Lorazepam extended-release

Table 1 presents clinically significant interactions with LOREEV XR. Use with Opioids: Increase the risk of respiratory depression ( 7 ) CNS depressants: Additive CNS depressant effects (7) Alcohol: Avoid use. Increases the release rate of LOREEV XR (7) UGT Inhibitors: Avoid initiation of UGT inhibitors. Dose reduction requires switching to lorazepam tablets for dose adjustment (7) Table 1: Clinically Significant Drug Interactions with LOREEV XR. Opioids Clinical Impact The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.

Benzodiazepines interact at gamma-aminobutyric acid (GABA A ) sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists [see Warnings and Precautions ( 5.1 )] . Intervention Limit dosage and duration of concomitant use of LOREEV XR and opioids, and monitor patients closely for respiratory depression and sedation. Alcohol Clinical Impact Based on an in vitro study, alcohol increases the release rate of LOREEV XR [see Clinical Pharmacology ( 12.3 )] .

Intervention Avoid concomitant use of alcohol during treatment with LOREEV XR [see Warnings and Precautions ( 5.4 )] . CNS-Depressants Clinical Impact Benzodiazepines, including LOREEV XR, increase CNS-depressant effects when administered with other CNS depressants. Concomitant use of clozapine and LOREEV XR may produce marked sedation, excessive salivation, hypotension, ataxia, delirium, and respiratory arrest. Intervention Avoid co-administration of alcohol with LOREEV XR. Use caution if LOREEV XR is co-administered with other CNS-depressants [see Warnings and Precautions (5.4)] .

Inhibitors of UGT Clinical Impact Concomitant use of LOREEV XR with UGT inhibitors may increase lorazepam exposure [see Clinical Pharmacology (12.3)] , which may increase the risk of adverse reactions. Intervention Avoid initiating an UGT inhibitor during treatment with LOREEV XR. If an UGT inhibitor is initiated, discontinue LOREEV XR and switch to lorazepam tablets [see Dosage and Administration ( 2.5 )] .

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LOREEV XR during pregnancy. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or by visiting online at https://womensmentalhealth.org/pregnancyregistry. Risk Summary Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions ( 5.8 ), Clinical Considerations] .

Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data) . In animal studies, administration of lorazepam during the organogenesis period of pregnancy resulted in increased incidences of fetal malformations at doses greater than those used clinically. Data for benzodiazepines suggest the possibility of increased neuronal cell death and long-term effects on neurobehavioral function based on findings in animals following prenatal or early postnatal exposure at clinically relevant doses (see Data) .

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia and sedation in neonates. Monitor neonates exposed to LOREEV XR during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems.

Monitor neonates exposed to LOREEV XR during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions ( 5.8 )] . Data Human Data Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and…