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Sertraline: Pediatric drug information

Sertraline: Pediatric drug information
(For additional information see "Sertraline: Drug information" and see "Sertraline: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidality and antidepressant drugs:

Antidepressants increased the risk of suicidal thoughts and behavior 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.

Brand Names: US
  • Zoloft
Brand Names: Canada
  • AG-Sertraline;
  • APO-Sertraline;
  • Auro-Sertraline;
  • BIO-Sertraline;
  • DOM-Sertraline;
  • JAMP-Sertraline [DSC];
  • Mar-Sertraline;
  • MINT-Sertraline;
  • NRA-Sertraline;
  • PMS-Sertraline;
  • Priva-Sertraline;
  • RAN-Sertraline [DSC];
  • RIVA-Sertraline;
  • SANDOZ Sertraline [DSC];
  • TEVA-Sertraline;
  • VAN-Sertraline [DSC];
  • Zoloft
Therapeutic Category
  • Antidepressant, Selective Serotonin Reuptake Inhibitor (SSRI)
Dosing: Pediatric

Note: Two solid oral dosage forms are available (tablets and capsules); the capsules are available in two strengths (150 mg and 200 mg) and should not be used to initiate sertraline therapy. Capsules may be considered in patients who have received 100 mg or 125 mg daily for at least 1 week.

Depression

Depression: Limited data available:

Note: In the management of pediatric depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, a selective serotonin reuptake inhibitor (SSRI) is recommended first line; sertraline is not typically recommended first line due to the availability of 2 SSRIs with FDA-approval for pediatric depression (fluoxetine, escitalopram); in practice, sertraline is often an alternative or subsequent medication early in pediatric depression treatment (Ref).

Children ≥6 years and Adolescents ≤17 years: Oral: Initial: 25 mg once daily; titrate in 12.5 to 25 mg increments at ≥1-week intervals; usual effective dose: 50 mg once daily; maximum daily dose: 200 mg/day; consider lower initial dose of 12.5 mg in patients who are sensitive to the higher 25 mg dose. For acute treatment in an inpatient setting and as an initial therapy, a more rapid dose titration may be considered with close monitoring (Ref).

Obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD):

Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be in combination with cognitive behavior therapy (CBT) and an SSRI should be used first line; a preferred agent has not been identified (Ref).

Children 6 to 12 years: Oral: Initial: 25 mg once daily; titrate dose upwards if clinically needed; increase by 25 to 50 mg/day increments at intervals of at least 1 week; range: 25 to 200 mg/day; maximum daily dose: 200 mg/day.

Adolescents 13 to 17 years: Oral: Initial: 50 mg once daily; titrate dose upwards if clinically needed; increase by 50 mg/day increments at intervals of at least 1 week; range: 25 to 200 mg/day; maximum daily dose: 200 mg/day.

When combined with CBT, the 12-week Pediatric OCD Treatment Study (POTS) Randomized Controlled Trial (Ref), which included 97 patients (age range: 7 to 17 years), reported mean highest daily sertraline doses of 133 ± 64 mg in the sertraline/CBT group, 170 ± 33 mg in the sertraline-only group, and 176 ± 40 mg for the group who received placebo equivalents; median doses were 150, 200, and 200 mg, respectively. Dosing used a fixed flexible upward titration from 25 mg/day to 200 mg/day over 6 weeks, after which the dosage could be adjusted based on adverse effects only.

Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant 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 limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).

Switching antidepressants: Evidence for ideal antidepressant 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 inhibitors. 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.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, sertraline pharmacokinetics does not appear to be affected by renal impairment.

Dosing: Hepatic Impairment: Pediatric

Children ≥6 years and Adolescents: Oral:

Mild impairment (Child-Pugh class A): Reduce dose to 50% of usual dose.

Moderate to severe impairment (Child-Pugh class B or C): Use is not recommended.

