Sertraline (Lexi-Drugs)

ALERT: US Boxed Warning
  Suicidality and antidepressant drugs:
Pronunciation

(SER tra leen)

Brand Names: US

Zoloft

Brand Names: Canada

ACT Sertraline [DSC]; AG-Sertraline; APO-Sertraline; Auro-Sertraline; BIO-Sertraline; DOM-Sertraline; GD-Sertraline [DSC]; JAMP-Sertraline; Mar-Sertraline; MINT-Sertraline; MYLAN-Sertraline [DSC]; PHL-Sertraline [DSC]; PMS-Sertraline; Priva-Sertraline; Q-Sertraline [DSC]; RAN-Sertraline; RIVA-Sertraline; SANDOZ Sertraline; TEVA-Sertraline; VAN-Sertraline; Zoloft

Dosing: Adult

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 (Hirsch 2018b; Stein 2019; WFSBP [Bandelow 2012]).

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 (Leombruni 2008). Based on limited data, some experts recommend doses used for major depressive disorder and slower titrations (eg, ≥1 week) (Sysko 2018).

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 (Phillips 2019). 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 (Phillips 2019).

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 (Milano 2004; Sloan 2004). Maximum dose: 300 mg/day (Crow 2019).

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 (Ball 2005; Brawman-Mintzer 2006; Dahl 2005).

Major depressive disorder (MDD) (unipolar): 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 (Simon 2018). More rapid titrations (every 3 days) in combination with an antipsychotic (eg, olanzapine) are used by some experts for patients with psychotic features (Meyers 2009; Rothschild 2018).

Obsessive-compulsive disorder: 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 (Ninan 2006), but adverse effects may be increased.

Panic disorder: Oral: Initial: 25 mg once daily for 3 to 7 days, then increase to 50 mg/day (APA 2009); 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 (PTSD): Oral: Initial: 25 to 50 mg once daily (VA/DoD 2017); 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 (Stein 2018).

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 (McMahon 1998b; Mendels 1995)

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 150 mg/day may be necessary in some patients for optimal response (Casper 2019).

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 (Casper 2019).

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 (Casper 2019).

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 (Yonkers 2015; manufacturer’s labeling).

Social anxiety disorder: Oral: Initial: 25 to 50 mg once daily (WFSBP [Bandelow 2012]); 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

Discontinuation of therapy: When discontinuing antidepressants, gradually taper the dose (eg, over 2 to 4 weeks) to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower titration (eg, over 4 weeks) include use of a drug with a half-life <24 hours (eg, paroxetine, venlafaxine), prior history of antidepressant withdrawal symptoms, high doses of antidepressants or treatment duration >3 weeks (APA 2010; Hirsch 2018a). If intolerable withdrawal symptoms occur following a dose reduction, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

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 (Hirsch 2018c; Ogle 2013; WFSBP [Bauer 2013]).

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.

Dosing: Geriatric

Use with caution (Beers Criteria [AGS 2015]). Refer to adult dosing; however, lower initial doses (25 mg once daily) may be better tolerated in older adults (Hirsch 2018b).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

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: Pediatric

Depression: Limited data available: Oral:

Children 6 to 12 years: Initial: 12.5 to 25 mg once daily; titrate dose upwards if clinically needed; may increase by 25 to 50 mg/day increments at intervals of at least 1 week; mean final dose in 21 children (8 to 18 years of age) was 100 ± 53 mg or 1.6 mg/kg/day (n=11); range: 25 to 200 mg/day; maximum daily dose: 200 mg/day (Dopheide 2006; Tierney 1995); avoid excessive dosing

Adolescents 13 to 17 years: Initial 25 to 50 mg once daily; titrate dose upwards if clinically needed; may increase by 50 mg/day increments at intervals of at least 1 week; mean final dose in 13 adolescents was 110 ± 50 mg or about 2 mg/kg/day (McConville 1996); in another study using a slower titration, the mean dose at week 6 was 93 mg (n=41) and at week 10 was 127 mg (n=34) (Ambrosini 1999); range: 25 to 200 mg/day; maximum daily dose: 200 mg/day (Dopheide 2006).

Obsessive-compulsive disorder: Oral:

Children 6 to 12 years: 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; avoid excessive dosing

Adolescents 13 to 17 years: 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

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

MAO inhibitor recommendations:

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

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

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

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

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

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

Dosing: Renal 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: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied). Use with caution due to extensive hepatic metabolism and risk of increased exposure. A lower dose or less frequent dosing is recommended. Use with caution and in reduced doses.

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder (MDD) in adults.

Obsessive-compulsive disorder: Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD).

Panic disorder: Treatment of panic disorder in adults with or without agoraphobia.

Posttraumatic stress disorder: Treatment of posttraumatic stress disorder (PTSD) in adults.

Premenstrual dysphoric disorder: Treatment of premenstrual dysphoric disorder (PMDD) in adults.

Social anxiety disorder: Treatment of social anxiety disorder (social phobia) in adults.

Use: Off-Label: Adult

  Binge eating disorderLevel of Evidence [B, G]

Data from two small, double-blind, randomized, controlled trials support the use of sertraline to improve weight loss, binge frequency, and binge behaviors in patients with binge eating disorder Ref.

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of eating disorders, sertraline may be effective and is recommended in the management of binge eating disorder Ref.

