Paroxetine: Package Insert and Label Information

PAROXETINE- paroxetine hydrochloride tablet, film coated
Preferred Pharmaceuticals Inc.

BOXED WARNING

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)]. Paroxetine is not approved for use in pediatric patients [see Use in Specific Populations (8.4)].

1. INDICATIONS AND USAGE

Paroxetine tablets are indicated in adults for the treatment of:

Major depressive disorder (MDD)
Obsessive compulsive disorder (OCD)
Panic disorder (PD)
Social anxiety disorder (SAD)
Generalized anxiety disorder (GAD)
Posttraumatic stress disorder (PTSD)

2. DOSAGE AND ADMINISTRATION

2.1 Administration Information

Administer paroxetine tablets as a single daily dose in the morning, with or without food.

2.2 Recommended Dosage for MDD, OCD, PD, and PTSD

The recommended starting dosages and maximum dosages of paroxetine tablets in patients with MDD, OCD, PD, and PTSD are presented in Table 1.

In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability.

Table 1 Recommended Daily Dosage of Paroxetine Tablets in Patients with MDD, OCD, PD, and PTSD

Indication

Starting Dose

Maximum Dose

MDD

20 mg

50 mg

OCD

20 mg

60 mg

PD

10 mg

60 mg

PTSD

20 mg

50 mg

2.3 Recommended Dosage for SAD and GAD

SAD

The starting and recommended dosage in patients with SAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets was demonstrated in patients dosed in a range of 20 mg to 60 mg daily.

While the safety of paroxetine tablets has been evaluated in patients with SAD at doses up to 60 mg daily, available information does not suggest any additional benefit for doses above 20 mg daily [see Clinical Studies (14.4)].

GAD

The starting and recommended dosage in patients with GAD is 20 mg daily. In clinical trials the effectiveness of paroxetine tablets in GAD was demonstrated in patients dosed in a range of 20 mg to 50 mg daily. There is not sufficient evidence to suggest a greater benefit to doses higher than 20 mg daily [see Clinical Studies (14.5)].

In patients with an inadequate response, increase dosage in increments of 10 mg per day at intervals of at least 1 week, depending on tolerability.

2.4 Screen for Bipolar Disorder Prior to Starting Paroxetine Tablets

Prior to initiating treatment with paroxetine 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 Recommended Dosage for Elderly Patients, Patients with Severe Renal Impairment, and Patients with Severe Hepatic Impairment

The recommended initial dosage is 10 mg per day for elderly patients, patients with severe renal impairment, and patients with severe hepatic impairment. Dosage should not exceed 40 mg/day.

2.6 Switching Patients to or from a Monoamine Oxidase Inhibitor (MAOI)

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

2.7 Discontinuation of Treatment with Paroxetine Tablets

Adverse reactions may occur upon discontinuation of paroxetine tablets [see Warnings and Precautions (5.7)]. Gradually reduce the dosage rather than stopping paroxetine abruptly whenever possible.

3. DOSAGE FORMS AND STRENGTHS

Paroxetine tablets, USP are available as:

10 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of ‘ZC, 15 and bisect’ on one side and plain on other side
20 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of ‘ZC, 16 and bisect’ on one side and plain on other side
30 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of ‘ZC17’ on one side and plain on other side
40 mg: White to off-white, round-shaped, biconvex, film- coated tablets debossed with the logo of ‘ZC18’ on one side and plain on other side

4. CONTRAINDICATIONS

Paroxetine 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) and 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 any of the inactive ingredients in paroxetine 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 1,000 patients treated are provided in Table 2.

Table 2 Risk Differences of the Number of Patients with 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 with Suicidal Thoughts and Behaviors per 1,000 Patients Treated

Increases Compared to Placebo

< 18 years old

14 additional cases

18 years to 24 years old

5 additional cases

Decreases Compared to Placebo

25 years to 64 years old

1 fewer case

≥ 65 years old

6 fewer cases

Paroxetine is not approved for use in pediatric 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, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

5.2 Serotonin Syndrome

SSRIs, including paroxetine, 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, 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)]. Serotonin syndrome can also occur when these drugs are used alone.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The concomitant use of paroxetine with MAOIs is contraindicated. In addition, do not initiate paroxetine in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking paroxetine discontinue paroxetine before initiating treatment with the MAOI [see Contraindications (4), Drug Interactions (7)].

Monitor all patients taking paroxetine for the emergence of serotonin syndrome. Discontinue treatment with paroxetine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of paroxetine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

5.3 Drug Interactions Leading to QT Prolongation

The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. Since thioridazine and pimozide given alone produce prolongation of the QTc interval and increase the risk of serious ventricular arrhythmias, the use of paroxetine is contraindicated in combination with thioridazine and pimozide [see Contraindications (4), Drug Interactions (7), Clinical Pharmacology (12.3)].

5.4 Embryofetal and Neonatal Toxicity

Paroxetine can cause fetal harm when administered to a pregnant woman. Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy have an increased risk of cardiovascular malformations. Exposure to paroxetine in late pregnancy may lead to an increased risk for persistent pulmonary hypertension of the newborn (PPNH) and/or neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding.

If paroxetine is used during pregnancy, or if the patient becomes pregnant while taking paroxetine, the patient should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

5.5 Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including paroxetine, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.

5.6 Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with paroxetine or another antidepressant may precipitate a mixed/manic episode. During controlled clinical trials of paroxetine, hypomania or mania occurred in approximately 1% of paroxetine-treated unipolar patients compared to 1.1% of active-control and 0.3% of placebo-treated unipolar patients. Prior to initiating treatment with paroxetine, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.

5.7 Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration (2.7)].

During clinical trials of GAD and PTSD, gradual decreases in the daily dose by 10 mg/day at weekly intervals followed by 1 week at 20 mg/day was used before treatment was discontinued. The following adverse reactions were reported at an incidence of 2% or greater for paroxetine and were at least twice that reported for placebo: Abnormal dreams, paresthesia, and dizziness. Adverse reactions have been reported upon discontinuation of treatment with paroxetine in pediatric patients. The safety and effectiveness of paroxetine in pediatric patients have not been established [see Boxed Warning, Warnings and Precautions (5.1), Use in Specific Populations (8.4)].

5.8 Seizures

Paroxetine tablets have not been systematically evaluated in patients with seizure disorders. Patients with history of seizures were excluded from clinical studies. During clinical studies, seizures occurred in 0.1% of patients treated with paroxetine. Paroxetine should be prescribed with caution in patients with a seizure disorder. Discontinue paroxetine in any patient who develops seizures.

DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.