FDA

Paroxetine Hydrochloride

Approved 2 Nov 2021OralTablet

The FDA lists this product in 60 strengths and forms.

Indications

1 INDICATIONS AND USAGE Paroxetine is 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) Paroxetine is a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of (1): Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD)

Contraindications

4 CONTRAINDICATIONS Paroxetine is 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)] . Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI. (4, 5.3, 7) Concomitant use of pimozide or thioridazine. (4, 5.3,7) Known hypersensitivity to paroxetine or to any of the inactive ingredients in paroxetine tablets.

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Warnings and precautions

5 WARNINGS AND PRECAUTIONS Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If occurs, discontinue paroxetine and initiate supportive measures. (5.2) Embryofetal and Neonatal Toxicity : Can cause fetal and neonatal harm. Increased risk of cardiovascular malformations with exposure during the first trimester. Exposure in late pregnancy may lead to an increased risk for persistent pulmonary hypertension of the newborn.

(5.4, 8.1) Increased Risk of Bleeding : Concomitant use of aspirin, nonsteroidal anti- inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. (5.5) Activation of Mania/Hypomania : Screen patients for bipolar disorder. (5.6) Seizures : Use with caution in patients with seizure disorders. (5.8) Angle-Closure Glaucoma : Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.

At a glance

Brand name: Paroxetine Hydrochloride
Route: Oral
Dosage form: Tablet
Applicant: Yiling
Status: Prescription
FDA approval: 2 Nov 2021
Application: ANDA211248-002

Indications

Contraindications

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Warnings and precautions

Interactions

7 DRUG INTERACTIONS Table 9 presents clinically significant drug interactions with paroxetine. Table 9: Clinically Significant Drug Interactions with Paroxetine Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including paroxetine, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.5),Contraindications (4), Warnings and Precautions (5.2)] .

Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Pimozide and Thioridazine Clinical Impact Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. Intervention Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications (4)] .

Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with paroxetine increases the risk of serotonin syndrome. Intervention Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2)] .

Examples other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort. Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) Clinical Impact The concurrent use of an antiplatelet agent or anticoagulant with paroxetine may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of paroxetine and antiplatelet agents and anticoagulants.

For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions (5.5)] . Examples aspirin, clopidogrel, heparin, warfarin Drugs Highly Bound to Plasma Protein Clinical Impact Paroxetine is highly bound to plasma protein. The concomitant use of paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of paroxetine or other tightly-bound drugs in plasma.

Intervention Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine is CYP2D6 inhibitor [see Clinical Pharmacology (12.3)] . The concomitant use of paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. Intervention Decrease the dosage of a CYP2D6 substrate if needed with concomitant paroxetine use.

Conversely, an increase in dosage of a CYP2D6 substrate may be needed if paroxetine is discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen Intervention Consider use of an alternative antidepressant with little or no CYP2D6 inhibition [see Warnings and Precautions (5.11)] .

Fosamprenavir/Ritonavir Clinical Impact Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. Intervention Any dose adjustment should be guided by clinical effect (tolerability and efficacy). Drugs Highly Bound to Plasma Protein : Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted. (7) Drugs Metabolized by CYP2D6 : Reduce dosage of drugs metabolized by CYP2D6 as warranted.

(7) Concomitant use with tamoxifen : Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. (5.11, 7)

Adverse reactions

6 ADVERSE REACTIONS The following adverse reactions are included in more detail in other sections of the prescribing information: Hypersensitivity reactions to paroxetine [see Contraindications (4)] Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1)] Serotonin Syndrome [see Warnings and Precautions (5.2)] Embryofetal and Neonatal Toxicity [see Warnings and Precautions (5.4)] Increased Risk of Bleeding [see Warnings and Precautions ( 5.5 )] Activation of Mania/Hypomania [see Warnings and Precautions (5.6)] Discontinuation Syndrome [see Warnings and Precautions (5.7)] Seizures [see Warnings and Precautions (5.8)] Angle-closure Glaucoma [see Warnings and Precautions (5.9)] Hyponatremia [see Warnings and Precautions (5.10)] Bone Fracture [see Warnings and Precautions (5.12)] Sexual Dysfunction [see Warnings and Precautions (5.13)] Most common adverse reactions (≥5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn.

(6) To report SUSPECTED ADVERSE REACTIONS, contact Yiling Pharmaceutical, Inc. at 1-877-736-5697 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data for paroxetine are from: 6-week clinical trials in MDD patients who received paroxetine 20 mg to 50 mg once daily 12-week clinical trials in OCD patients who received paroxetine 20 mg to 60 mg once daily 10- to 12-week clinical trials in PD patients who received paroxetine 10 mg to 60 mg once daily 12-week clinical trials in SAD patients who received paroxetine 20 mg to 50 mg once daily 8-week clinical trials in GAD patients who received paroxetine 10 mg to 50 mg once daily 12-week clinical trials in PTSD patients who received paroxetine 20 mg to 50 mg once daily Adverse Reactions Leading to Discontinuation Twenty percent (1,199/6,145) of patients treated with paroxetine in clinical trials in MDD and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and 11.7% (79/676) of patients treated with paroxetine in clinical trials in SAD, OCD, PD, GAD, and PTSD, respectively, discontinued treatment due to an adverse reaction.

