Version October 2024
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. Paroxetine is not approved for use in pediatric patients.
Dosage guidance:
Dosage form information: Immediate-release paroxetine is available in two salts, hydrochloride (eg, Paxil) and mesylate (eg, Brisdelle, Pexeva); use extra precaution to ensure correct product selection. Paroxetine is available as immediate-release and extended-release formulations; both formulations are dosed once daily but are not interchangeable on a mg to mg basis; based on adult bioavailability data, immediate-release 10 mg is equivalent to extended-release 12.5 mg (Ref).
Major depressive disorder (unipolar): Limited data available:
Note: The use of paroxetine should be reserved for refractory cases when other options are ineffective or unacceptable/intolerable to the patient; therapy should not be initiated in a primary care setting; patients should be closely monitored for adverse effects (eg, suicidal thoughts/behaviors) (Ref). Therapy should be initiated at a low dose and titrated every 1 to 2 weeks based on response and tolerability (Ref).
Children ≥12 years and Adolescents: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; usual reported effective dose: 20 mg/day; maximum daily dose: 60 mg/day (Ref).
Obsessive-compulsive disorder (OCD): Limited data available:
Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be in combination with cognitive behavioral therapy (CBT) and a selective serotonin reuptake inhibitor (SSRI) should be used first line; a preferred agent has not been identified (Ref).
Children ≥7 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate every 7 to 14 days in 10 mg/day increments; mean reported effective dose: 32 mg/day; maximum daily dose: 60 mg/day (Ref).
Social anxiety disorder: Limited data available:
Note: In pediatric patients, selective serotonin reuptake inhibitor (SSRI) therapy is considered first-line pharmacologic treatment for moderate to severe anxiety disorders in combination with cognitive behavioral therapy (CBT); a preferred SSRI has not been defined; therapeutic selection should be based on pharmacokinetic and pharmacodynamic data, patient tolerability, cost, and unique risks/precautions with specific agents (Ref).
Children ≥8 years and Adolescents <18 years: Oral: Immediate release (hydrochloride salt): Initial: 10 mg once daily; titrate at intervals of at least 7 days in 10 mg/day increments; maximum daily dose: 50 mg/day. Dosing based on a 16-week multicenter, randomized, double-blind, placebo-controlled trial that reported the efficacy of paroxetine in pediatric patients (aged 8 to 17 years) with social anxiety disorder; 163 patients were randomized to receive paroxetine; the overall mean dose was 21.7 mg/day for children and 26.1 mg/day for adolescents (Ref).
Discontinuation of therapy: Consider planning discontinuation of therapy during lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to OCD treatment discontinuation (Ref). To discontinue therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is sparse, particularly in pediatric patients; however, a general consensus is to taper over several weeks to months and to resume the previous OCD therapy if symptoms worsen; a plan for continued psychotherapy during serotonergic medication discontinuation is recommended (Ref). A unified taper protocol has been reported in adults with OCD in which serotonin reuptake inhibitor monotherapy was tapered over 12 weeks with biweekly psychiatrist visits (Ref). For the treatment of depression, experts suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; agents with a shorter half-life may need to be tapered more conservatively and if intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate; similar principles may also be applicable to OCD therapy discontinuation (Ref).
Switching selective serotonin reuptake inhibitor (SSRI): Evidence for ideal SSRI switching strategies in pediatric patients is sparse; strategies described in pediatric guidelines include a conservative approach (tapering and discontinuing the first SSRI before adding the second) and cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant). While consensus does not exist regarding which approach to utilize, it is important to note that the conservative approach runs the risk for exacerbation of symptoms or discontinuation syndrome; cross-titration may avoid these risks (Ref). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monamine oxidase inhibitor. While not as common of a strategy, a direct switch may be considered when switching to another agent in the same or similar class (eg, when switching between 2 SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥7 years and Adolescents: Oral: There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients, plasma concentration is 2 times that seen in normal function in mild to moderate renal impairment (CrCl 30 to 60 mL/minute), and in severe impairment (CrCl <30 mL/minute) mean plasma concentration is ~4 times that seen in normal function; dosing adjustment suggested.
There are no pediatric-specific recommendations; based on pharmacokinetics in adult patients with hepatic dysfunction, plasma concentration is 2 times that seen in normal function; dosing adjustment suggested.
(For additional information see "Paroxetine: Drug information")
Dosage guidance:
Dosing: Some experts suggest a lower starting dose of 5 to 10 mg once daily (immediate release) or 12.5 mg once daily (extended release) and gradual titration in increments of ≤10 mg (immediate release) or 12.5 mg (extended release), particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Dosage form information: Paroxetine is available as IR and ER formulations; both formulations are dosed once daily but are not interchangeable on a milligram to milligram basis. Where dosing for the ER formulation is not provided for an indication, may convert between formulations using equivalence shown in "Dosing conversions" section below.
Body dysmorphic disorder (off-label use): Immediate release: Oral: Initial: 20 mg once daily; may increase dose gradually based on response and tolerability in increments of 20 mg/day at intervals of every 2 to 3 weeks to a usual dose of 60 mg/day; doses up to 100 mg/day, if tolerated, may be necessary in some patients for optimal response (Ref). Note: An adequate trial for assessment of effect is 12 to 16 weeks, including a dose of 60 mg for at least 4 of those weeks, if needed and tolerated (Ref).
