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PARoxetine

Pronunciation

Pronunciation

(pa ROKS e teen)

Index Terms

  • Brisdelle
  • Paroxetine HCl
  • Paroxetine Hydrochloride
  • Paroxetine Mesylate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as mesylate [strength expressed as base]:

Brisdelle: 7.5 mg [contains fd&c red #40, fd&c yellow #6 (sunset yellow)]

Suspension, Oral, as hydrochloride [strength expressed as base]:

Paxil: 10 mg/5 mL (250 mL) [contains fd&c yellow #6 aluminum lake, methylparaben, propylene glycol, propylparaben, saccharin sodium; orange flavor]

Tablet, Oral, as hydrochloride [strength expressed as base]:

Paxil: 10 mg, 20 mg [scored]

Paxil: 30 mg, 40 mg

Generic: 10 mg, 20 mg, 30 mg, 40 mg

Tablet, Oral, as mesylate [strength expressed as base]:

Pexeva: 10 mg

Pexeva: 20 mg [scored]

Pexeva: 30 mg, 40 mg

Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:

Paxil CR: 12.5 mg [contains fd&c yellow #10 aluminum lake, fd&c yellow #6 aluminum lake]

Paxil CR: 25 mg

Paxil CR: 37.5 mg [contains fd&c blue #2 aluminum lake]

Generic: 12.5 mg, 25 mg, 37.5 mg

Brand Names: U.S.

  • Brisdelle
  • Paxil
  • Paxil CR
  • Pexeva

Pharmacologic Category

  • Antidepressant, Selective Serotonin Reuptake Inhibitor

Pharmacology

Paroxetine is a selective serotonin reuptake inhibitor, chemically unrelated to tricyclic, tetracyclic, or other antidepressants; presumably, the inhibition of serotonin reuptake from brain synapse stimulated serotonin activity in the brain

Absorption

Completely absorbed following oral administration

Distribution

Vd: 8.7 L/kg (3-28 L/kg)

Metabolism

Extensively hepatic via CYP2D6 enzymes; primary metabolites are formed via oxidation and methylation of parent drug, with subsequent glucuronide/sulfate conjugation; nonlinear pharmacokinetics (via 2D6 saturation) may be seen with higher doses and longer duration of therapy. Metabolites exhibit ~2% potency of parent compound. Cmin concentrations are 70% to 80% greater in the elderly compared to nonelderly patients; clearance is also decreased.

Excretion

Urine (64%, 2% as unchanged drug); feces (36% primarily via bile, <1% as unchanged drug)

Onset of Action

Depression: The onset of action is within a week, however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment; antiobsessional and antipanic effects: Up to several weeks

Time to Peak

Capsules: Median: 6 hours (range: 3 to 8 hours)

Tablets, oral suspension: Immediate release: Mean: 5.2 to 8.1 hours

Tablets: Controlled release: 6-10 hours

Half-Life Elimination

Paxil: 21 hours; Paxil CR: 15 to 20 hours; Pexeva: 33.2 hours

Protein Binding

93% to 95%

Special Populations: Renal Function Impairment

Mean plasma concentrations increased approximately 4 times, with CrCl <30 mL/minute. Plasma concentrations increased twofold with CrCl 30-60 mL/minute. Reduce initial dosage in patients with a CrCl <30 mL/minute; no dosage adjustment is necessary with Brisdelle.

Special Populations: Hepatic Function Impairment

Twofold increase in plasma concentrations; reduce the dose in patients with severe hepatic impairment; no dosage adjustment is necessary with Brisdelle.

Special Populations: Elderly

Minimum concentrations were 70% to 80% greater than in younger patients. Reduce initial dosage; no dosage adjustment is necessary with Brisdelle.

