In patients with depression, a possibility for suicide should be borne in mind; benzodiazepines should
not be used in such patients without adequate antidepressant therapy.
Lorazepam should be used with caution in patients with compromised respiratory function (e.g. COPD,
sleep apnea syndrome).
Elderly or debilitated patients may be more susceptible to the sedative effects of lorazepam. Therefore,
these patients should be monitored frequently and have their dosage adjusted carefully according to
patient response; the initial dosage should not exceed 2 mg.
Paradoxical reactions have been occasionally reported during benzodiazepine use. Such reactions may
be more likely to occur in children and the elderly. Should these occur, use of the drug should be
The usual precautions for treating patients with impaired renal or hepatic function should be observed.
As with all benzodiazepines, the use of lorazepam may worsen hepatic encephalopathy; therefore,
lorazepam should be used with caution in patients with severe hepatic insufficiency and/or
encephalopathy. Dosage for patients with severe hepatic insufficiency should be adjusted carefully
according to patient response; lower doses may be sufficient in such patients.
In patients where gastrointestinal or cardiovascular disorders coexist with anxiety, it should be noted
that lorazepam has not been shown to be of significant benefit in treating the gastrointestinal or
Esophageal dilation occurred in rats treated with lorazepam for more than one year at 6 mg/kg/day. The
no-effect dose was 1.25 mg/kg/day (approximately 6 times the maximum human therapeutic dose of 10
mg per day). The effect was reversible only when the treatment was withdrawn within two months of
first observation of the phenomenon. The clinical significance of this is unknown. However, use of
lorazepam for prolonged periods and in geriatric patients requires caution, and there should be frequent
monitoring for symptoms of upper G.I. disease.
Safety and effectiveness of Ativan (lorazepam) in children of less than 12 years have not been
Essential Laboratory Tests
Some patients on Ativan (lorazepam) have developed leukopenia, and some have had elevations of LDH.
As with other benzodiazepines, periodic blood counts and liver function tests are recommended for
patients on long-term therapy.
Carcinogenesis And Mutagenesis
No evidence of carcinogenic potential emerged in rats during an 18-month study with Ativan
(lorazepam). No studies regarding mutagenesis have been performed.
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.
The clinical significance of the above findings is not known. However, an increased risk of congenital
malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam, and
meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because the
use of these drugs is rarely a matter of urgency, the use of lorazepam during this period should be
avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution
of therapy should be considered. Patients should be advised that if they become pregnant, they should
communicate with their physician about the desirability of discontinuing the drug.
In humans, blood levels obtained from umbilical cord blood indicate placental transfer of lorazepam and
lorazepam glucuronide. Infants of mothers who ingested benzodiazepines for several weeks or more
preceding delivery have been reported to have withdrawal symptoms during the postnatal period.
Symptoms such as hypoactivity, hypotonia, hypothermia, respiratory depression, apnea, feeding
problems, and impaired metabolic response to cold stress have been reported in neonates born of
mothers who have received benzodiazepines during the late phase of pregnancy or at delivery.
Lorazepam has been detected in human breast milk; therefore, it should not be administered to breastfeeding
women, unless the expected benefit to the woman outweighs the potential risk to the infant.
Sedation and inability to suckle have occurred in neonates of lactating mothers taking benzodiazepines.
Infants of lactating mothers should be observed for pharmacological effects (including sedation and
Clinical studies of Ativan generally were not adequate to determine whether subjects aged 65 and over
respond differently than younger subjects; however, the incidence of sedation and unsteadiness was
observed to increase with age (see ADVERSE REACTIONS).
Age does not appear to have a significant effect on lorazepam kinetics (see CLINICAL PHARMACOLOGY).
Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal
impairment, should be considered. Greater sensitivity (e.g., sedation) of some older individuals cannot
be ruled out. In general, dose selection for an elderly patient should be cautious, and lower doses may
be sufficient in these patients (see DOSAGE AND ADMINISTRATION).