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Sertraline

Pronunciation

Pronunciation

(SER tra leen)

Index Terms

  • Sertraline HCl
  • Sertraline Hydrochloride

Dosage Forms

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

Concentrate, Oral:

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

Generic: 20 mg/mL (60 mL)

Tablet, Oral:

Zoloft: 25 mg [scored; contains fd&c blue #1 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

Brand Names: U.S.

  • Zoloft

Pharmacologic Category

  • Antidepressant, Selective Serotonin Reuptake Inhibitor

Pharmacology

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.

Absorption

Area under the plasma concentration time curve (AUC) slightly increased and mean peak plasma concentrations (Cmax) 25% greater when administered with food.

Metabolism

Hepatic; may involve CYP2C19 and CYP2D6; extensive first pass metabolism; forms metabolite N-desmethylsertraline (APA, 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)

Excretion

Urine (40% to 45%); feces (40% to 45%; 12% to 14% as unchanged drug)

Onset of Action

Depression: The onset of action is within a week, however, individual response varies greatly and full response may not be seen until 8-12 weeks after initiation of treatment.

Time to Peak

Plasma: Sertraline: 4.5-8.4 hours

Half-Life Elimination

Sertraline: Mean: 26 hours; N-desmethylsertraline: 66 hours (range: 62-104 hours)

Children 6 to 12 years: Mean: 26.2 hours

Children 13 to 17 years: Mean: 27.8 hours

Adults 18 to 45 years: Mean: 27.2 hours

Protein Binding

98%

Special Populations: Hepatic Function Impairment

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

Special Populations: Elderly

Plasma clearance 40% lower; steady state achieved after 2-3 weeks

Use: Labeled Indications

Major depressive disorder: Treatment of 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.

Post-traumatic stress disorder: Treatment of post-traumatic 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: Unlabeled

Binge-eating disorder; bulimia nervosa; generalized anxiety disorder (GAD)

Contraindications

Use of MAOIs intended to treat psychiatric disorders (concurrently or within 14 days of stopping an MAOI or sertraline); concurrent use with pimozide; initiation in patients treated with linezolid or methylene blue IV; hypersensitivity to sertraline or any component of the formulation; concurrent use with disulfiram (oral concentrate 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.

Dosing: Adult

Depression/obsessive-compulsive disorder: Oral: Initial: 50 mg daily. Note: May increase daily dose, at intervals of not less than 1 week, to a maximum of 200 mg daily.

Panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder: Oral: Initial: 25 mg once daily; increased after 1 week to 50 mg once daily; maximum dose: 200 mg daily

Premenstrual dysphoric disorder (PMDD): Oral: 50 mg daily either daily throughout menstrual cycle or limited to the luteal phase of menstrual cycle. Patients not responding to 50 mg daily may benefit from dose increases (50 mg increments per menstrual cycle) up to 150 mg daily when dosing throughout menstrual cycle or up to 100 mg day when dosing during luteal phase only. If a 100 mg daily dose has been established with luteal phase dosing, a 50 mg daily titration step for 3 days should be utilized at the beginning of each luteal phase dosing period.

Binge-eating disorder (off-label use): Oral: Initial: 25 mg daily after lunch for 3 days; increase at 25 mg increments every 3 days based on response and tolerability. Usual dose range: 100-200 mg daily. Maximum dose: 200 mg daily (Leombruni P, 2008).

Bulimia nervosa (off-label use): Oral: Initial: 50 mg daily; increase at 50 mg increments each week based on response and tolerability. Maximum dose: 200 mg daily (Milano 2004; Sloan 2003).

Generalized anxiety disorder (GAD) off-label use): Oral: Initial dose: 25 mg once daily for 1 week; increase based on response and tolerability. Maximum dose: 200 mg daily (Ball 2005; Brawman, 2006; Dahl, 2005).

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

Obsessive-compulsive disorder (OCD):

Children 6-12 years: Oral: Initial: 25 mg once daily. Note: May increase daily dose, at intervals of not less than 1 week, to a maximum of 200 mg daily.

Adolescents 13-17 years: Oral: Initial: 50 mg once daily. Note: May increase daily dose, at intervals of not less than 1 week, to a maximum of 200 mg daily.

Depression (off-label use):

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

Adolescents 13-17 years: Oral: Initial 25-50 mg once daily; titrate dose upwards if clinically needed; may increase by 50 mg daily 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: 25-200 mg daily; maximum dose: 200 mg daily (Dopheide, 2006).

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment is provided in manufacturer’s labeling; however, sertraline pharmacokinetics does not appear to be affected by renal impairment.

Dosing: Hepatic Impairment

No specific dosage adjustment 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.

Reconstitution

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.

Administration

Administer once daily either in the morning or evening; if somnolence is noted, administer at bedtime.

