Phenytoin (4 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, CHEWABLE, SUSPENSION.
Routes of administration: ORAL.
Brand Names
- DILANTIN
- DILANTIN-125
- DILANTIN-30
- PHENYTOIN
Indications and Usage
Extended phenytoin sodium capsules are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
Contraindications
Phenytoin sodium is contraindicated in patients with: A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5)] . Reactions have included angioedema. A history of prior acute hepatotoxicity attributable to phenytoin [see Warnings and Precautions (5.8)]. Coadministration with delavirdine because of the potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.1)] Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)] Serious Dermatologic Reactions [see Warnings and Precautions (5.3)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.4)] Hypersensitivity [see Warnings and Precautions (5.5)] Cardiac Effects [see Warnings and Precautions (5.6)] Angioedema [see Warnings and Precautions (5.7)] Hepatic Injury [see Warnings and Precautions (5.8)] Hematopoietic Complications [see Warnings and Precautions (5.9)] Effects on Vitamin D and Bone [see Warnings and Precautions (5.10)] Exacerbation of Porphyria [see Warnings and Precautions (5.12)] Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions (5.13)] Hyperglycemia [see Warnings and Precautions (5.14)] The following adverse reactions associated with the use of phenytoin sodium were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole:Allergic reactions in the form of rash and rarely more serious forms and DRESS have been observed, as has angioedema [see Warnings and Precautions (5.3, 5.4, 5.7)] . Anaphylaxis has also been reported. There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities. Digestive System:Acute hepatic failure, toxic hepatitis, liver damage, nausea, vomiting, constipation, enlargement of the lips, and gingival hyperplasia. Hematologic and Lymphatic System:Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have i
Drug Interactions
Phenytoin is extensively bound to plasma proteins and is prone to competitive displacement. Phenytoin is primarily metabolized by the hepatic cytochrome P450 enzyme CYP2C9 and to a lesser extent by CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Monitoring of phenytoin serum levels is recommended when a drug interaction is suspected. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes.
Mechanism of Action
The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges.
Overdosage
The lethal dose in pediatric patients is not known. The lethal dose in adults is estimated to be 2 to 5 grams. The initial symptoms are nystagmus, ataxia, and dysarthria. Other signs are tremor, hyperreflexia, lethargy, slurred speech, blurred vision, nausea, and vomiting. The patient may become comatose and hypotensive. Bradycardia and cardiac arrest have been reported [see Warnings and Precautions (5.6)]. Death is caused by respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin serum levels where toxicity may occur. Nystagmus, on lateral gaze, usually appears at 20 mcg/mL, ataxia at 30 mcg/mL; dysarthria and lethargy appear when the serum concentration is over 40 mcg/mL, but as high a concentration as 50 mcg/mL has been reported without evidence of toxicity. As much as 25 times the therapeutic dose has been taken to result in a serum concentration over 100 mcg/mL with complete recovery. Irreversible cerebellar dysfunction and atrophy have been reported. Treatment: Treatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients. In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in mind.