Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Suicidal
Behavior and Ideation
Additions and/or
revisions underlined:
Antiepileptic drugs (AEDs), including pregabalin,
the active ingredient in LYRICA CR, increase the risk of suicidal thoughts or
behavior in patients taking these drugs for any indication. Suicidal behavior
and ideation have also been reported in patients after discontinuation of
pregabalin [see Warnings and Precautions
(5.4)]. Monitor patients treated with any AED for any indication for the
emergence or worsening of depression, suicidal thoughts or behavior, and/or any
unusual changes in mood or behavior.
. . .
5.4 Increased Risk
of Adverse Reactions with Abrupt or Rapid Discontinuation
Newly added
subsection
Following
abrupt or rapid discontinuation of LYRICA CR, some patients reported symptoms
including, insomnia, nausea, headache, anxiety, and diarrhea [see Adverse Reactions (6.2), Drug Abuse and
Dependence (9.3)]. Suicidal behavior and ideation have also been reported
in patients after discontinuation of pregabalin [see Warnings and Precautions (5.3)]. Increased seizure frequency
may occur in patients with seizure disorders taking LYRICA CR for pain if
LYRICA CR is rapidly discontinued. Taper LYRICA CR gradually over a minimum of
1 week rather than discontinuing the drug abruptly. The efficacy of LYRICA CR
as adjunctive therapy for adult patients with partial onset seizures has not
been established.
6
Adverse Reactions
6.2 Postmarketing
Experience
Additions and/or
revisions underlined:
. . .
There are postmarketing reports of withdrawal
symptoms after discontinuation of pregabalin. Reported adverse reactions
include, but are not limited to, seizures, depression, suicidal ideation and
behavior, agitation, confusion, disorientation, psychotic symptoms, anxiety,
insomnia, nausea, pain, sweating, tremor, headache, dizziness, malaise, and
diarrhea.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or
revisions underlined:
. . .
Risk Summary
Observational studies on the use of Lyrica CR during
pregnancy suggest a possible small increase in the rate of overall major birth
defects, but there was no consistent or specific pattern of major birth defects
identified (see Data). Available
postmarketing data on miscarriage and other maternal, fetal, and long term
developmental adverse effects were insufficient to identify risk associated
with pregabalin.
Postmarketing data suggest that extended
gabapentinoid use with opioids close to delivery may increase the risk of
neonatal withdrawal versus opioids alone (see
Clinical Considerations).
There are no comparative epidemiologic studies
evaluating this association. Therefore, it is not known whether exposure to
pregabalin alone late in pregnancy may cause withdrawal signs and symptoms.
. . .
The estimated background risk of major birth defects
and miscarriage for the indicated populations are 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
Neonatal withdrawal syndrome has been reported in
newborns exposed to gabapentinoids in utero for an extended period of time when
also exposed to opioids close to delivery. Neonatal withdrawal signs and
symptoms reported have included tachypnea, vomiting, diarrhea, hypertonia,
irritability, sneezing, poor feeding, hyperactivity, abnormal sleep pattern,
and tremor. Reported signs and symptoms that may also be related to withdrawal
include tongue thrusting, wandering eye movements while awake, back arching, and
continuous extremity movements.
Observe neonates exposed to LYRICA CR and opioids
for signs and symptoms of neonatal withdrawal and manage accordingly.
. . .
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions and/or
revisions underlined:
.
. .
Suicidal
Thinking and Behavior
Counsel
patients, their caregivers, and families that AEDs, including pregabalin, the
active ingredient in LYRICA CR, may increase the risk of suicidal thoughts and
behavior and should be advised of the need to be alert for the emergence or
worsening of symptoms of depression, any unusual changes in mood or behavior,
or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Instruct patients, caregivers, and families to report behaviors of concern
immediately to a healthcare provider. Also inform patients who plan to or
have
discontinued
LYRICA CR that suicidal thoughts and behavior can appear even after the drug is
stopped [see Warnings and Precautions
(5.3)].
.
. .
Use
in Pregnancy
Instruct
patients to inform their healthcare provider if they are pregnant or
intend to become pregnant during therapy, and to notify their physician if they
are breast feeding or intend to breast feed during therapy [see Use in Specific Populations (8.1) and (8.2)].
Encourage
patients
to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry
if they become pregnant. This registry is collecting information about the
safety of antiepileptic drugs during pregnancy. To enroll, patients can call
the toll-free number 1-888-233- 2334 [see
Use in Specific Populations (8.1)].
.
. .
MEDICATION GUIDE
Additions and/or
revisions underlined:
.
. .
Like other
antiepileptic drugs, LYRICA CR may
cause suicidal thoughts or actions in a very small number of people, about 1 in
500. This can happen while you take LYRICA CR or after stopping.
. . .
