing considerations Assessment

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History: Hypersensitivity to hydantoins; sinus bradycardia, AV heart block, Stokes-Adams syndrome, acute intermittent porphyria, hypotension, severe myocardial insufficiency, diabetes mellitus, hyperglycemia, pregnancy, lactation Physical: T; skin color, lesions; lymph node palpation; orientation, affect, reflexes, vision exam; P, BP; R, adventitious sounds; bowel sounds, normal output, liver evaluation; periodontal exam; liver function tests, urinalysis, CBC and differential, blood proteins, blood and urine glucose, EEG and ECG

Interventions

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Use only clear parenteral solutions; a faint yellow color may develop, but this has no effect on potency. If the solution is refrigerated or frozen, a precipitate might form, but this will dissolve if the solution is allowed to stand at room temperature. Do not use solutions that have haziness or a precipitate.

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Administer IV slowly to prevent severe hypotension; the margin of safety between full therapeutic and toxic doses is small. Continually monitor patient's cardiac rhythm and check BP frequently and regularly during IV infusion. Suggest use of fosphenytoin sodium if IV route is needed. Monitor injection sites carefully; drug solutions are very alkaline and irritating. Monitor for therapeutic serum levels of 10–20 mcg/mL. Give oral drug with food to enhance absorption and to reduce GI upset. Recommend that the oral phenytoin prescription be filled with the same brand each time; differences in bioavailability have been documented. Suggest that adult patients who are controlled with 300-mg extended phenytoin capsules try once-a-day dosage to increase compliance and convenience. Reduce dosage, discontinue phenytoin, or substitute other antiepileptic medication gradually; abrupt discontinuation may precipitate status epilepticus. Phenytoin is ineffective in controlling absence (petit mal) seizures. Patients with combined seizures will need other medication for their absence seizures. Discontinue drug if rash, depression of blood count, enlarged lymph nodes, hypersensitivity reaction, signs of liver damage, or Peyronie's disease (induration of the corpora cavernosa of the penis) occurs. Institute another antiepileptic drug promptly. Monitor hepatic function periodically during long-term therapy; monitor blood counts, urinalysis monthly. Monitor blood or urine sugar of patients with diabetes mellitus regularly. Adjustment of dosage of hypoglycemic drug may be necessary because antiepileptic drug may inhibit insulin release and induce hyperglycemia. Have lymph node enlargement occurring during therapy evaluated carefully. Lymphadenopathy that simulates Hodgkin's disease has occurred. Lymph node hyperplasia may progress to lymphoma. Monitor blood proteins to detect early malfunction of the immune system (eg, multiple myeloma). Arrange dental instruction in proper oral hygiene technique for long-term patients to prevent development of gum hyperplasia.

Teaching points

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Take this drug exactly as prescribed, with food to enhance absorption and reduce GI upset; be especially careful not to miss a dose if you are on once-a-day therapy. Do not discontinue this drug abruptly or change dosage, except on the advice of your prescriber. Maintain good oral hygiene (regular brushing and flossing) to prevent gum disease; arrange frequent dental checkups to prevent serious gum disease. Arrange for frequent checkups to monitor your response to this drug. Monitor your blood or urine sugar regularly, and report any abnormality to your health care provider if you have diabetes.

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This drug is not recommended for use during pregnancy. It is advisable to use some form of contraception other than hormonal contraceptives. Wear a medical alert tag so that any emergency medical personnel will know that you have epilepsy and are taking antiepileptic medication. These side effects may occur: Drowsiness, dizziness, confusion, blurred vision (avoid driving or performing other tasks requiring alertness or visual acuity); GI upset (take drug with food, eat frequent small meals). Report rash, severe nausea or vomiting, drowsiness, slurred speech, impaired coordination (ataxia), swollen glands, bleeding, swollen or tender gums, yellowish discoloration of the skin or eyes, joint pain, unexplained fever, sore throat, unusual bleeding or bruising, persistent headache, malaise, any indication of an infection or bleeding tendency, abnormal erection, pregnancy.

Adverse effects in Italic are most common; those in Bold are life-threatening.