  Body dysmorphic disorderLevel of Evidence [G]

Based on the National Institute for Health and Care Excellence (NICE) guidelines for treatment of obsessive-compulsive disorder and body dysmorphic disorder, SSRIs given as monotherapy or in combination with cognitive behavior therapy are recommended in the management of body dysmorphic disorder in adults with moderate or severe functional impairment, respectively.

  Bulimia nervosaLevel of Evidence [B]

Data from one small, randomized, controlled trial and another study of lower quality (open-label, flexible-dose study) in patients with bulimia nervosa support the use of sertraline to reduce the number of binge eating crises and purging in these patients Ref.

  Generalized anxiety disorderLevel of Evidence [A, G]

Data from several double-blind, randomized, controlled trials in patients with generalized anxiety disorder, support the use of sertraline to reduce anxiety symptoms in these patients Ref.

Based on the World Federation of Societies of Biological Psychiatry guidelines for the pharmacological treatment of anxiety disorders, sertraline is effective and recommended in the management of generalized anxiety disorder Ref.

  Premature ejaculationLevel of Evidence [B, G]

Data from randomized controlled trials suggest that sertraline may be beneficial for the treatment of premature ejaculation Ref.

According to the International Society for Sexual Medicine guidelines, sertraline is effective and recommended in the management of premature ejaculation; however, paroxetine may have a more robust effect. Access Full Off-Label Monograph

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Anxiety Disorders:

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Panic Disorder,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Biliary Cirrhosis:

American Association for the Study of Liver Diseases (AASLD), “Primary Biliary Cirrhosis,” 2009

Binge Eating Disorder:

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Eating Disorders,” 2011

Bipolar Disorder:

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD), “Collaborative Update of CANMAT Guidelines for the Management of Patients with Bipolar Disorder – Update 2013,” February 2013

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania,” 2009

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the Long-term Treatment of Bipolar Disorder,” 2013

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

Canadian Network for Mood and Anxiety Treatments (CANMAT), “Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments,” 2016

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013.

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder and Treatment of Chronic Depressive Disorders and Subthreshold Depressions,” 2002.

Eating Disorders:

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Eating Disorders,” 2011

Obsessive-Compulsive Disorder (OCD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder,” 2007

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Premature Ejaculation:

International Society of Sexual Medicine, “An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE),” 2014

Post Traumatic Stress Disorder (PTSD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” Guideline Watch (March 2009)

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision,” 2008

World Federation of Societies of Biological Psychiatry (WFSBP), “Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorder in Primary Care,” 2012

Administration: Oral

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 (Pfizer Medical Information, written communication, February 2, 2016). Note: Use with caution in patients with latex sensitivity; dropper dispenser contains dry natural rubber.

Administration: Pediatric

Oral: May be administered without regard to food; do not administer with grapefruit juice; administer once daily dosage either in morning or evening.

Oral concentrate: Must dilute oral concentrate before use; measure dose with dropper provided and mix with 4 ounces of water, orange juice, lemonade, ginger ale, or lemon/lime soda; do not mix with other liquids; take dose immediately after mixing, do not mix ahead of time; sometimes a slight haze may be seen after mixing (this is normal). 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).

Preparation for Administration: Adult

Oral solution: Must be diluted before use. Immediately before administration, use the dropper provided to measure the required amount of solution; mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice only. Do not mix with any other liquids than these. The dose should be taken immediately after mixing; do not mix in advance. A slight haze may appear after mixing; this is normal.

Preparation for Administration: Pediatric

Oral concentrate: Must be diluted before use. Immediately before administration, use the dropper provided to measure the required amount of concentrate; mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice only. Do not mix with any other liquids than these. The dose should be taken immediately after mixing; do not mix in advance. A slight haze may appear after mixing; this is normal.

Medication Patient Education with HCAHPS Considerations

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

• Patient may experience dizziness, fatigue, loss of strength and energy, anxiety, nausea, dry mouth, diarrhea, constipation, insomnia, sweating a lot, tremors, abdominal pain, or lack of appetite. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of serotonin syndrome (dizziness, severe headache, agitation, hallucinations, tachycardia, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), abnormal heartbeat, tachycardia, passing out, vision changes, eye pain, eye irritation, eye edema, eye redness, agitation, panic attacks, irritability, behavioral changes, angina, seizures, urinary incontinence, severe headache, excessive weight gain or loss, decreased libido, menstrual changes, sexual dysfunction, or priapism (HCAHPS).

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

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

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019839S74S86S87_20990S35S44S45lbl.pdf, must be dispensed with this medication.

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

Major psychiatric warnings:

• [US Boxed Warning]: Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.

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

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

Concerns related to adverse effects:

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

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

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

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

• 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.

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

• Sexual dysfunction: May cause or exacerbate sexual dysfunction.

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

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and plasma concentrations are increased; use reduced dose in mild impairment; use is not recommended in moderate or severe impairment.

• Mania/hypomania: May precipitate a mixed/manic episode in patients at risk for bipolar disorder. Use with caution in patients with a family history of bipolar disorder, mania, or hypomania. Patients presenting with depressive symptoms should be screened for bipolar disorder. Sertraline is not FDA approved for the treatment of bipolar depression.

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

Concurrent drug therapy issues:

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

Special populations:

• 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.

Other warnings/precautions:

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

Geriatric Considerations

Sertraline’s favorable side effect profile makes it a preferred SSRI in older adults. It has the shortest half-life of the currently marketed serotonin-reuptake inhibitors. The elderly are more prone to SSRI/SNRI-induced hyponatremia.

