Phenytoin (Dilantin, Pfizer)
Phenytoin was introduced in 1938 as the first non-sedating antiepileptic medication. It is the most popular drug in the United States for treatment of partial and secondarily generalized seizures.
A typical phenytoin dose is 100 mg orally, three times a day, but with brand name Dilantin the half-life is 24 hours and the medication can usually be tolerated in a single daily 300 mg dose. The therapeutic serum level of phenytoin is 10-20 mg/L.
Advantages of phenytoin include long experience, single daily dose regimen for good compliance, no need for a taper-up schedule, relatively quick disappearance of the medication after stopping.
Disadvantages include mild to moderate sedation and cognitive effects. The medication can have unpleasant cosmetic side effects, such as thickening of skin, acne, undesired hair growth, and gum swelling. Some of these cosmetic side effects may not be reversible after stopping medication. A moderate number of people are allergic to phenytoin, and one in ten thousand suffer the serious Stevens-Johnson allergic skin reaction, which can be fatal.
Phenytoin can cause a deficiency of folate (folic acid, a vitamin) and vitamin D, occasionally leading to anemia and bone problems. Phenytoin also can produce a peripheral neuropathy, which may be felt as numbness and tingling or weakness in the feet and fingers. People who are on phenytoin for years may benefit from a daily multivitamin, since the B complex may counteract neuropathy, the D the bony changes, and the folic acid a tendency of phenytoin to reduce that vitamin.
Small increases in phenytoin dose sometimes produce skyrocketing levels with toxicity. Note that the 100 mg and 30 mg brand-name pill are long-acting, but the 50 mg chewable Infa-tab is short-acting. Note that generic phenytoin may show variable absorption and half-life. In an acute situation where i.v. administration is needed, the fosphenytoin (Cerebyx) form is less irritating to veins, and tissues, and may be less likely than is phenytoin to produce cardiac arrhythmias. It is, however, more expensive.
Summary Data for Phenytoin
Pill sizes:
30 mg (white capsule / pink stripe, long-acting)
50 mg (triangular chewable tab, short-acting)
100 mg (white capsule / orange stripe, long-acting)
Liquid for oral: 125 mg/5 ml.
Injectable: 50 mg/ml injectable i.v. only (not a Pfizer product). Preferable to give fosphenytoin 20 mg phenytoin equivalent/kg load at <150 mg/min.
Typical adult dose: 300 mg per day (no titration only), with a target maintenance of 200-500/day in 1-3 divided doses. Load in emergency: i.v. load 20 mg per kg, max 50 mg/min. Oral load 20 mg/kg in 3 divided doses over a day.
Typical pediatric dose: 5-10 mg/kg/d, divided into two.
Metabolism: Liver (CYP 2C9).
Half-life: around 24 hours.
Therapeutic plasma concentrations: 10-20 mcg/ml.
Therapeutic unbound (free) concentrations: 1-2 mcg/ml.
Pregnancy: Category D - known to cause birth defects in humans.
Drugs that raise PHT levels: amiodarone, cimetidine, diltiazem, erythomycins, fluconazole, fluoxetine, isoniazid, methsuximide, methylphenidate, metronidazole, modafenil, omeprazole, oxcarbazepine, phenobarbital (sometimes), ritoniavir, sertraline, ticlopidine, topiramate, trimethaprim, valproate.
Drugs that lower PHT levels: antacids, carbamazepine, ciprofloxin, doxyrubicin, phenobarbital (sometimes), primidone, rifampin, sucralfate
PHT increases effects of: Coumadin (interaction sometimes raises INR, decreases clotting), acetaminophen
PHT decreases effects of other drugs: antipsychotics, antifungals, buproprion, buspirone, carbamazepine, clozapine, corticosteroids, Coumadin (interaction usually lowers INR, increases clotting), cyclosporin, felbamate, lamotrigine, mifepristone, narcotics, neuromuscular blockers, oral contraceptives, protease inhibitors, quetiapine, quinadine, thyroid hormone, tiagabine, theophylline, topiramate, tricyclics, valproate, zonisamide.
Dangerous Side Effects
Blood toxicity, liver toxicity, Stevens-Johnson skin rash, lupus-like syndrome, worsening of certain seizure types (atypical absence), birth defects; rare worsening of seizures with toxic doses.
Common Side Effects
Unsteadiness, mild fatigue, mild cognitive slowing.
Other Side Effects
Dizziness, unsteadiness, cosmetic problems increased face/body hair and coarser skin), gum over-growth, acne, skin rash, sensitivity to the sun, swollen lymph nodes (rare), anemia (rare), nausea (uncommon), tremor (uncommon), slurred speech, blurred vision, confusion, sleepiness, behavior and personality changes, fever, headache, inactivation of birth control pills, sexual dysfunction, neuropathy (tingling/numbness), weakening of the bones from vitamin D block.