Dosing: Adult

(For additional information see "Sertraline: Drug information")

Note: In patients sensitive to side effects, some experts suggest a lower starting dose of 12.5 to 25 mg daily and gradual titration in increments of no more than 25 mg, particularly in patients with anxiety who are generally more sensitive to overstimulation effects (eg, anxiety, insomnia) with antidepressants (Ref). Do not initiate treatment with capsules; other sertraline products should be used for initial dosage, titration, and doses <150 mg once daily; capsules may be initiated in patients receiving sertraline 100 mg or 125 mg for ≥1 week or sertraline ≥150 mg/day.

Binge eating disorder

Binge eating disorder (off-label use): Based on limited data: Oral: Initial: 25 mg once daily after lunch; may increase dose based on response and tolerability in increments of 25 mg every 3 days. Usual dose range: 100 to 200 mg daily. Maximum dose: 200 mg/day (Ref). Based on limited data, some experts recommend doses used for major depressive disorder and slower titrations (eg, ≥1 week) (Ref).

Body dysmorphic disorder

Body dysmorphic disorder (BDD) (off-label use): Based on limited data: Oral: Some experts suggest an initial dose of 50 mg once daily; may increase dose gradually based on response and tolerability in increments of 25 to 50 mg at intervals of every 2 to 3 weeks to a usual dose of 200 mg/day; doses up to 400 mg/day may be necessary in some patients for optimal response (Ref). Note: An adequate trial for assessment of effect in BDD is 12 to 16 weeks, including maximum tolerated doses for at least 3 to 4 of those weeks (Ref).

Bulimia nervosa

Bulimia nervosa (alternative agent) (off-label use): Oral: Initial: 50 mg daily; may increase dose based on response and tolerability in increments of 50 mg at intervals ≥1 week (Ref). Maximum dose: 300 mg/day (Ref).

Generalized anxiety disorder

Generalized anxiety disorder (GAD) (off-label use): Oral: Initial: 25 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 to 2 weeks. Usual dose: 50 to 150 mg/day. Maximum dose: 200 mg/day (Ref).

Major depressive disorder

Major depressive disorder (MDD) (unipolar):

Tablets, oral solution: Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to manufacturer's labeling); however, doses up to 300 mg/day have been used in clinical practice for MDD and may provide further benefit (Ref). More rapid titrations (every 3 days) in combination with an antipsychotic (eg, olanzapine) are used by some experts for patients with psychotic features (Ref).

Capsules:

Note: Capsules may be initiated in patients receiving sertraline 100 mg/day or 125 mg/day for ≥1 week or sertraline ≥150 mg/day.

Oral: Usual dose: 150 or 200 mg once daily. Maximum dose: 200 mg/day; however, doses up to 300 mg/day have been used in clinical practice for MDD and may provide further benefit (Ref).

Obsessive-compulsive disorder

Obsessive-compulsive disorder:

Tablets, oral solution: Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to the manufacturer's labeling). Doses up to 400 mg/day may have modest clinical benefit in patients with inadequate response to standard doses (Ref), but adverse effects may be increased.

Capsules:

Note: Capsules may be initiated in patients receiving sertraline 100 mg/day or 125 mg/day for ≥1 week or sertraline ≥150 mg/day.

Oral: Usual dose: 150 mg or 200 mg once daily. Maximum dose: 200 mg/day. Doses up to 400 mg/day may have modest clinical benefit in patients with inadequate response to standard doses (Ref), but adverse effects may be increased.

Panic disorder

Panic disorder: Oral: Initial: 25 mg once daily for 3 to 7 days, then increase to 50 mg/day (Ref); thereafter, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day.

Posttraumatic stress disorder

Posttraumatic stress disorder (PTSD): Oral: Initial: 25 to 50 mg once daily (Ref); may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day (according to the manufacturer's labeling); however, doses up to 250 mg/day have been used in clinical practice and may provide further benefit (Ref).