A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence “suggestive” of efficacy but not of sufficient strength to “confirm” efficacy (Nelson 2011). Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects.

Warnings: Additional Pediatric Considerations

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).

Pregnancy Considerations

Sertraline crosses the human placenta. Available studies evaluating teratogenic effects following maternal use of sertraline in the first trimester have not shown an overall increased risk of major birth defects. Studies evaluating specific birth defects have provided inconsistent results. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require adjusted doses of sertraline to achieve euthymia. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

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

Breast-Feeding Considerations

Sertraline and the active metabolite desmethylsertraline are present in breast milk.

Using pooled data, the relative infant dose (RID) of sertraline was calculated to be 0.5% to 3.0% of the weight-adjusted maternal dose (Berle 2011); a RID of 3.7% was noted in one review (Orsolini 2015). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000); however, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015). When an RID is >25%, breastfeeding should generally be avoided (Anderson 2016; Ito 2000). When evaluated, desmethylsertraline milk concentrations were higher than sertraline (Stowe 1997; Stowe 2003). Peak milk concentrations occurred 7 to 8 hours (sertraline) and 5 to 11 hours (desmethylsertraline) after the maternal dose (Stowe 1997). However, avoiding breastfeeding during the expected peak concentrations will generally not decrease infant exposure significantly for antidepressants with long half-lives (Berle 2011). Most available studies evaluated serum concentrations of sertraline in the breastfeeding infant as opposed to those in breast milk. Using data from 53 mother-infant pairs, the manufacturer notes sertraline concentrations in exclusively breastfed infants is 2% (range: 0% to 15%) of the mothers serum concentration.

Adverse events have been reported in breastfeeding infants following maternal use of sertraline in some studies (Hale 2010; Müller 2013; Uguz 2016). Infants of mothers using psychotropic medications should be monitored daily for changes in sleep, feeding patterns, and behavior (Bauer 2013) as well as infant growth and neurodevelopment (Sachs 2013; Sriraman 2015). Maternal use of an SSRI during pregnancy may cause delayed lactogenesis (Marshall 2010).

When first initiating an antidepressant in a breastfeeding woman, sertraline is one of the preferred agents. Women successfully treated with sertraline during pregnancy may continue use while breastfeeding if there are no other contraindications (Berle 2011). According to the manufacturer, the decision to breastfeed during therapy should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

>10%:

Central nervous system: Insomnia (20%), dizziness (12%), fatigue (12%), drowsiness (11%)

Gastrointestinal: Nausea (26%), diarrhea (20%), xerostomia (14%)

1% to 10%:

Cardiovascular: Palpitations (4%), edema (<2%), hypertension (<2%), syncope (<2%), tachycardia (<2%), vasodilation (<2%)

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

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

Endocrine & metabolic: Decreased libido (4% to 7%), weight loss (>7% of body weight; children: 7%; adolescents: 2%), diabetes mellitus (<2%), galactorrhea (<2%), hypercholesterolemia (<2%), hypoglycemia (<2%), hypothyroidism (<2%)

Gastrointestinal: Dyspepsia (8%), decreased appetite (7%), constipation (6%), abdominal pain (≥5%), vomiting (4%), bruxism (<2%), hematochezia (<2%), increased appetite (<2%), melena (<2%)

Genitourinary: Ejaculation failure (8%), erectile dysfunction (4%), ejaculatory disorder (3%), urinary incontinence (≥2%), sexual disorder (males: 2%), hematuria (<2%), priapism (<2%), vaginal hemorrhage (<2%)

Hematologic & oncologic: Hemorrhage (<2%), rectal hemorrhage (<2%)

Hepatic: Increased liver enzymes (<2%)

Hypersensitivity: Anaphylaxis (<2%)

Neuromuscular & skeletal: Tremor (9%), hyperkinesia (children and adolescents: ≥2%), muscle spasm (<2%)

Ophthalmic: Visual disturbance (4%), blurred vision (<2%), mydriasis (<2%)

Otic: Tinnitus (<2%)

Respiratory: Bronchospasm (<2%)

Frequency not defined:

Central nervous system: Aggressive behavior

Hematologic & oncologic: Purpura

Neuromuscular & skeletal: Arthralgia, muscle twitching

Respiratory: Epistaxis

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Acute renal failure, agranulocytosis, angioedema, angle-closure glaucoma, aplastic anemia, atrial arrhythmia, atrioventricular block, blindness, bradycardia, cataract, cerebrovascular spasm (including Call-Fleming syndrome, reversible cerebral vasoconstriction syndrome), coagulation time increased (altered platelet function), diabetes mellitus, edema, extrapyramidal reaction (including akathisia, dystonia), gynecomastia, hepatic failure, hepatitis, hyperglycemia, hyperprolactinemia, hypersensitivity reaction, hypomania, hyponatremia, jaundice, leukopenia, lupus-like syndrome, mania, menstrual disease, neuroleptic malignant syndrome (Stevens 2008), nightmares, oculogyric crisis, optic neuritis, pancreatitis, pancytopenia, prolonged Q-T interval on ECG, psychosis, pulmonary hypertension, rhabdomyolysis, serotonin syndrome, serum sickness, SIADH, skin photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, torsades de pointes, toxic epidermal necrolysis, trismus, vasculitis, ventricular tachycardia, withdrawal syndrome

