Approved Drug Label (PDF)
5
Warnings and Precautions
5.4 Embryofetal Toxicity
Additions and revisions underlined:
Based on
meta-analyses of epidemiological studies, exposure to paroxetine in
the first trimester of pregnancy is associated with a less than 2-fold
increase in the rate of cardiovascular malformations among infants. For women who intend to become pregnant
or who are in their
first trimester of pregnancy, PAXIL, should be initiated only after consideration of the
other available treatment options [see
Use in Specific Populations (8.1)].
8
Use in Specific Populations
8.1 Pregnancy
PLLR conversion; please refer to label
8.2 Lactation
Newly added subsection:
Risk Summary
Data from the published
literature report the presence of paroxetine in human milk (see Data). There are reports of agitation, irritability, poor feeding and poor weight
gain in infants exposed to paroxetine
through breast milk (see Clinical
Considerations). There are no data on the effect of paroxetine on milk
production. The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for Paxil and any potential adverse effects on
the breastfed child from Paxil or from underlying maternal condition.
Clinical Considerations
Infants exposed
to PAXIL should be monitored for agitation, irritability, poor feeding and poor weight gain.
Data
Published literature
suggests the presence of paroxetine in human milk with relative infant doses
ranging between 0.4% to 2.2%, and a milk/plasma ratio of <1. No significant
amounts were detected in the plasma of infants after breastfeeding.
8.3 Females and Males of Reproductive Potential
Newly added subsection:
Infertility
Male
Based on findings from clinical studies, paroxetine
may affect sperm quality which may impair fertility; it is not known if this
effect is reversible [see Nonclinical
Toxicology (13.1)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
Newly added information:
o
Taking PAXIL during your first trimester of pregnancy may cause your
baby to be at an increased risk of having a heart problem (cardiac
malformations) at birth.
o
Taking PAXIL during your third trimester of pregnancy may cause your
baby to have breathing, temperature, and feeding problems, low muscle
tone, and irritability after birth and may cause your baby to be at an increased risk of a serious lung problem at birth.
o
There is a pregnancy registry for females who are exposed to PAXIL during
pregnancy. The purpose of the registry is to collect information about the health
of females exposed
to PAXIL and their baby. If you become pregnant
during treatment with PAXIL talk to your healthcare provider about registering with the
National Pregnancy Registry for Antidepressants at 1-866-961-2388 or visit
online at
https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Serotonin Syndrome
Additions
and revisions underlined:
SSRIs, including PAXIL, can precipitate serotonin
syndrome, a potentially life-threatening condition. The risk is increased
with concomitant use of other
serotonergic drugs (including triptans, tricyclic
antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan,
buspirone, amphetamines and St.
John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7.1)].
5.5 Increased Risk of Bleeding
Newly
added information:
Based on data from the
published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated
with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)].
6
Adverse Reactions
6.2 Postmarketing Experience
Additions
and revisions underlined:
The following reactions have been identified during
post approval use of PAXIL. Because
these reactions are reported
voluntarily from a population of unknown size, it is not always
possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.
Acute pancreatitis, elevated liver function tests
(the most severe
cases were deaths
due to liver necrosis, and grossly elevated transaminases associated
with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome,
toxic epidermal necrolysis, drug reaction with eosinophilia and systemic
symptoms (DRESS), syndrome of inappropriate ADH secretion, prolactinemia and
galactorrhea; extrapyramidal symptoms which have included akathisia,
bradykinesia, cogwheel rigidity, oculogyric crisis which has been associated
with concomitant use of pimozide; status epilepticus, acute renal failure,
pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis,
eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome
(RLS), ventricular fibrillation, ventricular tachycardia (including torsade de
pointes), hemolytic anemia, events related to impaired hematopoiesis (including
aplastic anemia, pancytopenia, bone marrow aplasia,
and agranulocytosis), vasculitic syndromes (such as Henoch-Schönlein purpura), and
premature births in pregnant women.
7
Drug Interactions
Drug Interactions
Addition of opioids and amphetamines to table 9
8
Use in Specific Populations
8.1 Pregnancy
Newly
added information:
Risk Summary
Based on data from published observational studies, exposure
to SSRIs, particularly in the month before delivery, has been
associated with a less than 2-fold increase in the risk of postpartum
hemorrhage [see Warnings and Precautions
(5.5) and Clinical Considerations].
Maternal Adverse
Reactions
Use of PAXIL
in the month before delivery
may be associated with an increased risk of
postpartum hemorrhage [see Warnings and
Precautions (5.5)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
Additions
and revisions underlined:
Especially tell your healthcare provider if you take:
tramadol, fentanyl, meperidine, methadone, or other opioids
PATIENT COUNSELING INFORMATION
Additions
and revisions underlined:
Caution patients about the risk of
serotonin syndrome, particularly with the concomitant use of PAXIL with other
serotonergic drugs including triptans, tricyclic antidepressants, opioids,
lithium, tryptophan, buspirone, amphetamines, St. John’s Wort, and with drugs
that impair metabolism of serotonin (in particular, MAOIs, both those
intended to treat
psychiatric disorders and also
others, such as linezolid).
Approved Drug Label (PDF)
5
Warnings and Precautions
5.13 Sexual Dysfunction
(Newly added
subsection)
Use
of SSRIs, including PAXIL, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)]. In male
patients, SSRI use may result in ejaculatory delay or failure, decreased
libido, and erectile dysfunction. In female patients, SSRI use may result in
decreased libido and delayed or absent orgasm. It is important for prescribers
to inquire about sexual function prior to initiation of PAXIL and to inquire
specifically about changes in sexual function during treatment, because sexual
function may not be spontaneously reported. When evaluating changes in sexual
function, obtaining a detailed history (including timing of symptom onset) is
important because sexual symptoms may have other causes, including the
underlying psychiatric disorder. Discuss potential management strategies to
support patients in making informed decisions about treatment.
6
Adverse Reactions
(Addition of the
following to the bulleted line listing)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(Additions and/or
revisions underlined)
…
Sexual problems
(dysfunction). Taking selective serotonin reuptake inhibitors
(SSRIs), including PAXIL, may cause sexual problems.
Symptoms
in males may include:
- Problems getting or
keeping an erection
Symptoms
in females may include:
Decreased sex
drive
Delayed orgasm or
inability to have an orgasm
Talk
to your healthcare provider if you develop any changes in your sexual function
or if you have any questions or concerns about sexual problems during treatment
with PAXIL. There may be treatments your healthcare provider can suggest.
…
PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
…
Sexual
Dysfunction
Advise patients that use of PAXIL may cause
symptoms of sexual dysfunction in both male and female patients. Inform
patients that they should discuss any changes in sexual function and potential
management strategies with their healthcare provider [see Warnings and Precautions
(5.13)].
…
Approved Drug Label (PDF)
5
Warnings and Precautions
Serotonin Syndrome:
Additions
and/or revisions underlined:
The development of a potentially
life-threatening serotonin syndrome has been reported with SNRIs and SSRIs,
including PAXIL alone but particularly with concomitant use of other
serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl,
lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s
Wort) …
If concomitant use
of PAXIL with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan,
amphetamines and
St. John’s Wort is clinically warranted
…
7
Drug Interactions
Additions
and/or revisions underlined:
Serotonergic Drugs: Based
on the mechanism of
action of paroxetine
and the potential for
serotonin syndrome, caution is advised when
paroxetine is
coadministered with other drugs or agents that
may
affect the serotonergic neurotransmitter systems,
such as triptans, linezolid (an
antibiotic which is a reversible
non-selective MAOI),
lithium, fentanyl, tramadol, amphetamines, or St. John’s Wort.