Premature ejaculation

Premature ejaculation (off-label use): Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability at intervals of ~3 to 4 weeks in 50 mg increments up to 200 mg/day (Ref).

Premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD):

Continuous daily dosing regimen: Oral: Initial: 25 mg once daily; over the first month, increase to the usual effective dose of 50 mg once daily; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 200 mg/day may be necessary in some patients for optimal response (Ref).

Intermittent regimens:

Luteal phase dosing regimen: Oral: Initial: 25 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, increase to the usual effective dose of 50 mg/day; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 150 mg/day during the luteal phase may be necessary in some patients for optimal response (Ref).

Symptom-onset dosing regimen (off-label dosing): Oral: Initial: 25 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, increase to the usual effective dose of 50 mg/day; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 150 mg/day may be necessary for some patients for optimal response (Ref).

Note: If a daily dose ≥100 mg was established in previous cycles, may begin with 50 mg once daily for 2 to 3 days in subsequent cycles, then increase to previously established dose (Ref).

Social anxiety disorder

Social anxiety disorder: Oral: Initial: 25 to 50 mg once daily (Ref); after ~6 weeks, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day (according to the manufacturer's labeling); however, doses up to 250 mg/day have been used in clinical practice and may provide further benefit (Ref).

Discontinuation of therapy: Due to its prolonged half-life (parent and active metabolite), withdrawal symptoms are typically not observed after abrupt discontinuation; however, tapering should still be considered to assess for symptom reoccurrence. 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 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). When tapering the dose of sertraline capsules, doses <150 mg will require the use of another sertraline product.

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, and 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 sertraline.

Allow 14 days to elapse between discontinuing sertraline 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.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).

Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref): No dosage adjustment necessary (Ref).

Peritoneal dialysis: No dosage adjustment necessary (Ref).

CRRT: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

Capsules: Not recommended in hepatic impairment; dosage adjustments are not possible with the available strengths of capsules.

Tablets, oral solution:

Mild impairment (Child-Pugh class A): Reduce dose to 50% of usual dose; some experts recommend a maximum dose of 100 mg/day (Ref).

Moderate to severe impairment (Child-Pugh class B or C): Use is not recommended.

Dosage Forms: US

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

Capsule, Oral, as hydrochloride:

Generic: 150 mg, 200 mg

Concentrate, Oral:

Zoloft: 20 mg/mL (60 mL) [contains alcohol, usp, menthol]

Generic: 20 mg/mL (60 mL)

Tablet, Oral:

Zoloft: 25 mg [scored; contains fd&c blue #1 (brill blue) aluminum lake, fd&c red #40(allura red ac)aluminum lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]

Zoloft: 50 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake]

Zoloft: 100 mg [scored; contains polysorbate 80]

Generic: 25 mg, 50 mg, 100 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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

Capsule, Oral:

Zoloft: 25 mg [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]

Zoloft: 50 mg [contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]

Zoloft: 100 mg [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]

Generic: 25 mg, 50 mg, 100 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/019839s100,020990s057lbl.pdf#page=27, must be dispensed with this medication.

Administration: Pediatric

Oral: May be administered without regard to food; administer once daily dosage either in morning or evening.

Capsules: Swallow whole; do not open, crush, or chew.

Oral concentrate: Must dilute oral concentrate before use; see "Preparation for Administration: Pediatric." Direct administration of the pure solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed extensively (Ref).

Administration: Adult

Oral:

Capsules: Swallow capsules whole; do not open, chew, or crush.

Oral solution: Must be diluted immediately before use to make the preparation more palatable. Direct administration of the pure solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed extensively (Ref). Note: Use with caution in patients with latex sensitivity; dropper dispenser contains dry natural rubber.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Use

Treatment of obsessive-compulsive disorder (FDA approved in ages ≥6 years and adults); treatment of major depressive disorder, panic disorder (with or without agoraphobia), posttraumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder (social phobia) (FDA approved in adults).