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

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

Drug Interactions 

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

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

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 Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy

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

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

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

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. 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. Specifically, the risk for seizures and serotonin syndrome may be increased. Risk C: Monitor therapy

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

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

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 adverse/toxic effect of Serotonin Modulators. 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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

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

Disulfiram: May enhance the adverse/toxic effect of Sertraline. This is specifically related to sertraline oral concentrate due to its alcohol content (12%). Management: Sertraline Oral Concentrate contains 12% alcohol, and its use should be avoided with disulfiram. Risk X: Avoid combination

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

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

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

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

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Fosphenytoin: May decrease the serum concentration of Sertraline. Sertraline may increase the serum concentration of Fosphenytoin. 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

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

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

Haloperidol: QT-prolonging Agents (Indeterminate Risk – Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

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

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

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

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. Management: Consider alternatives to this combination whenever possible. If clinically acceptable, wait at least 2 weeks (5 weeks for fluoxetine) after SSRI discontinuation to initiate linezolid. Risk D: Consider therapy modification

Linezolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely. Risk D: Consider therapy modification

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

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

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

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Risk C: Monitor therapy

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

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

Mivacurium: Sertraline may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

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

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 using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification

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

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

Opioid Agonists: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. 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: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Risk C: Monitor therapy

Phenytoin: Sertraline may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Sertraline. Risk C: Monitor therapy

Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk X: Avoid combination

Propafenone: Sertraline may enhance the QTc-prolonging effect of Propafenone. Sertraline may increase the serum concentration of Propafenone. Risk C: Monitor therapy

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 – 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

RisperiDONE: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of RisperiDONE. Risk C: Monitor therapy

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

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

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

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

Succinylcholine: Sertraline may increase the serum concentration of Succinylcholine. Risk C: Monitor therapy

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

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

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

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

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

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

Test Interactions

May interfere with urine detection of benzodiazepines (false-positive)

Monitoring Parameters

Weight, height, BMI (longitudinal monitoring); mental status for depression, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased), anxiety, social functioning, mania, panic attacks, or other unusual changes in behavior; signs/symptoms of serotonin syndrome; serum sodium in at-risk populations.

Advanced Practitioners Physical Assessment/Monitoring

Assess mental status for worsening of depression, suicide ideation, anxiety, social functioning, mania, or panic attack (especially during initiation of therapy and when dosage is changed). Taper dosage slowly with initiation and discontinuation. Pediatric patients: Monitor growth pattern.

Nursing Physical Assessment/Monitoring

Assess mental status for worsening of depression, suicide ideation, anxiety, social functioning, mania, or panic attack (especially during initiation of therapy and when dosage is changed). Pediatric patients: Monitor growth pattern.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Concentrate, Oral:

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

Generic: 20 mg/mL (60 mL)

Tablet, Oral:

Zoloft: 25 mg [scored; contains fd&c blue #1 aluminum lake, fd&c red #40 aluminum lake, fd&c yellow #10 aluminum lake, polysorbate 80]

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

Zoloft: 100 mg [scored; contains polysorbate 80]

Generic: 25 mg, 50 mg, 100 mg

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, FD&C YELLOW #10 (QUINOLINE YELLOW)]

Zoloft: 50 mg [contains FD&C YELLOW #10 (QUINOLINE YELLOW), FD&C YELLOW #6 (SUNSET YELLOW)]

Zoloft: 100 mg [contains FD&C RED #40, FD&C YELLOW #10 (QUINOLINE YELLOW)]

Generic: 25 mg, 50 mg, 100 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • N06AB06
Generic Available (US)

Yes

Pricing: US

Concentrate (Sertraline HCl Oral)

20 mg/mL (per mL): $1.12

Tablets (Sertraline HCl Oral)

25 mg (per each): $2.71 – $2.85

50 mg (per each): $2.84 – $2.85

100 mg (per each): $2.84 – $2.92

Tablets (Zoloft Oral)

25 mg (per each): $13.38

50 mg (per each): $13.38

100 mg (per each): $13.38

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.

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.

Pharmacodynamics/Kinetics

Onset of action: Depression: The onset of action is within a week, however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment (APA [Gelenberg 2010]).

Protein binding: 98%

Metabolism: Hepatic; may involve CYP2C19 and CYP2D6; 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: 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)

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Sertraline clearance was reduced in patients with chronic mild liver impairment resulting in a 3-fold greater exposure.

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)

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

Local Anesthetic/Vasoconstrictor Precautions

Although caution should be used in patients taking tricyclic antidepressants, no interactions have been reported with vasoconstrictor and sertraline, a nontricyclic antidepressant which acts to increase serotonin; no precautions appear to be needed

Dental Health Professional Considerations

Problems with SSRI-induced bruxism have been reported and may preclude their use; clinicians attempting to evaluate any patient with bruxism or involuntary muscle movement, who is simultaneously being treated with an SSRI drug, should be aware of the potential association.

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) (see Effects on Bleeding and Dental Health Professional Considerations).

Effects on Bleeding

May impair platelet aggregation resulting in increased risk of bleeding events, particularly if used concomitantly with aspirin, NSAIDs, warfarin, or other anticoagulants. Bleeding related to SSRI use has been reported to range from relatively minor bruising and epistaxis to life-threatening hemorrhage. Routine interruption of therapy for most dental procedures is not warranted. In medically complicated patients or extensive oral surgery, the decision to interrupt therapy must be based on the risk to benefit in an individual patient and a medical consult is suggested. If therapy is continued without interruption, the clinician should anticipate the potential for a prolonged bleeding time.

