1 INDICATIONS & USAGE Parenteral Phenytoin Sodium Injection is indicated for the treatment of generalized tonic-clonic status epilepticus, and prevention and treatment of seizures occurring during neurosurgery.

Intravenous phenytoin can also be substituted, as short-term use, for oral phenytoin.

Parenteral phenytoin should be used only when oral phenytoin administration is not possible [see Dosage and Administration- 2 (2.1, 2.3) and Warnings and Precautions- 5 (5.1)].

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Cardiovascular Risk Associated with Rapid Infusion [see Warnings and Precautions- 5 (5.1)] Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions- 5 (5.2)] Serious Dermatologic Reactions [see Warnings and Precautions- 5 (5.3)] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions- 5 (5.4)] Hypersensitivity [see Warnings and Precautions- 5 (5.5)] Hepatic Injury [see Warnings and Precautions- 5 (5.6)] Hematopoietic Complications [see Warnings and Precautions- 5 (5.7)] Local toxicity (Including Purple Glove Syndrome) [see Warnings and Precautions- 5 (5.8)] Exacerbation of Porphyria [see Warnings and Precautions- 5 (5.10)] Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions- 5 (5.11)] Hyperglycemia [see Warnings and Precautions- 5 (5.13)] The following adverse reactions associated with the use of Phenytoin Sodium Injection 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.

The most notable signs of toxicity associated with the intravenous use of this drug are cardiovascular collapse and/or CNS depression.

Hypotension does occur when the drug is administered rapidly by the intravenous route.

The rate of administration is very important; it 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 [See Boxed Warning, Dosage and Administration- 2 (2.1), and Warnings and Precautions- 5 (5.1)].

Body As a Whole: Allergic reactions in the form of rash and rarely more serious forms (see Skin and Appendages paragraph below) and DRESS [see Warnings and Precautions- 5 (5.4)] have been observed.

Anaphylaxis has also been reported.

There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.

Cardiovascular: Severe cardiovascular events and fatalities have been reported with atrial and ventricular conduction depression and ventricular fibrillation.

Severe complications are most commonly encountered in elderly or critically ill patients [see BOXED WARNING and Warnings and Precautions- 5 (5.1)] .

Digestive System: Acute hepatic failure [see Warnings and Precautions- 5 (5.6)], 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 [see Warnings and Precautions- 5 (5.7)].

These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression.

While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy.

Lymphadenopathy, including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin's Disease have been reported [see Warnings and Precautions- 5 (5.7)].

Laboratory Test Abnormality: Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in the absence of clinical hypothyroidism.

Phenytoin may also produce lower than normal values for dexamethasone or metyrapone tests.

Phenytoin may also cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).

Nervous System: The most common adverse reactions encountered with phenytoin therapy are nervous system reactions and are usually dose-related.

Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion.

Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesia, and headaches have also been observed.

There have also been rare reports of phenytoin induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs.

Cerebellar atrophy has been reported, and appears more likely in settings of elevated phenytoin levels and/or long-term phenytoin use [see Warnings and Precautions- 5 (5.14)].

A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.

Skin and Appendages: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes.

A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely.

Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis [see Warnings and Precautions- 5 (5.3)].

There have also been reports of hypertrichosis.

Local irritation, inflammation, tenderness, necrosis, and sloughing have been reported with or without extravasation of intravenous phenytoin [see Warnings and Precautions- 5 (5.8)].

Special Senses: Altered taste sensation including metallic taste.

Urogenital: Peyronie’s disease