Use: Labeled Indications

Generalized anxiety disorder (immediate release): For the treatment of generalized anxiety disorder (GAD)

Major depressive disorder (immediate and controlled release): For the treatment of major depressive disorder (MDD)

Obsessive-compulsive disorder (immediate release): For the treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD)

Panic disorder (immediate and controlled release): For the treatment of panic disorder, with or without agoraphobia

Post-traumatic stress disorder (immediate release): For the treatment of post-traumatic stress disorder (PTSD)

Premenstrual dysphoric disorder (controlled release): For the treatment of premenstrual dysphoric disorder (PMDD)

Social anxiety disorder (immediate and controlled release): For the treatment of social anxiety disorder, also known as social phobia

Vasomotor symptoms of menopause (Brisdelle only): For the treatment of moderate to severe vasomotor symptoms associated with menopause

Use: Unlabeled

Treatment of obsessive-compulsive disorder (OCD) in children

Contraindications

Concurrent use with or within 14 days of MAOIs intended to treat psychiatric disorders; initiation in patients being treated with linezolid or methylene blue IV; concomitant use with pimozide or thioridazine; hypersensitivity to paroxetine or any of its inactive ingredients; pregnancy (Brisdelle only).

Dosing: Adult

Major depressive disorder (MDD): Oral:

Paxil, Pexeva: Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day

Paxil CR: Initial: 25 mg once daily; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 62.5 mg/day

Generalized anxiety disorder (GAD) (Paxil, Pexeva): Oral: Initial: 20 mg once daily, preferably in the morning (if dose is increased, adjust in increments of 10 mg/day at 1-week intervals); doses of 20-50 mg/day were used in clinical trials, however, no greater benefit was seen with doses >20 mg.

Obsessive-compulsive disorder (OCD) (Paxil, Pexeva): Oral: Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; recommended dose: 40 mg/day; range: 20-60 mg/day; maximum dose: 60 mg/day

Panic disorder: Oral:

Paxil, Pexeva: Initial: 10 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; recommended dose: 40 mg/day; range: 10-60 mg/day; maximum dose: 60 mg/day

Paxil CR: Initial: 12.5 mg once daily; increase if needed by 12.5 mg/day at intervals of at least 1 week; maximum dose: 75 mg/day

Premenstrual dysphoric disorder (PMDD) (Paxil CR): Oral: Initial: 12.5 mg once daily in the morning; may be increased to 25 mg/day; dosing changes should occur at intervals of at least 1 week. May be given daily throughout the menstrual cycle or limited to the luteal phase.

Post-traumatic stress disorder (PTSD) (Paxil): Oral: Initial: 20 mg once daily, preferably in the morning; increase if needed by 10 mg/day increments at intervals of at least 1 week; range: 20-50 mg. Limited data suggest doses of 40 mg/day were not more efficacious than 20 mg/day.

Social anxiety disorder: Oral:

Paxil: Initial: 20 mg once daily, preferably in the morning; recommended dose: 20 mg/day; range: 20-60 mg/day; doses >20 mg may not have additional benefit

Paxil CR: Initial: 12.5 mg once daily, preferably in the morning; may be increased by 12.5 mg/day at intervals of at least 1 week; maximum dose: 37.5 mg/day

Vasomotor symptoms of menopause:

Brisdelle: 7.5 mg once daily at bedtime

Paxil CR (off-label use): 12.5-25 mg once daily (Stearns, 2003)

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4-6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA, 2010; Bauer, 2002; Haddod, 2001; NCCMH, 2010; Schatzberg, 2006; Shelton, 2001; Warner, 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of paroxetine.

Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Use with other MAO inhibitors (linezolid or IV methylene blue):

Do not initiate paroxetine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving paroxetine and potential benefits outweigh potential risks, discontinue paroxetine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume paroxetine 24 hours after the last dose of linezolid or IV methylene blue.