Generalized anxiety disorder: Immediate release: Oral: Initial: 10 to 20 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to 50 mg/day (Ref). Doses may be increased every 3 to 4 days if warranted in inpatient settings. Some experts recommend maintaining the initial therapeutic dose day for 4 to 6 weeks to assess for efficacy before increasing further (Ref).
Major depressive disorder (unipolar):
Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week to a maximum of 50 mg/day. Usual dose: 20 to 40 mg/day (Ref).
Extended release: Oral: Initial: 25 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week to a maximum of 62.5 mg/day. Usual dose: 25 to 50 mg/day (Ref).
Obsessive-compulsive disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a recommended dose of 40 to 60 mg/day; maximum dose: 60 mg/day (Ref). Note: An adequate trial for assessment of effect in obsessive-compulsive disorder is considered ≥6 weeks at the maximum tolerated dose (Ref).
Panic disorder:
Immediate release: Oral: Initial: 10 mg once daily for 3 to 7 days; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week up to a usual dose of 20 to 40 mg/day (Ref); maximum dose: 60 mg/day. Some experts maintain dose at 20 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Extended release: Oral: Initial: 12.5 mg once daily; may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 75 mg/day. Some experts maintain dose at 25 mg for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Posttraumatic stress disorder: Immediate release: Oral: Initial: 20 mg once daily; may increase dose based on response and tolerability in increments of 10 to 20 mg/day at intervals ≥1 week up to 60 mg/day (Ref).
Premature ejaculation (off-label use): Immediate release: Oral: Initial: 10 mg once daily; may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a usual dosage of 20 mg/day (Ref). Some patients may require up to 40 mg/day for optimal response (Ref); some experts suggest 3- to 4-week titration intervals (Ref).
Premenstrual dysphoric disorder: Note: Some experts prefer selective serotonin reuptake inhibitors (SSRIs) other than paroxetine for this use (Ref).
Continuous daily dosing regimen:
Immediate release (off-label): Oral: Initial: 10 mg once daily; increase to usual effective dose of 20 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 40 mg/day may be necessary in some patients for optimal response (Ref).
Extended release: Oral: Initial: 12.5 mg once daily; increase to usual effective dose of 25 mg once daily over the first month; in a subsequent menstrual cycle, a further increase to 50 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).
Intermittent regimens:
Luteal phase dosing regimen:
Immediate release (off-label): Oral: Initial: 10 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 20 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 30 mg/day during the luteal phase may be necessary in some patients for optimal response (Ref).
Extended release: Oral: Initial: 12.5 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, may increase to usual effective dose of 25 mg once daily during the luteal phase; in a subsequent menstrual cycle, a further increase to 37.5 mg/day (based on equivalent IR dose) during the luteal phase may be necessary in some patients for optimal response (Ref).
Symptom-onset dosing regimen (off-label): Immediate release: Oral: Initial: 10 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, may increase dose based on response and tolerability up to 20 mg/day; in a subsequent menstrual cycle, a further increase to 30 mg/day may be necessary in some patients for optimal response (Ref).
Social anxiety disorder:
Immediate release: Oral: Initial: 10 to 20 mg once daily; after 4 to 6 weeks at this dose, may increase dose based on response and tolerability in increments of 10 mg/day at intervals ≥1 week to a maximum of 60 mg/day (Ref).
Extended release: Oral: Initial: 12.5 to 25 mg once daily; after 4 to 6 weeks at this dose, may increase dose based on response and tolerability in increments of 12.5 mg/day at intervals ≥1 week up to a maximum of 37.5 mg/day (Ref). Note: Doses up to 75 mg/day (based on equivalent IR dose) may be necessary in some patients for optimal response (Ref).
Vasomotor symptoms associated with menopause (alternative agent): Note: Nonhormonal alternative in patients unable or unwilling to take estrogen (Ref).
Immediate release :
Capsule: Oral: 7.5 mg once daily at bedtime.
Tablet (off-label): Oral: 10 to 20 mg once daily at bedtime (Ref).
Extended release (off-label): Oral: 12.5 to 25 mg once daily at bedtime (Ref).
Dosing conversions: Immediate release 10 mg is equivalent to extended release 12.5 mg (Ref).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). Reasons for a slower taper (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from an MAOI:
Allow 14 days to elapse between discontinuing an MAOI and initiation of paroxetine.
Allow 14 days to elapse between discontinuing paroxetine and initiation of an MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to 60 mL/minute: There are no dosage adjustments provided in manufacturer's labeling; however, AUCs after a single paroxetine dose were approximately 2 times that of individuals with normal function (Ref). Consider a 25% to 50% reduction in initial dose and titrate based on efficacy and tolerability, not to exceed the usual indication-specific maximum recommended dose (refer to dosing in adults) (Ref).
CrCl <30 mL/minute: AUCs after a single paroxetine dose were ~3.5 times that of patients with normal kidney function (Ref).
Immediate release: Initial: 5 to 10 mg/day; increase if needed by increments of no more than 10 mg/day at intervals of at least 1 week based on efficacy and tolerability; maximum dose: 40 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).
Extended release: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week based on efficacy and tolerability to a maximum dose of 50 mg/day or the indication-specific maximum recommended dose (refer to dosing in adults), whichever is less (Ref).
Hemodialysis, intermittent (thrice weekly): Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).
Oral: Dose for CrCl <30 mL/minute (Ref).
Peritoneal dialysis: Not likely to be significantly dialyzable due to large Vd and high protein binding (Ref).
