t.
Intervention: Reserve concomitant prescribing of these drugs for use inpatients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required [seeWarnings and Precautions (5.3)].
Examples: Other benzodiazepines and sedatives/hypnotics, anxiolytics,ranquilizers, muscle relaxants, general anesthetics,antipsychotics, opioids, alcohol.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposedto antiepileptic drugs (AEDs), such as NAYZILAM, during pregnancy. Encourage womenwho are taking NAYZILAM during pregnancy to enroll in the North American AntiepilepticDrug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting
http://www.aedpregnancyregistry.org/.
Risk Summary
There are no adequate and well-controlled studies of NAYZILAM in pregnant women.
Available data suggest that the class of benzodiazepines is not associated with markedincreases in risk for congenital anomalies. Although some early epidemiological studiessuggested a relationship between benzodiazepine drug use in pregnancy and congenitalanomalies such as cleft lip and or palate, these studies had considerable limitations. Morerecently completed studies of benzodiazepine use in pregnancy have not consistentlydocumented elevated risks for specific congenital anomalies. There is insufficient evidence toassess the effect of exposure to benzodiazepines during pregnancy on neurodevelopment.
There are clinical considerations regarding exposure to benzodiazepines during the secondand third trimesters of pregnancy or immediately prior to or during childbirth.
These risksinclude decreased fetal movement and/or fetal heart rate variability, “floppy infantsyndrome,” dependence, and withdrawal (see Clinical Considerations and Human Data).
Administration of midazolam to rats and rabbits during the period of organogenesis or to ratsduring late pregnancy and throughout lactation at doses greater than those used clinically didnot result in any apparent adverse effects on development (see Animal Data). However,published data for midazolam and other benzodiazepines suggest the possibility of neuronalcell death and long-term effects on neurobehavioral and immunological function in animalsfollowing prenatal or early postnatal exposure at clinically relevant doses. NAYZILAMshould be used during pregnancy only if the potential benefit to the mother justifies thepotential risk to the fetus. Advise a pregnant woman and women of childbearing age of thepotential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects andmiscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Thebackground risk of major birth defects and miscarriage for the indicated population isunknown.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Infants born to mothers who have taken benzodiazepines during the later stages of pregnancycan develop dependence, and subsequently withdrawal, during the postnatal period. Clinicalmanifestations of withdrawal or neonatal abstinence syndrome may include hypertonia,hyperreflexia, hypoventilation, irritability, tremors, diarrhea, and vomiting. These complications can appear shortly after delivery to 3 weeks after birth and persist from h |
