• Dilantin Oral Suspension is indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures.

• Dilantin Injection is indicated for the treatment of generalized tonic-clonic status epilepticus, and prevention and treatment of seizures occurring during neurosurgery. Intravenous DILANTIN can also be substituted, as short-term use, for oral phenytoin. Parenteral DILANTIN should be used only when oral DILANTIN administration is not possible.

• Dilantin Infatabs are indicated for the treatment of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.

Cardiovascular Risk Associated with Rapid Infusion: The rate of intravenous DILANTIN administration should not exceed 50 mg per minute in adults and 1 to 3 mg/kg/min (or 50 mg per minute, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous DILANTIN. Although the risk of cardiovascular toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate. Reduction in rate of administration or discontinuation of dosing may be needed.

As non-emergency therapy, DILANTIN should be administered more slowly as either a loading dose or by intermittent infusion. Because of the risks of cardiac and local toxicity associated with intravenous DILANTIN, oral phenytoin should be used whenever possible.

Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak serum levels may require up to 24 hours.

Because of the risk of local toxicity, intravenous DILANTIN should be administered directly into a large peripheral or central vein through a large-gauge catheter.

NOT FOR ONCE-A-DAY DOSING. DILANTIN INFATABS can be either chewed thoroughly before being swallowed or swallowed whole.

The free acid form of phenytoin is used in DILANTIN-125 Suspension and DILANTIN Infatabs. DILANTIN extended capsules and parenteral DILANTIN are formulated with the sodium salt of phenytoin. Because there is approximately an 8% increase in drug content with the free acid form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt and vice versa.

Antiepileptic drugs (AEDs), including Dilantin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Cases of acute hepatotoxicity, including infrequent cases of acute hepatic failure, have been reported with DILANTIN. These events may be part of the spectrum of DRESS or may occur in isolation.

Because the fraction of unbound phenytoin is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.

Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When, in the judgment of the clinician, the need for dosage reduction, discontinuation, or substitution of alternative anticonvulsant medication arises, this should be done gradually.

Phenytoin is not indicated for seizures due to hypoglycemic or other metabolic causes.

Phenytoin is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present, combined drug therapy is needed.

DILANTIN can cause severe cutaneous adverse reactions (SCARs), which may be fatal. Reported reactions in phenytoin-treated patients have included toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). The onset of symptoms is usually within 28 days, but can occur later. DILANTIN should be discontinued at the first sign of a rash, unless the rash is clearly not drug-related.

Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine. Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.

There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s disease.

Hematopoietic complications, some fatal, have occasionally been reported in association with administration of DILANTIN. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression.

Phenytoin may also raise the serum glucose level in diabetic patients.

The chronic use of phenytoin in patients with epilepsy has been associated with decreased bone mineral density (osteopenia, osteoporosis, and osteomalacia) and bone fractures. Phenytoin induces hepatic metabolizing enzymes. This may enhance the metabolism of vitamin D and decrease vitamin D levels, which may lead to vitamin D deficiency, hypocalcemia, and hypophosphatemia.

Cases of bradycardia and cardiac arrest have been reported in DILANTIN-treated patients, both at recommended phenytoin doses and levels, and in association with phenytoin toxicity.

Angioedema has been reported in patients treated with DILANTIN in the post marketing setting. DILANTIN
should be discontinued immediately if symptoms of angioedema, such as facial, perioral, or upper airway
swelling occur

In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be exercised in using this medication in patients suffering from this disease.

DILANTIN Injection is contraindicated in patients with:

• Sinus bradycardia, sino-atrial block, second and third degree A-V block, and Adams-Stokes syndrome because of the effect of parenteral phenytoin on ventricular automaticity
• A history of prior acute hepatotoxicity attributable to phenytoin 
• Co-administration 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 

DILANTIN Oral Suspension is contraindicated in patients with:

• A history of prior acute hepatotoxicity attributable to phenytoin
• Co-administration 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

DILANTIN Infatabs are contraindicated in patients with:

• A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins
• A history of prior acute hepatotoxicity attributable to phenytoin 
• Co-administration 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

Drugs that may increase phenytoin serum levels: ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate, fluconazole, ketoconazole, itraconazole, miconazole, voriconazole, capecitabine, fluorouracil, fluoxetine, fluvoxamine, sertraline, H2 antagonists (cimetidine), omeprazole, sulfonamides, acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, disulfiram, estrogen, fluvastatin, isoniazid, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, trazodone and warfarin.

Drugs that may decrease phenytoin serum levels: antacids, bleomycin, carboplatin, cisplatin, doxorubicin, methotrexate, fosamprenavir, nelfinavir, ritonavir, carbamazepine, vigabatrin, chronic alcohol abuse, diazepam, diazoxide, folic acid, reserpine, rifampin, St. John’s wort, sucralfate and theophylline.

Drugs whose efficacy is impaired by phenytoin: azoles, antineoplastic agents, Delavirdine, neuromuscular blocking agents, Warfarin, corticosteroids, doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D.

Drugs whose level is decreased by phenytoin: antiepileptic drugs, antilipidemic agents, antiviral agents, calcium channel blockers, albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel and quetiapine.

DILANTIN may cause fetal harm when administered to a pregnant woman. Prenatal exposure to phenytoin may increase the risks for congenital malformation and other adverse developmental outcomes.

Phenytoin is secreted in human milk.

GoToSource (solution)   

GoToSource (injection) 

GoToSource (Infatabs)

• Seizures due to hypoglycemic or other metabolic causes. GoToSource

• Absence (petit mal) seizures. GoToSource 

• Mania. GoToSource 

• Seizure prophylaxis after traumatic brain injury. GoToSource

• Trigeminal neuralgia. GoToSource

• Prevention of motion sickness. GoToSource

• Bipolar disorder. GoToSource

• Post-traumatic stress disorder. GoToSource

• Cluster headache and trigeminal neuralgia. GoToSource

• Cardiac arrhythmias. GoToSource 

• Eating disorders. GoToSource

• Autism. GoToSource

Decreased bone mineral density (osteopenia, osteoporosis, and osteomalacia) and bone fractures with chronic use. GoToSource

Acute hepatotoxicity (drug-related liver injury) including acute liver failure. GoToSource

Thrombocytopenia (low blood platelet count) and leukopenia (decreased white blood cells). GoToSource

Toxic epidermal necrolysis and stevens-johnson syndrome (life-threatening skin disorders). GoToSource

Development of acne. GoToSource

Congenital malformations. GoToSource

Constipation. GoToSource

Drug reaction with eosinophilia and systemic symptoms (life-threatening, drug-induced hypersensitivity reaction). GoToSource

Depression. GoToSource

Gingival enlargement. GoToSource

Systemic lupus erythematosus (autoimmune disease). GoToSource

Altered or loss of taste sensation including metallic taste. GoToSource

Increased risk of suicidal thoughts and behavior. GoToSource

Exacerbation of porphyria (group of disorders causing nerve or skin problems). GoToSource

Coarsening of facial features, purple-hand syndrome, vasculitis (inflammation of blood vessels), pseudolymphoma (accumulation of inflammatory cells), and hirsutism (abnormal hair growth). GoToSource

Lawsuits filed for stevens-johnson syndrome and toxic epidermal necrolysis.