PAROXETINE- paroxetine hydrochloride hemihydrate tablet, film coated, extended release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PAROXETINE HYDROCHLORIDE (UNII: X2ELS050D8) (PAROXETINE - UNII:41VRH5220H)

Available from:

Rhodes Pharmaceuticals L.P.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Paroxetine Extended-Release Tablets, USP are indicated in adults for the treatment of: - Major depressive disorder (MDD) - Panic disorder (PD) - Social anxiety disorder (SAD) - Premenstrual dysphoric disorder (PMDD) Paroxetine Extended-Release Tablets are contraindicated in patients: - Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2), Drug Interactions (7)]. - Taking thioridazine because of risk of QT prolongation [see Warnings and Precautions (5.3), Drug Interactions (7)] . - Taking pimozide because of risk of QT prolongation [see Warnings and Precautions (5.3), Drug Interactions (7)] . - With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or to any of the inactive ingredients in Paroxetine Extended-Release Tablets [see Adverse Reactions (6.1, 6.2)] . 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]. Paroxetine Extended-Release Tablets are associated with a less than 2-fold increase in cardiovascular malformations when administered to a pregnant woman during the first trimester. While individual epidemiological studies on the association between paroxetine use and cardiovascular malformations have reported inconsistent findings, some meta-analyses of epidemiological studies have identified an increased risk of cardiovascular malformations (see Data). There are risks of persistent pulmonary hypertension of the newborn (PPHN) (see Data) and/or poor neonatal adaptation with exposure to selective serotonin reuptake inhibitors (SSRIs), including Paroxetine Extended-Release Tablets, during pregnancy. There also are risks associated with untreated depression in pregnancy (see Clinical Considerations). For women who intend to become pregnant or who are in their first trimester of pregnancy, paroxetine should be initiated only after consideration of the other available treatment options. No evidence of treatment related malformations was observed in animal reproduction studies, when paroxetine was administered during the period of organogenesis at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m2 basis. When paroxetine was administered to female rats during the last trimester of gestation and continued through lactation, there was an increase in the number of pup deaths during the first four days of lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis (see Data). The estimated background risks 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 US 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 Disease-associated maternal and/or embryo/fetal risk Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants. This finding is from a prospective longitudinal study of 201 pregnant women with a history of major depressive disorder who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum. Maternal Adverse Reactions Use of Paroxetine Extended-Release Tablets in the month before delivery may be associated with an increased risk of postpartum hemorrhage [see Warnings and Precautions (5.5)]. Fetal/Neonatal adverse reactions Neonates exposed to Paroxetine Extended-Release Tablets and other SSRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, jitteriness, irritability, and constant crying. These findings are consistent with either a direct toxic effect of SSRIs or possibly a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions (5.4)] . Data Human Data Published epidemiological studies on the association between first trimester paroxetine use and cardiovascular malformations have reported inconsistent results; however, meta-analyses of population-based cohort studies published between 1996-2017 indicate a less than 2-fold increased risk for overall cardiovascular malformations. Specific cardiac malformations identified in two meta-analyses include approximately 2 to 2.5-fold increased risk for right ventricular outflow tract defects. One meta-analysis also identified an increased risk (less than 2- fold) for bulbus cordis anomalies and anomalies of cardiac septal closure, and an increased risk for atrial septal defects (pooled OR 2.38, 95% CI 1.14-4.97). Important limitations of the studies included in these meta-analyses include potential confounding by indication, depression severity, and potential exposure misclassification. Exposure to SSRIs, particularly later in pregnancy, may have an increased risk for PPHN. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Animal Data Reproduction studies were performed at doses up to 50 mg/kg/day in rats and 6 mg/kg/day in rabbits administered during organogenesis. These doses are approximately 6 (rat) and less than 2 (rabbit) times the maximum recommended human dose (MRHD – 75 mg) on an mg/m2 basis. These studies have revealed no evidence of malformations. However, in rats, there was an increase in pup deaths during the first 4 days of lactation when dosing occurred during the last trimester of gestation and continued throughout lactation. This effect occurred at a dose of 1 mg/kg/day which is less than the MRHD on an mg/m2 basis. The no-effect dose for rat pup mortality was not determined. The cause of these deaths is not known. 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 effects of paroxetine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Paroxetine Extended-Release Tablets and any potential adverse effects on the breastfed infant from Paroxetine Extended-Release Tablets or the underlying maternal condition. Clinical Considerations Infants exposed to Paroxetine Extended-Release Tablets 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. 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)] . The safety and effectiveness of Paroxetine Extended-Release Tablets in pediatric patients have not been established [see Boxed Warning, Warnings and Precautions (5.1)]. Three placebo-controlled trials in 752 pediatric patients with MDD have been conducted with immediate-release paroxetine, and effectiveness was not established in pediatric patients. Decreased appetite and weight loss have been observed in association with the use of SSRIs. In placebo-controlled clinical trials conducted with pediatric patients, the following adverse reactions were reported in at least 2% of pediatric patients treated with immediate-release paroxetine hydrochloride and at a rate at least twice that for pediatric patients receiving placebo: emotional lability (including self-harm, suicidal thoughts, attempted suicide, crying, and mood fluctuations), hostility, decreased appetite, tremor, sweating, hyperkinesia, and agitation. Adverse reactions upon discontinuation of treatment with immediate-release paroxetine hydrochloride in the pediatric clinical trials that included a taper phase regimen, which occurred in at least 2% of patients and at a rate at least twice that of placebo, were: emotional lability (including suicidal ideation, suicide attempt, mood changes, and tearfulness), nervousness, dizziness, nausea, and abdominal pain. SSRIs and SNRIs, including Paroxetine Extended-Release Tablets, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse reaction [see Warnings and Precautions (5.9)]. In premarketing clinical trials with immediate-release paroxetine hydrochloride, 17% of paroxetine treated patients (approximately 700) were 65 years or older. Pharmacokinetic studies revealed a decreased clearance in the elderly, and a lower starting dose is recommended; however, no overall differences in safety or effectiveness were observed between these subjects and younger subjects [see Dosage and Administration (2.5), Clinical Pharmacology (12.3)]. Increased plasma concentrations of paroxetine occur in patients with renal and hepatic impairment. The initial dosage of Paroxetine Extended-Release Tablets should be reduced in patients with severe renal impairment and patients with severe hepatic impairment [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)].

