|
Information for Healthcare
Professionals
Paroxetine (marketed as Paxil)
Selective Serotonin Reuptake Inhibitors (SSRIs)
FDA ALERT [7/2006]: Increased Risk of Neonatal
Persistent Pulmonary Hypertension
A recently published case-control study has shown that
infants born to mothers who took selective serotonin reuptake
inhibitors (SSRIs) after the 20th week of pregnancy were 6 times
more likely to have persistent pulmonary hypertension (PPHN) than
infants born to mothers who did not take antidepressants during
pregnancy (see SSRI drug names at the bottom of this sheet). The
background risk of a woman giving birth to an infant affected by
PPHN in the general population is estimated to be about 1 to 2
infants per 1000 live births. Neonatal PPHN is associated with
significant morbidity and mortality. The FDA is updating the
prescribing information for all SSRIs with this new information.
The FDA is also accruing data from additional sources pertaining
to the potential association between SSRIs and neonatal PPHN. The
FDA will provide additional information when it becomes
available. In the interim, the FDA recommends that physicians
carefully consider and discuss with patients the potential risks
and benefits of SSRI treatment throughout pregnancy, including
late pregnancy.
This information reflects
FDA’s current analysis of data available to FDA concerning these
drugs. FDA intends to update this sheet when additional
information or analyses become available.
To report any unexpected adverse or serious
events associated with the use of this drug, please contact the
FDA MedWatch program at 1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Considerations
Physicians should consider the benefits and risks of treating
pregnant women with SSRIs, alternative treatments, or no treatment
late in pregnancy.
Data Summary
A retrospective case-control study published on February 9, 2006, in
the New England Journal of Medicine assessed the risk for persistent
pulmonary hypertension of the newborn (PPHN) following exposure to
SSRIs during pregnancy. 377 women whose infants were born with PPHN
and 836 women whose infants were healthy were enrolled in the study
in four United States metropolitan areas between 1998 and 2003. The
study showed that infants born to mothers who took SSRIs after the
completion of the 20th week of gestation were 6 times more likely to
have PPHN than infants who were not exposed to antidepressants
during pregnancy. 14 infants with PPHN and 6 healthy control infants
had been exposed to an SSRI after the 20th week of gestation. There
were too few cases of PPHN with each individual SSRI to compare
risks for PPHN with individual SSRIs. The study did not find an
association between exposure to SSRIs during the first 20 weeks of
gestation and PPHN.
Exposure to non-SSRI antidepressants did not appear to be associated
with an increased risk of PPHN, although the number of infants with
exposure to non-SSRI antidepressants was too small to permit a
reliable risk estimate or comparison with the risk observed for
SSRIs.
In weighing the risks and benefits of treatment with SSRIs and other
antidepressants during pregnancy for individual patients, physicians
should also note the recent publication of a prospective
longitudinal study of 201 pregnant women with a history of major
depression in the February 1, 2006, issue of JAMA. In this study,
women who discontinued antidepressant medication during pregnancy
had a higher risk of relapse of major depression during pregnancy
(68%) than women who maintained antidepressant medication throughout
pregnancy (26%).
SSRI Drug Names
- Celexa (citalopram)
- Fluvoxamine
- Lexapro (escitalopram)
- Paxil (paroxetine)
- Prozac (fluoxetine)
- Symbyax (olanzepine/fluoxetine)
- Zoloft (sertraline)
Information for Healthcare
Professionals
Paroxetine (marketed as Paxil)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
5-Hydroxytryptamine Receptor Agonists (Triptans)
FDA ALERT [7/2006]: Potentially Life-Threatening
Serotonin Syndrome with Combined Use of SSRIs or SNRIs and Triptan
Medications
There is the potential for life-threatening serotonin
syndrome (a syndrome of changes in mental status, autonomic
instability, neuromuscular abnormalities, and gastrointestinal
symptoms) in patients taking 5-hydroxytryptamine receptor agonists
(triptans) and selective serotonin reuptake inhibitors (SSRIs) or
selective serotonin/norepinephrine reuptake inhibitors (SNRIs)
concomitantly (see drug names at the bottom of this sheet). This
information is based on reports of serotonin syndrome occurring in
patients treated with triptans and SSRIs/SNRIs, and the biological
plausibility of such a reaction in persons receiving two
serotonergic medications. The FDA recommends that patients treated
concomitantly with a triptan and an SSRI/SNRI be informed of the
possibility of serotonin syndrome (which may be more likely to
occur when starting or increasing the dose of an SSRI, SNRI, or
triptan) and be carefully followed.
