PAROXETINE (Page 7 of 9)

14.5 Generalized Anxiety Disorder

The effectiveness of paroxetine in the treatment of generalized anxiety disorder (GAD) was demonstrated in two 8-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients with GAD (DSM-IV).

Study 1 was an 8-week study comparing fixed doses of paroxetine 20 mg or 40 mg daily with placebo. Doses of paroxetine 20 mg or 40 mg were both demonstrated to be statistically significantly superior to placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score.

There was not sufficient evidence in this study to suggest a greater benefit for the paroxetine 40 mg daily dose compared to the 20 mg daily dose.

Study 2 was a flexible-dose study comparing paroxetine 20 mg to 50 mg daily and placebo. Paroxetine demonstrated statistically significant superiority over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score.

A third study, a flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo, did not demonstrate statistically significant superiority of paroxetine over placebo on the Hamilton Rating Scale for Anxiety (HAM-A) total score, the primary outcome.

Subgroup analyses did not indicate differences in treatment outcomes as a function of race or gender. There were insufficient elderly patients to conduct subgroup analyses on the basis of age.

In a long-term trial, 566 patients meeting DSM-IV criteria for GAD, who had responded during a single-blind, 8-week acute treatment phase with paroxetine 20 mg to 50 mg daily, were randomized to continuation of paroxetine at their same dose, or to placebo, for up to 24 weeks of observation for relapse. Response during the single-blind phase was defined by having a decrease of ≥2 points compared to baseline on the CGI-Severity of Illness scale, to a score of ≤3. Relapse during the double-blind phase was defined as an increase of ≥2 points compared to baseline on the CGI- Severity of Illness scale to a score of ≥4, or withdrawal due to lack of efficacy. Patients continuing to receive paroxetine experienced a statistically significantly lower relapse rate over the subsequent 24 weeks compared to those receiving placebo.

14.6 Posttraumatic Stress Disorder

The effectiveness of paroxetine in the treatment of Posttraumatic Stress Disorder (PTSD) was demonstrated in two 12-week, multicenter, placebo-controlled studies (Studies 1 and 2) of adult outpatients who met DSM-IV criteria for PTSD. The mean duration of PTSD symptoms for the 2 studies combined was 13 years (ranging from 0.1 year to 57 years). The percentage of patients with secondary MDD or non-PTSD anxiety disorders in the combined 2 studies was 41% (356 out of 858 patients) and 40% (345 out of 858 patients), respectively. Study outcome was assessed by (1) the Clinician-Administered PTSD Scale Part 2 (CAPS-2) score and (2) the Clinical Global Impression-Global Improvement Scale (CGI-I). The CAPS-2 is a multi-item instrument that measures 3 aspects of PTSD with the following symptom clusters: Reexperiencing/intrusion, avoidance/numbing and hyperarousal. The 2 primary outcomes for each trial were (1) change from baseline to endpoint on the CAPS-2 total score (17 items), and (2) proportion of responders on the CGI-I, where responders were defined as patients having a score of 1 (very much improved) or 2 (much improved).

Study 1 was a 12-week study comparing fixed doses of paroxetine 20 mg or 40 mg daily to placebo. Doses of paroxetine 20 mg and 40 mg were demonstrated to be statistically significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I. There was not sufficient evidence in this study to suggest a greater benefit for the 40 mg daily dose compared to the 20 mg daily dose. Study 2 was a 12-week flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo. Paroxetine was demonstrated to be significantly superior to placebo on change from baseline for the CAPS-2 total score and on proportion of responders on the CGI-I.

A third study, a flexible-dose study comparing paroxetine 20 mg to 50 mg daily to placebo, demonstrated paroxetine to be statistically significantly superior to placebo on change from baseline for CAPS-2 total score, but not on proportion of responders on the CGI-I.