Index Terms

Sertraline HCl; Sertraline Hydrochloride

FDA Approval Date
December 30, 1991
References

Aigner M, Treasure J, Kaye W, Kasper S; WFSBP Task Force on Eating Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of eating disorders. World J Biol Psychiatry. 2011;12(6):400-443. doi: 10.3109/15622975.2011.602720.[PubMed 21961502]

Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597.[PubMed 3960626]

Alderman J, Wolkow R, Chung M, et al. Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy. J Am Acad Child Adolesc Psychiatry. 1998;37(4):386-394.[PubMed 9549959]

Althof SE, McMahon CG, Waldinger MD, et al. An update of the International Society of Sexual Medicine’s guidelines for the diagnosis and treatment of premature ejaculation (PE). Sex Med. 2014;2(2):60-90. doi: 10.1002/sm2.28.[PubMed 25356302]

Ambrosini PJ, Wagner KD, Biederman J, et al. Multicenter open-label sertraline study in adolescent outpatients with major depression. J Am Acad Child Adolesc Psychiatry. 1999;38(5):566-572.[PubMed 10230188]

American College of Obstetricians and Gynecologists, ACOG Practice Bulletin: Clinical Management Guidelines for Obstetricians-Gynecologists No. 92 April 2008 (Replaces Practice Bulletin Number 87, November 2007), “Use of Psychiatric Medications During Pregnancy and Lactation,” Obstet Gynecol, 2008, 111(4):1001-20.[PubMed 18378767]

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227-2246. doi:10.1111/jgs.13702[PubMed 26446832]

American Psychiatric Association (APA). Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Published October 2010. Accessed May 2018.

American Psychiatric Association (APA). Practice guideline for the treatment of patients with panic disorder. 2nd edition.http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf. Published January 2009. Accessed May 2018.

Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52.[PubMed 27060684]

Arafa M, Shamloul R. Efficacy of sertraline hydrochloride in treatment of premature ejaculation: a placebo-controlled study using a validated questionnaire. Int J Impot Res. 2006;18(6):534-538.[PubMed 16554853]

Ball SG, Kuhn A, Wall D, Shekhar A, Goddard AW. Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline. J Clin Psychiatry. 2005;66(1):94-99.[PubMed 15669894]

Bandelow B, Zohar J, Hollander E, Kasper S, Möller HJ; WFSBP Task Force on Treatment Guidelines for Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders – first revision. World J Biol Psychiatry. 2008;9(4):248-312. doi: 10.1080/15622970802465807.[PubMed 18949648]

Bandelow B, Sher L, Bunevicius R, et al; WFSBP Task Force on Mental Disorders in Primary Care; WFSBP Task Force on Anxiety Disorders, OCD and PTSD. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care [published corrections appear in: Int J Psychiatry Clin Pract. 2012;16(3):242. Int J Psychiatry Clin Pract. 2013;17(1):76]. Int J Psychiatry Clin Pract. 2012;16(2):77-84. doi: 10.3109/13651501.2012.667114.[PubMed 22540422]

Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Möller HJ; World Federation of Societies of Biological Psychiatry Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013;14(5):334-385.[PubMed 23879318]

Bauer M, Severus E, Köhler S, Whybrow PC, Angst J, Möller HJ; WFSBP Task Force on Treatment Guidelines for Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 2: maintenance treatment of major depressive disorder-update 2015. World J Biol Psychiatry. 2015;16(2):76-95. doi: 10.3109/15622975.2014.1001786.[PubMed 25677972]

Berle JO, Spigset O. Antidepressant use during breastfeeding. Curr Womens Health Rev. 2011;7(1):28-34.[PubMed 22299006]

Brawman-Mintzer O, Knapp RG, Rynn M, Carter RE, Rickels K. Sertraline treatment for generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2006;67(6):874-881.[PubMed 16848646]

Casper RF, Yonkers KA. Treatment of premenstrual syndrome and premenstrual dysphoric disorder. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 21, 2019.

Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. http://www.cdc.gov/mmwr/preview/mmwrhtml/00000319.htm.[PubMed 6423951]

Crow SJ. Bulimia nervosa in adults: Pharmacotherapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 3, 2019.

Dahl AA, Ravindran A, Allgulander C, Kutcher SP, Austin C, Burt T. Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors. Acta Psychiatr Scand. 2005;111(6):429-435.[PubMed 15877709]

Dopheide JA. Recognizing and treating depression in children and adolescents. Am J Health Syst Pharm. 2006;63(3):233-243.[PubMed 16434782]

Fava M. Prospective studies of adverse events related to antidepressant discontinuation. J Clin Psychiatry. 2006; 67(suppl 4):14-21.[PubMed 16683858]

Haddad PM. Antidepressant discontinuation syndromes. Drug Saf. 2001;24(3):183-197.[PubMed 11347722]

Hale TW, Kendall-Tackett K, Cong Z, et al, “Discontinuation Syndrome in Newborns Whose Mothers Took Antidepressants While Pregnant or Breastfeeding,” Breastfeed Med, 2010, 5(6):283-8.[PubMed 20807106]

Hirsch M, Birnbaum RJ. Discontinuing antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 11, 2018a.

