sion, ataxia, delirium, and respiratory arrest. concurrent administration of lorazepam with valproate results in increased plasma concentrations and reduced clearance of lorazepam. lorazepam dosage should be reduced to approximately 50% when coadministered with valproate. concurrent administration of lorazepam with probenecid may result in a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. lorazepam dosage needs to be reduced by approximately 50% when coadministered with probenecid. the effects of probenecid and valproate on lorazepam may be due to inhibition of glucuronidation. administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lorazepam.

ower initial dose of the opioid and titrate based upon clinical response. advise both patients and caregivers about the risks of respiratory depression and sedation when ativan is used with opioids. advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined (see precautions: drug interactions ). abuse, misuse, and addiction the use of benzodiazepines, including ativan, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death (see drug abuse and dependence: abuse ). before prescribing ativan and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). use of ativan, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of ativan along with monitoring for signs and symptoms of abuse, misuse, and addiction. prescribe the lowest effective dosage; avoid or minimize concomitant use of cns depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. if a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. dependence and withdrawal reactions to reduce the risk of withdrawal reactions, use a gradual taper to discontinue ativan or reduce the dosage (a patient-specific plan should be used to taper the dose) (see dosage and administration: discontinuation or dosage reduction of ativan ). patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. acute withdrawal reactions the continued use of benzodiazepines, including ativan, may lead to clinically significant physical dependence. abrupt discontinuation or rapid dosage reduction of ativan after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see drug abuse and dependence: dependence ) . protracted withdrawal syndrome in some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see drug abuse and dependence: dependence ). pre-existing depression may emerge or worsen during use of benzodiazepines including lorazepam. ativan (lorazepam) is not recommended for use in patients with a primary depressive disorder or psychosis. use of benzodiazepines, including lorazepam, both used alone and in combination with other cns depressants, may lead to potentially fatal respiratory depression (see precautions: drug interactions ). as with all patients on cns-depressant drugs, patients receiving lorazepam should be warned not to operate dangerous machinery or motor vehicles and that their tolerance for alcohol and other cns depressants will be diminished. neonatal sedation and withdrawal syndrome use of ativan late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (see precautions: pregnancy ). monitor neonates exposed to ativan during pregnancy or labor for signs of sedation and monitor neonates exposed to ativan during pregnancy for signs of withdrawal; manage these neonates accordingly.

ime doses. discontinuation or dosage reduction of ativan to reduce the risk of withdrawal reactions, use a gradual taper to discontinue ativan or reduce the dosage. if a patient develops withdrawal reactions, consider pausing the taper or increasing the dosage to the previous tapered dosage level. subsequently decrease the dosage more slowly (see warnings: dependence and withdrawal reactions and drug abuse and dependence: dependence ).

obstructive pulmonary disease; gastrointestinal symptoms including nausea, change in appetite, constipation, jaundice, increase in bilirubin, increase in liver transaminases, increase in alkaline phosphatase; hypersensitivity reactions, anaphylactoid reactions; dermatological symptoms, allergic skin reactions, alopecia; syndrome of inappropriate antidiuretic hormone (siadh), hyponatremia; thrombocytopenia, agranulocytosis, pancytopenia; hypothermia; and autonomic manifestations. paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by ativan (lorazepam). to report suspected adverse reactions, contact bausch health us, llc at 1-800-321-4576 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

sion, ataxia, delirium, and respiratory arrest. concurrent administration of lorazepam with valproate results in increased plasma concentrations and reduced clearance of lorazepam. lorazepam dosage should be reduced to approximately 50% when coadministered with valproate. concurrent administration of lorazepam with probenecid may result in a more rapid onset or prolonged effect of lorazepam due to increased half-life and decreased total clearance. lorazepam dosage needs to be reduced by approximately 50% when coadministered with probenecid. the effects of probenecid and valproate on lorazepam may be due to inhibition of glucuronidation. administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lorazepam.

or other adverse outcomes. in the u.s. general population, the estimated risk of major birth defects and of 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 ativan during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. monitor neonates exposed to ativan during pregnancy for signs of withdrawal. manage these neonates accordingly (see warnings: neonatal sedation and withdrawal syndrome ). 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 other medications, have not confirmed these findings. animal data reproductive studies in animals were performed in mice, rats, and two strains of rabbits. occasional anomalies (reduction of tarsals, tibia, metatarsals, malrotated limbs, gastroschisis, malformed skull, and microphthalmia) were seen in drug-treated rabbits without relationship to dosage. although all of these anomalies were not present in the concurrent control group, they have been reported to occur randomly in historical controls. at doses of 40 mg/kg and higher, there was evidence of fetal resorption and increased fetal loss in rabbits which was not seen at lower doses.

iven. there is no evidence of accumulation of lorazepam on administration up to 6 months. studies comparing young and elderly subjects have shown that advancing age does not have a significant effect on the pharmacokinetics of lorazepam. however, in one study involving single intravenous doses of 1.5 to 3 mg of ativan injection, mean total body clearance of lorazepam decreased by 20% in 15 elderly subjects of 60 to 84 years of age compared to that in 15 younger subjects of 19 to 38 years of age.

. steinbach, mb r5g 1z7, canada ativan is a trademark of bausch health companies inc. or its affiliates. © 2023 bausch health companies inc. or its affiliates 9644303 rev. 01/2023

seek medical help if they develop these signs and/or symptoms; and on the proper disposal of unused drug (see warnings: abuse misuse, and addiction and drug abuse and dependence ). withdrawal reactions inform patients that the continued use of ativan may lead to clinically significant physical dependence and that abrupt discontinuation or rapid dosage reduction of ativan may precipitate acute withdrawal reactions, which can be life-threatening. inform patients that in some cases, patients taking benzodiazepines have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months. instruct patients that discontinuation or dosage reduction of ativan may require a slow taper (see warnings: dependence and withdrawal reactions and drug abuse and dependence ). pregnancy advise pregnant females that use of ativan late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see warnings: neonatal sedation and withdrawal syndrome and precautions: pregnancy ). instruct patients to inform their healthcare provider if they are pregnant. advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ativan during pregnancy (see precautions: pregnancy ). nursing instruct patients to notify their healthcare provider if they are breastfeeding or intend to breastfeed. instruct breastfeeding patients using ativan to monitor infants for excessive sedation, poor feeding and poor weight gain, and to seek medical attention if they notice these signs (see precautions: nursing mothers ).