The majority of patients in these trials were women (68% women: 377 out of 551 subjects in Study 1 and 66% women: 202 out of 303 subjects in Study 2). Subgroup analyses did not indicate differences in treatment outcomes as a function of gender. There were an insufficient number of patients who were 65 years and older or were non-Caucasian to conduct subgroup analyses on the basis of age or race, respectively.

16 HOW SUPPLIED/STORAGE AND HANDLING

Paroxetine tablets, USP are oval shaped film-coated tablets supplied as:

Tablet Strength Color Engraved Descriptors Package Configuration NDC Number
10 mg White to off-white Engraved “APO” & partial bisect score on one side,“097” on the other. Bottles of 30 NDC 60429-734-30
10 mg White to off-white Engraved “APO” & partial bisect score on one side,“097” on the other Bottles of 90 NDC 60429-734-90
10 mg White to off-white Engraved “APO” & partial bisect score on one side,“097” on the other Bottles of 1000 NDC 60429-734-10
20 mg White to off-white Engraved “APO” & partial bisect score on one side,“083” on the other Bottles of 30 NDC 60429-735-30
20 mg White to off-white Engraved “APO” & partial bisect score on one side,“083” on the other Bottles of 90 NDC 60429-735-90
20 mg White to off-white Engraved “APO” & partial bisect score on one side,“083” on the other Bottles of 1000 NDC 60429-735-10
30 mg White to off-white Engraved “APO” on one side & “084” on the other side Bottles of 30 NDC 60429-736-30
30 mg White to off-white Engraved “APO” on one side & “084” on the other side Bottles of 90 NDC 60429-736-90
30 mg White to off-white Engraved “APO” on one side & “084” on the other side Bottles of 1000 NDC 60429-736-10
40 mg White to off-white Engraved “APO” on one side & “101” on the other side Bottles of 30 NDC 60429-737-30
40 mg White to off-white Engraved “APO” on one side & “101” on the other side Bottles of 90 NDC 60429-737-90
40 mg White to off-white Scored, “APO” on one side and “101” on the other side Bottles of 1000 NDC 660429-737-10

Store tablets between 20°C and 25°C (68°F and 77°F) excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behaviors

Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [see Boxed Warning and Warnings and Precautions ( 5.1)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of paroxetine with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, 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). Instruct patients to contact their healthcare provider or report to the emergency room if they
experience signs or symptoms of serotonin syndrome [see Warnings and Precautions ( 5.2), Drug Interactions ( 7)].

Concomitant Medications

Advise patients to inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for drug-drug interactions [see Warning and Precautions ( 5.3), Drug Interactions ( 7)].

Increased Risk of Bleeding

Inform patients about the concomitant use of paroxetine with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the counter medications that increase the risk of bleeding [see Warnings and Precautions ( 5.5)].

Activation of Mania/Hypomania

Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [see Warnings and Precautions ( 5.6)].

Discontinuation Syndrome

Advise patients not to abruptly discontinue paroxetine and to discuss any tapering regimen with their healthcare provider. Inform patients that adverse reactions can occur when paroxetine is discontinued [see Warnings and Precautions ( 5.7)].

Sexual Dysfunction

Advise patients that use of paroxetine 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)].

Allergic Reactions

Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing
[see Adverse Reactions ( 6.1, 6.2)].

Embryo-Fetal Toxicity

Advise women of the potential risk to the fetus [see Warnings and Precautions ( 5.4), Use in Specific Populations ( 8.1)]. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy
because of the risk to the fetus.

Nursing

Advise women to notify their healthcare provider if they are breastfeeding an infant [see Use In Specific Populations ( 8.3)].

Dispense with Medication Guide available at www1.apotex.com/products/us

APOTEX INC.

PAROXETINE TABLETS, USP

10 mg, 20 mg, 30 mg and 40 mg

Manufactured by: Manufactured for:
Apotex Inc. Apotex Corp.
Toronto, Ontario Weston, Florida
Canada M9L 1T9 USA 33326

Revised: November 2021

Revision : 16

Marketed/Packaged by:

GSMS, Inc.

Camarillo, CA USA 93012

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