PAROXETINE

Paroxetine Extended-Release Tablets, USP contain 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 hemihydrate and has the empirical formula of C 19 H 20 FNO 3 ∙HCl∙1/2H 2 O. The molecular weight is 374.8 g/mol (329.4 g/mol as free base). The structural formula of paroxetine hydrochloride is: Paroxetine hydrochloride is an odorless, off-white powder, having a melting point range of 120°C to 138°C and a solubility of 5.4 mg/mL in water. Each enteric coated, extended-release tablet contains paroxetine base of 12.5 mg (white tablet), 25 mg (brown tablet), 37.5 mg (orange tablet), which is equivalent to 14.25 mg, 28.51 mg, or 42.76 mg of paroxetine hydrochloride, respectively. Each tablet consists of a hydrophilic matrix that contains the active material. Inactive ingredients consist of carboxymethylcellulose sodium, copovidone, glyceryl monostearate, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid – ethyl acrylate copolymer (1:1), polysorbate 80, silicon dioxide, sodium lauryl sulfate, talcum, titanium dioxide, and triethyl citrate. In addition, the 25 mg tablets also contain the following coloring agents: iron oxide black and iron oxide red and the 37.5 mg tablets contain iron oxide red and iron oxide yellow. USP dissolution test is pending. Chemical Structure

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) Paroxetine Extended-Release Tablets are a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of ( 1 ): Major Depressive Disorder (MDD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Premenstrual Dysphoric Disorder (PMDD)

Swallow tablet whole; do not chew or crush. ( 2.1 ) Recommended starting and maximum daily dosage: ( 2.2 , 2.3 ) Indication Starting Dose Maximum Dose MDD 25 mg/day 62.5 mg/day PD 12.5 mg/day 75 mg/day SAD 12.5 mg/day 37.5 mg/day PMDD 12.5 mg/day 25 mg/day For PMDD, dose continuously or intermittently (luteal phase only). ( 2.3 ) If inadequate response to starting dosage, titrate in 12.5 mg per day increments once weekly. ( 2.2 , 2.3 ) Elderly patients, patients with severe renal impairment, or severe hepatic impairment: Starting dose is 12.5 mg per day. Do not exceed 50 mg per day for treatment of MDD and PD and 37.5 mg per day for treatment of SAD. ( 2.5 ) When discontinuing Paroxetine Extended-Release Tablets, reduce dose gradually. ( 2.7 ) 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 37.5 mg 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 (5.7) ]. Gradually reduce the dosage rather than stopping Paroxetine Extended-Release Tablets abruptly whenever possible.

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) ] . Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOIs. ( 4 , 5.2 , 7 ) Concomitant use of pimozide or thioridazine. ( 4 , 5.3 , 7 ) Known hypersensitivity to paroxetine or to any of the inactive ingredients in Paroxetine Extended-Release Tablets. ( 4 )