Dosing: Geriatric

Major depressive disorder (MDD), obsessive compulsive disorder (OCD), panic attack, social anxiety disorder:

Paxil, Pexeva: Oral: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day

Paxil CR: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Dosing: Pediatric

Obsessive-compulsive disorder (OCD) (off-label use): Children and Adolescents 7-17 years: Oral: Initial: 10 mg daily; titrate every 7-14 days in increments of 10 mg daily as necessary to a maximum of 60 mg daily; trials have typically continued for a 10- to 12-week treatment course (Geller, 2004; Rosenberg, 1999)

Social anxiety disorder (off-label use): Children and Adolescents 8-17 years: Oral: Initial: 10 mg once daily; titrate at intervals of at least 7 days in increments of 10 mg daily; maximum daily dose: 50 mg daily; trials have typically continued for a 16-week treatment course (Wagner, 2004)

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Dosing: Renal Impairment

Adults:

Brisdelle: No dosage adjustment necessary.

Paxil, Paxil CR, Pexeva:

CrCl 30-60 mL/minute: Plasma concentration is 2 times that seen in normal function. There are no dosage adjustments provided in manufacturer's labeling.

Severe impairment (CrCl <30 mL/minute): Mean plasma concentration is ~4 times that seen in normal function.

Paxil, Pexeva: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day

Paxil CR: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day

Dosing: Hepatic Impairment

Adults: In hepatic dysfunction, plasma concentration is 2 times that seen in normal function.

Brisdelle: No dosage adjustment necessary.

Paxil, Paxil CR, Pexeva:

Mild-to-moderate impairment: There are no dosage adjustments provided in manufacturer's labeling.

Severe impairment:

Paxil, Pexeva: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day

Paxil CR: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week; maximum dose: 50 mg/day

Administration

May be administered without regard to meals. Paxil, Paxil CR, and Pexeva should preferentially be administered in the morning; whereas Brisdelle is recommended to be administered at bedtime. Do not crush, break, or chew controlled-release tablets or Pexeva tablets (film-coated).

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Dietary Considerations

May be taken without regard to meals.

Storage

Capsules: Store between 20°C and 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light and humidity.

Tablets: Store immediate-release tablets between 15°C and 30°C (59°F and 86°F) and controlled-release tablets at or below 25°C (77°F).

Suspension: Store at or below 25°C (77°F).

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Consider therapy modification

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Consider therapy modification

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

Aprepitant: PARoxetine may decrease the serum concentration of Aprepitant. Aprepitant may decrease the serum concentration of PARoxetine. Monitor therapy

ARIPiprazole: PARoxetine may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of neuroleptic malignant syndrome may be increased. ARIPiprazole may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose adjustment is recommended, except when used adjunctively for depression. Consult full interaction monograph or aripiprazole prescribing information for complete details. Consider therapy modification

ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Please refer to the full interaction monograph for details concerning the recommended dose adjustments. Consider therapy modification

Asenapine: PARoxetine may enhance the QTc-prolonging effect of Asenapine. Asenapine may increase the serum concentration of PARoxetine. Consider therapy modification

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification

AtoMOXetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of AtoMOXetine. Management: Initiate atomoxetine at a reduced dose (adult doses -- patients up to 70kg: 0.5mg/kg/day; patients 70kg or more: 40mg/day) in patients receiving a strong CYP2D6 inhibitor. Consider therapy modification

Beta-Blockers: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Sotalol. Monitor therapy

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with a strong CYP2D6 inhibitor; this recommendation does not apply if treating major depressive disorder. Reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a CYP3A4 inhibitor. Consider therapy modification

BuPROPion: May enhance the adverse/toxic effect of PARoxetine. BuPROPion may increase the serum concentration of PARoxetine. Monitor therapy

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

CarBAMazepine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of CarBAMazepine. Specifically those SSRIs that inhibit CYP3A4 isoenzymes. CarBAMazepine may increase the metabolism of Selective Serotonin Reuptake Inhibitors. Specifically those agents metabolized via CYP1A2, 2C, and/or 3A4 isoenzymes. Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Consider therapy modification

Clarithromycin: May enhance the adverse/toxic effect of PARoxetine. Clarithromycin may enhance the QTc-prolonging effect of PARoxetine. Monitor therapy