Approved Drug Label (PDF)
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions underlined)
…
Risk Summary
Observational studies
on the use of Lyrica CR during
pregnancy suggest a possible small
increase in the rate of overall major birth defects, but there
was no consistent or specific pattern of major birth defects identified (see
Data). Available postmarketing data on miscarriage and other maternal, fetal,
and long term developmental adverse effects were insufficient to identify risk
associated with pregabalin.
…
Data
Human
Data
One database study, which included over 2,700 pregnancies exposed to
pregabalin (monotherapy) during the first trimester compared
to 3,063,251 pregnancies unexposed to antiepileptics demonstrated prevalence ratios for major malformations overall of
1.14 (CI 95% 0.96-1.35) for pregabalin, 1.29 (CI 95% 1.01-1.65) for lamotrigine,
1.39 (CI 95% 1.07-1.82) for duloxetine, and 1.24 (CI 95% 1.00-1.54) for
exposure to either lamotrigine or duloxetine. Important study limitations include uncertainty of whether women who filled
a prescription took the medication and inability to adequately control
for the underlying disease and other potential confounders.
A published
study included results
from two separate
databases. One database, which included 353 pregnancies
exposed to pregabalin (monotherapy) during the first trimester compared to
368,489 pregnancies unexposed to antiepileptics, showed no increase in risk of major birth defects; adjusted relative risk 0.87 (CI
95% 0.53-1.42). The second database, which included 118 pregnancies
exposed to pregabalin (monotherapy) during the first trimester compared to
380,347 pregnancies unexposed to antiepileptics, suggested a small increase in
risk of major birth defects; adjusted relative risk 1.26 (CI 95% 0.64-2.49).
The risk estimates crossed the null, and the study had limitations similar to
the prior study.
Other
published epidemiologic studies
reported inconsistent findings.
No specific pattern
of birth defects
was identified across studies. All of the studies had limitations due to
their retrospective design.
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Respiratory Depression
(Newly added subsection)
There
is evidence from case reports, human studies, and animal studies associating
pregabalin with serious, life- threatening, or fatal respiratory depression
when co-administered with central nervous system (CNS) depressants, including
opioids, or in the setting of underlying respiratory impairment. When the
decision is made to co-prescribe LYRICA CR with another CNS depressant, particularly
an opioid, or to prescribe LYRICA CR to patients with underlying respiratory
impairment, monitor patients for symptoms of respiratory depression and
sedation, and consider initiating LYRICA CR at a low dose. The management of
respiratory depression may include close observation, supportive measures, and
reduction or withdrawal of CNS depressants (including LYRICA CR).
There
is more limited evidence from case reports, animal studies, and human studies
associating pregabalin with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.
6
Adverse Reactions
(Additions and/or revisions underlined)
The
following adverse reactions are described elsewhere in the labeling:
Angioedema
Hypersensitivity
Reactions
Suicidal
Behavior and Ideation
Respiratory Depression
Dizziness and Somnolence
Risks Associated with Abrupt or
Rapid Discontinuation
Peripheral Edema
6.2
Postmarketing
Experience with LYRICA
(Additions and/or revisions underlined)
The following adverse reactions have been identified
during post-approval use of LYRICA. These adverse reactions have not been
listed above and data are insufficient to support an estimate of their
incidence or to establish causation. The listing is alphabetized: breast
enlargement, bullous pemphigoid, gynecomastia.
There
are postmarketing reports of life-threatening or fatal respiratory depression
in patients taking pregabalin with opioids or other CNS depressants,
or in the setting of underlying respiratory impairment.
In
addition, there are postmarketing reports of events related to reduced lower
gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus,
constipation) when LYRICA was co-administered with medications that have the
potential to produce constipation, such as opioid analgesics.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions
underlined)
(Additions and/or revisions underlined)
Respiratory Depression
Inform
patients about the risk of respiratory depression. Include information that the
risk is greatest for those using concomitant central nervous system (CNS)
depressants (such as opioid analgesics) or in those with underlying respiratory
impairment. Teach patients how to recognize respiratory depression and advise
them to seek medical attention immediately if it occurs.
CNS Depressants
Inform patients who require concomitant treatment with central nervous
system depressants such as opiates or benzodiazepines that they may experience
additive CNS side effects, such as respiratory depression, somnolence, and dizziness. Advise patients to avoid consuming alcohol while
taking LYRICA CR, as LYRICA CR may potentiate the impairment of motor skills
and sedating effects of alcohol.
Missed
Dose
Instruct
patients that if they miss taking their dose of LYRICA CR after an evening
meal, then they should take their usual dose of LYRICA CR prior to bedtime
following a snack. If they miss taking the dose of LYRICA CR prior to bedtime,
then they should take their usual dose of LYRICA CR following a morning meal. If
they miss taking the dose of LYRICA CR following the morning meal, then
they should take their usual dose of LYRICA CR at the usual time that evening
following an evening meal.
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