Hirsch M, Birnbaum RJ. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 18, 2018b.

Hirsch M, Birnbaum RJ. Switching antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 11, 2018c.

Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313.[PubMed 12534540]

Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126.[PubMed 10891521]

Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28.[PubMed 26344706]

Leombruni P, Pierò A, Lavagnino L, Brustolin A, Campisi S, Fassino S. A randomized double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with binge eating disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1599-1605.[PubMed 18598735]

Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172.[PubMed 10985636]

Marshall AM, Nommsen-Rivers LA, Hernandez LL, et al, “Serotonin Transport and Metabolism in the Mammary Gland Modulates Secretory Activation and Involution,” J Clin Endocrinol Metab, 2010, 95(2):837-46.[PubMed 19965920]

McConville BJ, Minnery KL, Sorter MT, West SA, Friedman LM, Christian K. An open study of the effects of sertraline on adolescent major depression. J Child Adolesc Psychopharmacol. 1996;6(1):41-51.[PubMed 9231298]

McElroy SL, Casuto LS, Nelson EB, et al. Placebo-controlled trial of sertraline in the treatment of binge eating disorder. Am J Psychiatry. 2000;157(6):1004-1006.[PubMed 10831483]

McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride: a single-blind placebo controlled crossover study. J Urol. 1998a;159(6):1935-1938.[PubMed 9598491]

McMahon CG. Treatment of premature ejaculation with sertraline hydrochloride. Int J Impot Res. 1998b;10(3):181-184; discussion 185.[PubMed 9788108]

Mendels J, Camera A, Sikes C. Sertraline treatment for premature ejaculation. J Clin Psychopharmacol. 1995;15(5):341-346.[PubMed 8830065]

Meyers BS, Flint AJ, Rothschild AJ, et al; STOP-PD Group. A double-blind randomized controlled trial of olanzapine plus sertraline vs olanzapine plus placebo for psychotic depression: the study of pharmacotherapy of psychotic depression (STOP-PD) [published correction appears in Arch Gen Psychiatry. 2011 Jun;68(6):626]. Arch Gen Psychiatry. 2009;66(8):838-847. doi:10.1001/archgenpsychiatry.2009.79.[PubMed 19652123]

Milano W, Petrella C, Sabatino C, Capasso A. Treatment of bulimia nervosa with sertraline: a randomized controlled trial. Adv Ther. 2004;21(4):232-237.[PubMed 15605617]

Müller MJ, Preuß C, Paul T, Streit F, Brandhorst G, Seeliger S. Serotonergic overstimulation in a preterm infant after sertraline intake via breastmilk. Breastfeed Med. 2013;8(3):327-329.[PubMed 23249132]

National Institute for Health and Care Excellence (NICE). Obsessive-compulsive disorder and body dysmorphic disorder: treatment. https://www.nice.org.uk/guidance/cg31. Published November 2005. Accessed July 6, 2018.

Ninan PT, Koran LM, Kiev A, et al. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial. J Clin Psychiatry. 2006;67(1):15-22.[PubMed 16426083]

Ogle NR, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract. 2013;26(4):389-396. doi: 10.1177/0897190012467210.[PubMed 23459282]

Orsolini L, Bellantuono C. Serotonin reuptake inhibitors and breastfeeding: a systematic review. Hum Psychopharmacol. 2015;30(1):4-20.[PubMed 25572308]

Pfizer Medical Information, written communication, February 2, 2016.

Phillips KA. Body dysmorphic disorder: Choosing treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 8, 2019.

Rabenda V, Nicolet D, Beaudart C, et al. Relationship between use of antidepressants and risk of fractures: a meta-analysis [published online ahead of print May 26, 2012]. Osteoporos Int. 2013;24(1):127-137.[PubMed 22638709]

Rizzoli R, Cooper C, Reginster JY, et al. Antidepressant medications and osteoporosis. Bone. 2012; 51(3):606-613.[PubMed 22659406]

Rothschild AJ. Unipolar major depression with psychotic features: acute treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 17, 2018.

Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-809.[PubMed 23979084]

Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8980):1312-1313.[PubMed 7746084]

Shelton, RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174.[PubMed 15014601]

Simon G. Unipolar major depression in adults: Choosing initial treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2018.

Sloan DM, Mizes JS, Helbok C, Muck R. Efficacy of sertraline for bulimia nervosa. Int J Eat Disord. 2004;36(1):48-54.[PubMed 15185271]

Sriraman NK, Melvin K, Meltzer-Brody S. ABM clinical protocol #18: use of antidepressants in breastfeeding mothers. Breastfeed Med. 2015;10(6):290-299.[PubMed 26204124]

Stein MB. Pharmacotherapy for posttraumatic stress disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 18, 2018.

Stein MB. Pharmacotherapy for social anxiety disorder in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 17, 2019.

Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42(9):1290-1297.[PubMed 18628446]

Stowe ZN, Owens MJ, Landry JC, et al, “Sertraline and Desmethylsertraline in Human Breast Milk and Nursing Infants,” Am J Psychiatry, 1997, 154(9):1255-60.[PubMed 9286185]

Stowe ZN, Hostetter AL, Owens MJ, et al, “The Pharmacokinetics of Sertraline Excretion Into Human Breast Milk: Determinants of Infant Serum Concentrations,” J Clin Psychiatry, 2003, 64(1):73-80.[PubMed 12590627]

Sysko R, Devlin M. Binge eating disorder in adults: Overview of treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 6, 2018.

