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Sertraline Hydrochloride

Pronunciation

Pronunciation: SER-tra-leen HYE-droe-KLOR-ide
Class: Selective serotonin reuptake inhibitor

Trade Names

Zoloft
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Solution, oral concentrate 20 mg/mL

Apo-Sertraline (Canada)
Novo-Sertraline (Canada)
ratio-Sertraline (Canada)

Pharmacology

Selectively blocks reuptake of serotonin, enhancing serotonergic function.

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Pharmacokinetics

Absorption

T max is 4.5 to 8.4 h postdose. Steady state should be achieved after approximately 1 wk of once-daily dosing. AUC was slightly increased when the tablet was given with food but C max was 25% greater; T max decreased from 8 h postdosing to 5.5 h. T max of the oral concentrate was prolonged from 5.9 to 7 h with food.

Distribution

Sertraline is 98% protein bound.

Metabolism

Sertraline undergoes extensive first-pass metabolism. The principal initial metabolic pathway is N-demethylation. The liver is the primary site of metabolism.

Elimination

Sertraline half-life is 26 h; half-life of metabolite is 62 to 104 h.

Special Populations

Renal Function Impairment

Sertraline multiple-dose pharmacokinetics are unaffected by renal impairment.

Hepatic Function Impairment

Liver function impairment can affect the elimination of sertraline. Give a lower, less frequent dose.

Elderly

Plasma Cl 40% lower; steady state achieved after 2 to 3 wk.

Children

Children metabolize sertraline with slightly greater efficacy than adults.

Indications and Usage

Treatment of major depressive disorder; treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD); treatment of panic disorder with or without agoraphobia; treatment of posttraumatic stress disorder (PTSD); treatment of premenstrual dysphoric disorder; treatment of social anxiety disorder (social phobia).

Unlabeled Uses

Cholestatic pruritus, hot flashes, nocturnal enuresis.

Contraindications

Hypersensitivity to any components; concomitant use in patients taking MAOIs or pimozide; oral concentrate is contraindicated with disulfiram because of the alcohol content in the oral concentrate.

Dosage and Administration

Major Depressive Disorder
Adults

PO 50 mg once daily (max, 200 mg/day). Dose changes should not occur at intervals of less than 1 wk.

OCD
Adults and Children 13 to 17 yr of age

PO 50 mg once daily (max, 200 mg/day). Dose changes should not occur at intervals of less than 1 wk.

Children 6 to 12 yr of age

PO 25 mg once daily (max, 200 mg/day). Dose changes should not occur at intervals of less than 1 wk.

Panic Disorder, PTSD, and Social Anxiety Disorder
Adults

PO 25 mg once daily; the dosage should be increased to 50 mg once daily after 1 wk (max, 200 mg/day). Dose changes should not occur at intervals of less than 1 wk.

Premenstrual Dysphoric Disorder
Adults

PO 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle. Patients not responding to 50 mg/day may benefit from increases (at 50 mg increments/menstrual cycle) up to 150 mg/day when dosing throughout the menstrual cycle, or 100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100 mg/day dosage has been established with luteal dosing, use a 50 mg/day titration step for 3 days at the beginning of each luteal phase dosing period.

Hepatic Function Impairment

Give lower or less frequent dosage. Use with caution.

Switching Patients To or From MAOIs

At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with sertraline and 14 days should be allowed after stopping sertraline before starting an MAOI.

General Advice

  • Oral concentrate must be diluted before use. Mix required amount of sertraline with 4 oz of water, ginger ale, lemon/lime soda, lemonade, or orange juice only. Administer immediately. Do not mix in advance.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

5-HT 1 agonists (eg, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Weakness, hyperreflexia, and incoordination reported rarely.

Alcohol, CNS depressants

May enhance CNS depressant effects. Alcohol use is not recommended.

Carbamazepine

Sertraline plasma levels may be reduced, decreasing the pharmacologic effects.

Cimetidine

Increased sertraline AUC (50%), C max (24%), and half-life (26%).

Cisapride

Concurrent use reduced cisapride AUC and C max by approximately 35%.

Clozapine

Elevated serum clozapine levels have occurred. Closely monitor patients during coadministration.