Medication Safety Issues
Sound-alike/look-alike issues:

Sertraline may be confused with cetirizine, selegiline, Serevent, Soriatane

Zoloft may be confused with Zocor

Older Adult: High-Risk Medication:

Beers Criteria: Selective Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2019]).

Adverse Reactions (Significant): Considerations
Activation of mania or hypomania

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)

Bleeding risk

Selective serotonin reuptake inhibitors (SSRIs), including sertraline, may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematomas, petechiae, purpuric disease and epistaxis to stroke, upper GI bleeding, intracranial hemorrhage, postpartum hemorrhage, and perioperative bleeding, although conflicting evidence also exists (Ref).

Mechanism: Possibly via inhibition of serotonin-mediated platelet activation (inhibition of the serotonin reuptake transporter) and subsequent platelet dysfunction. Sertraline is considered to display high affinity for the serotonin reuptake receptor (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 agents (NSAIDs). For upper GI bleeding, 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 upper GI bleeding (Ref).

Fragility fractures

Limited data from observational studies involving mostly older adults (≥50 years) 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). An increased tendency for falls may also contribute to the increased risk of fractures associated with SSRIs (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).

Hyponatremia

Selective serotonin reuptake inhibitors 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)

Ocular effects

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: 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

Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs but can occur following a single serotonergic agent at therapeutic doses (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 [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.

Sexual dysfunction

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, 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)

Suicidal thinking and behavior

Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults >24 years of age, 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 is associated with major depression and may persist until remission occurs)

Withdrawal syndrome

Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, electric-shock sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), has been reported, primarily following abrupt discontinuation. 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 gradual dosage reduction) of an antidepressant that has lasted >3 weeks, particularly a drug with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)

• Prior history of antidepressant withdrawal symptoms (Ref)

• High dose (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Gastrointestinal: Diarrhea (20%), nausea (26%), xerostomia (14%)

Nervous system: Dizziness (12%), drowsiness (adults: 11%; literature suggests incidence occurs less frequently in children and adolescents compared to adults [Safer 2006]), fatigue (12%), insomnia (20%)

1% to 10%:

Cardiovascular: Edema (<2%), hypertension (<2%), palpitations (4%), syncope (<2%), tachycardia (<2%), vasodilation (<2%)

Dermatologic: Alopecia (<2%), bullous dermatitis (<2%), dermatitis (<2%), diaphoresis (<2%), erythematous rash (<2%), follicular rash (<2%), hyperhidrosis (7%), maculopapular rash (<2%), pruritus (<2%), urticaria (<2%)

Endocrine & metabolic: Decreased libido (4% to 7%) (table 1), diabetes mellitus (<2%), galactorrhea not associated with childbirth (<2%), hypercholesterolemia (<2%), hypoglycemia (<2%), hypothyroidism (<2%), weight loss (>7% of body weight; children: 7%; adolescents: 2%)

Sertraline: Adverse Reaction: Decreased Libido

Drug (Sertraline)

Placebo

Population

Dose

Indication

Number of Patients (Sertraline)

Number of Patients (Placebo)

7%

2%

Males

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,316

973

4%

2%

Females

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,750

1,320

Gastrointestinal: Abdominal pain (≥5%), bruxism (<2%), constipation (6%), decreased appetite (7%), dyspepsia (8%), hematochezia (<2%), increased appetite (<2%), melena (<2%), rectal hemorrhage (<2%), vomiting (adults: 4%; literature suggests incidence is higher in adolescents compared to adults, and is two- to threefold higher in children compared to adults [Safer 2006])

Genitourinary: Ejaculation failure (8%) (table 2), ejaculatory disorder (3%) (table 3), erectile dysfunction (4%) (table 4), hematuria (<2%), priapism (<2%), sexual disorder (males: 2%; literature suggests an incidence ranging from 54% to 63% [Higgins 2010; Montejo 2001]) (table 5), urinary incontinence (≥2%), vaginal hemorrhage (<2%)