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 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) in placebo-controlled MDD, PD, SAD, and PMDD clinical trials: abnormal ejaculation, abnormal vision, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, insomnia, libido decreased, nausea, somnolence, sweating, tremor. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rhodes Pharmaceuticals at 1-888-827-0616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical 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. Safety data for Paroxetine Extended-Release Tablets is from 11 short-term, placebo-controlled clinical trials including 3 studies in patients with major depressive disorder (MDD) (Studies 1, 2, and 3), 3 studies in patients with panic disorder (PD) (Studies 4, 5, and 6), 1 study in patients with social anxiety disorder (SAD) (Study 7), and 4 studies in female patients with premenstrual dysphoric disorder (PMDD) (Studies 8, 9, 10, and 11) [see Clinical Studies (14) ] . These 11 trials included 1627 patients treated with Paroxetine Extended-Release Tablets. Studies 1 and 2 were 12-week studies that enrolled patients 18 to 65 years old who received Paroxetine Extended-Release Tablets at doses ranging from 25 mg to 62.5 mg once daily. Study 3 was a 12-week study in patients 60 to 88 years old who received Paroxetine Extended-Release Tablets at doses ranging from 12.5 mg to 50 mg once daily. Studies 4, 5, and 6 were 10-week studies in patients 19 to 72 years old who received Paroxetine Extended-Release Tablets at doses ranging from 12.5 mg to 75 mg once daily. Study 7 was a 12-week study that enrolled adult patients who received Paroxetine Extended-Release Tablets at doses ranging from 12.5 mg to 37.5 mg once daily. Studies 8, 9, and 10 were 12-week, placebo-controlled trials in female patients 18 to 46 years old who received Paroxetine Extended-Release Tablets at doses of 12.5 mg or 25 mg once daily. Study 11 was a 12-week placebo-controlled trial in patients 18 to 46 years old who received Paroxetine Extended-Release Tablets 2 weeks prior to the onset of menses (luteal phase dosing) at doses of 12.5 mg or 25 mg once daily. Adverse Reactions Leading to Discontinuation in Patients with MDD, PD, SAD, and PMDD In pooled studies in patients with MDD, PD and SAD, the most common adverse reactions leading to study withdrawal were: nausea (up to 4% of patients), asthenia, headache, depression, insomnia, and abnormal liver function tests (each occurring in up to 2% of patients), and dizziness, somnolence, and diarrhea (each occurring in up to 1% of patients). In pooled studies for PMDD, the most common adverse reactions leading to study withdrawal were: nausea (occurring in up to 6% of patients), asthenia (occurring in up to 5% of patients), somnolence (occurring in up to 4% of patients), insomnia (occurring in approximately 2% of patients); and impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, yawn, and diarrhea (occurring in less than or equal to 2% of patients). Adverse Reactions in MDD, PD, and SAD Table 3 presents the most common adverse reactions in Paroxetine Extended-Release Tablets-treated patients (incidence ≥5% and greater than placebo within at least 1 of the indications) in controlled trials in patients with MDD, PD, and SAD. Table 3. Adverse Reactions (≥5% of Patients Treated with Paroxetine Extended-Release Tablets and Greater than Placebo) in 10 to 12 Week Studies of MDD, PD, and SAD MDD 18 to 65 year olds MDD ≥60 years old Panic Disorder Social Anxiety Disorder Body System/Adverse Reaction Paroxetine Extended-Release Tablets (N=212) % Placebo (N=211) % Paroxetine Extended-Release Tablets (N=104) % Placebo (N=109) % Paroxetine Extended-Release Tablets (N=444) % Placebo (N=445) % Paroxetine Extended-Release Tablets (N=186) % Placebo (N=184) % Hyphen = the reaction listed occurred in <5% of patients treated with Paroxetine Extended-Release Tablets NA = the adverse reaction listed did not occur in this group of patients Body as a Whole Headache 27 20 17 13 NA NA 23 17 Asthenia 14 9 15 14 15 10 18 7 Abdominal Pain 7 4 - - 6 4 5 4 Back Pain 5 3 - - NA NA 4 1 Digestive System Nausea 22 10 - - 23 17 22 6 Diarrhea 18 7 15 9 12 9 9 8 Dry Mouth 15 8 18 7 13 9 3 2 Constipation 10 4 13 5 9 6 5 2 Flatulence 6 4 - - NA NA NA NA Decreased Appetite 2 12 5 8 6 1 <1 Dyspepsia NA NA 13 10 NA NA 2 <1 Musculoskeletal System Myalgia NA NA - - 5 3 NA NA Nervous System Somnolence 22 8 21 12 20 9 9 4 Insomnia 17 9 10 8 20 11 9 4 Dizziness 14 4 9 5 NA NA 7 4 Libido Decreased 7 3 8 <1 9 4 1 Nervousness NA NA - - 8 7 NA NA Tremor 7 1 7 0 8 2 4 2 Anxiety NA NA - - 5 4 2 1 Respiratory System Sinusitis NA NA - - 8 5 NA NA Yawn 0 - - 3 0 2 0 Skin and Appendages Sweating 6 2 10 <1 7 2 14 3 Special Senses Abnormal Vision Mostly blurred vision 5 1 - - 3 <1 2 0 Urogenital System Abnormal Ejaculation Based on the number of males or females , Mostly anorgasmia or delayed ejaculation 26 1 17 3 27 3 15 1 Female Genital Disorder , Mostly anorgasmia or delayed orgasm 10 <1 - - 7 1 3 0 Impotence 5 3 9 3 10 1 9 0 Other Adverse Reactions Observed During the Premarketing Evaluation of Paroxetine Extended-Release Tablets Adverse reactions from studies in MDD (not including Study 3 in elderly patients), PD, and SAD that occurred between 1% and 5% of patients treated with Paroxetine Extended-Release Tablets and at a rate greater than in placebo-treated patients include: allergic reaction, tachycardia, vasodilatation, hypertension, migraine, vomiting, weight loss, weight gain, hypertonia, paresthesia, agitation, confusion, myoclonus, concentration impaired, depression, rhinitis, cough increased, bronchitis, photosensitivity, eczema, taste perversion, UTI, menstrual disorder, urinary frequency, urination impaired, and vaginitis. Adverse Reactions in Patients with PMDD Table 4 displays adverse reactions that occurred (incidence of 5% or more and greater than placebo within at least 1 of the studies) in patients treated with Paroxetine Extended-Release Tablets in Studies 8, 9, 10, and 11. Table 4. Adverse Reactions (≥5% of Patients Treated with Paroxetine Extended-Release Tablets and Greater than Placebo) in Pooled Studies PMDD (Studies 8, 9, 11), and in Study 10 <1% means greater than zero and less than 1%. , The luteal phase and continuous dosing PMDD trials were not designed for making direct comparisons between the 2 dosing regimens. , Mostly anorgasmia or difficulty achieving orgasm. Body System/Adverse Reaction % Reporting Adverse Reaction Continuous Dosing Studies 8, 9, and 10 Luteal Phase Dosing Study 11 Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo (n = 681) % (n = 349) % (n = 246) % (n = 120) % NA= the adverse reaction information is not available in this population. Body as a Whole Asthenia 17 6 15 4 Headache 15 12 NA NA Infection 6 4 NA NA Digestive System Nausea 17 7 18 2 Diarrhea 6 2 6 0 Constipation 5 1 2 <1 Nervous System Libido Decreased 12 5 9 6 Somnolence 9 2 3 <1 Insomnia 8 2 7 3 Dizziness 7 3 6 3 Tremor 4 <1 5 0 Skin and Appendages Sweating 7 <1 6 <1 Urogenital System Female Genital Disorders 8 1 2 0 Dose Dependent Adverse Reactions Comparison of the incidence of adverse reactions (placebo vs. 12.5 mg Paroxetine Extended-Release Tablets vs. 25 mg Paroxetine Extended-Release Tablets) from studies 8, 9, 10 showed the following adverse reactions to be dose-related: nausea, somnolence, sweating, dry mouth, dizziness, decreased appetite, tremor, impaired concentration, yawn, paresthesia, hyperkinesia, and vaginitis. Male and Female Sexual Dysfunction Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. The percentage of patients reporting symptoms of sexual dysfunction in the Studies 1 and 2 (nonelderly patients with MDD), 4, 5, 6, 7, 8, 9, 10, and 11 are presented in Table 5: Table 5. Adverse Reactions Related To Sexual Dysfunction In Patients Treated With Paroxetine Extended-Release Tablets in Pooled 10-12 Week Studies of MDD, PD, SAD, and PMDD Studies 1 and 2 % Studies 4, 5, and 6 % Study 7 % Studies 8, 9, and 11 (Continuous Dosing) % Study 10 (Luteal Phase Dosing) % Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo Paroxetine Extended-Release Tablets Placebo NA = the adverse reaction listed did not occur in this group of patients. n (males) 78 78 162 194 88 97 NA NA NA NA Decreased Libido 10 5 9 6 13 1 NA NA NA NA Abnormal ejaculation 26 1 27 3 15 1 NA NA NA NA Impotence 5 3 10 1 9 0 NA NA NA NA n (females) 134 133 282 251 98 87 681 349 246 120 Decreased Libido 4 2 8 2 4 1 12 5 9 6 Orgasmic Disturbance 10 <1 7 1 3 0 8 1 2 0 Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae. Less Common Adverse Reactions The following adverse reactions occurred during the clinical studies of Paroxetine Extended-Release Tablets and are not included elsewhere in the labeling. Reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare reactions are those occurring in fewer than 1/1,000 patients. Cardiovascular System : Infrequent was postural hypotension. Hemic and Lymphatic System: Rare was thrombocytopenia. Metabolic and Nutritional Disorders: Infrequent were generalized edema and hypercholesteremia. Nervous System: Infrequent were convulsion, akathisia, and manic reaction. Psychiatric : Infrequent were hallucinations. Skin and Appendages: Frequent was rash; infrequent was urticaria; rare was angioedema and erythema multiforme. Urogenital System: Infrequent was urinary retention; rare was urinary incontinence. 6.2 Postmarketing Experience The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), priapism, syndrome of inappropriate ADH secretion (SIADH), prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anosmia, hyposmia, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic syndromes (such as Henoch-Schönlein purpura).