This information reflects
FDA’s current analysis of data available to FDA concerning these
drugs. FDA intends to update this sheet when additional
information or analyses become available.
To report any unexpected adverse or serious
events associated with the use of this drug, please contact the
FDA MedWatch program at 1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Considerations
- Weigh the potential risk of concomitant SSRI/SNRI and
triptan use with the benefit expected from using each drug,
prior to prescribing these drugs together.
- When prescribing an SSRI or a triptan, physicians should
discuss the possibility of serotonin syndrome with patients if
an SSRI and a triptan will be used concomitantly. Healthcare
providers should keep in mind that triptans are often used
intermittently, and that the SSRI, SNRI, or triptan may be
prescribed by a different healthcare provider.
- Healthcare providers should be alert to the highly variable
signs and symptoms of serotonin syndrome. Serotonin syndrome
symptoms may include mental status changes (e.g., agitation,
hallucinations, coma), autonomic instability (e.g., tachycardia,
labile blood pressure, hyperthermia), neuromuscular aberrations
(e.g. hyperreflexia, incoordination) and/or gastrointestinal
symptoms (e.g., nausea, vomiting, diarrhea).
- If concomitant treatment with an SSRI or SNRI and triptan is
clinically warranted, the patient should be carefully observed,
particularly during treatment initiation and dose increases.
Data Summary
The FDA has reviewed 27 reports of serotonin syndrome reported in
association with concomitant SSRI or SNRI and triptan use. Two
reports described life-threatening events and 13 reports stated
that the patients required hospitalization. Some of the cases
occurred in patients who had previously used concomitant SSRIs or
SNRIs and triptans without experiencing serotonin syndrome. The
reported signs and symptoms of serotonin syndrome were highly
variable and included respiratory failure, coma, mania,
hallucinations, confusion, dizziness, hyperthermia, hypertension,
sweating, trembling, weakness, and ataxia. In 8 cases, recent dose
increases or addition of another serotonergic drug to an SSRI/triptan
or SNRI/triptan combination were temporally related to symptom
onset. The median time to onset subsequent to the addition of
another serotonergic drug or dose increase of a serotonergic drug
was 1 day, with a range of 10 minutes to 6 days.
Serotonin syndrome following concomitant SSRI or SNRI and triptan
use is biologically plausible. SSRIs, SNRIs, and triptans
independently increase serotonin levels. Therefore, it is expected
that concomitant use of SSRIs or SNRIs and triptans would result
in higher serotonin levels than the serotonin levels observed with
the use of SSRIs, SNRIs, or triptans alone, potentially leading to
serotonin syndrome.
SSRIs
and a Combination
Drug Containing an SSRI |
SNRIs |
Triptans |
- Celexa (citalopram)
- Fluvoxamine
- Lexapro (escitalopram)
- Paxil (paroxetine)
- Prozac (fluoxetine)
- Symbyax (olanzapine/fluoxetine)
- Zoloft (sertraline)
|
- Cymbalta (duloxetine)
- Effexor (venlafaxine)
|
- Amerge (naratriptan)
- Axert (almotriptan)
- Frova (frovatriptan)
- Imitrex (sumatriptan)
- Maxalt and Maxalt-MLT (rizatriptan)
- Relpax (eletriptan
- Zomig and Zomig ZMT(zolmitriptan)
|
Additional Information
http://www.fda.gov/cder/drug/antidepressants/default.htm
Report serious adverse events to
FDA’s MedWatch reporting system by completing a form on line at
http://www.fda.gov/medwatch/report.htm, by faxing
(1-800-FDA-0178),
by mail using the postage-paid address form provided online
(5600 Fishers Lane, Rockville, MD 20852-9787),
or by telephone (1-800-FDA-1088).
Back
to Top
Back to Paroxetine
Date created: May 2005, updated July 19, 2006 |
|