Sertraline: Adverse Reaction: Ejaculation Failure

Drug (Sertraline)

Placebo

Dose

Indication

Number of Patients (Sertraline)

Number of Patients (Placebo)

8%

1%

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,316

973

Sertraline: Adverse Reaction: Ejaculatory Disorder

Drug (Sertraline)

Placebo

Dose

Indication

Number of Patients (Sertraline)

Number of Patients (Placebo)

3%

0%

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,316

973

Sertraline: Adverse Reaction: Erectile Dysfunction

Drug (Sertraline)

Placebo

Dose

Indication

Number of Patients (Sertraline)

Number of Patients (Placebo)

4%

1%

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,316

973

Sertraline: Adverse Reaction: Sexual Disorder

Drug (Sertraline)

Placebo

Population

Dose

Indication

Number of Patients (Sertraline)

Number of Patients (Placebo)

2%

0%

Males

Mostly 50 mg to 200 mg per day

Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder

1,316

973

Hematologic & oncologic: Hemorrhage (<2%)

Hepatic: Increased liver enzymes (<2%)

Hypersensitivity: Anaphylaxis (<2%)

Nervous system: Abnormal gait (<2%), agitation (8%), anxiety (children and adolescents: ≥2%), ataxia (<2%), coma (<2%), confusion (<2%), euphoria (<2%), hallucination (<2%), hypertonia (<2%), hypoesthesia (<2%), impaired consciousness (<2%), irritability (<2%), lethargy (<2%), malaise (≥5%), psychomotor agitation (<2%), seizure (<2%), tremor (9%), yawning (<2%)

Neuromuscular & skeletal: Hyperkinetic muscle activity (children and adolescents: ≥2%), muscle spasm (<2%)

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

Otic: Tinnitus (<2%)

Respiratory: Bronchospasm (<2%)

Frequency not defined:

Nervous system: Aggressive behavior

Neuromuscular & skeletal: Arthralgia, muscle twitching

Respiratory: Epistaxis

Miscellaneous: Fever

Postmarketing:

Cardiovascular: Atrial arrhythmia, atrioventricular block, bradycardia, prolonged QT interval on ECG (Beach 2014; Funk 2013), torsades de pointes (Danielsson 2016), vasculitis, ventricular tachycardia (Patel 2013)

Dermatologic: Erythema multiforme (Khan 2012), skin photosensitivity, Stevens-Johnson syndrome (Jan 1999), toxic epidermal necrolysis

Endocrine & metabolic: Gynecomastia (Kaufman 2013), hyperglycemia (Khoza 2011), hyperprolactinemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranging from <1% to as high as 32%) (Jacob 2006; Varela Piñón 2017), menstrual disease, secondary amenorrhea (Ekinci 2019), SIADH (Jacob 2006), weight gain (slight increase, primarily in adults with long-term therapy) (Fava 2000)

Gastrointestinal: Pancreatitis (Malbergier 2004)

Genitourinary: Decreased penile sensation (Bolton 2006), orgasm disturbance (Jing 2016)

Hematologic & oncologic: Agranulocytosis (Trescoli-Serrano 1996), aplastic anemia, coagulation time increased (altered platelet function) (Apseloff 1997), immune thrombocytopenia (Krivy 1995), leukopenia, neutropenia (Ozcanli 2005), pancytopenia, purpuric disease (periorbital) (rare: <1%) (Kayhan 2015)

Hepatic: Hepatic failure, hepatitis (Persky 2003), hepatotoxicity (Persky 2003), jaundice (Verrico 2000)

Hypersensitivity: Angioedema (Gales 1994), hypersensitivity reaction (Dadic-Hero 2011), serum sickness