Oral: Dose for CrCl <30 mL/minute (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) and minimal residual kidney function unless otherwise noted. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: Dose as for CrCl <30 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral: Dose as for CrCl <30 mL/minute (Ref).
Mild to moderate impairment: There are no dosage adjustments provided in manufacturer's labeling.
Severe impairment:
Immediate release: Initial: 10 mg/day; increase if needed by 10 mg/day increments at intervals of at least 1 week; maximum dose: 40 mg/day.
Extended release: Initial: 12.5 mg/day; increase if needed by 12.5 mg/day increments at intervals of at least 1 week to a maximum of 37.5 mg/day (social anxiety disorder) or 50 mg/day (major depressive disorder, panic disorder).
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).
Mechanism: Non-dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Female sex (Ref)
Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants in adult and pediatric patients. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematoma, petechiae, purpuric disease, and epistaxis to cerebrovascular accident, upper GI bleeding (UGIB), intracranial hemorrhage, postpartum hemorrhage, and intraoperative bleeding, although conflicting evidence also exists (Ref).
Mechanism: Possibly via decreased platelet serotonin concentrations and inhibition of serotonin-mediated platelet activation leading to subsequent platelet dysfunction (Ref). SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory drugs (NSAIDs). For UGIB, some studies have found risk to be the highest in the first 28 to 30 days (Ref), whereas another study reported a median time of onset of 25 weeks (Ref).
Risk factors:
• Concomitant use of anticoagulants and/or antiplatelets (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
• Concomitant use of NSAIDs increases the risk for UGIB (Ref)
Limited data from observational studies involving mostly older adults (≥50 years of age) suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). SSRIs may also contribute to fall risk, contributing to the incidence of fractures (Ref).
Onset: Delayed; risk appears to increase after initiation and may continue to increase with long-term use. A meta-analysis found risk of fracture increased from 2.9% over 1 year to 5.4% over 2 years; within 5 years, risk increased to 13.4% (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia, including severe cases, predominantly in the elderly (Ref). Hyponatremia is reversible with discontinuation of therapy (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; usually develops within the first few weeks of treatment (Ref).
Risk factors:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factor) (Ref)
• Symptoms of psychosis (potential risk factor) (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-controlled study. AACG may cause symptoms including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with an increased risk of cataract development (Ref).
Mechanism: AACG: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).
Risk factors:
For AACG:
• Females (Ref)
• ≥50 years of age (slight increase) (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Inuit or Asian descent (Ref)
Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs. Only a handful of cases of serotonin syndrome have been reported with paroxetine monotherapy at therapeutic doses, in addition to a case which occurred following paroxetine overdose (Ref). The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).
Mechanism: Dose-related; overstimulation of serotonin receptors by serotonergic agents (Ref).
Onset: Rapid; in the majority of cases (74%), onset occurred within 24 hours of treatment initiation, overdose, or change in dose (Ref).
Risk factors:
• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake and/or impair serotonin metabolism (eg, monamine oxidase inhibitors [MAO inhibitors]). Of note, concomitant use of some serotonergic agents, such as MAO inhibitors, are contraindicated.
Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorders in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory delay, orgasm disturbance, erectile dysfunction, and decreased libido (Ref). Priapism and decreased penile sensation have also been reported (Ref).
Mechanism: Increases in serotonin may affect other hormones and neurotransmitters involved in sexual function, in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years) in short-term studies. In adults >24 years, short-term studies did not show an increased risk of suicidal thinking and behavior and in older adults ≥65 years of age, a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.
Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may produce a worsening of depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), have been reported, primarily following abrupt discontinuation in adult and pediatric patients (Ref). Withdrawal symptoms may also occur following gradual tapering (Ref).
Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the selective serotonin reuptake inhibitor (SSRI). Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as the hypothalamic-pituitary-adrenal axis (Ref).
Onset: Intermediate; expected onset is 1 to 10 days (following either abrupt or tapered discontinuation) (Ref).
