PHENYTOIN SODIUM injection

Страна: САЩ

Език: английски

Източник: NLM (National Library of Medicine)

Активна съставка:

PHENYTOIN SODIUM (UNII: 4182431BJH) (PHENYTOIN - UNII:6158TKW0C5)

Предлага се от:

Hikma Pharmaceuticals USA Inc.

INN (Международно Name):

PHENYTOIN SODIUM

Композиция:

PHENYTOIN SODIUM 50 mg in 1 mL

Начин на приложение:

INTRAMUSCULAR

Вид предписание :

PRESCRIPTION DRUG

Терапевтични показания:

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 (2.1, 2.3) and Warnings and Precautions (5.1)] . Phenytoin Sodium Injection is contraindicated in patients with: - A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins [see Warnings and Precautions (5.5)] . - 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 [see Warnings and Precautions (5.6)]. - 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 P regnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as Phenytoin Sodium Injection, during pregnancy. Physicians are advised to recommend that pregnant patients taking phenytoin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/ . Risk Summary In humans, prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Prenatal phenytoin exposure is associated with an increased incidence of major malformations (including orofacial clefts and cardiac defects). In addition, the fetal hydantoin syndrome a pattern of abnormalities including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits has been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy [see Data] . There have been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. Administration of phenytoin to pregnant animals resulted in an increased incidence of fetal malformations and other manifestations of developmental toxicity (including embryofetal death, growth impairment, and behavioral abnormalities) in multiple species at clinically relevant doses [see Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Clinical Considerations Disease-associated maternal risk An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of serum phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage [see Dosage and Administration (2.1, 2.7)] . However, postpartum restoration of the original dosage will probably be indicated. Fetal/Neonatal adverse reactions A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero . This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth. Data Human Data Meta-analyses using data from published observational studies and registries have estimated an approximately 2.4-fold increased risk for any major malformation in children with prenatal phenytoin exposure compared to controls. An increased risk of heart defects, facial clefts, and digital hypoplasia has been reported. The fetal hydantion syndrome is a pattern of congenital anomalies including craniofacial anomalies, nail and digital hypoplasia, prenatal-onset growth deficiency, and neurodevelopmental deficiencies. Animal Data Administration of phenytoin to pregnant rats, rabbits, and mice during organogenesis resulted in embryofetal death, fetal malformations, and decreased fetal growth retardation. Malformations (including craniofacial, cardiovascular, neural, limb, and digit abnormalities) were observed in rats, rabbits, and mice at doses as low as 100, 75, and 12.5 mg/kg, respectively. Risk Summary Phenytoin is secreted in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Phenytoin Sodium Injection and any potential adverse effects on the breastfed infant from Phenytoin Sodium Injection or from the underlying maternal condition. A loading dose of 15 to 20 mg/kg of Phenytoin Sodium Injection intravenously will usually produce serum concentrations of phenytoin within the generally accepted serum total concentrations between 10 and 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL). Because of the increased risk of adverse cardiovascular reactions associated with rapid administration Phenytoin Sodium Injection should be injected slowly intravenously at a rate not exceeding 1 to 3 mg/kg/min or 50 mg per minute, whichever is slower [see Dosage and Administration (2.8) and Warnings and Precautions (5.1)]. Phenytoin clearance tends to decrease with increasing age [see Clinical Pharmacology (12.3)] . Lower or less frequent dosing may be required [see Dosage and Administration (2.6)]. The liver is the site of biotransformation. Patients with impaired liver function, elderly patients, or those who are gravely ill may show early toxicity. 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. Patients who are intermediate or poor metabolizers of CYP2C9 substrates (e.g.,*1/*3, *2/*2, *3/*3) may exhibit increased phenytoin serum concentrations compared to patients who are normal metabolizers (e.g., *1/*1 ). Thus, patients who are known to be intermediate or poor metabolizers may ultimately require lower doses of phenytoin to maintain similar steady-state concentrations compared to normal metabolizers. If early signs of dose-related central nervous system (CNS) toxicity develop, serum concentrations should be checked immediately [see Clinical Pharmacology (12.5)] .

Каталог на резюме:

Phenytoin Sodium Injection, USP—50 mg/mL 2 mL (100 mg) Single Dose vials packaged in 25s (NDC 0641-0493-25) 5 mL (250 mg) Single Dose vials packaged in 10s (NDC 0641-2555-10) For single-dose only. After opening, any unused product should be discarded.

Статус Оторизация:

Abbreviated New Drug Application

Данни за продукта

PHENYTOIN SODIUM- PHENYTOIN SODIUM INJECTION
HIKMA PHARMACEUTICALS USA INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PHENYTOIN SODIUM
INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
PHENYTOIN SODIUM
INJECTION.
PHENYTOIN SODIUM INJECTION FOR INTRAVENOUS OR INTRAMUSCULAR USE
INITIAL U.S. APPROVAL: 1953
WARNING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_.
THE RATE OF INTRAVENOUS PHENYTOIN SODIUM INJECTION 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
PHENYTOIN SODIUM INJECTION.
REDUCTION IN RATE OF ADMINISTRATION OR DISCONTINUATION OF DOSING MAY
BE NEEDED
_(2.1, 5.1)._
RECENT MAJOR CHANGES
Warnings and Precautions (5.3) 02/2021
INDICATIONS AND 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. (1)
DOSAGE AND ADMINISTRATION
For Status Epilepticus and Non-emergent Loading Dose:
Adult loading dose is 10 to 15 mg/kg at a rate not exceeding 50
mg/min. (2.2)
Pediatric loading dose is 15 to 20 mg/kg at a rate not exceeding 1 to
3 mg/kg/min or 50 mg/min,
whichever is slower. (2.8)
Continuous monitoring of the electrocardiogram, blood pressure, and
respiratory function is essential.
(2.2)
Maintenance Dosing:
Initial loading dose should be followed by maintenance doses of oral
or intravenous Phenytoin Sodium
Injection every 6 to 8 hours. (2.2, 2.3)
Intramuscular Administration:
Because of erratic absorpt