Nervous system: Akathisia (Madhusoodanan 2010), hyperactive behavior (agitation, hyperactivation, hyperkinesis, restlessness occurring in children at a two- to threefold higher incidence compared to adolescents [Safer 2006]), hypomania (Kumar 2000), intracranial hemorrhage (Douros 2018), mania (Ghaziuddin 1994), neuroleptic malignant syndrome (Stevens 2008), nightmares, psychosis (Popli 1997), reversible cerebral vasoconstriction syndrome (Bain 2013), serotonin syndrome (rare: <1%) (Duignan 2019), suicidal ideation (children and adolescents) (Hammad 2006), suicidal tendencies (children and adolescents) (Hammad 2006), trismus (Holmberg 2018), withdrawal syndrome (Fava 2015)

Neuromuscular & skeletal: Bone fracture (Rabenda 2013), dystonia (Madhusoodanan 2010), lupus-like syndrome (Hussain 2008), rhabdomyolysis (Gareri 2009)

Ophthalmic: Acute angle-closure glaucoma (rare: <1%) (Kirkham 2017), blindness, cataract (Erie 2014), maculopathy (Dang 2016), oculogyric crisis, optic neuritis

Renal: Acute kidney injury

Respiratory: Hypersensitivity pneumonitis (Virdee 2019), pulmonary hypertension

Contraindications

Use of MAOIs including linezolid or methylene blue (concurrently or within 14 days of stopping an MAOI or sertraline); concurrent use with pimozide; hypersensitivity (eg, anaphylaxis, angioedema) to sertraline or any component of the formulation; concurrent use with disulfiram (oral solution only).

Documentation of allergenic cross-reactivity for SSRIs is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

Concerns related to adverse effects:

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

• QT prolongation: QTc prolongation and torsades de pointes have been reported with sertraline use. Most reports involved other risk factors; use with caution in patients with risk factors for QTc prolongation. Studies have shown correlations with serum sertraline concentrations.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and half-life and plasma concentrations are increased; use reduced dose in mild impairment; use is not recommended in moderate or severe impairment (Mauri 2014; manufacturer's labeling).

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

Special populations:

• Pediatric: Monitor growth in pediatric patients. Given their lower body weight, lower doses are advisable in pediatric patients in order to avoid excessive plasma levels, despite slightly greater metabolism efficiency than adults.

Dosage form specific issues:

• Latex sensitivity: Use oral solution formulation with caution in patients with latex sensitivity; dropper dispenser contains dry, natural rubber.

• 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.

• Tartrazine: Capsules contain tartrazine (FD&C Yellow No. 5), which may cause allergic-type reactions (including bronchial asthma) in susceptible individuals, particularly those who also have aspirin sensitivity.

Warnings: Additional Pediatric Considerations

Selective serotonin reuptake inhibitor (SSRI)-associated behavioral activation (ie, restlessness, hyperkinesis, hyperactivity, agitation) is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults. Somnolence (including sedation and drowsiness) is more common in adults compared to children and adolescents and SSRI-associated vomiting is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults (Safer 2006).

Metabolism/Transport Effects

Substrate of CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)

Drug Interactions

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 Lexicomp 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 Lexicomp drug interactions program

Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). 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

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 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). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. 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

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

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

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

Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination

BuPROPion: May enhance the adverse/toxic effect of Sertraline. 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

CarBAMazepine: May decrease the serum concentration of Sertraline. 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

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

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

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Sertraline. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Sertraline. 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 Sertraline. 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

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 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

Dipyrone: May decrease the serum concentration of Sertraline. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination

DULoxetine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of DULoxetine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of DULoxetine. 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

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

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

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

Erythromycin (Systemic): May enhance the adverse/toxic effect of Sertraline. Risk C: Monitor therapy

Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: Sertraline may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Sertraline. 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

Grapefruit Juice: May increase the serum concentration of Sertraline. Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect 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

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

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

Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. 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

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

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

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

Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination

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: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring 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

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

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

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

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 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): 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

Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

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

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

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

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

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) 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

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

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

Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

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

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

Succinylcholine: Sertraline may increase the serum concentration of Succinylcholine. 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

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 (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification

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

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor therapy

Tricyclic Antidepressants: Sertraline may enhance the serotonergic effect of Tricyclic Antidepressants. Sertraline 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 C: Monitor therapy

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

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

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

Vortioxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Vortioxetine 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

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Reproductive Considerations

Sertraline is approved for the treatment of unipolar major depressive disorder. If treatment for major depressive disorder is initiated for the first time in patients planning to become pregnant, sertraline is one of the preferred selective serotonin reuptake inhibitors (SSRIs) (Larsen 2015).