Risk factors:
• Abrupt discontinuation (rather than dose taper) or tapering the antidepressant too quickly (Ref)
• Drugs with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Higher doses (Ref)
• Longer duration of treatment (eg, ≥4 weeks) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Diaphoresis (5% to 14%)
Endocrine & metabolic: Decreased libido (≤15%) (table 1)
|
Drug (Paroxetine) |
Placebo |
Population |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
0% to 9% |
0% to 2% |
Females |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,822 |
1,340 |
Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction |
|
6% to 15% |
0% to 5% |
Males |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
Multiple placebo-controlled clinical trials evaluating different components of sexual dysfunction |
Gastrointestinal: Constipation (2% to 16%), decreased appetite (1% to 12%), diarrhea (6% to 18%), dyspepsia (2% to 13%), nausea (17% to 26%), xerostomia (3% to 18%)
Genitourinary: Ejaculatory disorder (13% to 28%) (table 2)
|
Drug (Paroxetine) |
Placebo |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
13% to 28% |
0% to 2% |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
Nervous system: Asthenia (12% to 22%), dizziness (6% to 14%), drowsiness (3% to 24%, less frequent in children and adolescents) (Safer 2006), headache (6% to 27%, including vascular headache), insomnia (7% to 24%), tremor (4% to 11%)
1% to 10%:
Cardiovascular: Chest pain (3%), hypertension (≥1%), palpitations (2% to 3%), tachycardia (≥1%), vasodilation (2% to 4%)
Dermatologic: Pruritus (≥1%), skin rash (2% to 3%)
Endocrine & metabolic: Weight gain (≥1%)
Gastrointestinal: Abdominal pain (4% to 7%), dysgeusia (2%), flatulence (4% to 6%), increased appetite (2% to 4%), nausea and vomiting (4%), vomiting (2% to 3%; more frequent in children [two- to threefold] and adolescents) (Safer 2006)
Genitourinary: Abnormal orgasm (2% to 10%) (table 3), difficulty in micturition (3%), dysmenorrhea (5%), erectile dysfunction (2% to 10%) (table 4), female genital tract disease (2% to 10%), male genital disease (10%), urinary frequency (2% to 3%), urinary tract infection (2%), urination disorder (3%)
|
Drug (Paroxetine) |
Placebo |
Population |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% to 9% |
0% to 1% |
Females |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,822 |
1,340 |
|
Drug (Paroxetine) |
Placebo |
Dosage Form |
Indication |
Number of Patients (Paroxetine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% to 9% |
0% to 3% |
Tablet |
Multiple trials in a variety of conditions: MDD, OCD, PD, social anxiety disorder, GAD, and PTSD |
1,446 |
1,042 |
|
5% to 10% |
0% to 3% |
Tablet, controlled release N/A |
Multiple trials in a variety of conditions: MDD, panic disorder, and social anxiety disorder |
328 |
369 |
Infection: Infection (5% to 6%)
Nervous system: Abnormal dreams (3% to 4%), agitation (3% to 5%), amnesia (2%), anxiety (2% to 5%), chills (2%), confusion (1%), depersonalization (3%), emotional lability (≥1%), fatigue (≤5%), hypomania (≤1%), intoxicated feeling (2%), lack of concentration (3% to 4%), lethargy (≤5%) malaise (≤5%), mania (≤1%), manic reaction (2%), myasthenia (1%), myoclonus (2% to 3%), nervousness (4% to 9%), paresthesia (4%), vertigo (≥1%), yawning (2% to 5%)
Neuromuscular & skeletal: Arthralgia (≥1%), back pain (3% to 5%), myalgia (2% to 5%), myopathy (2%)
Ophthalmic: Blurred vision (4%), visual disturbance (2% to 5%)
Otic: Tinnitus (≥1%)
Respiratory: Pharyngeal edema (2%), pharyngitis (4%), rhinitis (3%), sinusitis (4% to 8%)
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, atrial fibrillation, atrioventricular nodal arrhythmia, bradycardia, bundle branch block, edema, heart block, heart failure, hypotension, ischemic heart disease, orthostatic hypotension, peripheral edema, phlebitis, premature ventricular contractions, pulmonary embolism, supraventricular extrasystole, syncope, thrombophlebitis, thrombosis
Dermatologic: Alopecia, dermal ulcer, ecchymoses, eczema, erythema multiforme, erythema nodosum, exfoliative dermatitis, maculopapular rash, skin discoloration, skin hypertrophy, skin photosensitivity, urticaria, vesicobullous dermatitis, xeroderma
Endocrine & metabolic: Adrenergic syndrome, amenorrhea, dehydration, diabetes mellitus, heavy menstrual bleeding, hirsutism, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperphosphatemia, hyperthyroidism, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranges from <1% to as high as 32%) (Gandhi 2017; Jacob 2006), hypothyroidism, increased libido, increased thirst, ketosis, thyroiditis, weight loss
Gastrointestinal: Ageusia, aphthous stomatitis, bloody diarrhea, bruxism, cholelithiasis, colitis, dental bleeding (gums), duodenitis, dysphagia, enteritis, eructation, esophageal achalasia, esophagitis, fecal impaction, fecal incontinence, gastric ulcer, gastritis, gingivitis, glossitis, hematemesis, hiccups, ileitis, intestinal obstruction, melena, oral mucosal ulcer, oral paresthesia, peptic ulcer, peritonitis, rectal hemorrhage, sialadenitis, sialorrhea, stomatitis (including angular) (Verma 2012), tongue discoloration
