IMPORTANT SAFETY INFORMATION
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and
behavior (suicidality) in children, adolescents, and young adults in short term
studies of major depressive disorder (MDD) and other psychiatric disorders.
Anyone considering the use of paroxetine mesylate or any other antidepressant in a
child, adolescent, or young adult must balance this risk with the clinical need.
Short-term studies did not show an increase in the risk of suicidality with
antidepressants compared to placebo in adults beyond age 24; there was a reduction
in risk with antidepressants compared to placebo in adults aged 65 and older.
Depression and certain other psychiatric disorders are themselves associated with
increases in the risk of suicide. Patients of all ages who are started on
antidepressant therapy should be monitored appropriately and observed closely for
clinical worsening, suicidality, or unusual changes in behavior. Families and
caregivers should be advised of the need for close observation and communication
with the prescriber. PEXEVA (paroxetine mesylate) is not approved for use in
pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk,
Precautions: Information for Patients, and Precautions: Pediatric Use)
Concomitant use of PEXEVA in patients taking monoamine oxidase inhibitors (MAOIs)
(or within 14 days of use of MAOIs), thioridazine, or pimozide is contraindicated and can
become life threatening. PEXEVA is also contraindicated in patients with a
hypersensitivity to paroxetine or any of the inactive ingredients in PEXEVA tablets.
Warnings and Precautions:
Clinical Worsening and Suicide Risk: All patients being treated with
antidepressants for any indication should be monitored appropriately and observed
closely for clinical worsening, suicidality, and unusual changes in behavior,
especially during the initial few months of a course of drug therapy, or at times of
dose changes, either increases or decreases.
Families and caregivers of patients being treated with PEXEVA should be alerted
about the need to monitor patients for the emergence of agitation, irritability,
unusual changes in behavior, and the other symptoms described above, as well as
the emergence of suicidality, and to report such symptoms immediately to
healthcare providers. The prescriber or healthcare professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents.
PEXEVA is not approved for use in bipolar depression. Prior to initiating treatment with
an antidepressant, patients should be adequately screened to determine the risk of them
having bipolar disorder, since PEXEVA may activate mania or hypomania.
Potential for Interaction with Monoamine Oxidase Inhibitors:
In patients receiving SSRIs in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity,
myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and
mental status changes that include extreme agitation progressing to delirium and coma.
Some cases presented with features resembling a potentially life-threatening Serotonin
Syndrome or Neuroleptic Malignant Syndrome (NMS). Paroxetine should not be used in
combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI.
Potentially life-threatening Serotonin Syndrome or Neuroleptic Malignant
Syndrome-like reactions have been reported with SNRIs and SSRIs alone, including
PEXEVA, but particularly with concomitant use of serotonergic drugs, including triptans,
with drugs that impair the metabolism of serotonin (including MAOIs), or with
antipsychotics or other dopamine antagonists. If concomitant use with a triptan is
clinically warranted, careful observation of the patient is advised, particularly during
treatment initiation and dose increases. Concomitant use of PEXEVA with serotonin
precursors (such as tryptophan) is not recommended.
Thioridazine with PEXEVA is contraindicated because elevated blood levels of
thioridazine can prolong QTc interval and contribute to arrhythmias and sudden
Usage in Pregnancy: Teratogenic Effect:
Infants exposed to paroxetine in the first
trimester of pregnancy have an increased risk of congenital malformations, particularly
cardiovascular malformations; ventricular septal defects (VSDs), atrial septal defects
(ASDs), and right ventricular outflow tract obstructions.
Neonates exposed to PEXEVA late in the third trimester have developed complications
requiring prolonged hospitalization, respiratory support, and tube feeding. Respiratory
distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting,
hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and
constant crying have been known to occur. Infants exposed to SSRIs in late pregnancy
may have an increased risk for persistent pulmonary hypertension of the newborn
For women who intend to become pregnant or are in their first trimester of pregnancy,
paroxetine should only be initiated after consideration of the other available treatment
Discontinuation of Treatment with PEXEVA®:
Patients should be monitored for
symptoms when discontinuing PEXEVA. Dysphoric mood, irritability, agitation,
dizziness, sensory disturbances (e.g. paresthesias such as electric shock sensations and
tinnitus), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and
hypomania have been seen to occur. A gradual reduction in the dose, rather than abrupt
cessation, is recommended whenever possible.
Tamoxifen: Some studies have shown that the efficacy of tamoxifen, as measured by the
risk of breast cancer relapse/mortality may be reduced when co-prescribed with
paroxetine as a result of paroxetine’s irreversible inhibition of CYP2D6. However other
studies have failed to show such a risk. When Tamoxifen is used for the treatment or
prevention of breast cancer, alternative antidepressants with little or no CYP2D6
inhibition should be considered.
Akathisia, hyponatremia, abnormal bleeding have been known to occur. Discontinuation
of PEXEVA should be considered in patients with symptomatic hyponatremia. Patients
should be cautioned about the concomitant use of PEXEVA and NSAIDs, aspirin,
warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs
that interfere with serotonin reuptake and these agents has been associated with an
increased risk of bleeding.
Mydriasis can occur and can cause acute angle closure in patients with narrow angle
glaucoma, so caution should be used when paroxetine is prescribed for patients with
narrow angle glaucoma.
As with all antidepressants, PEXEVA should be used cautiously in patients with a history
or family history of mania or hypomania, or with a history of seizure disorder.
The most common side effects (incidence of 5% or greater and incidence for paroxetine
at least twice that of placebo) that have been reported with PEXEVA include nausea, dry
mouth, constipation, decreased appetite, infection drowsiness, tremor, sweating, muscle
weakness, trouble sleeping, abnormal ejaculation, impotence, and other male genital
disorders and female genital disorders.