Approved Drug Label (PDF)
5
Warnings and Precautions
PRECAUTIONS
Newly added information:
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).
Pregnancy Exposure
Registry
There is a pregnancy registry that
monitors pregnancy outcomes in women exposed to psychiatric medications, including Ativan, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy
Registry for Psychiatric Medications at 1-866-961-2388 or 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: Neonatal Sedation and Withdrawal Syndrome and
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).
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 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.
Nursing Mothers
Risk Summary
Lorazepam is present in breast milk. There are reports of sedation, poor feeding and poor weight
gain in infants exposed to
benzodiazepines through breast milk. The effects of lorazepam on milk production are
unknown. The developmental and health benefits of breastfeeding should be considered along
with the mother’s
clinical need for Ativan and any potential adverse effects on the breastfed infant from Ativan or
from the underlying maternal condition.
Clinical Considerations
Infants exposed to Ativan
through breast milk should be monitored for sedation, poor feeding
and poor weight gain.
WARNINGS
Newly added information:
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.
Approved Drug Label (PDF)
Boxed Warning
(Additions and/or revisions underlined)
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE,
MISUSE, AND
ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS
• Concomitant use of benzodiazepines and opioids may result
in profound sedation, respiratory
depression, coma, and death. Reserve concomitant prescribing
of these drugs for patients for
whom alternative treatment options are inadequate. Limit
dosages and durations to the
minimum required. Follow patients for signs and symptoms of
respiratory depression and
sedation (see WARNINGS and PRECAUTIONS).
• The use of benzodiazepines, including Ativan, exposes
users to risks of abuse, misuse, and
addiction, which can lead to overdose or death. Abuse and
misuse of benzodiazepines
commonly involve concomitant use of other medications,
alcohol, and/or illicit substances,
which is associated with an increased frequency of
serious adverse outcomes. Before
prescribing Ativan and throughout treatment, assess each
patient’s risk for abuse, misuse, and
addiction (see WARNINGS).
• The continued use of benzodiazepines, including Ativan
may lead to clinically significant
physical dependence. The risks of dependence and
withdrawal increase with longer treatment
duration and higher daily dose. Abrupt discontinuation or
rapid dosage reduction of Ativan
after continued use may precipitate acute withdrawal
reactions, which can be life-threatening.
To reduce the risk of withdrawal reactions, use a gradual
taper to discontinue Ativan or reduce
the dosage (DOSAGE AND ADMINISTRATION and
WARNINGS).
5
Warnings and Precautions
Warnings
(Newly
added information)
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
ADMINSTRATION: 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).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Information for Patients
(Newly
added information)
Advise the patient
to read the FDA-approved patient labeling (Medication Guide).
Risks from Concomitant Use with Opioids
Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when Ativan
is used with opioids
and not to use such drugs concomitantly unless supervised by a health care provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid
have been determined (see WARNINGS: Risks from Concomitant Use of Opioids and PRECAUTIONS: Drug Interactions).
Abuse,
Misuse, and Addiction
Inform patients that the use of Ativan even at recommended doses, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose
and death, especially when used in combination with other medications (e.g., opioid analgesics), alcohol, and/or illicit substances. Inform
patients about the
signs and symptoms
of benzodiazepine abuse, misuse,
and addiction; to 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).
Medication Guide
(Extensive
changes; please refer to label)
Approved Drug Label (PDF)
Boxed Warning
(New section added)
WARNING: RISKS FROM
CONCOMITANT USE WITH OPIOIDS
Concomitant use of
benzodiazepines and opioids may result in profound sedation, respiratory
depression, coma, and death.
· Reserve concomitant
prescribing of these drugs for use in patients for whom alternative treatment
options are inadequate.
· Limit dosages and
durations to the minimum required.
· Follow patients for
signs and symptoms of respiratory depression and sedation.
5
Warnings and Precautions
WARNINGS
(additions underlined)
Concomitant use of
benzodiazepines, including Ativan, and opioids may result in profound sedation,
respiratory depression, coma, and death. Because of these risks, reserve
concomitant prescribing of these drugs for use in patients for whom alternative
treatment options are inadequate.
Observational studies
have demonstrated that concomitant use of opioid analgesics and benzodiazepines
increases the risk of drug-related mortality compared to use of opioids alone.
If a decision is made to prescribe Ativan concomitantly with opioids, prescribe
the lowest effective dosages and minimum durations of concomitant use, and
follow patients closely for signs and symptoms of respiratory depression and
sedation. In patients already receiving an opioid analgesic, prescribe a lower
initial dose of Ativan than indicated in the absence of an opioid and titrate
based on clinical response. If an opioid is initiated in a patient already
taking Ativan, prescribe a lower 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.
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.
7
Drug Interactions
(additions underlined)
Clinically
Significant Drug Interactions
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 GABAA 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. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation
.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(Newly added; please refer to label)