Sertraline Hydrochloride – ZOLOFT®

• ZOLOFT^®

• Selective Serotonin-reuptake Inhibitors (SSRIs)
• Anti-depressant, Anti-panic, Anti-obsessional Agent

1. Capsular-shaped scored tablets: 25, 50 and 100 mg

2. Oral Concentrate: 20 mg/mL:

• Must be diluted just before usage
• ONLY mix with 4oz (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice

1. Depression: Major Depressive Disorder (MDD in adults)
2. Obsessive-Compulsive Disorder (OCD)
3. Panic Disorder
4. Post-traumatic Stress Disorder (PTSD)
5. Pre-menstrual Dysphoric Disorder (PMDD)
6. Social Anxiety Disorder

• Inhibition of CNS neuronal uptake of serotonin (5HT)

1. Bioavailability:

• Peak Plasma Concentrations: 4.5-8.4 hrs
• Half-life: 26 hrs
• Same bio-availability for tablets and solution

2. Metabolism:

• Undergoes extensive first pass metabolism
• Protein Binding: Bound to serum proteins (98%)

3. Pediatric Pharmacokinetics:

• Pediatric patients metabolize sertraline with slightly greater efficiency than adults

4. Excretion:

• Excretion of unchanged drug in urine
• Sertraline pharmacokinetics unaffected by renal impairment

Initial Treatment

1. Dosage for Adults:

• Major Depressive Disorder and Obsessive-Compulsive Disorder:
  • 50 mg/day (max 200 mg)
• Panic Disorder, Posttraumatic Stress Disorder and Social Anxiety Disorder:
  • 25 mg/day. Increase dosage to 50/day after one week (max 200 mg)
• Premenstrual Dysphoric Disorder:
  • 50 mg/day, throughout the menstrual cycle or luteal phase (max 200 mg)

2. Dosage for Pediatric Population (Children and Adolescents)

• Obsessive-Compulsive Disorder:
  • 25 mg/day in children (ages 6–12)
  • 50 mg/day in adolescents (ages 13–17)

Maintenance/Continuation/Extended Treatment

1. Major Depressive Disorder:

• Require several months of therapy

2. Posttraumatic Stress Disorder:

• Require several months of therapy
• Patients should be periodically reassessed to determine the need for maintenance treatment

3. Social Anxiety Disorder

• Require several months of therapy with lowest effective dose
• Periodically reassessed for long-term treatment

4. Obsessive-Compulsive Disorder and Panic Disorder:

• Require several months or longer therapy.
• Periodically reassessed to determine the need for maintenance treatment.

5. Premenstrual Dysphoric Disorder:

• ZOLOFT treatment in long term (more than 3 menstrual cycles) has not been evaluated.

Special Populations

1. Treatment of Hepatically Impaired Patients: Used with caution.

2. Treatment of Pregnant Women during the Third Trimester:

• Carefully consider the potential risks and benefits of treatment.

Discontinuation of Treatment with ZOLOFT

1. Gradual reduction in the dose rather than abrupt cessation

1. Drugs Highly Bound to Plasma Proteins: Warfarin, Digoxin

2. Cimetidine

3. CNS Active Drugs:

• Diazepam
• Lithium: monitor plasma lithium levels>>>do dose adjustment
• Pimozide: effect on QT interval
• Phenytoin: monitor plasma phenytoin levels>>>do dose adjustment
• Valproate: monitor plasma Valproate levels>>>do dose adjustment

4. Monoamine Oxidase Inhibitors (MAO inhibitors)

5. Drugs Metabolized by P450 3A4: 

• Terfenadine,
• Carbamazepine,
• Cisapride

6. Drugs Metabolized by P450 2D6:

• Tricyclic Antidepressant (TCA)
• Type 1C Anti-Arrhythmic: Propafenone, Flecainide

7. Serotonergic Drugs:

• Triptans: careful observation is advised, particularly during treatment.
• Sumatriptan: Concomitant use may result in: weakness, hyperreflexia, and incoordination

8. Hypoglycemic Drugs: Tolbutamides

9. Microsomal Enzyme Induction: Significant decrease in anti-pyrine metabolism half-life

10. Drugs That Interfere With Hemostasis:

• Non-selective NSAIDs,
• Aspirin,
• Warfarin, etc.