CloZAPine: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of CloZAPine. Management: Reduce the dose of clozapine by one-third of the original dose when adding fluvoxamine; return to the original clozapine dose when fluvoxamine is removed. Routine dose-adjustment is not recommended for other SSRIs, but increased monitoring is warranted. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Codeine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Consider therapy modification

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

CYP2D6 Substrates: CYP2D6 Inhibitors (Strong) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Ajmaline; Dapoxetine; Tamoxifen; Timolol (Ophthalmic); Tropisetron. Consider therapy modification

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May decrease the serum concentration of PARoxetine. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Consider therapy modification

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Avoid combination

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to strong CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

DULoxetine: May enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. PARoxetine may increase the serum concentration of DULoxetine. Management: Coadminister with caution. If duloxetine and paroxetine are used in combination, monitor for signs and symptoms of serotonin toxicity/serotonin syndrome, as well as other toxic effects of duloxetine. Consider therapy modification

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy

Fosamprenavir: May decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect. Monitor therapy

Fosaprepitant: PARoxetine may decrease serum concentrations of the active metabolite(s) of Fosaprepitant. Fosaprepitant may decrease the serum concentration of PARoxetine. Monitor therapy

Galantamine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Galantamine. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

HYDROcodone: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Monitor therapy

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Iloperidone: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Management: Reduce iloperidone dose by half when administered with a strong CYP2D6 inhibitor. Consider therapy modification

Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Iobenguane I 123: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

MAO Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Mexiletine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Mexiletine. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Monitor therapy

Nicergoline: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MMDL metabolite may be increased. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Nicergoline. Specifically, concentrations of the MDL metabolite may be decreased. Monitor therapy

NSAID (COX-2 Inhibitor): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). NSAID (COX-2 Inhibitor) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

NSAID (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification

Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Avoid combination

Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Avoid combination

Pravastatin: May enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Monitor therapy

Propafenone: PARoxetine may increase the serum concentration of Propafenone. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, strong CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Avoid combination

Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Monitor therapy

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Tetrabenazine adult dose should be reduced by 50% when starting a strong CYP2D6 inhibitor. Maximum tetrabenazine adult dose is 50 mg/day when used with a strong CYP2D6 inhibitor. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Monitor therapy

Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

TraMADol: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of TraMADol. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of TraMADol. CYP2D6 Inhibitors (Strong) may increase the serum concentration of TraMADol. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tricyclic Antidepressants: PARoxetine may enhance the adverse/toxic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with paroxetine. Consider therapy modification

Tropisetron: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tropisetron. Monitor therapy

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vortioxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with a strong CYP2D6 inhibitor. Following cessation of the strong CYP2D6 inhibitor, the vortioxetine dose should be returned to the normal level. Consider therapy modification

Adverse Reactions

Frequency varies by dose and indication. Adverse reactions reported as a composite of all indications.

>10%:

Central nervous system: Drowsiness (15% to 24%), insomnia (11% to 24%), headache (6% to 18%), dizziness (6% to 14%)

Dermatologic: Diaphoresis (5% to 14%)

Endocrine & metabolic: Decreased libido (3% to 15%)

Gastrointestinal: Nausea (19% to 26%), xerostomia (9% to 18%), constipation (5% to 16%), diarrhea (9% to 12%)

Genitourinary: Ejaculatory disorder (13% to 28%)

Neuromuscular & skeletal: Weakness (12% to 22%), tremor (4% to 11%)

1% to 10%:

Cardiovascular: Vasodilatation (2% to 4%), chest pain (3%), palpitations (2% to 3%), hypertension (≥1%), tachycardia (≥1%)

Central nervous system: Nervousness (4% to 9%), anxiety (5%), fatigue (5%), agitation (3% to 5%), paresthesia (4%), abnormal dreams (3% to 4%), lack of concentration (3% to 4%), yawning (2% to 4%), depersonalization (≤3%), myoclonus (2% to 3%), amnesia (2%), chills (2%), emotional lability (≥1%), vertigo (≥1%), confusion (1%), myasthenia (1%)