Drugs Highly Bound to Plasma Protein : Monitor for adverse reactions and reduce dosage of Paroxetine Extended-Release Tablets 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 ) 7.1 Clinically Significant Drug Interactions with Paroxetine Extended-Release Tablets Table 6 includes clinically significant drug interactions with Paroxetine Extended-Release Tablets Table 6: Clinically Significant Drug Interactions with Paroxetine Extended-Release Tablets Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including Paroxetine Extended-Release Tablets, and MAOIs increases the risk of serotonin syndrome. Intervention Paroxetine Extended-Release Tablets are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.6) , 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 Extended-Release Tablets are contraindicated in patients taking pimozide or thioridazine [see Contraindications (4) ]. Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with Paroxetine Extended-Release Tablets 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 Extended-Release Tablets and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ] . Examples Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, 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 Extended-Release Tablets may potentiate the risk of bleeding. Intervention Inform patients of the increased risk of bleeding associated with the concomitant use of Paroxetine Extended-Release Tablets 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 Extended-Release Tablets are highly bound to plasma protein. The concomitant use of Paroxetine Extended-Release Tablets with another drug that is highly bound to plasma protein may increase free concentrations of Paroxetine Extended-Release Tablets or other tightly-bound drugs in plasma. Intervention Monitor for adverse reactions and reduce dosage of Paroxetine Extended-Release Tablets or other protein-bound drugs as warranted. Examples warfarin Drugs Metabolized by CYP2D6 Clinical Impact Paroxetine Extended-Release Tablets are a CYP2D6 inhibitor [see Clinical Pharmacology (12.3) ] . The concomitant use of Paroxetine Extended-Release Tablets 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 Extended-Release Tablets use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Paroxetine Extended-Release Tablets are discontinued. Examples propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. Tamoxifen Clinical Impact Concomitant use of tamoxifen with Paroxetine Extended-Release Tablets may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen. Intervention Consider use of an alternative antidepressant 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).

Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].