PAROXETINE

PAROXETINE- paroxetine hydrochloride hemihydrate tablet, film coated, extended release
Lupin Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

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)

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions

Administer paroxetine extended-release tablets as a single daily dose in the morning, with or without food. Swallow tablets whole and do not chew or crush.

2.2 Dosage In Patients With Major Depressive Disorder, Panic Disorder, And Social Anxiety Disorder

The recommended initial dosage and maximum dosage of paroxetine extended-release tablets in patients with MDD, PD, and SAD are presented in Table 1.

In patients with an inadequate response, dosage may be increased in increments of 12.5 mg per day at intervals of at least 1 week, depending on tolerability.

Table 1: Recommended Daily Dosage Of Paroxetine Extended-Release Tablets In Patients With MDD, PD, and SAD

Indication	Starting Dose	Maximum Dose
MDD	25 mg	62.5 mg
PD	12.5 mg	75 mg
SAD	12.5 mg	37.5mg

2.3 Dosage in Patients with Premenstrual Dysphoric Disorder

The recommended starting dosage in women with PMDD is 12.5 mg per day. Paroxetine extended-release tablets may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses).

Intermittent dosing is repeated with each new cycle.

In patients with an inadequate response, the dosage may be increased to the maximum recommended dosage of 25 mg per day, depending on tolerability. Institute dosage adjustments at intervals of at least 1 week.

2.4 Screen For Bipolar Disorder Prior To Starting Paroxetine Extended-Release Tablets

Prior to initiating treatment with paroxetine extended-release tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions (5.6)].

2.5 Dosage Modifications For Elderly Patients, Patients With Severe Renal Impairment And Patients With Severe Hepatic Impairment

The recommended initial dose of paroxetine extended-release tablets is 12.5 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Reduce initial dose and increase up-titration intervals if necessary. Dosage should not exceed 50 mg per day for MDD or PD and should not exceed 37.5 mg per day for SAD [see Use in Specific Populations (8.5, 8.6)].

2.6 Switching Patients To Or From A Monoamine Oxidase Inhibitor Antidepressant

At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of paroxetine extended-release tablets. In addition, at least 14 days must elapse after stopping paroxetine extended-release tablets before starting an MAOI antidepressant [see Contraindications (4), Warnings and Precautions (5.2)].

2.7 Discontinuation Of Treatment With Paroxetine Extended-Release Tablets

Adverse reactions may occur upon discontinuation of paroxetine extended-release tablets [see Warnings and Precautions (5.6)]. Gradually reduce the dosage rather than stopping paroxetine extended-release tablets abruptly whenever possible.

3 DOSAGE FORMS AND STRENGTHS

Paroxetine extended-release tablets USP are available as:

• 12.5 mg yellow colored, round shaped, biconvex, film coated tablets imprinted with “L067” on one side and plain on other side.
• 25 mg pink colored, round shaped, biconvex, film coated tablets imprinted with “L068” on one side and plain on other side.
• 37.5 mg blue colored, round shaped, biconvex tablets imprinted with “L069” on one side and plain on other side.

4 CONTRAINDICATIONS

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)].

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2.

Table 2: Risk Differences Of The Number Of Patients Of Suicidal Thoughts And Behaviors In The Pooled Placebo-Controlled Trials Of Antidepressants In Pediatric And Adult Patients

Age Range	Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated
	Increases Compared to Placebo
<18 years old	14 additional patients
18-24 years old	5 additional patients
	Decreases Compared to Placebo
25-64 years old	1 fewer patient
≥65 years old	6 fewer patients

It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing paroxetine extended-release tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.