Tierney E, Joshi PT, Llinas JF, Rosenberg LA, Riddle MA. Sertraline for major depression in children and adolescents: preliminary clinical experience. J Child Adolesc Psychopharmacol. 1995;5(1):13-27.

Uguz F, Arpaci N. Short-term safety of paroxetine and sertraline in breastfed infants: a retrospective cohort study from a university hospital. Breastfeed Med. 2016;11:487-489.[PubMed 27575664]

US Department of Veterans Affairs/Department of Defense (VA/DoD). VA/DoD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder. https://www.healthquality.va.gov/guidelines/MH/ptsd/VADoDPTSDCPGFinal012418.pdf Updated June 2017. Accessed December 2017.

Warner, CH, Bobo W, Warner C, Reid S, Rachal J. Antidepressant discontinuation syndrome. Am Fam Physician. 2006;74(3):449-456.[PubMed 16913164]

Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114(3):703-713.[PubMed 19701065]

Yonkers KA, Kornstein SG, Gueorguieva R, Merry B, Van Steenburgh K, Altemus M. Symptom-onset dosing of sertraline for the treatment of premenstrual dysphoric disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72(10):1037-1044. doi: 10.1001/jamapsychiatry.2015.1472.[PubMed 26351969]

Zoloft (sertraline) [prescribing information]. New York, NY: Pfizer; January 2018.

Brand Names: International

Adjuvin (RO); Agrelocit (EG); Aleval (MX); Altisben (ES); Altruline (CR, DO, GT, HN, MX, NI, PA, SV); Aluprex (MX); Andep (BD); Aremis (ES); Asentra (LV, UA); Aserin (ES); Aurasert (BH); Besiran (ES); Chear (BD); Conexine (EC); Deprax (CL, PY); Depreger (IE); Deprine (LB); Deptral (ID); Dominum (CO); Doxime (PY); Eleva (AU); Emergen (PE); Fatral (ID); Freedep (LK); Fridep (ID); Gladem (AT, DE); Iglodep (ID); Inosert (SG); J Zoloft (JP); Lesefer (CO); Lustral (EG, GB, IE, IL, MT, SA, TR); Lustraline (TW); Prosertin (MX); Purtraline (TW); Selrotine (TH); Seltra (KR); Serdep (LK); Serenada (IL); Serenorm (EG); Seretral (IE); Serimel (IE); Serlain (BE); Serlife (ZA); Serlift (TH, UA, VN); Serlin (TH); Sernade (ID, PH); Serolox (CR, GT, HN, NI, PA, SV); Serolux (DO, MX); 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); Setaloft (HK); Setra (BD); Setrax (CO); Setrof (HK); Setrona (AU, NZ); Solotik (BH, LB); Sosser (CO); Starin (TH); Startline-50 (PH); Stimuloton (BM, BS, BZ, GY, JM, SR, TT); Suprisec (CR, DO, GT, HN, NI, PA, SV); Syche (BD); Tatig (NZ); Xydep (AU); You-Jet (TW); 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, ID, 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); Zosert (IN, LK, PH); Zotaline (TH)

Sertraline (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(SER tra leen)

Brand Names: US

Zoloft

Brand Names: Canada

Zoloft

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat obsessive-compulsive problems.
  • It is used to treat panic attacks.
  • It is used to treat post-traumatic stress.
  • It is used to treat mood problems caused by monthly periods.
  • It is used to treat social anxiety problems.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • All products:
  • If you have an allergy to sertraline or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have liver disease.
  • If you are taking any of these drugs: Linezolid or methylene blue.
  • If you are taking pimozide.
  • If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson’s disease like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
  • Liquid:
  • If you have a latex allergy. The dropper has rubber.
  • If you are taking disulfiram.
  • If you are pregnant or may be pregnant. Do not take this form of this drug if you are pregnant.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert until you see how this drug affects you.
  • Avoid drinking alcohol while taking this drug.
  • Talk with your doctor before you use other drugs and natural products that slow your actions.
  • This drug may raise the chance of a broken bone. Talk with the doctor.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • A type of abnormal heartbeat (prolonged QT interval) has happened with this drug. Sometimes, this has led to another type of unsafe abnormal heartbeat (torsades de pointes). Call your doctor right away if you have a fast or abnormal heartbeat, or if you pass out.
  • Some people may have a higher chance of eye problems with this drug. Your doctor may want you to have an eye exam to see if you have a higher chance of these eye problems. Call your doctor right away if you have eye pain, change in eyesight, or swelling or redness in or around the eye.
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if you take this drug with drugs for depression, migraines, or certain other drugs. Call your doctor right away if you have agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • This drug is not approved for use in all children. Talk with the doctor to be sure that this drug is right for your child.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • Taking this drug late in pregnancy may raise the chance of breathing or feeding problems, low body temperature, or withdrawal symptoms in the newborn. Talk with the doctor.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
  • Tablets and capsules:
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Seizures.
  • Chest pain or pressure.
  • Not able to control bladder.
  • Very bad headache.
  • A big weight gain or loss.
  • Sex problems like lowered interest in sex or ejaculation problems.
  • Erection that lasts more than 4 hours.
  • For females, menstrual changes. These include lots of bleeding, spotting, or bleeding between cycles
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Feeling nervous and excitable.
  • Upset stomach.
  • Diarrhea.
  • Dry mouth.
  • Constipation.
  • Not able to sleep.
  • Sweating a lot.
  • Shakiness.
  • Not hungry.
  • Belly pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Tablets:
  • Take with or without food.
  • Capsules:
  • Take this drug with food.
  • Liquid:
  • Only use the measuring device that comes with this liquid drug.
  • Mix liquid with 1/2 cup of water, ginger ale, lemon-lime soda, lemonade, or orange juice.
  • After mixing, take your dose right away. Do not store for future use.
  • This drug may look hazy after mixing. This is normal.
  • All products:
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • To gain the most benefit, do not miss doses.
  • Do not stop taking this drug all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this drug, you will want to slowly stop it as ordered by your doctor.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
  • In depression, sleep and appetite may get better soon after starting this drug. Other low mood signs may take up to 4 weeks to get better.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Keep lid tightly closed.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Sertraline (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(SER tra leen)

