OXCARBAZEPINE (Page 4 of 8)
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of oxcarbazepine tablets. 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.
Body as a Whole: multi-organ hypersensitivity disorders characterized by features such as rash, fever, lymphadenopathy, abnormal liver function tests, eosinophilia and arthralgia [ see Warnings and Precautions (5.8) ]
Cardiovascular System: atrioventricular block
Immune System Disorders: anaphylaxis [ see Warnings and Precautions (5.2) ]
Digestive System: pancreatitis and/or lipase and/or amylase increase
Hematologic and Lymphatic Systems: aplastic anemia [ see Warnings and Precautions (5.9) ]
Metabolism and Nutrition Disorders: hypothyroidism and syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Skin and Subcutaneous Tissue Disorders: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis [ see Warnings and Precautions (5.4) ], Acute Generalized Exanthematous Pustulosis (AGEP)
Musculoskeletal, Connective Tissue and Bone Disorders: There have been reports of decreased bone mineral density, osteoporosis and fractures in patients on long-term therapy with oxcarbazepine tablets.
Injury, Poisoning, and Procedural Complications: fall
Nervous System Disorders: dysarthria
7 DRUG INTERACTIONS
7.1 Effect of Oxcarbazepine Tablets on Other Drugs
Phenytoin levels have been shown to increase with concomitant use of oxcarbazepine tablets at doses greater than 1200 mg/day [see Clinical Pharmacology (12.3)] . Therefore, it is recommended that the plasma levels of phenytoin be monitored during the period of oxcarbazepine tablets titration and dosage modification. A decrease in the dose of phenytoin may be required .
7.2 Effect of Other Drugs on Oxcarbazepine Tablets
Strong inducers of cytochrome P450 enzymes and/or inducers of UGT (e.g., rifampin, carbamazepine, phenytoin and phenobarbital) have been shown to decrease the plasma/serum levels of MHD, the active metabolite of oxcarbazepine tablets (25% to 49%) [see Clinical Pharmacology (12.3)]. If oxcarbazepine tablets and strong CYP3A4 inducers or UGT inducers are administered concurrently, it is recommended that the plasma levels of MHD be monitored during the period of oxcarbazepine tablets titration. Dose adjustment of oxcarbazepine tablets may be required after initiation, dosage modification, or discontinuation of such inducers.
7.3 Hormonal Contraceptives
Concurrent use of oxcarbazepine tablets with hormonal contraceptives may render these contraceptives less effective [see Use in Specific Populations (8.3) and Clinical Pharmacology (12.3)] . Studies with other oral or implant contraceptives have not been conducted.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as oxcarbazepine tablets, during pregnancy. Encourage women who are taking oxcarbazepine tablets during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.
There are no adequate data on the developmental risks associated with the use of oxcarbazepine tablets in pregnant women; however, oxcarbazepine tablets is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine tablets monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts, and cardiac malformations such as ventricular septal defects). Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD).
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.
An increase in seizure frequency may occur during pregnancy because of altered levels of the active metabolite of oxcarbazepine. Monitor patients carefully during pregnancy and through the postpartum period [see Warnings and Precautions (5.10)] .
Data from published registries have reported craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects in children with prenatal oxcarbazepine exposure.
When pregnant rats were given oxcarbazepine (0, 30, 300, or 1000 mg/kg/day) orally throughout the period of organogenesis, increased incidences of fetal malformations (craniofacial, cardiovascular, and skeletal) and variations were observed at the intermediate and high doses (approximately 1.2 and 4 times, respectively, the MRHD on a mg/m 2 basis). Increased embryofetal death and decreased fetal body weights were seen at the high dose. Doses ≥300 mg/kg/day were also maternally toxic (decreased body weight gain, clinical signs), but there is no evidence to suggest that teratogenicity was secondary to the maternal effects.
In a study in which pregnant rabbits were orally administered MHD (0, 20, 100, or 200 mg/kg/day) during organogenesis, embryofetal mortality was increased at the highest dose (1.5 times the MRHD on a mg/m 2 basis). This dose produced only minimal maternal toxicity.
In a study in which female rats were dosed orally with oxcarbazepine (0, 25, 50, or 150 mg/kg/day) during the latter part of gestation and throughout the lactation period, a persistent reduction in body weights and altered behavior (decreased activity) were observed in offspring exposed to the highest dose (less than the MRHD on a mg/m 2 basis). Oral administration of MHD (0, 25, 75, or 250 mg/kg/day) to rats during gestation and lactation resulted in a persistent reduction in offspring weights at the highest dose (equivalent to the MRHD on a mg/m 2 basis).
Oxcarbazepine and its active metabolite (MHD) are present in human milk after oxcarbazepine tablets administration. The effects of oxcarbazepine and its active metabolite (MHD) on the breastfed infant or on milk production are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxcarbazepine tablets and any potential adverse effects on the breastfed infant from oxcarbazepine tablets or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Use of oxcarbazepine tablets with hormonal contraceptives containing ethinylestradiol or levonorgestrel is associated with decreased plasma concentrations of these hormones and may result in a failure of the therapeutic effect of the oral contraceptive drug. Advise women of reproductive potential taking oxcarbazepine tablets who are using a contraceptive containing ethinylestradiol or levonorgestrel to use additional or alternative non-hormonal birth control [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)] .
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.