PAROXETINE

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

BOXED WARNING SECTION

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 tablets are not approved for use in pediatric patients [see Use in Specific Populations ( 8.4 )].

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

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

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Paroxetine tablets, USP are available as: 10 mg white to off-white, oval-shaped, biconvex, film-coated tablet engraved “APO” & partial bisect score on one side, “097” on the other. 20 mg white to off-white, oval-shaped, biconvex, film-coated tablet engraved “APO” & partial bisect score on one side, “083” on the other. 30 mg white to off-white, oval-shaped, biconvex, film-coated tablet engraved “APO” & partial bisect score on one side, “084” on the other. 40 mg white to off-white, oval-shaped, biconvex, film-coated tablet engraved “APO” & partial bisect score on one side, “101” on the other.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

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

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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 )]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

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 andventricular 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, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) 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 inplasma. 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 a CYP2D6 inhibitor [see Clinical Pharmacology ( 12.3 )]. Theconcomitant 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).

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

Human Experience Since the introduction of paroxetine in the United States, spontaneous cases of deliberate or accidental overdosage during paroxetine treatment have been reported worldwide. These include overdoses with paroxetine alone and in combination with other substances. There are reports of fatalities that appear to involve paroxetine alone. Commonly reported adverse reactions associated with paroxetine overdosage include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including torsade de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention. Overdosage Management No specific antidotes for paroxetine are known. If overdosage occurs, call your poison control center at 1-800-222-1222 for latest recommendations.

11 DESCRIPTION

DESCRIPTION SECTION

Paroxetine tablets, USP contains paroxetine hydrochloride, an SSRI. It is the hydrochloride salt of a phenylpiperidine compound identified chemically as (-)- trans -4 R -(4'-fluorophenyl)-3 S -[(3',4'- methylenedioxyphenoxy) methyl] piperidine hydrochloride anhydrous and has the empirical formula of C 19 H 20 FNO 3 ·HCl. The molecular weight is 365.8 (329.4 as free base). The structural formula of paroxetine hydrochloride is: Paroxetine hydrochloride is an odorless, off-white powder, having a melting point range of 116° to 120°C and a solubility of 5.4 mg/mL in water. Each film-coated tablet, for oral administration, contains paroxetine hydrochloride equivalent to paroxetine as follows: 10 mg; 20 mg; 30 mg; 40 mg. Inactive ingredients consist of anhydrous lactose, hydroxypropyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, sodium starch glycolate and titanium dioxide. Paroxetine tablets comply with USP Related Impurities Test 1.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Product: 50090-5566 NDC: 50090-5566-0 1 TABLET, FILM COATED in a BLISTER PACK / 32 in a BOX, UNIT-DOSE

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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 )]. 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 )]. 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: May 2021 Revision : 14

MEDICATION GUIDE

SPL MEDGUIDE SECTION

Paroxetine Tablets, USP (pa rox ' e teen) What is the most important information I should know about paroxetine tablets? Paroxetine tablets can cause serious side effects, including: Increased risk of suicidal thoughts or actions. Paroxetine tablets and other antidepressant medicines may increase suicidal thoughts and actions in some people 24 years of age and younger, especially within the first few months of treatment or when the dose is changed . Paroxetine tablets are not for use in children. Depression or other mental illnesses are the most important causes of suicidal thoughts and actions. How can I watch for and try to prevent 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 does 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 paroxetine tablets? Paroxetine tablets are the prescription medicine used in adults to treat: A certain type of depression called Major Depressive Disorder (MDD) Obsessive Compulsive Disorder (OCD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Generalized Anxiety Disorder (GAD) Posttraumatic Stress Disorder (PTSD) Do not take paroxetine tablets if you: take a monoamine oxidase inhibitor (MAOI) have stopped taking an MAOI in the last 14 days are being treated with the antibiotic linezolid or the intravenous methylene blue are taking pimozide are taking thioridazine are allergic to paroxetine or any of the ingredients in paroxetine tablets. See the end of this Medication Guide for a complete list of ingredients in paroxetine tablets. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI or one of these medicines, including the antibiotic linezolid or intravenous methylene blue. Do not start taking an MAOI for at least 14 days after you stop treatment with paroxetine tablets. Before taking paroxetine tablets, tell your healthcare provider about all your medical conditions, including if you: have heart problems have or had bleeding problems have, or have a family history of, bipolar disorder, mania or hypomania have or had seizures or convulsions have glaucoma (high pressure in the eye) have low sodium levels in your blood have bone problems have kidney or liver problems are pregnant or plan to become pregnant. paroxetine may harm your unborn baby. Talk to your healthcare provider about the risks to your unborn baby if you take paroxetine tablets during pregnancy. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with paroxetine tablets. are breastfeeding or plan to breastfeed. Paroxetine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with paroxetine tablets. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. Paroxetine tablets and some other medicines may affect each other causing possible serious side effects. Paroxetine tablets may affect the way other medicines work and other medicines may affect the way paroxetine tablets works. Especially tell your healthcare provider if you take: medicines used to treat migraine headaches called triptans tricyclic antidepressants fentanyl lithium tramadol tryptophan buspirone amphetamines St. John’s Wort medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin diuretics tamoxifen medicines used to treat mood, anxiety, psychotic, or thought disorders, including selective serontonin reuptake (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare provider can tell you if it is safe to take paroxetine tablets with your other medicines. Do not start or stop any other medicines during treatment with paroxetine tablets without talking to your healthcare provider first. Stopping paroxetine tablets suddenly may cause you to have serious side effects. See, “What are the possible side effects of paroxetine tablets?” Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine. How should I take paroxetine tablets? Take paroxetine tablets exactly as prescribed. Your healthcare provider may need to change the dose of paroxetine tablets until it is the right dose for you. Take paroxetine tablets 1 time each day in the morning. paroxetine tablets may be taken with or without food. If you take too much paroxetine tablets, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are possible side effects of paroxetine tablets? Paroxetine tablets can cause serious side effects, including: See, “What is the most important information I should know about paroxetine tablets?” Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take paroxetine tablets with certain other medicines. See, “Who should not take paroxetine tablets?” Call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of serotonin syndrome: agitation seeing or hearing things that are not real (hallucinations) confusion coma fast heart beat changes in blood pressure dizziness sweating flushing high body temperature (hyperthermia) shaking (tremors), stiff muscles, or muscle twitching loss of coordination seizures nausea, vomiting, diarrhea Eye problems (angle-closure glaucoma). Paroxetine tablets may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye . Medicine interactions. Taking paroxetine tablets with certain other medicines including thioridazine and pimozide may increase the risk of developing a serious heart problem called QT prolongation . Seizures (convulsions). Manic episodes. Manic episodes may happen in people with bipolar disorder who take paroxetine tablets. Symptoms may include: greatly increased energy severe problems sleeping racing thoughts reckless behavior unusually grand ideas excessive happiness or irritability talking more or faster than usual Discontinuation syndrome. Suddenly stopping paroxetine tablets may cause you to have serious side effects. Your healthcare provider may want to decrease your dose slowly. Symptoms may include: nausea sweating changes in your mood irritability and agitation dizziness electric shock feeling (paresthesia) tremor anxiety confusion headache tiredness problems sleeping hypomania ringing in your ears (tinnitus) seizures Low sodium levels in your blood (hyponatremia). Low sodium levels in your blood that ma...

PAROXETINE (PAROXETINE HYDROCHLORIDE) TABLET, FILM COATED

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL