Sertraline Hydrochloride (Page 6 of 9)

Labor and Delivery

The effect of sertraline on labor and delivery in humans is unknown.

Nursing Mothers

It is not known whether, and if so in what amount, sertraline or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when sertraline is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients with major depressive disorder have not been established (see BOX WARNING and WARNINGS, Clinical Worsening and Suicide Risk). Two placebo controlled trials (n = 373) in pediatric patients with MDD have been conducted with sertraline, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of sertraline hydrochloride tablets in a child or adolescent must balance the potential risks with the clinical need.

Sertraline pharmacokinetics were evaluated in a group of 61 pediatric patients between 6 and 17 years of age and revealed similar drug exposures to those of adults when plasma concentration was adjusted for weight (see Pharmacokinetics under CLINICALPHARMACOLOGY).

Approximately 600 pediatric patients between 6 and 17 years of age have received sertraline in clinical trials, both controlled and uncontrolled. The adverse event profile observed in these patients was generally similar to that observed in adult studies with sertraline (see ADVERSE REACTIONS). As with other SSRIs, decreased appetite and weight loss have been observed in association with the use of sertraline. In a pooled analysis of two 10-week, double-blind, placebo-controlled, flexible dose (50 — 200 mg) outpatient trials for major depressive disorder (n = 373), there was a difference in weight change between sertraline and placebo of roughly 1 kilogram, for both children (ages 6 — 11) and adolescents (ages 12 — 17), in both cases representing a slight weight loss for sertraline compared to a slight gain for placebo. At baseline the mean weight for children was 39.0 kg for sertraline and 38.5 kg for placebo. At baseline the mean weight for adolescents was 61.4 kg for sertraline and 62.5 kg for placebo. There was a bigger difference between sertraline and placebo in the proportion of outliers for clinically important weight loss in children than in adolescents. For children, about 7% had a weight loss > 7% of body weight compared to none of the placebo patients; for adolescents, about 2% had a weight loss > 7% of body weight compared to about 1% of the placebo patients. A subset of these patients who completed the randomized controlled trials (sertraline n = 99, placebo n = 122) were continued into a 24-week, flexible-dose, open-label, extension study. A mean weight loss of approximately 0.5 kg was seen during the first eight weeks of treatment for subjects with first exposure to sertraline during the open-label extension study, similar to the mean weight loss observed among sertraline treated subjects during the first eight weeks of the randomized controlled trials. The subjects continuing in the open label study began gaining weight compared to baseline by week 12 of sertraline treatment. Those subjects who completed 34 weeks of sertraline treatment (10 weeks in a placebo controlled trial + 24 weeks open label, n = 68) had weight gain that was similar to that expected using data from age-adjusted peers. Regular monitoring of weight and growth is recommended if treatment of a pediatric patient with an SSRI is to be continued long term. Safety and effectiveness in pediatric patients with major depressive disorder have not been established.

The risks, if any, that may be associated with sertraline’s use beyond 1 year in children and adolescents have not been systematically assessed. The prescriber should be mindful that the evidence relied upon to conclude that sertraline is safe for use in children and adolescents derives from clinical studies that were 10 to 52 weeks in duration and from the extrapolation of experience gained with adult patients. In particular, there are no studies that directly evaluate the effects of long-term sertraline use on the growth, development, and maturation of children and adolescents. Although there is no affirmative finding to suggest that sertraline possesses a capacity to adversely affect growth, development or maturation, the absence of such findings is not compelling evidence of the absence of the potential of sertraline to have adverse effects in chronic use (see WARNINGS — Clinical Worsening and Suicide Risk).

Geriatric Use

U.S. geriatric clinical studies of sertraline in major depressive disorder included 663 sertraline-treated subjects ≥ 65 years of age, of those, 180 were ≥ 75 years of age. No overall differences in the pattern of adverse reactions were observed in the geriatric clinical trial subjects relative to those reported in younger subjects (see ADVERSE REACTIONS), and other reported experience has not identified differences in safety patterns between the elderly and younger subjects. As with all medications, greater sensitivity of some older individuals cannot be ruled out. There were 947 subjects in placebo-controlled geriatric clinical studies of sertraline in major depressive disorder. No overall differences in the pattern of efficacy were observed in the geriatric clinical trial subjects relative to those reported in younger subjects.

Other Adverse Events in Geriatric Patients

In 354 geriatric subjects treated with sertraline in placebo-controlled trials, the overall profile of adverse events was generally similar to that shown in Table 2 . Urinary tract infection was the only adverse event not appearing in Table 2 and reported at an incidence of at least 2% and at a rate greater than placebo in placebo-controlled trials.

As with other SSRIs, sertraline has been associated with cases of clinically significant hyponatremia in elderly patients (see Hyponatremia under PRECAUTIONS).

ADVERSE REACTIONS

During its premarketing assessment, multiple doses of sertraline were administered to over 4000 adult subjects as of February 18, 2000. The conditions and duration of exposure to sertraline varied greatly, and included (in overlapping categories) clinical pharmacology studies, open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies, and studies for multiple indications, including major depressive disorder.

Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, a World Health Organization dictionary of terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the over 4000 adult individuals exposed to multiple doses of sertraline who experienced a treatment-emergent adverse event of the type cited on at least one occasion while receiving sertraline. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is important to emphasize that events reported during therapy were not necessarily caused by it.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.

Incidence in Placebo-Controlled Trials

Table 2 enumerates the most common treatment-emergent adverse events associated with the use of sertraline (incidence of at least 5% for sertraline and at least twice that for placebo within at least one of the indications) for the treatment of adult patients with major depressive disorder/other 1 in placebo-controlled clinical trials. Most patients in major depressive disorder/other 1 studies received doses of 50 to 200 mg/day.

TABLE 2 MOST COMMON TREATMENT-EMERGENT ADVERSE EVENTS: INCIDENCE IN PLACEBO-CONTROLLED CLINICAL TRIALS

* Primarily ejaculatory delay. Denominator used was for male patients only (N = 271 sertraline major depressive disorder/ other*; N = 271 placebo major depressive disorder/other*)
	Percentage of Patients Reporting Event
	Major Depressive Disorder/Other 1
Body System/ Adverse Event	Sertraline (N = 861)	Placebo (N = 853)
Autonomic Nervous System Disorders
Ejaculation Failure *	7	<1
Mouth Dry	16	9
Sweating Increased	8	3
Centr. & Periph. Nerv. System Disorders
Somnolence	13	6
Tremor	11	3
Dizziness	12	7
General
Fatigue	11	8
Pain	1	2
Malaise	<1	1
Gastrointestinal Disorders
Abdominal Pain	2	2
Anorexia	3	2
Constipation	8	6
Diarrhea/Loose Stools	18	9
Dyspepsia	6	3
Nausea	26	12
Psychiatric Disorders
Agitation	6	4
Insomnia	16	9
Libido Dereased	1	<1