Genitourinary: Cystitis, dysuria, epididymitis, hematuria, lactation, leukorrhea, mastitis, nocturia, oliguria, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, urolithiasis, uterine hemorrhage, vaginal hemorrhage
Hematologic & oncologic: Anemia (hypochromic, microcytic, normocytic, and iron deficiency), basophilia, eosinophilia, hematoma, hypergammaglobulinemia, leukocytosis, leukopenia, lymphadenopathy, lymphedema, monocytosis, prolonged bleeding time, purpuric disease, thrombocytopenia, thrombocytosis
Hepatic: Hepatic, hyperbilirubinemia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, jaundice
Hypersensitivity: Angioedema, facial edema, hypersensitivity reaction, tongue edema
Nervous system: Abnormal gait, akathisia, akinesia, altered sense of smell, antisocial behavior, aphasia, ataxia, bulimia nervosa, cerebral ischemia, cerebrovascular accident, choreoathetosis, delirium, delusion, depression with psychosis, drug dependence, dysarthria, euphoria, extrapyramidal reaction, hallucination, hostility, hyperacusis, hyperalgesia, hyperesthesia, hyperreflexia, hypertonia, hyporeflexia, hysteria, lack of emotion, manic depressive reaction, migraine, neuralgia, neuropathy, neurosis, paralysis, paranoid ideation, peripheral neuritis, psychosis, seizure, stupor, suicidal ideation, suicidal tendencies, trismus
Neuromuscular & skeletal: Arthritis, bursitis, dyskinesia, dystonia, fasciculations, gout, hypokinesia, muscle spasm, myelitis, myositis, osteoarthritis, osteoporosis, tenosynovitis, tetany, torticollis
Ophthalmic: Accommodation disturbance, amblyopia, anisocoria, blepharitis, blepharoptosis, cataract, conjunctival edema, corneal ulcer, diplopia, exophthalmos, keratoconjunctivitis, mydriasis, night blindness, nystagmus disorder, photophobia, retinal hemorrhage, visual field defect
Otic: Deafness
Renal: Increased blood urea nitrogen, nephritis, nephrolithiasis
Respiratory: Asthma, bronchitis, dyspnea, epistaxis, hemoptysis, pneumonia, pulmonary edema, pulmonary emphysema, pulmonary fibrosis, stridor
Postmarketing:
Cardiovascular: Torsades de pointes (Wenzel-Seifert 2011), vasculitis (Margolese 2001; Welsh 2006), ventricular fibrillation (Lee 2018), ventricular tachycardia
Dermatologic: Acute generalized exanthematous pustulosis (Mameli 2013), hyperhidrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Ahmed 2008)
Endocrine & metabolic: Galactorrhea not associated with childbirth (Gonzales 2000; Morrison 2001), hyperprolactinemia (Evrensel 2016), porphyria, SIADH (Gandhi 2017), uncontrolled diabetes mellitus
Gastrointestinal: Acute pancreatitis, hemorrhagic pancreatitis
Genitourinary: Preeclampsia, priapism (Ahmad 1995), sexual disorder (Montejo 2019; Montejo-Gonzalez 1997)
Hematologic & oncologic: Agranulocytosis, aplastic anemia, bone marrow aplasia, hemolytic anemia, Henoch-Schönlein purpura, immune thrombocytopenia, pancytopenia
Hepatic: Hepatic failure, hepatic necrosis, hepatotoxicity (Azaz-Livshits 2002; Benbow 1997)
Hypersensitivity: Anaphylaxis, drug reaction with eosinophilia and systemic symptoms, nonimmune anaphylaxis
Nervous system: Aggressive behavior (Nishida 2008; Sharma 2016), anosmia (including hyposmia), cogwheel rigidity, disorientation (Wakeno 2007), Guillain-Barre syndrome, homicidal ideation (Moore 2010), hyperactive behavior (including hyperkinetic muscle activity; more frequent in children [two- to threefold] and adolescents) (Safer 2006), intracranial hemorrhage (Douros 2018), neuroleptic malignant syndrome (with drug interactions) (Tanii 2006; Uguz 2013), restless leg syndrome (Rottach 2008; Sanz-Fuentenebro 1996), restlessness (Naslund 2017), serotonin syndrome (Hudd 2020; Velez 2004), status epilepticus (Taniguchi 2014), withdrawal syndrome (Fava 2015)
Neuromuscular & skeletal: Bradykinesia
Ophthalmic: Acute angle-closure glaucoma (Eke 1997; Kirwan 1997; Lewis 1997), optic neuritis
Renal: Acute kidney injury
Respiratory: Hypersensitivity pneumonitis (Maia 2015), laryngismus, pulmonary alveolitis (allergic), pulmonary hypertension
Hypersensitivity (eg, anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or any component of the formulation; concurrent use with or within 14 days of monoamine oxidase inhibitors (MAOIs) (including IV methylene blue); concomitant use with pimozide or thioridazine; pregnancy (Brisdelle only).
Note: Although paroxetine is contraindicated per the manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006a).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Initiation of paroxetine within 2 weeks of pimozide or thioridazine discontinuation.
Concerns related to adverse effects:
• Akathisia: Inability to remain still due to feelings of agitation or restlessness has been observed with paroxetine and other selective serotonin reuptake inhibitors (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.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
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 myocardial infarction 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. However, selective serotonin reuptake inhibitors such as paroxetine are considered the safest antidepressants to use in chronic liver disease because of their relative lack of side effects and high therapeutic index (Mullish 2014).
• 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 seizure disorder.