The most common adverse reactions (≥1%) associated with discontinuation (i.e., those adverse reactions associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) are presented in Table 3: Table 3: Adverse Reactions Reported as Leading to Discontinuation ( ≥ 1% of Paroxetine- Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials MDD OCD PD SAD GAD PTSD Paroxetine % Placebo % Paroxetine % Placebo % Paroxetine % Placebo % Paroxetine % Placebo % Paroxetine % Placebo % Paroxetine % Placebo % CNS Somnolence 2.3 0.7 — 1.9 0.3 3.4 0.3 2.0 0.2 2.8

0.6 Insomnia — — 1.7 0 1.3 0.3 3.1 0 — — Agitation 1.1 0.5 — — — Tremor 1.1 0.3 — 1.7 0 1.0

0.2 Anxiety — — — 1.1 0 — — Dizziness — — 1.5 0 1.9 0 1.0 0.2 — — Gastroin- testinal Constipation — 1.1 0 — — Nausea 3.2 1.1 1.9 0 3.2 1.2 4.0 0.3 2.0 0.2 2.2

0.6Diarrhea 1.0

0.3 — Dry mouth 1.0 0.3 — — — Vomiting 1.0 0.3 — 1.0 0 — — Flatulence 1.0 0.3 — — Other Asthenia 1.6 0.4 1.9 0.4 2.5 0.6 1.8 0.2 1.6

0.2Abnormal Ejaculationa a 1.6 0 2.1 0 4.9 0.6 2.5

0.5 — — Sweating 1.0 0.3 — 1.1 0 1.1 0.2 — — Impotencea a — 1.5 0 — — Libido Decreased 1.0 0 — — Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not >1% or was not greater than or equal to 2 times the incidence of placebo. a. Incidence corrected for gender. Most Common Adverse Reactions The most commonly observed adverse reactions associated with the use of paroxetine (incidence of 5% or greater and at least twice that for placebo) were: MDD: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.

OCD : Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation. PD: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence. SAD: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.

GAD: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation. PTSD: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence. Adverse Reactions in Patients with MDD Table 4 presents the adverse reactions that occurred at an incidence of 1% or more and greater than placebo in clinical trials of paroxetine-treated patients with MDD.

Table 4: Adverse Reactions ( ≥ 1% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD Body System/ Adverse Reaction Paroxetine (n = 421) % Placebo (n = 421) % Body as a Whole Headache 18 17 Asthenia 15 6 Cardiovascular Palpitation 3 1 Vasodilation 3 1 Dermatologic Sweating 11 2 Rash 2 1 Gastrointestinal Nausea 26 9 Dry Mouth 18 12 Constipation 14 9 Diarrhea 12 8 Decreased Appetite 6 2 Flatulence 4 2 Oropharynx Disorder a 2 0 Dyspepsia 2 1 Musculoskeletal Myopathy 2 1 Myalgia 2 1 Myasthenia 1 0 Nervous System Somnolence 23 9 Dizziness 13 6 Insomnia 13 6 Tremor 8 2 Nervousness 5 3 Anxiety 5 3 Paresthesia 4 2 Libido Decreased 3 0 Drugged Feeling 2 1 Confusion 1 0 Respiration Yawn 4 0 Special Senses Blurred Vision 4 1 Taste Perversion 2 0 Urogenital System Ejaculatory Disturbance b,c 13 0 Other Male Genital Disorders b,d 10 0 Urinary Frequency 3 1 Urination Disorder e 3 0 Female Genital Disorders b,f 2 0 a.

Includes mostly “lump in throat” and “tightness in throat.” b. Percentage corrected for gender. c. Mostly “ejaculatory delay.” d. Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction,” and “impotence.” e. Includes mostly “difficulty with micturition” and “urinary hesitancy.” f. Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm.” Adverse Reactions in Patients with OCD, PD, and SAD Table 5 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD, PD, and SAD.

Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA

Paroxetine Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Paroxetine Hydrochloride

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.2Serotonin Syndrome

Interactions

Adverse reactions

6.1Clinical Trials Experience

0.6Diarrhea 1.0

0.2Abnormal Ejaculationa a 1.6 0 2.1 0 4.9 0.6 2.5

Composition

Strengths and forms

Official product information