CARNEXIV- carbamazepine injection, powder, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

CARBAMAZEPINE (UNII: 33CM23913M) (CARBAMAZEPINE - UNII:33CM23913M)

Available from:

Lundbeck Pharmaceuticals LLC

INN (International Name):

CARBAMAZEPINE

Composition:

CARBAMAZEPINE 10 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

CARNEXIV is indicated as replacement therapy for oral carbamazepine formulations, when oral administration is temporarily not feasible, in adults with the following seizure types: - Partial seizures with complex symptomatology - Generalized tonic-clonic seizures - Mixed seizure patterns which include the above, or other partial or generalized seizures Limitations of Usage CARNEXIV is not indicated for the treatment of absence seizures (including atypical absence). Carbamazepine has been associated with increased frequency of generalized convulsions in these patients.  CARNEXIV is contraindicated in patients with: - Bone marrow depression [see Warnings and Precautions (5.2)] Bone marrow depression [see Warnings and Precautions (5.2)] - Known hypersensitivity to carbamazepine [see Warnings and Precautions (5.5)] Known hypersensitivity to carbamazepine [see Warnings and Precautions (5.5)] - Known hypersensitivity to any of the tricyclic antidepressants (e.g., amitriptyline, imipramine, and nortriptyline) [see Drug Interactions (7.1)] Known hypersensitivity to any of the tricyclic antidepressants (e.g., amitriptyline, imipramine, and nortriptyline) [see Drug Interactions (7.1)] - Concomitant use of boceprevir; CARNEXIV can reduce boceprevir concentrations through induction of CYP3A4; this can diminish boceprevir’s virologic activity [see Drug Interactions (7.1)] Concomitant use of boceprevir; CARNEXIV can reduce boceprevir concentrations through induction of CYP3A4; this can diminish boceprevir’s virologic activity [see Drug Interactions (7.1)] - Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days; concomitant use can cause serotonin syndrome [see Drug Interactions (7.3)] Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days; concomitant use can cause serotonin syndrome [see Drug Interactions (7.3)] - Concomitant use of nefazodone; this may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect [see Drug Interactions (7.1)] Concomitant use of nefazodone; this may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect [see Drug Interactions (7.1)] -   Concomitant use of delavirdine or other non-nucleoside reverse transcriptase inhibitors. CARNEXIV can substantially reduce the concentrations of these drugs through induction of CYP3A4. This can lead to loss of virologic response and possible resistance to these medications [see Drug Interactions (7.1)]   Concomitant use of delavirdine or other non-nucleoside reverse transcriptase inhibitors. CARNEXIV can substantially reduce the concentrations of these drugs through induction of CYP3A4. This can lead to loss of virologic response and possible resistance to these medications [see Drug Interactions (7.1)] Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including CARNEXIV, during pregnancy. Encourage women who are taking CARNEXIV during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org, and must be done by the patient herself.    Risk Summary Carbamazepine can cause fetal harm when administered to a pregnant woman. An association between the use of carbamazepine during pregnancy and congenital malformations, including spina bifida and malformations involving other body systems (e.g., craniofacial defects and cardiovascular malformations) has been demonstrated. Developmental delays have been reported.  In animal studies, administration of carbamazepine during pregnancy resulted in developmental toxicity, including increased incidences of fetal malformations. Women of childbearing potential should be informed of the potential risk to the fetus.   In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.   Clinical Considerations Disease-associated Maternal and/or Embryofetal Risk Consideration should be given to discontinuing carbamazepine in women who are pregnant or attempting to become pregnant if the benefits of discontinuation outweigh the risks of recurrent seizures. Women with epilepsy should not discontinue carbamazepine abruptly due to the risk of status epilepticus and less severe seizures which may be life-threatening.   Fetal/Neonatal Adverse Reactions There have been a few cases of neonatal seizures and/or respiratory depression associated with maternal carbamazepine in combination with other antiepileptic drugs. A few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal carbamazepine use. These symptoms may represent a neonatal withdrawal syndrome.  Tests to detect birth defects using currently accepted procedures should be considered a part of routine prenatal care in childbearing women receiving carbamazepine. Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. It is not known whether the risk of neural tube defects in the offspring of women receiving carbamazepine is reduced by folic acid supplementation, but dietary folic acid supplementation both prior to conception and during pregnancy should be recommended for patients using carbamazepine. Data Human Data Pregnancy registry and epidemiological data suggest that there may be an association between the use of carbamazepine during pregnancy and congenital malformations, including spina bifida and malformations involving other body systems (e.g., craniofacial defects and cardiovascular malformations). The North American Antiepileptic Drug (NAAED) Pregnancy Registry has reported a rate of major congenital malformations of 3.0% (95% CI: 2.1, 4.2) among mothers exposed to carbamazepine monotherapy (n=1,033) during the first trimester with a relative risk of 2.7 (95% CI: 1.0, 7.0) compared to pregnant women not taking an antiepileptic drug. There have also been postmarketing reports of developmental delays based on neurobehavioral assessments.  Animal Data In studies in which pregnant rodents were administered carbamazepine orally during organogenesis, dose-related increases in the rates of fetal structural abnormalities (craniofacial, skeletal, cardiac, and urogenital defects), intrauterine growth retardation, and embryofetal death occurred at clinically relevant doses. Risk Summary Carbamazepine and its epoxide metabolite are excreted in human milk. There are no data to assess the effects of carbamazepine or its metabolites on milk production, or on the breastfed infant, of mothers taking CARNEXIV.  The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CARNEXIV and any potential adverse effects on the breastfed infant from CARNEXIV or from the underlying maternal condition. Safety and effectiveness in pediatric patients have not been established. No studies in geriatric patients have been conducted with CARNEXIV. Though no dose adjustment is necessary for patients with mild renal impairment, close monitoring during CARNEXIV treatment should be conducted due to potential accumulation of sulfobutylether beta-cyclodextrin sodium salt. Accumulation of sulfobutylether beta-cyclodextrin sodium salt is associated with a greater risk for an adverse effect on renal function in patients with moderate or severe renal impairment. Therefore, CARNEXIV should generally not be used in patients with moderate or severe renal impairment [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)] . Monitor serum carbamazepine concentrations in patients with hepatic impairment treated with CARNEXIV, as the first-pass effect may be reduced in these patients [see Clinical Pharmacology (12.3)] .