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.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Pexeva has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as mesylate [strength expressed as base]:
Brisdelle: 7.5 mg [DSC] [contains fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]
Generic: 7.5 mg
Suspension, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg/5 mL (250 mL) [contains fd&c yellow #6(sunset yellow)alumin lake, methylparaben, propylene glycol, propylparaben, saccharin sodium; orange flavor]
Generic: 10 mg/5 mL (250 mL)
Tablet, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg [DSC]
Paxil: 10 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil: 20 mg [DSC]
Paxil: 20 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil: 30 mg [DSC]
Paxil: 30 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil: 40 mg [DSC]
Paxil: 40 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 10 mg, 20 mg, 30 mg, 40 mg
Tablet, Oral, as mesylate [strength expressed as base]:
Pexeva: 10 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC]
Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:
Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 25 mg [DSC]
Paxil CR: 25 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 37.5 mg [DSC] [contains fd&c blue #2 (indigo carm) aluminum lake]
Paxil CR: 37.5 mg [contains fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake, quinoline (d&c yellow #10) aluminum lake]
Generic: 12.5 mg, 25 mg, 37.5 mg
Yes
Capsules (PARoxetine Mesylate Oral)
7.5 mg (per each): $6.60
Suspension (PARoxetine HCl Oral)
10 mg/5 mL (per mL): $1.58
Suspension (Paxil Oral)
10 mg/5 mL (per mL): $2.13
Tablet, 24-hour (PARoxetine HCl ER Oral)
12.5 mg (per each): $0.80 - $5.58
25 mg (per each): $0.86 - $5.82
37.5 mg (per each): $0.92 - $5.99
Tablet, 24-hour (Paxil CR Oral)
12.5 mg (per each): $11.04
25 mg (per each): $11.52
37.5 mg (per each): $11.87
Tablets (PARoxetine HCl Oral)
10 mg (per each): $1.95 - $2.67
20 mg (per each): $2.29 - $2.73
30 mg (per each): $2.70 - $2.83
40 mg (per each): $2.88 - $3.18
Tablets (Paxil Oral)
10 mg (per each): $10.72
20 mg (per each): $11.18
30 mg (per each): $11.52
40 mg (per each): $12.17
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride [strength expressed as base]:
Paxil: 10 mg, 20 mg, 30 mg [contains polysorbate 80]
Generic: 10 mg, 20 mg, 30 mg
Tablet Extended Release 24 Hour, Oral, as hydrochloride [strength expressed as base]:
Paxil CR: 12.5 mg [contains fd&c yellow #6(sunset yellow)alumin lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]
Paxil CR: 25 mg [contains polysorbate 80]
Oral: May be administered without regard to meals; administration with food may decrease GI side effects; shake suspension well before use. Paxil should preferentially be administered in the morning. Do not chew or crush immediate- or controlled-release tablet; swallow whole.
Oral: May be administered without regard to meals. Administer preferably in the morning; when used for vasomotor symptoms of menopause, administer at bedtime. Do not crush, break, or chew ER or IR film-coated tablets. Shake suspension well before use.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER tablets should be swallowed whole. IR tablet, capsule, and oral suspension formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
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 between 20°C and 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).
Suspension: Store at or below 25°C (77°F).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Brisdelle:https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204516s013lbl.pdf#page=18
Paxil: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020031s082,020710s050lbl.pdf#page=39
Paxil CR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020936s057s064lbl.pdf#page=30
Pexeva: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021299s035s038lbl.pdf#page=18
Brisdelle: Treatment of moderate to severe vasomotor symptoms associated with menopause (FDA approved in adults).
Paxil: Treatment of major depressive disorder (MDD), panic disorder (with or without agoraphobia), obsessive-compulsive disorder (OCD), social anxiety disorder (social phobia), generalized anxiety disorder (GAD), and post-traumatic stress disorder (All indications: FDA approved in adults).
Paxil CR: Treatment of MDD, panic disorder (with or without agoraphobia), social anxiety disorder (social phobia), and premenstrual dysphoric disorder (FDA approved in adults).
Pexeva: Treatment of MDD, OCD, panic disorder (with or without agoraphobia), and GAD (FDA approved in adults).
PARoxetine may be confused with DULoxetine, FLUoxetine, PACLitaxel, piroxicam, pyridoxine, vortioxetine
Paxil may be confused with Doxil, PACLitaxel, Plavix, PROzac, Taxol, Trexall
Pexeva [DSC] may be confused with Lexiva
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy [Brisdelle]) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Beers Criteria: Paroxetine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its strong anticholinergic properties and potential for sedation and orthostatic hypotension. In addition, use the SSRIs with caution due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (strong)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abrocitinib: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Ajmaline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Ajmaline. Risk C: 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. Risk D: Consider therapy modification
Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Antiplatelet Agents (P2Y12 Inhibitors): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: 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. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of ARIPiprazole. Management: Aripiprazole dose reductions or avoidance are required for indications other than major depressive disorder. Dose adjustments vary based on formulation, initial starting dose, and the additional use of CYP3A4 inhibitors. See interact monograph for details Risk D: Consider therapy modification
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of ARIPiprazole Lauroxil. Management: Decrease aripiprazole lauroxil dose to next lower strength if used with strong CYP2D6 inhibitors for over 14 days. No dose adjustment needed if using the lowest dose (441 mg) or if a CYP2D6 PM. Max dose is 441 mg if also taking strong CYP3A4 inhibitors. Risk D: Consider therapy modification
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asenapine: May increase the serum concentration of PARoxetine. Management: Decrease the paroxetine dose by half when used concomitantly with asenapine. Monitor patients receiving this combination closely for signs and symptoms of increased paroxetine toxicity. Risk D: Consider therapy modification
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Atomoxetine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Atomoxetine. Management: Initiate atomoxetine at a reduced dose (patients who weigh up to 70 kg: 0.5 mg/kg/day; adults or patients who weigh 70 kg or more: 40 mg/day) in patients receiving a strong CYP2D6 inhibitor. Increase to usual target dose after 4 weeks if needed. Risk D: Consider therapy modification
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Brexpiprazole. Management: Reduce brexpiprazole dose to 50% of usual with strong CYP2D6 inhibitors, reduce to 25% of usual if used with both a strong CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor; these recommendations do not apply if treating major depressive disorder Risk D: Consider therapy modification
Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination
Broom: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Broom. Specifically, the concentrations of sparteine, a constituent of broom, may be increased. Risk C: Monitor therapy
BuPROPion: May enhance the adverse/toxic effect of PARoxetine. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Carvedilol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Risk C: Monitor therapy
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Chlorpheniramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Chlorpheniramine. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Citalopram: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Citalopram may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
CloZAPine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of PARoxetine. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: 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. Risk C: Monitor therapy
Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Darunavir: May decrease the serum concentration of PARoxetine. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: 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. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Deutetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Deutetrabenazine. Management: The total daily dose of deutetrabenazine should not exceed 36 mg with concurrent use of a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Dextromethorphan. Management: Consider alternatives to this drug combination. The dose of dextromethorphan/bupropion product should not exceed 1 tablet once daily. Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Strong) may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DULoxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). DULoxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of DULoxetine. Management: Monitor for increased duloxetine effects/toxicities and signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperthermia, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Eliglustat: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider therapy modification