Cyclosporine

Elevated cyclosporine levels may occur.

Cyproheptadine

May decrease the pharmacologic effects of sertraline.

Diazepam IV

Cl for diazepam decreased 32%.

Disulfiram

Sertraline oral concentrate is contraindicated with disulfiram because of the oral concentrate's alcohol content.

Drugs highly bound to plasma proteins (eg, warfarin, digitoxin)

May cause a shift in plasma concentrations resulting in adverse reactions.

Drugs interfering with hemostasis (eg, aspirin, non-selective NSAIDs [eg, ibuprofen], warfarin)

Risk of bleeding may be increased.

Drugs metabolized by CYP2D6 (eg, carvedilol, risperidone)

Plasma concentrations of these drugs may be elevated, increasing the pharmacologic effects and adverse reactions.

Hydantoins (eg, phenytoin)

Plasma levels may be increased by sertraline, increasing the pharmacologic effects and adverse reactions.

L-tryptophan

Concurrent use is not recommended.

Lithium, macrolide antibiotics (eg, erythromycin), metoclopramide, sibutramine, sympathomimetics, tramadol, trazodone

Risk of serotonin syndrome may be increased.

MAOIs, linezolid

May cause serious, even fatal reactions. Concomitant use is contraindicated. Discontinue MAOIs at least 14 days before starting sertraline; at least 14 days should be allowed after stopping sertraline before starting an MAOI.

Pimozide

Increase in pimozide AUC and C max of about 40%; coadministration is contraindicated.

St. John's wort

Sedative-hypnotic effects of sertraline may be increased. Avoid concurrent use.

Tolbutamide

Sertraline significantly decreased the Cl of tolbutamide (16%).

Tricyclic antidepressants (eg, amitriptyline)

Pharmacologic and toxic effects may be increased by sertraline; “serotonin syndrome” has been reported.

Type 1C antiarrhythmics (eg, flecainide, propafenone)

Plasma levels may be increased. Monitor cardiac function.

Zolpidem

Onset of action of zolpidem may be shortened and the effect increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations, chest pain (at least 1%); increased coagulation times, bradycardia, AV block, atrial arrhythmias, QT-interval prolongation, ventricular tachycardia (including torsades de pointes) (postmarketing).

CNS

Headache (25%); insomnia (21%); somnolence (13%); dizziness, fatigue (12%); malaise (9%); tremor (8%); decreased libido (6%); agitation, nervousness (5%); anxiety (4%); aggressive reaction, hyperkinesia (at least 2%); paresthesia (2%); asthenia, hypertonia, hypesthesia (at least 1%); extrapyramidal symptoms, NMS, oculogyric crisis, psychosis, serotonin syndrome (postmarketing).

Dermatologic

Sweating (7%); rash (3%); photosensitivity, Stevens-Johnson syndrome, vasculitis (postmarketing).

EENT

Abnormal vision (3%); tinnitus (at least 1%); blindness, cataract, optic neuritis (postmarketing).

GI

Nausea (25%); diarrhea (20%); dry mouth (14%); dyspepsia (8%); abdominal pain, anorexia, constipation (6%); vomiting (4%); increased appetite (at least 1%); pancreatitis (postmarketing).

Genitourinary

Abnormal ejaculation (14%); sexual dysfunction, urinary incontinence (at least 2%); impotence (at least 1%); priapism; acute renal failure (postmarketing).

Hematologic

Purpura (at least 2%); agranulocytosis, aplastic anemia, leukopenia, lupus-like syndrome, pancytopenia, serum sickness, thrombocytopenia (postmarketing).

Hepatic

Elevated liver enzymes (1%); increased bilirubin, hepatomegaly, hepatitis, jaundice, liver failure (postmarketing).

Lab Tests

Decrease in serum uric acid (7%); increased triglycerides (5%); increase in total cholesterol (3%).

Metabolic

Increased weight (at least 1%); hyperglycemia, hypothyroidism (postmarketing).

Respiratory

Epistaxis, sinusitis (at least 2%); rhinitis (at least 1%).

Miscellaneous

Pain (6%); fever, pain, weight loss (at least 2%); back pain, myalgia, yawning (at least 1%); anaphylaxis, angioedema, galactorrhea, hyperprolactinemia, pulmonary hypertension (postmarketing).