Product summary:

CARNEXIV (carbamazepine) 200 mg/20 mL (10 mg/mL) injection is a clear, colorless, sterile solution. It is supplied in single-dose 20 mL glass vials, available in cartons of one vial (NDC 67386-621-52). Not made with natural rubber latex. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Authorization status:

New Drug Application

Summary of Product characteristics

CARNEXIV- CARBAMAZEPINE INJECTION, POWDER, FOR SOLUTION
LUNDBECK PHARMACEUTICALS LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CARNEXIV™ SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CARNEXIV.
CARNEXIV™ (CARBAMAZEPINE) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 1968
WARNING: SERIOUS DERMATOLOGIC REACTIONS AND
APLASTIC ANEMIA AND AGRANULOCYTOSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING. _
SERIOUS DERMATOLOGIC REACTIONS
SERIOUS AND SOMETIMES FATAL DERMATOLOGIC REACTIONS, INCLUDING TOXIC
EPIDERMAL
NECROLYSIS (TEN) AND STEVENS-JOHNSON SYNDROME (SJS), HAVE OCCURRED
WITH
CARBAMAZEPINE. DISCONTINUE CARNEXIV IF THESE REACTIONS OCCUR (5.1)
PATIENTS OF ASIAN ANCESTRY HAVE A 10-FOLD GREATER RISK OF TEN/SJS,
COMPARED TO OTHER
POPULATIONS. AVOID USE OF CARNEXIV IN GENETICALLY AT-RISK PATIENTS,
INCLUDING THOSE
POSITIVE FOR THE HLA-B*1502 ALLELE (5.1)
APLASTIC ANEMIA AND AGRANULOCYTOSIS
APLASTIC ANEMIA AND AGRANULOCYTOSIS CAN OCCUR WITH CARNEXIV (5.2)
OBTAIN COMPLETE CBC PRIOR TO INITIATION OF CARNEXIV. CONSIDER
DISCONTINUING
CARNEXIV IF SIGNIFICANT BONE MARROW DEPRESSION DEVELOPS (5.2)
INDICATIONS AND USAGE
CARNEXIV is indicated as replacement therapy for oral carbamazepine
formulations, when oral
administration is temporarily not feasible, in adults with the
following seizure types (1):
Partial seizures with complex symptomatology
Generalized tonic-clonic seizures
Mixed seizure patterns which include the above, or other partial or
generalized seizures
DOSAGE AND ADMINISTRATION
CARNEXIV total daily dose is 70% of the total daily dose of oral
carbamazepine from which patients are
being switched; divide the total daily dose of CARNEXIV equally in
four infusions separated by 6 hours;
dilute each dose of CARNEXIV in 100 mL of diluent and infuse
intravenously over 30 minutes (2.1, 2.2)
Use of CARNEXIV is not recommended for periods longer than 7 days
(2.1)
Closely monitor patients with renal impairment; CARNEXI