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Epinephrine (Racemic). Risk X: Avoid combination
Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Fenfluramine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP2D6 inhibitor. Risk D: Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Flecainide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Flecainide. Risk C: Monitor therapy
FLUoxetine: May enhance the antiplatelet effect of PARoxetine. FLUoxetine may enhance the serotonergic effect of PARoxetine. This could result in serotonin syndrome. FLUoxetine may increase the serum concentration of PARoxetine. PARoxetine may increase the serum concentration of FLUoxetine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes), bleeding, and increased SSRI toxicities when these agents are combined. Risk C: Monitor therapy
FluPHENAZine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of FluPHENAZine. Risk C: Monitor therapy
Fosamprenavir: May decrease the serum concentration of PARoxetine. The active metabolite amprenavir is likely responsible for this effect. Risk C: Monitor therapy
Galantamine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Galantamine. Risk C: Monitor therapy
Gefitinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Gefitinib. Risk C: Monitor therapy
Gepirone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Gilteritinib: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Haloperidol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Haloperidol. Risk C: Monitor therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Iboga: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Iboga. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: 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 and monitor for increased iloperidone toxicities, including QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification
Indoramin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Indoramin. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Levomethadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lofexidine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Lofexidine. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Maprotiline: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Maprotiline. Risk C: Monitor therapy
Mavorixafor: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Mequitazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mequitazine. Risk X: Avoid combination
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methadone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Methadone. Risk C: Monitor therapy
Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoclopramide. Management: For gastroparesis: reduce metoclopramide dose to 5mg 4 times/day and limit to 20mg/day; nasal spray not recommended. For GERD: reduce metoclopramide dose to 5mg 4 times/day or to 10mg 3 times/day and limit to 30mg/day. Monitor for toxicity when combined. Risk D: Consider therapy modification
Metoprolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Metoprolol. Risk C: Monitor therapy
Mexiletine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy
Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: 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. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Oliceridine: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Oliceridine. Management: Monitor for increased opioid effects (eg, respiratory depression, sedation) and for serotonin syndrome/serotonin toxicity when these agents are combined. Risk C: Monitor therapy
Olmutinib: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Olmutinib. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for decreased therapeutic response (eg, analgesia) and opioid withdrawal when coadministered with SSRIs that strongly inhibit CYP2D6. Additionally, monitor for serotonin syndrome/serotonin toxicity if these drugs are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: 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. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Perhexiline: PARoxetine may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of PARoxetine. Risk C: Monitor therapy
Perphenazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Perphenazine. Risk C: Monitor therapy
Pimozide: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pitolisant: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Risk D: Consider therapy modification
Pravastatin: May enhance the adverse/toxic effect of PARoxetine. Specifically, blood glucose elevations may occur with the combination. Risk C: Monitor therapy
Primaquine: CYP2D6 Inhibitors (Strong) may diminish the therapeutic effect of Primaquine. CYP2D6 Inhibitors (Strong) may decrease serum concentrations of the active metabolite(s) of Primaquine. Risk C: Monitor therapy
Procyclidine: PARoxetine may increase the serum concentration of Procyclidine. Risk C: Monitor therapy
Propafenone: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Propranolol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Propranolol. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Psilocybin: Antidepressants may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid combination
RisperiDONE: CYP2D6 Inhibitors (Strong) may increase the serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Sertindole: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Sertindole. Management: Consider alternatives to this combination when possible. If combined, consider using lower doses of sertindole and monitor the ECG closely for evidence of QTc interval prolongation. Risk D: Consider therapy modification
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: 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. Management: Avoid concurrent use of strong CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with a reduced clinical effectiveness of tamoxifen. Risk D: Consider therapy modification
Tamsulosin: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tamsulosin. Risk C: Monitor therapy
Tetrabenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Management: Limit the tetrabenazine dose to 50 mg per day (25 mg per single dose) in patients taking strong CYP2D6 inhibitors. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Thioridazine. Risk X: Avoid combination
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy
Timolol (Ophthalmic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Ophthalmic). Risk C: Monitor therapy
Timolol (Systemic): CYP2D6 Inhibitors (Strong) may increase the serum concentration of Timolol (Systemic). Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Tolterodine: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Tolterodine. Risk C: Monitor therapy
TraMADol: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the adverse/toxic effect of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect of TraMADol. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes), seizures, and decreased tramadol efficacy when these agents are combined. Risk C: Monitor therapy
Tricyclic Antidepressants: PARoxetine may enhance the serotonergic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider therapy modification
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Valbenazine: CYP2D6 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Valbenazine. Management: Reduce valbenazine dose to 40 mg once daily when combined with a strong CYP2D6 inhibitor. Monitor for increased valbenazine effects/toxicities. Risk D: Consider therapy modification
Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy
Venlafaxine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). Venlafaxine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease serum concentrations of the active metabolite(s) of Venlafaxine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Venlafaxine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Volanesorsen: May enhance the antiplatelet effect of Agents with Antiplatelet Effects. Risk C: Monitor therapy
Vortioxetine: Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the antiplatelet effect of Vortioxetine. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may enhance the serotonergic effect of Vortioxetine. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Vortioxetine. Management: Consider alternatives to this drug combination. If combined, reduce the vortioxetine dose by half and monitor for signs and symptoms of bleeding and serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, autonomic instability). Risk D: Consider therapy modification
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zuclopenthixol: CYP2D6 Inhibitors (Strong) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Peak concentration is increased, but bioavailability is not significantly altered by food. Management: Administer without regard to meals.
