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|Sertraline Hydrochloride

Sertraline Hydrochloride

Trade Names:
Zoloft
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Oral concentrate 20 mg/mL

Mechanism of Action

Pharmacology

Selectively blocks reuptake of serotonin, enhancing serotonergic function.

Pharmacokinetics

Absorption

T _max is 4.5 to 8.4 hr postdose. Steady state should be achieved after approximately 1 wk of once daily dosing.

AUC was slightly increased when the drug was given with food and C _max was 25% greater while T _max decreased from 8 hr postdosing to 5.5 hr.

T _max was prolonged from 5.9 to 7 hr 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 t _½ is 26 to 104 hr.

Special Populations

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

Pediatric patients metabolize sertraline with slightly greater efficacy than adults.

Indications and Usage

Treatment of major depression; treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD), as defined in the DSM-III-R; treatment of panic disorder with or without agoraphobia, as defined in DSM-IV; posttraumatic stress disorder (PTSD); treatment of premenstrual dysphoric disorder, treatment of social anxiety disorder (social phobia).

Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder.

Contraindications

Hypersensitivity to any components; concomitant use in patients taking MAO inhibitors, pimozide, or disulfiram (because of alcohol content in oral concentrate).

Dosage and Administration

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

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

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

PO 25 mg once daily; the dose 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.

PO 50 mg/day, either daily throughout the menstrual cycle or limited to the luteal phase of the menstrual cycle, depending on physician assessment. 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 dose 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.

At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of therapy with sertraline. In addition, at least 14 days should be allowed after stopping sertraline before starting an MAO inhibitor.

Storage/Stability

Store tablets and oral concentrate at controlled room temperature (59° to 86°F).

Drug Interactions

Weakness, hyperreflexia, and incoordination reported rarely.

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

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

Increased sertraline AUC (50%), C _max (24%), and t _½ (26%). Clinical significance is unknown.

Elevated serum clozapine levels occurred. Closely monitor patients on coadministration.

Elevated cyclosporine levels may occur.

Cyproheptadine is a serotonin antagonist and may decrease the pharmacologic effects of sertraline.

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

Risk of bleeding may be increased.

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

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

Risk of serotonin syndrome may be increased.

May cause serious, even fatal reactions. Concomitant use is contraindicated. Discontinue MAO inhibitors at least 14 days before starting sertraline.

Increase in pimozide AUC and C _max of about 40%; concomitant administration is contraindicated.

Serotonin syndrome may occur.

Sedative-hypnotic effects of sertraline may be increased.

Sertraline significantly decreased the Cl of tolbutamide (16%). Clinical significance is unknown.

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

Plasma levels may be increased. Monitor cardiac function.

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

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hot flushes, hypotension (postural), hypertension, syncope, tachycardia (at least 2%); 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

Agitation, anxiety, nervousness, headache, insomnia, dizziness, tremor, fatigue, tingling, diminished sensation, twitching, confusion, somnolence, depression, decreased libido, emotional lability, vertigo, apathy, hypokinesia/hyperkinesia, abnormal dreams (at least 2%); asthenia, hypertonia, hypoesthesia, malaise (at least 1%); extrapyramidal symptoms, neuroleptic malignant syndrome, oculogyric crisis, serotonin syndrome, psychosis (postmarketing).

Dermatologic

Sweating, rash, pruritus, acne (at least 2%); Stevens-Johnson syndrome, vasculitis, photosensitivity (postmarketing).

EENT

Abnormal vision, ringing in the ears, pharyngitis (at least 2%); blindness, optic neuritis, cataract (postmarketing).

GI

Nausea, diarrhea, dry mouth, anorexia, vomiting, constipation, abdominal pain, dyspepsia, gastroenteritis, tooth disorder/caries, dysphagia (at least 2%); increased appetite (at least 1%); pancreatitis (postmarketing).

Genitourinary

Sexual dysfunction, urinary frequency, urinary disorder, menstrual disorder, abnormal ejaculation, impotence (at least 2%); acute renal failure (postmarketing).

Hematologic

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

Hepatic

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

Lab Tests

Increase in total cholesterol and triglycerides, decrease in serum uric acid (at least 2%).

Metabolic

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

Respiratory

Sinusitis, increased cough, dyspnea, rhinitis, epistaxis (at least 2%).

Miscellaneous

Weight loss or gain, pain, arthralgia, asthenia, fever, chills, edema, yawning (at least 2%); back pain, myalgia (at least 1%); anaphylaxis, angioedema, galactorrhea, hyperprolactinemia, pulmonary hypertension (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

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

Hepatic Function

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

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 selective serotonin reuptake inhibitors.

Discontinuation

Serious adverse reactions (eg, dysphoric mood, irritability, anxiety, emotional lability, insomnia, hypomania) may occur upon sertraline discontinuation, particularly when abrupt.

Hyponatremia

Several cases of sertraline-induced hyponatremia have occurred.

MAO inhibitors

Cases of serious, sometimes fatal, reactions have been reported when an MAO inhibitor is used in combination with sertraline.

Seizures

Use drug with caution in patients with history of seizures.

Uricosuric effect

May cause a decrease in serum uric acid.

Weight loss

Weight loss has been reported.

Overdosage

Symptoms

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

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• 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 noted above. Advise patient or caregiver that a slight haze may appear after mixing oral concentrate but that this is expected and is not a concern.
• Advise patient not to change the dose or stop taking unless advised by health care provider.
• 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, worsen, or if bothersome side effects (eg, unusual sweating, headache, drowsiness, insomnia, nausea, diarrhea, nervousness, changes in sexual function) occur.
• Advise patient being treated for depression, 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.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Advise patient that follow-up visits may be necessary to monitor therapy and to keep appointments.