phenytoin sodium 100 MG in 2 ML Injection


Warnings Intravenous administration should not exceed 50 mg per minute in adults. In neonates, the drug should be administered at a rate not exceeding 1#3 mg/kg/min. Severe cardiotoxic reactions and fatalities have been reported with atrial and ventricular conduction depression and ventricular fibrillation. Severe complications are most commonly encountered in elderly or gravely ill patients. Phenytoin should be used with caution in patients with hypotension and severe myocardial insufficiency. Hypotension usually occurs when the drug is administered rapidly by the intravenous route. The intramuscular route is not recommended for the treatment of status epilepticus since blood levels of phenytoin in the therapeutic range cannot be readily achieved with doses and methods of administration ordinarily employed. 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. Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. Lymph node involvement may occur with or without symptoms and signs resembling serum sickness e.g., fever, rash and liver involvement. In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs. Acute alcoholic intake may increase phenytoin serum levels while chronic alcoholic use may decrease serum levels. Usage in Pregnancy: A number of reports suggests an association between the use of antiepileptic drugs by women with epilepsy and a higher incidence of birth defects in children born to these women. Data are more extensive with respect to phenytoin and phenobarbital, but these are also the most commonly prescribed antiepileptic drugs; less systematic or anecdotal reports suggest a possible similar association with the use of all known antiepileptic drugs. The reports suggesting a higher incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodologic problems in obtaining adequate data on drug teratogenicity in humans; genetic factors or the epileptic condition itself may be more important than drug therapy in leading to birth defects. The great majority of mothers on antiepileptic medication deliver normal infants. It is important to note that antiepileptic drugs should not be discontinued in patients in whom the drug is administered to prevent major seizures, because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus. The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of childbearing potential. In addition to the reports of increased incidence of congenital malformation, such as cleft lip/palate and heart malformations in children of women receiving phenytoin and other antiepileptic drugs, there have more recently been reports of a fetal hydantoin syndrome. This consists of prenatal growth deficiency, microcephaly and mental deficiency in children born to mothers who have received phenytoin, barbiturates, alcohol, or trimethadione. However, these features are all interrelated and are frequently associated with intrauterine growth retardation from other causes. There have been isolated reports of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. An increase in seizure frequency during pregnancy occurs in a high proportion of patients, because of altered phenytoin absorption or metabolism. Periodic measurement of serum phenytoin levels is particularly valuable in the management of a pregnant epileptic patient as a guide to an appropriate adjustment of dosage. However, postpartum restoration of the original dosage will probably be indicated. Neonatal coagulation defects have been reported within the first 24 hours in babies born to epileptic mothers receiving phenobarbital and/or phenytoin. Vitamin K has been shown to prevent or correct this defect and has been recommended to be given to the mother before delivery and the neonate after birth.


Overdosage The lethal dose in children 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, hyperflexia, lethargy, slurred speech, nausea, vomiting. The patient may become comatose and hypertensive. Death is due to respiratory and circulatory depression. There are marked variations among individuals with respect to phenytoin plasma 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 plasma 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. 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 children. In acute overdosage the possibility of other CNS depressants, including alcohol, should be borne in mind.


Description IMPORTANT NOTE This drug must be administered slowly. In adults do not exceed 50 mg per minute intravenously. In neonates, the drug should be administered at a rate not exceeding 1#3 mg/kg/min. Phenytoin Sodium Injection, USP is a sterile, nonpyrogenic solution of phenytoin sodium and water for injection. Each milliliter (mL) contains phenytoin sodium 50 mg, propylene glycol 40% and alcohol 10%. Headspace nitrogen gassed. Also contains sodium hydroxide for pH adjustment; pH is 11.9 (10.0 to 12.3). The solution contains no bacteriostat, antimicrobial agent or added buffer. Single-dose, discard unused portion. NOTE: Do not use Injection if it is hazy or contains a precipitate. Phenytoin Sodium, USP is an anticonvulsant chemically designated 5,5-diphenyl hydantoin sodium salt. It has the following structural formula: Formula1.jpg