Dermatologic: Skin rash (2% to 3%), pruritus (≥1%)

Endocrine & metabolic: Weight gain (≥1%)

Gastrointestinal: Decreased appetite (5% to 9%), dyspepsia (2% to 5%), flatulence (4%), abdominal pain (4%), nausea and vomiting (4%), increased appetite (2% to 4%), vomiting (2% to 3%), dysgeusia (2%)

Genitourinary: Male genital disease (10%), female genital tract disease (2% to 9%), impotence (2% to 9%), orgasm disturbance (2% to 9%), dysmenorrhea (5%), urinary frequency (2% to 3%), urinary tract infection (2%)

Infection: Infection (5% to 6%)

Neuromuscular & skeletal: Myalgia (2% to 4%), back pain (3%), myopathy (2%), arthralgia (≥1%)

Ophthalmic: Blurred vision (4%), visual disturbance (2% to 4%)

Otic: Tinnitus (≥1%)

Respiratory: Dyspnea (≤7%), pharyngitis (4%), sinusitis (≤4%), rhinitis (3%)

<1% (Limited to important or life-threatening): Abnormal erythrocytes, abnormal hepatic function tests, acute renal failure, adrenergic syndrome, agranulocytosis, akathisia, akinesia, anaphylactoid reaction, anaphylaxis, anemia (various), angina pectoris, angioedema, angle-closure glaucoma, aphasia, aphthous stomatitis, aplastic anemia, asthma, atrial fibrillation, bloody diarrhea, bone marrow aplasia, bradycardia, bronchitis, bulimia nervosa, bundle branch block, cardiac failure, cataract, cellulitis, cerebral ischemia, cerebrovascular accident, change in platelet count, cholelithiasis, colitis, deafness, dehydration, delirium, depression, diabetes mellitus, disorientation, drug dependence, dyskinesia, dysphagia, dystonia, eclampsia, emphysema, esophageal achalasia, exfoliative dermatitis, extrapyramidal reaction, fecal impaction, fungal dermatitis, gastroenteritis, goiter, Guillain-Barre syndrome, hallucination, hematemesis, hematologic disease, hematoma, hemoptysis, hemorrhage (eye, gingival, rectal, retinal, vaginal), hemorrhagic pancreatitis, hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity, homicidal ideation, hyperbilirubinemia, hypercholesteremia, hypergammaglobulinemia, hyperglycemia, hyperhidrosis, hypersensitivity reaction, hyperthyroidism, hypoglycemia, hyponatremia, hypotension, hypothyroidism, immune thrombocytopenia, increased blood urea nitrogen, increased creatine phosphokinase, increased lactate dehydrogenase, increased serum alkaline phosphatase, intestinal obstruction, ischemic heart disease, jaundice, ketosis, low cardiac output, lymphadenopathy, meningitis, migraine, mydriasis, myelitis, myocardial infarction, neuroleptic malignant syndrome (Stevens, 2008), neuropathy, nodal arrhythmia, osteoarthritis, osteoporosis, pancreatitis, pancytopenia, peptic ulcer, peritonitis, phlebitis, pneumonia, prolonged bleeding time, pulmonary edema, pulmonary embolism, pulmonary fibrosis, pulmonary hypertension, restlessness, seizure, sepsis, serotonin syndrome, status epilepticus, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, syncope, tetany, thrombophlebitis, thrombosis, torsades de pointes, toxic epidermal necrolysis, uncontrolled diabetes mellitus, vasculitis, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, withdrawal syndrome (including increased dreaming/nightmares, muscle cramps/spasms/twitching, headache, nervousness/anxiety, fatigue/tiredness, restless feeling in legs, and trouble sleeping/insomnia)

ALERT: U.S. Boxed Warning

Suicidality and antidepressant drugs:

Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of paroxetine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Closely observe and appropriately monitor patients of all ages who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Paroxetine is not approved for use in pediatric patients.