Product summary:

Paroxetine Extended-Release Tablets, USP are supplied as a round, extended-release tablet as follows: Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Rhodes Pharmaceuticals L.P.
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MEDICATION GUIDE
PAROXETINE (PAR OX' E TEEN)
EXTENDED-RELEASE TABLETS, USP
This Medication Guide has been approved by the U.S. Food and
Drug Administration.
Revised: 9/2023
What is the most important information I should know about Paroxetine
Extended-Release Tablets?
Paroxetine Extended-Release Tablets can cause serious side effects,
including:
•
Increased risk of suicidal thoughts or actions. Antidepressant
medicines may increase suicidal
thoughts and actions in some children and young adults within the
first few months of treatment
or when the dose is changed. Paroxetine Extended-Release Tablets are
not for use in people
younger than 18 years of age.
How can I watch for and try to prevent suicidal thoughts and actions?
•
Depression or other serious mental illnesses are the most important
causes of suicidal
thoughts and actions.
•
Pay close attention to any changes, especially sudden changes in mood,
behavior, thoughts
or feelings or if you develop suicidal thoughts or actions. This is
very important when an
antidepressant medicine is started or when the dose is changed.
•
Call your healthcare provider right away to report new or sudden
changes in mood,
behavior, thoughts or feelings or if you develop suicidal thoughts or
actions.
•
Keep all follow-up visits with your healthcare provider as scheduled.
Call your healthcare
provider between visits as needed, especially if you have concerns
about symptoms.
Call your healthcare provider or get emergency medical help right away
if you have any of the following
symptoms, especially if they are new, worse, or worry you:
•
attempts to commit suicide
•
acting aggressive or violent
•
new or worse depression
•
feeling agitated, restless, angry, or irritable
•
an increase in activity and talking more than
what is normal for you
•
acting on dangerous impulses
•
thoughts about suicide or dying
•
new or worse anxiety or panic attacks
•
trouble sleeping
•
other unusual changes in behavior or mood
What are Par

Summary of Product characteristics

PAROXETINE- PAROXETINE HYDROCHLORIDE HEMIHYDRATE TABLET, FILM COATED,
EXTENDED RELEASE
RHODES PHARMACEUTICALS L.P.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PAROXETINE EXTENDED-
RELEASE TABLETS, USP SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR PAROXETINE
EXTENDED-RELEASE TABLETS, USP.
PAROXETINE EXTENDED-RELEASE TABLETS, USP FOR ORAL USE
INITIAL U.S. APPROVAL: 1992
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED RISK OF SUICIDAL THOUGHTS AND BEHAVIOR IN PEDIATRIC AND
YOUNG ADULT PATIENTS
TAKING ANTIDEPRESSANTS. CLOSELY MONITOR ALL ANTIDEPRESSANT-TREATED
PATIENTS FOR CLINICAL
WORSENING AND EMERGENCE OF SUICIDAL THOUGHTS AND BEHAVIORS. PAROXETINE
EXTENDED-
RELEASE TABLETS ARE NOT APPROVED FOR USE IN PEDIATRIC PATIENTS. (5.1,
8.4)
RECENT MAJOR CHANGES
Warnings and Precautions (5.2, 5.4, 5.5)
8/2023
INDICATIONS AND USAGE
Paroxetine Extended-Release Tablets are a selective serotonin reuptake
inhibitor (SSRI) indicated in adults
for the treatment of (1):
Major Depressive Disorder (MDD)
Panic Disorder (PD)
Social Anxiety Disorder (SAD)
Premenstrual Dysphoric Disorder (PMDD)
DOSAGE AND ADMINISTRATION
Swallow tablet whole; do not chew or crush. (2.1)
Recommended starting and maximum daily dosage: (2.2, 2.3)
INDICATION
STARTING DOSE
MAXIMUM DOSE
MDD
25 mg/day
62.5 mg/day
PD
12.5 mg/day
75 mg/day
SAD
12.5 mg/day
37.5 mg/day
PMDD
12.5 mg/day
25 mg/day
For PMDD, dose continuously or intermittently (luteal phase only).
(2.3)
If inadequate response to starting dosage, titrate in 12.5 mg per day
increments once weekly. (2.2, 2.3)
Elderly patients, patients with severe renal impairment or severe
hepatic impairment: Starting dose is
12.5 mg per day. Do not exceed 50 mg per day for treatment of MDD and
PD and 37.5 mg per day for
treatment of SAD. (2.5)
When discontinuing Paroxetine Extended-Release Tablets, reduce dose
gradually. (2.7)
DOSAGE FORMS AND STRENGTHS
Extended-release