Brand Names: US

Zoloft

Brand Names: Canada

Zoloft

Warning
  • Drugs like this one have raised the chance of suicidal thoughts or actions in children and young adults. The risk may be greater in people who have had these thoughts or actions in the past. All people who take this drug need to be watched closely. Call the doctor right away if signs like low mood (depression), nervousness, restlessness, grouchiness, panic attacks, or changes in mood or actions are new or worse. Call the doctor right away if any thoughts or actions of suicide occur.
What is this drug used for?
  • It is used to treat low mood (depression).
  • It is used to treat obsessive-compulsive problems.
  • It is used to treat panic attacks.
  • It is used to treat post-traumatic stress.
  • It is used to treat mood problems caused by monthly periods.
  • It is used to treat social anxiety problems.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • All products:
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has liver disease.
  • If your child is taking any of these drugs: Linezolid or methylene blue.
  • If your child is taking pimozide.
  • If your child has taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for certain other health problems in the last 14 days. Taking this drug within 14 days of those drugs can cause very bad high blood pressure.
  • If your child is taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask the doctor or pharmacist if you are not sure.
  • Liquid:
  • If your child has a latex allergy. The dropper has rubber.
  • If your child is taking disulfiram.
  • If your child is pregnant or may be pregnant. Do not give this form of this drug to your child if she is pregnant.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles.
  • Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of side effects. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • Talk with the doctor before giving your child other drugs and natural products that may slow your child’s actions.
  • In depression, sleep and appetite may get better soon after starting this drug. Other low mood signs may take up to 4 weeks to get better.
  • This drug may raise the chance of a broken bone. Talk with the doctor.
  • This drug may raise the chance of bleeding. Sometimes, bleeding can be life-threatening. Talk with the doctor.
  • This drug can cause low sodium levels. Very low sodium levels can be life-threatening, leading to seizures, passing out, trouble breathing, or death. Talk with the doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • This drug is not approved for use in all children. Talk with the doctor to be sure that this drug is right for your child.
  • Use with care in children. Talk with the doctor.
  • This drug may affect growth in children and teens in some cases. They may need regular growth checks. Talk with the doctor.
  • If your child is pregnant:
  • Taking this drug late in pregnancy may raise the chance of breathing or feeding problems, low body temperature, or withdrawal symptoms in the newborn. Talk with the doctor.
  • If your child is breast-feeding a baby:
  • Tell the doctor if your child is breast-feeding a baby. You will need to talk about any risks to the baby.
  • Tablets and capsules:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Seizures.
  • Chest pain or pressure.
  • Not able to control bladder.
  • Very bad headache.
  • A big weight gain or loss.
  • Erection that lasts more than 4 hours.
  • For females, menstrual changes. These include lots of bleeding, spotting, or bleeding between cycles
  • A very bad and sometimes deadly health problem called serotonin syndrome may happen. The risk may be greater if your child takes this drug with drugs for depression, migraines, or certain other drugs. Call your child’s doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; a fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; very bad diarrhea, upset stomach, or throwing up; or very bad headache.
  • Some people may have a higher chance of eye problems with this drug. The doctor may want your child to have an eye exam to see if your child has a higher chance of these eye problems. Call the doctor right away if your child has eye pain, change in eyesight, or swelling or redness in or around the eye.
  • A type of abnormal heartbeat (prolonged QT interval) has happened with this drug. Sometimes, this has led to another type of unsafe abnormal heartbeat (torsades de pointes). Call your child’s doctor right away if your child has a fast or abnormal heartbeat, or if your child passes out.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your child’s doctor right away if your child has signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • If your child is or may be sexually active:
  • Sex problems like lowered interest in sex or ejaculation problems.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • Dizziness.
  • Feeling sleepy.
  • Feeling tired or weak.
  • Upset stomach.
  • Diarrhea.
  • Feeling nervous and excitable.
  • Dry mouth.
  • Constipation.
  • Not able to sleep.
  • Sweating a lot.
  • Shakiness.
  • Not hungry.
  • Belly pain.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Tablets:
  • Give this drug with or without food.
  • Capsules:
  • Give this drug with food.
  • Liquid:
  • Only use the measuring device that comes with this liquid drug.
  • Mix liquid with 1/2 cup of water, ginger ale, lemon-lime soda, lemonade, or orange juice.
  • After mixing, give the dose right away. Do not store for future use.
  • This drug may look hazy after mixing. This is normal.
  • All products:
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Keep lid tightly closed.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.