Paroxetine is approved for the treatment of generalized anxiety disorder, panic disorder, posttraumatic stress disorder, social anxiety disorder, unipolar major depressive disorder, and obsessive-compulsive disorder. If treatment for any of these indications is initiated for the first time in a patient planning to become pregnant, agents other than paroxetine are recommended (use of paroxetine is not preferred for use during pregnancy) (Larsen 2015; WFSBP [Bandelow 2012]).
Paroxetine is also approved for the treatment of premenstrual dysphoric disorder. For patients attempting to conceive, symptom-onset dosing may be beneficial to minimize potential fetal exposure (Ismaili 2016; Lanza di Scalea 2019).
Selective serotonin reuptake inhibitors (SSRIs) may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido and orgasmic disturbances have been reported in females; abnormal ejaculation, decreased libido, and impotence have been reported in males with use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with paroxetine is not known; however, the risk of treatment-emergent sexual dysfunction may be greater with paroxetine than other SSRIs. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).
Paroxetine is used off label for the treatment of premature ejaculation. Although data are limited, some studies have shown SSRIs may impair the motility of spermatozoa; therefore, use of other treatments may be preferred in males planning to father a child (Althof 2014; Siroosbakht 2019; Sylvester 2019).
Paroxetine crosses the placenta (Hendrick 2003).
As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).
Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of paroxetine may be altered. The maternal CYP2D6 genotype also influences if paroxetine plasma concentrations increase or decrease during pregnancy (Hostetter 2000; Ververs 2009; Westin 2017). A case report describes symptoms of antidepressant discontinuation syndrome (night sweats, nightmares) in a patient during the first trimester of pregnancy, requiring a continued increase of her paroxetine dose as pregnancy progressed for resolution. The patient was found to be an extensive metabolizer of CYP2D6 (Javelot 2020). Close clinical monitoring as pregnancy progresses and therapeutic drug monitoring to detect patterns of changing plasma concentrations is recommended to assist dose adjustment when needed; CYP2D6 genotyping may also be considered (Schoretsanitis 2020).
If treatment is initiated for the first time during pregnancy, paroxetine is not recommended (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]). The American College of Obstetricians and Gynecologists 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 (ACOG 2008). If pregnancy occurs during paroxetine therapy, treatment should be changed, except in extraordinary circumstances (Larsen 2015). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).
Menopausal vasomotor symptoms do not occur during pregnancy; therefore, the use of paroxetine for the treatment of menopausal vasomotor symptoms is contraindicated in pregnant patients.
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).
Blood pressure, heart rate, liver and renal function, serum sodium in at-risk populations (as clinically indicated). Monitor patient periodically for symptom resolution; monitor for worsening depression, suicidality, and associated behaviors (especially at the beginning of therapy or when doses are increased or decreased); signs and symptoms of serotonin syndrome; akathisia.
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
Onset of action:
Anxiety disorders (generalized anxiety, obsessive-compulsive, panic, and posttraumatic stress disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Issari 2016; Varigonda 2016; WFSBP [Bandelow 2023a]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder and posttraumatic stress disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2023a]; WFSBP [Bandelow 2023b]).
Body dysmorphic disorder: Initial effects may be observed within 2 weeks; some experts suggest up to 12 to 16 weeks of treatment may be necessary for response in some patients (Phillips 2008).
Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009; Taylor 2006b).
Premenstrual dysphoric disorder: Initial effects may be observed within the first few days of treatment, with response at the first menstrual cycle of treatment (ISPMD [Nevatte 2013]).
Absorption: Completely absorbed following oral administration
Distribution: Vd: 8.7 L/kg (3 to 28 L/kg)
Protein binding: 93% to 95%
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.
Bioavailability: Immediate release tablet and oral suspension have equal bioavailability
Half-life elimination: Paxil: 21 hours; Paxil CR: 15 to 20 hours; Pexeva: 33.2 hours
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 to 10 hours
Excretion: Urine (64%, 2% as unchanged drug); feces (36% primarily via bile, <1% as unchanged drug)
Altered kidney function: AUC increased approximately 3.5 times with CrCl <30 mL/minute. AUC increased 2-fold with CrCl 30 to 60 mL/minute (Doyle 1989).
Hepatic function impairment: 2-fold increase in plasma concentrations and AUC after 14 days of daily administration in patients with alcohol-related cirrhosis (Dalhoff 1991).
Older adult: Minimum concentrations were 70% to 80% greater than in younger patients. Reduce initial dosage; no dosage adjustment is necessary with Brisdelle.
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