How Supplied Phenytoin Sodium Injection, USP, 50 mg/mL is supplied in single-dose containers as follows: List No. Container Container Size 1317 Ampule 2 mL 1317 Ampule 5 mL Store at 20 to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] ©Hospira 2004 EN-0532 Printed in USA HOSPIRA, INC., LAKE FOREST, IL 60045 USA


Indications and Usage Phenytoin Sodium Injection is indicated for the control of status epilepticus of the grand mal type, and prevention and treatment of seizures occurring during neurosurgery.


Dosage and Administration The addition of Phenytoin Sodium Injection solution to intravenous infusions is not recommended due to lack of solubility and resultant precipitation. Not to exceed 50 mg per minute, intravenously in adults, and not exceeding 1#3 mg/kg/min in neonates. There is a relatively small margin between full therapeutic effect and minimally toxic doses of this drug. The solution is suitable for use as long as it remains free of haziness and precipitate. Upon refrigeration or freezing, a precipitate might form; this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. Only a clear solution should be used. A faint yellow coloration may develop; however, this has no effect on the potency of the solution. In the treatment of status epilepticus, the intravenous route is preferred because of the delay in absorption of phenytoin when administered intramuscularly. Serum concentrations should be monitored and care should be taken when switching a patient from the sodium salt to the free acid form. 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. Status Epilepticus: In adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg per minute (this will require approximately 20 minutes in a 70-kg patient). The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6#8 hours. Recent work in neonates and children has shown that absorption of phenytoin is unreliable after oral administration, but a loading dose of 15#20 mg/kg of phenytoin sodium intravenously will usually produce plasma concentrations of phenytoin within the generally accepted therapeutic range (10#20 mcg/mL). The drug should be injected slowly intravenously at a rate not exceeding 1#3 mg/kg/min. Phenytoin Sodium Injection should be injected slowly and directly into a large vein through a large-gauge needle or intravenous catheter. Each injection of intravenous phenytoin should be followed by an injection of sterile saline through the same needle or catheter to avoid local venous irritation due to alkalinity of the solution. Continuous infusion should be avoided; the addition of Phenytoin Sodium Injection to intravenous infusion fluids is not recommended because of the likelihood of precipitation. Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression. Determination of phenytoin plasma levels is advised when using phenytoin in the management of status epilepticus and in the subsequent establishment of maintenance dosage. Other measures, including concomitant administration of an intravenous benzodiazepine such as diazepam, or an intravenous shortacting barbiturate, will usually be necessary for rapid control of seizures because of the required slow rate of administration of Phenytoin Sodium Injection. If administration of Phenytoin Sodium Injection does not terminate seizures, the use of other anticonvulsants, intravenous barbiturates, general anesthesia, and other appropriate measures should be considered. Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak plasma levels may require up to 24 hours. Neurosurgery: Prophylactic dosage#100 to 200 mg (2 to 4 mL) intramuscularly at approximately 4-hour intervals during surgery and continued during the postoperative period. When intramuscular administration is required for a patient previously stabilized orally, compensating dosage adjustments are necessary to maintain therapeutic plasma levels. An intramuscular dose 50% greater than the oral dose is necessary to maintain these levels. When returned to oral administration, the dose should be reduced by 50% of the original oral dose for one week to prevent excessive plasma levels due to sustained release from intramuscular tissue sites. If the patient requires more than a week of I.M. phenytoin, alternative routes should be explored, such as gastric intubation. For time periods less than one week, the patient shifted back from I.M. administration should receive one half the original oral dose for the same period of time the patient received I.M. phenytoin. Monitoring plasma levels would help prevent a fall into the subtherapeutic range. Serum blood level determinations are especially helpful when possible drug interactions are suspected. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.