Precautions

Warnings

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorders and other psychiatric disorders. Closely observe all patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior.


Monitor

Ensure patient with depressive symptoms is screened to determine risk for bipolar disorder before initiating therapy with sertraline.


Pregnancy

Category C . Consider tapering dosing in the third trimester.

Lactation

Excreted.

Children

Safety and efficacy not established, except in children 6 to 18 yr of age with OCD.

Elderly

May be at greater risk of hyponatremia.

Hepatic Function

Use drug with caution. Lower or less frequent dosing schedule may be required.

Special Risk Patients

Use with caution in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Abnormal bleeding

Bleeding episodes have been reported in patients taking psychotropic drugs that interfere with serotonin reuptake.

Activation of mania/hypomania

Activation of mania/hypomania occurs infrequently in patients taking SSRIs.

Discontinuation

Serious adverse reactions (eg, dysphoric mood, irritability, anxiety, emotional lability, insomnia, hypomania) may occur upon sertraline discontinuation, particularly when abrupt. A gradual reduction in dose is recommended.

Duration of therapy

Periodically reassess patients to determine the need for maintenance treatment.

Hyponatremia

Several cases of sertraline-induced hyponatremia have occurred.

Latex allergy

The dropper dispenser supplied with the oral concentrate may contain dry natural rubber.

Seizures

Use drug with caution in patients with history of seizures.

Serotonin syndrome

May occur.

Uricosuric effect

May cause a decrease in serum uric acid.

Weight loss

Weight loss has been reported.

Overdosage

Symptoms

Agitation, alopecia, bradycardia, bundle branch block, coma, convulsions, decreased libido, delirium, diarrhea, dizziness, ejaculation disorder, fatigue, hallucinations, hypertension, hypotension, insomnia, manic reaction, nausea, pancreatitis, QT-interval prolongation, serotonin syndrome, somnolence, stupor, syncope, tachycardia, tremor, vomiting.

Patient Information

  • Advise patient to read patient information leaflet before starting therapy and with each refill.
  • If patient is a child or adolescent, advise patient, family, or caregiver to read the Medication Guide About Using Antidepressants in Children and Teenagers before starting therapy and with each refill.
  • Advise patient that medication usually is started at a low dose and then gradually increased until max benefit is obtained.
  • Advise patient to take prescribed dose once daily in the morning or evening without regard to meals but to take with food if stomach upset occurs.
  • Caution patient or caregiver that oral concentrate must be diluted before administration. Advise patient or caregiver to measure prescribed dose of oral concentrate using calibrated syringe and mix, immediately before use, with 4 oz (½ cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice, and administer immediately after mixing. Caution patient or caregiver not to prepare ahead of time.
  • Caution patient or caregiver not to dilute oral concentrate with any other liquid than those previously noted. Advise patient or caregiver that a slight haze may appear after mixing oral concentrate but that this is expected and is not a concern.
  • Inform patient that it may take 1 to 4 wk to note improvement in symptoms and to continue with the prescribed therapy once improvement has been noted.
  • Instruct patient to notify health care provider if symptoms do not appear to be getting better, or if they worsen, or if bothersome adverse reactions (eg, unusual sweating, headache, drowsiness, insomnia, nausea, diarrhea, nervousness, changes in sexual function) occur.
  • Advise all patients, and family or caregiver of patient, to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: anxiety; agitation; panic attacks; insomnia; irritability; hostility or aggressiveness; impulsivity; akathisia (psychomotor restlessness); suicidal thoughts or behavior. Advise families and caregivers of patients to observe for emergence on a day-to-day basis, because changes may be abrupt.
  • Advise patient that if medication needs to be discontinued it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patient to avoid alcoholic beverages and other depressants while taking sertraline.
  • Advise patient that drug may impair judgment, thinking, or reflexes, and to use caution while driving or performing other activities requiring mental alertness until tolerance is determined.
  • Instruct patient not to take any prescription or OTC drugs, including aspirin or NSAIDs (eg, ibuprofen), herbal preparations, or dietary supplements without consulting health care provider.

Copyright © 2009 Wolters Kluwer Health.

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