Oral concentrate: Must be diluted immediately before use. Note: Use with caution in patients with latex sensitivity; dropper dispenser contains dry natural rubber.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

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

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

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

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

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

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

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

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

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

ARIPiprazole: Sertraline may enhance the adverse/toxic effect of ARIPiprazole. Sertraline may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph. Aripiprazole dose adjustment may not be required when used as adjunctive therapy for major depressive disorder. Consider therapy modification

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

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

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

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

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

Cilostazol: CYP2C19 Inhibitors may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in patients who are also receiving inhibitors of CYP2C19. Consider therapy modification

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

Citalopram: CYP2C19 Inhibitors (Moderate) may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with a moderate CYP2C19 inhibitor. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation, etc.). Consider therapy modification

Clopidogrel: CYP2C19 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Monitor therapy

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

CYP2C19 Substrates: CYP2C19 Inhibitors (Moderate) may decrease the metabolism of CYP2C19 Substrates. Monitor therapy

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

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

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

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

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

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

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

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

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. Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tricyclic Antidepressants: 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. Consider therapy modification

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

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

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

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

Test Interactions

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

Adverse Reactions

>10%:

Central nervous system: Insomnia (12% to 28%), headache (25%), dizziness (6% to 17%), fatigue (10% to 16%), drowsiness (2% to 15%)

Dermatologic: Diaphoresis (4% to 11%)

Endocrine & metabolic: Decreased libido (1% to 11%)

Gastrointestinal: Nausea (13% to 30%), diarrhea (13% to 24%), xerostomia (6% to 16%), dyspepsia (6% to 13%), anorexia (3% to 11%)

Genitourinary: Ejaculatory disorder (7% to 19%)

Neuromuscular & skeletal: Tremor (<1% to 11%)

1% to 10%:

Cardiovascular: Chest pain (≥1%), palpitations (≥1%)

Central nervous system: Malaise (7% to 9%), pain (3% to 6%), agitation (1% to 6%), nervousness (5%), paresthesia (2%), aggressive behavior (children ≥2%), hypertonia (≥1%), hypoesthesia (≥1%), yawning (≥1%), anxiety

Dermatologic: Skin rash (3%)

Endocrine & metabolic: Weight gain (≥1%)

Gastrointestinal: Constipation (5% to 8%), abdominal pain (6% to 7%), vomiting (4%), increased appetite (≥1%)

Genitourinary: Urinary incontinence (children ≥2%), impotence (≥1%)

Hematologic & oncologic: Purpura (children ≥2%)

Neuromuscular & skeletal: Hyperkinesia (children ≥2%), back pain (≥1%), myalgia(≥1%), weakness (≥1%)

Ophthalmic: Visual disturbance (3%)

Otic: Tinnitus (≥1%)

Respiratory: Epistaxis (children ≥2%), sinusitis (children ≥2%), rhinitis (≥1%)

Miscellaneous: Fever (children ≥2%)

<1% (Limited to important or life-threatening): Acute renal failure, agranulocytosis, altered platelet function, anaphylactoid reaction, angle-closure glaucoma, aplastic anemia, apnea, ataxia, atrial arrhythmia, atrioventricular block, bradycardia, cerebrovascular spasm, choreoathetosis, colitis, coma, cystitis, depression, diverticulitis, dystonia, edema, esophagitis, extrapyramidal reaction, hematuria, hemoptysis, hepatic failure, hepatitis, hepatomegaly, hypertension, hypoglycemia, hyponatremia, increased INR, increased serum bilirubin, increased serum transaminases, leukopenia, myocardial infarction, neuroleptic malignant syndrome (Stevens, 2008), oculogyric crisis, orthostatic hypotension, pancreatitis, peptic ulcer bleed, peripheral ischemia, proctitis, prolonged Q-T interval on ECG, pulmonary hypertension, pyelonephritis, rectal hemorrhage, serotonin syndrome, SIADH, Stevens-Johnson syndrome, suicidal ideation, thrombocytopenia, torsades de pointes, urinary frequency, ventricular tachycardia, withdrawal syndrome

ALERT: U.S. Boxed Warning

Suicidality and antidepressant drugs:

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

Warnings/Precautions

Major psychiatric warnings:

[US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Sertraline is not FDA approved for use in children with major depressive disorder (MDD). However, it is approved for the treatment of obsessive-compulsive disorder (OCD) in children ≥6 years of age.

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

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

Concerns related to adverse effects:

• 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.

• 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.

• Weight loss: May cause weight loss; use caution in patients where weight loss is undesirable.

Disease-related concerns:

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

• 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.

• Other concurrent illness: Use caution in patients with certain concomitant systemic illnesses, such as conditions that affect metabolism or hemodynamic processes, due to limited experience.

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

• Uric acid nephropathy: Use with caution in patients at risk of uric acid nephropathy; sertraline acts as a mild uricosuric.

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 concentrate 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).

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

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.

Pregnancy Risk Factor

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Pregnancy Considerations

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

Due to pregnancy-induced physiologic changes, 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.

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

Patient Education

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

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

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

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

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