11. Alcohol: Concomitant use is not recommended.

Frequent:

• Autonomic Nervous System Disorders: impotence
• Cardiovascular: palpitations, chest pain
• Central and Peripheral Nervous System Disorders: hypertonia, hypoesthesia
• Gastrointestinal Disorders: appetite increased
• General: back pain, asthenia, malaise, weight increase
• Musculoskeletal System Disorders: myalgia
• Psychiatric Disorders: yawning, other male sexual dysfunction, other female sexual dysfunction
• Respiratory System Disorders: rhinitis
• Special Senses: tinnitus

Infrequent:

• General Disorders: allergic reaction, allergy
• Autonomic Nervous System Disorders: flushing, increased saliva
• Cardiovascular: hypertension, tachycardia
• Central and Peripheral Nervous System Disorders: twitching, confusion
• Disorders of Skin and Appendages: pruritus, acne
• Gastrointestinal Disorders: dysphagia, tooth caries aggravated
• General: fever, rigors
• Metabolic and Nutritional Disorders: thirst
• Musculoskeletal System Disorders: arthralgia, dystonia
• Psychiatric Disorders: depression, amnesia
• Reproductive: menstrual disorder, dysmenorrhea
• Respiratory System Disorders: coughing, dyspnea
• Special Senses: conjunctivitis, earache
• Urinary System Disorders: micturition frequency, polyuria
•  Laboratory Tests:
  • Asymptomatic elevations in serum transaminases (SGOT/AST and SGPT/ALT)
  • Increases in serum total cholesterol and triglycerides
  • Decrease in serum uric acid

1. MAOI: Concomitant use within 14 days of stopping an MAOI is contraindicated-because of an increased risk of serotonin syndrome.
2. Pimozide: Concomitant use is contraindicated.
3. Hypersensitivity to sertraline or any of the inactive ingredients in ZOLOFT
4. Disulfiram: in concomitant ZOLOFT

• Pregnancy: Category C
• Lactation: caution should be exercised

1. Clinical Worsening and Suicide Risk: May Increase the suicidality (suicidal ideation):

• In certain patients especially during the initial few months of a course of drug therapy/at times of dose changes, either increases or decreases
• Changing the therapeutic regimen, possibly discontinuing in patients whose depression is persistently worse / experiencing emergent suicidality.

2. Serotonin Syndrome:

• Concomitant use of SNRIs and SSRIs, including: MAOIs, Linezolid, Intravenous methylene blue, Triptans, Tricyclic antidepressants, Fentanyl, Lithium, Tramadol, Tryptophan, Buspirone, St. John’s Wort

3. Angle-Closure Glaucoma: Patients should be advised about mild pupillary dilation, which can lead to an episode of angle closure glaucoma.

4. Activation of Mania/Hypomania

5. Weight Loss

6. Seizure: Should be introduced with care in patients with a seizure disorder.

7. Abnormal Bleeding Or Purpura: Discontinuation of Treatment

8. Impair performance in tasks requiring complex motor and mental: Patients should be careful doing activities that they need to be alert, such as driving a car or operating machinery.

9. Concomitant use of ZOLOFT and NSAIDs, aspirin, warfarin, or other drugs that affect: Increased risk of bleeding

10. Alcohol: Concomitant use of ZOLOFT and alcohol is not advised

11. OTC: Concomitant use of ZOLOFT and over-the-counter (OTC) drugs

12. Pregnancy/Breast Feeding: Notify your physician in case of pregnancy/breast feeding.

13. Discontinuation of Treatment: Gradual reduction in the dose rather than abrupt cessation is recommended

14. Disulfiram: ZOLOFT is contraindicated with disulfiram

15. Urine Test: False-positive urine immunoassay screening tests for benzodiazepines

16. Carcinogenesis: Uterine adenocarcinomas in rats receiving sertraline at 10–40 mg/kg, unknown significance to humans

17. Fertility Impairment: Decrease fertility in rat at a dose of 80 mg/kg (4 times the maximum recommended human dose on a mg/m2 basis)

18. Neonates: Those exposed to ZOLOFT, late in the third trimester, have developed complications:

• Prolonged hospitalization, respiratory support and Tube feeding.
• Respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying.

19. Infants: Those exposed to SSRIs in pregnancy have increased risk for persistent pulmonary hypertension of the newborn (PPHN)

20. Pediatric: In a child/adolescent must balance the potential risks with the clinical needs

21. Geriatric:

• Elderly >65 y/o: use with caution (association with hyponatremia)