Sertraline 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).

SSRIs may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido has been reported in females and males; ejaculation failure, ejaculation dysfunction, and ejaculation disorders have been reported in males with sertraline use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with sertraline is not known. 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).

Sertraline 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 patients planning to father a child (Althof 2014; Siroosbakht 2019; Sylvester 2019).

Pregnancy Considerations

Sertraline crosses the human placenta. Cord blood and amniotic fluid concentrations are less than those in the maternal serum; concentrations in the amniotic fluid correlate with maternal dose (Newport 2003; Paulzen 2017).

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 sertraline may be altered. Serum concentrations may be decreased in the third trimester; however, due to the wide therapeutic reference range, dose adjustments may not be needed. 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 (Schoretsanitis 2020).

If treatment for major depressive disorder is initiated for the first time during pregnancy, sertraline is one of the preferred SSRIs (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]). 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).

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/).

Monitoring Parameters

Weight, height, BMI (longitudinal monitoring); closely monitor patients for depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, social functioning), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures; serum sodium in at-risk populations.

Mechanism of Action

Antidepressant with selective inhibitory effects on presynaptic serotonin (5-HT) reuptake and only very weak effects on norepinephrine and dopamine neuronal uptake. In vitro studies demonstrate no significant affinity for adrenergic, cholinergic, GABA, dopaminergic, histaminergic, serotonergic, or benzodiazepine receptors.

Pharmacokinetics (Adult data unless noted)

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 2012]); 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 2012]).

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 2006).

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]).

Protein binding: 98%.

Metabolism: Hepatic; may involve CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (Chen 2020; Markowitz 2000; Rajasingham 2018); extensive first pass metabolism; forms metabolite N-desmethylsertraline (APA [Gelenberg 2010]); Note: Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels).

Bioavailability: Bioavailability of tablets and solution are equivalent.

Half-life elimination: Sertraline: Mean: 26 hours; N-desmethylsertraline (not as active as parent drug): 62 to 104 hours.

Children 6 to 12 years: Mean: 26.2 hours (Alderman 1998).

Children 13 to 17 years: Mean: 27.8 hours (Alderman 1998).

Adults 18 to 45 years: Mean: 27.2 hours (Alderman 1998).

Time to peak, plasma: Sertraline: 4.5 to 8.4 hours.

Excretion: Urine (40% to 45% as metabolites); feces (40% to 45%; 12% to 14% as unchanged drug).

Pharmacokinetics: Additional Considerations

Altered kidney function: Sertraline clearance was reduced in patients with chronic mild liver impairment resulting in a 3-fold greater exposure. Sertraline Cmax, AUC and half-life were 1.7-fold, 4-fold, and 2.5-fold higher following a single dose of sertraline in patients with stable chronic cirrhosis (Démolis 1996).

Pediatric: Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels)

Older adult: Plasma clearance 40% lower; steady state achieved after 2 to 3 weeks

Pricing: US

Capsules (Sertraline HCl Oral)

150 mg (per each): $5.88

200 mg (per each): $5.88

Concentrate (Sertraline HCl Oral)

20 mg/mL (per mL): $0.68 - $1.13

Concentrate (Zoloft Oral)

20 mg/mL (per mL): $5.31

Tablets (Sertraline HCl Oral)

25 mg (per each): $0.05 - $2.87

50 mg (per each): $0.06 - $2.87

100 mg (per each): $0.05 - $2.87

Tablets (Zoloft Oral)

25 mg (per each): $15.45

50 mg (per each): $15.45

100 mg (per each): $15.45

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.