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Paroxetine is not FDA approved for use in children.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Akathisia: Inability to remain still due to feelings of agitation or restlessness has been observed with paroxetine and other SSRIs. Usually occurs within the first few weeks of therapy.

• Anticholinergic effects: Has low potential for sedation and anticholinergic effects relative to cyclic antidepressants; however among the SSRI class these effects are relatively higher.

• Bleeding risk: May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage.

• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda, 2013; Rizzoli, 2012).

• Ocular effects: May cause mild pupillary dilation, which can lead to an episode of narrow-angle glaucoma in susceptible individuals. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St John’s wort, tryptophan) or agents that impair metabolism of serotonin (eg, MAO inhibitors intended to treat psychiatric disorders, other MAO inhibitors [ie, linezolid and intravenous methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

• SIADH and hyponatremia: SSRIs and SNRIs have been associated with the development of SIADH; hyponatremia has been reported rarely (including severe cases with serum sodium <110 mmol/L), predominately in the elderly. Volume depletion and/or concurrent use of diuretics likely increases risk.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; paroxetine has not been systemically evaluated in patients with a recent history of MI or unstable heart disease.

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.

• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Paroxetine is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with renal impairment; clearance is decreased and plasma concentrations are increased; a lower dosage may be needed.

• Seizure disorder: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pregnancy: Avoid use in the first trimester. Menopausal vasomotor symptoms do not occur during pregnancy; therefore, the use of paroxetine for the treatment of menopausal vasomotor symptoms is contraindicated in pregnant women.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

Dosage form specific issues:

• Brisdelle: Brisdelle contains a lower dose than what is required for the treatment of psychiatric conditions. Patients who require paroxetine for the treatment of psychiatric conditions should discontinue Brisdelle and begin treatment with a paroxetine-containing medication which provides an adequate dosage.

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA, 2010; Fava, 2006; Haddod, 2001; Shelton, 2001; Warner, 2006).

• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

Monitoring Parameters

Mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks; signs/symptoms of serotonin syndrome; akathisia

Pregnancy Risk Factor

D//X (product specific)

Pregnancy Considerations

Studies in pregnant women have demonstrated a risk to the fetus. Paroxetine crosses the placenta. An increased risk of teratogenic effects, including cardiovascular defects, may be associated with maternal use of paroxetine or other SSRIs; however, available information is conflicting. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of paroxetine may be altered. The maternal CYP2D6 genotype also influences paroxetine plasma concentrations during pregnancy.

The manufacturer suggests discontinuing paroxetine or switching to another antidepressant unless the benefits of therapy justify continuing treatment during pregnancy; consider other treatment options for women who are planning to become pregnant. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. The ACOG also recommends that therapy with paroxetine be avoided during pregnancy if possible and that fetuses exposed in early pregnancy be assessed with a fetal echocardiography. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. The use of paroxetine is not recommended as first line therapy during pregnancy. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy. Menopausal vasomotor symptoms do not occur during pregnancy; therefore, the use of paroxetine for the treatment of menopausal vasomotor symptoms is contraindicated in pregnant women.

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, headache, nausea, vomiting, constipation, diarrhea, dry mouth, insomnia, loss of strength and energy, lack of appetite, or yawning. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, arrhythmia, flushing, tremors, sweating a lot, change in balance, severe nausea, severe diarrhea), signs of low sodium (headache, trouble focusing, memory problems, illogical thinking, weakness, seizures, or change in balance), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), vision changes, eye pain, severe eye irritation, illogical thinking, change in balance, agitation, twitching, sweating, muscle rigidity, severe anxiety, arrhythmia, hallucinations, severe dizziness, passing out, bone pain, excessive weight loss, burning or numbness feeling, sexual dysfunction, or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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