Prescription Drug Information: SERTRALINE HYDROCHLORIDE

SERTRALINE HYDROCHLORIDE- sertraline hydrochloride tablet
ACI Healthcare USA, Inc.

1 INDICATIONS AND USAGE

Sertraline hydrochloride tablets are indicated for the treatment of the following [See Clinical Studies (14)]:

• Major depressive disorder (MDD)
• Obsessive-compulsive disorder (OCD)
• Panic disorder (PD)
• Post-traumatic stress disorder (PTSD)
• Social anxiety disorder (SAD)Premenstrual dysphoric disorder (PMDD)

2 DOSAGE AND ADMINISTRATION

2.1 Dosage in Patients with MDD, OCD, PD, PTSD, and SAD

The recommended initial dosage and maximum sertraline hydrochloride tablet dosage in patients with MDD, OCD, PD, PTSD, and SAD are displayed in Table 1 below. A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage.

For adults and pediatric patients, subsequent dosages may be increased in case of an inadequate response in 25 to 50 mg per day increments once a week, depending on tolerability, up to a maximum of 200 mg per day. Given the 24-hour elimination half-life of sertraline hydrochloride tablet, the recommended interval between dose changes is one week.

Table 1: Recommended Daily Dosage of Sertraline Hydrochloride Tablets in Patients with MDD, OCD, PD, PTSD, and SAD
Indication	Starting Dose	Therapeutic Range
Adults
MDD	50 mg	50-200 mg
OCD	50 mg
PD,PTSD, SAD	25 mg
Pediatric Patients
OCD (ages 6-12 years old)	25 mg	50-200 mg
OCD (ages 13-17 years old)	25 mg

2.2 Dosage in Patients with PMDD

The recommended sertraline hydrochloride tablet starting dosage in adult women with PMDD is 50 mg per day. Sertraline hydrochloride tablets may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses). Intermittent dosing would be repeated with each new cycle.

• When dosing continuously, patients not responding to a 50 mg dosage may benefit from dosage increases at 50 mg increments per menstrual cycle up to 150 mg per day.

• When dosing intermittently, patients not responding to a 50 mg dosage may benefit from increasing the dosage up to a maximum of 100 mg per day during the next menstrual cycle (and subsequent cycles) as follows: 50 mg per day during the first 3 days of dosing followed by 100 mg per day during the remaining days in the dosing cycle.

2.3 Screen for Bipolar Disorder Prior to Starting Sertraline Hydrochloride Tablets

Prior to initiating treatment with sertraline hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [See Warnings and Precautions (5.4)].

2.4 Dosage Modifications in Patients with Hepatic Impairment

Both the recommended starting dosage and therapeutic range in patients with mild hepatic impairment (Child Pugh scores 5 or 6) are half the recommended daily dosage [See Dosage and Administration (2.1, 2.2)]. The use of sertraline hydrochloride tablets in patients with moderate (Child Pugh scores 7 to 9) or severe hepatic impairment (Child Pugh scores 10-15) is not recommended [See Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

2.5 Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant

At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of sertraline hydrochloride tablets. In addition, at least 14 days must elapse after stopping sertraline hydrochloride tablets before starting an MAOI antidepressant [See Contraindications (4), Warnings and Precautions (5.2)].

2.6 Discontinuation of Treatment with Sertraline Hydrochloride Tablets

Adverse reactions may occur upon discontinuation of sertraline hydrochloride tablets [See Warnings and Precautions (5.5)]. Gradually reduce the dosage rather than stopping sertraline hydrochloride tablets abruptly whenever possible.

3 DOSAGE FORMS AND STRENGTHS

Sertraline Hydrochloride Tablets, USP are available containing sertraline hydrochloride, USP equivalent to 25 mg, 50 mg, or 100 mg of sertraline.

Sertraline Hydrochloride Tablets are round, white to off white, biconvex uncoated tablets debossed with “ET52” on one side and break line on the other side.
Sertraline Hydrochloride Tablets are round, white to off white, biconvex uncoated tablets debossed with “ET53” on one side and break line on the other side.
Sertraline Hydrochloride Tablets are round, white to off white, biconvex uncoated tablets debossed with “ET54” on one side and break line on the other side.

4 CONTRAINDICATIONS

Sertraline hydrochloride tablets are contraindicated in patients:

• Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions (5.2), Drug Interactions (7.1)].
• Taking pimozide [See Drug Interactions (7.1)].
• With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1,6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2.

No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.

Table 2: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

Age Range (years)	Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1000 Patients Treated
	Increases Compared to Placebo
<18	14 additional patients
18-24	5 additional patients
	Decreases Compared to Placebo
25-64	1 fewer patient
≥65	6 fewer patients

It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.

Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing sertraline hydrochloride tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

5.2 Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including sertraline hydrochloride tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [See Contraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can also occur when these drugs are used alone.

Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The concomitant use of sertraline hydrochloride tablets with MAOIs is contraindicated. In addition, do not initiate sertraline hydrochloride tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking sertraline hydrochloride tablets, discontinue sertraline hydrochloride tablets before initiating treatment with the MAOI [See Contraindications (4), Drug Interactions (7.1)].

Monitor all patients taking sertraline hydrochloride tablets for the emergence of serotonin syndrome. Discontinue treatment with sertraline hydrochloride tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of sertraline hydrochloride tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.