Brand Names: International
  • Adjuvin (AT, RO);
  • Agrelocit (EG);
  • Aleval (MX, RU);
  • Altisben (ES);
  • Altruline (CR, DO, GT, HN, MX, NI, PA, SV);
  • Aluprex (MX);
  • Andep (BD);
  • Aremis (ES);
  • Asentra (CZ, HU, LV, NL, PL, PT, UA);
  • Aserin (ES);
  • Aurasert (BH, MY);
  • Besiran (ES);
  • Censir (IN);
  • Chear (BD);
  • Conexine (EC);
  • Deprax (CL, PY);
  • Depreger (IE);
  • Deprine (LB);
  • Deptral (ID);
  • Dominum (CO);
  • Doxime (PY);
  • Eleva (AU);
  • Eleval (CL);
  • Emergen (PE);
  • Enore (NL);
  • Episod (IN);
  • Fatral (ID);
  • Freedep (LK);
  • Fridep (ID);
  • Iglodep (ID);
  • Inosert (SG);
  • J Zoloft (JP);
  • Lesefer (CO);
  • Linsed (IN);
  • Lomaz (VE);
  • Lustral (EG, GB, IE, IL, MT, SA, TR);
  • Lustraline (TW);
  • Nudep (ID);
  • Oralin (SE);
  • Prosertin (MX);
  • Selrotine (TH);
  • Seltra (KR);
  • Seralin (CH);
  • Serdep (HK, LK);
  • Sered (VE);
  • Serenada (IL);
  • Serenata (BR, PH);
  • Serenorm (EG);
  • Seretral (IE);
  • Serimel (IE);
  • Serlain (BE);
  • Serlife (ZA);
  • Serlift (RU, TH, UA, VN);
  • Serlin (TH);
  • Sernade (PH);
  • Serolox (CR, GT, HN, NI, PA, SV);
  • Serolux (DO, MX);
  • Sertadepi (HU);
  • Sertex (MX);
  • Sertra (AU, TH);
  • Sertral (MT);
  • Sertram (KR);
  • Sertranex (AE, CO, CY, IL, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE);
  • Sertranquil (CO);
  • Sertrix (DK);
  • Setaloft (CZ, HK);
  • Setra (BD);
  • Setrax (CO);
  • Setrof (HK);
  • Setrona (AU, NO, NZ);
  • Solotik (BH, LB);
  • Somidal (PT);
  • Sosser (CO);
  • Starin (TH);
  • Startline-50 (PH);
  • Stimuloten (HK);
  • Stimuloton (BM, BS, BZ, GY, JM, SR, TT);
  • Suprisec (CR, DO, GT, HN, NI, PA, SV);
  • Syche (BD);
  • Tatig (IT);
  • Tralisen (IT);
  • Tralix (DK);
  • Tresleen (AT);
  • Xydep (AU);
  • You-Jet (TW);
  • Zeleft (TR);
  • Zerlin (ID, LK);
  • Zolodin (PH);
  • Zoloft (AE, AR, AU, BB, BF, BG, BH, BJ, BM, BR, BS, BZ, CH, CI, CN, CY, CZ, DE, DK, EC, EE, ET, FI, FR, GH, GM, GN, GR, GY, HK, HR, HU, IQ, IR, IS, IT, JM, JO, KE, KR, KW, LB, LR, LT, LV, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, NZ, OM, PE, PH, PK, PL, PT, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SR, SY, TH, TN, TT, TW, TZ, UA, UG, UY, VE, YE, ZA, ZM, ZW);
  • Zolotral (PH);
  • Zortal (GR);
  • Zosert (LK);
  • Zotaline (TH);
  • Zotral (PL);
  • Zylin (ZA)


For country code abbreviations (show table)
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