CONTRAINDICATIONS
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is
contraindicated (see WARNINGS).
Additional Information for Oral Concentrate: Sertraline HCl oral concentrate is
contraindicated with disulfuram (Antabuse) due to the alcohol content of the concentrate.
WARNINGS
Cases of serious, sometimes fatal, reactions have been reported in patients
receiving sertraline HCl, a selective serotonin reuptake inhibitor (SSRI), in
combination with a monoamine oxidase inhibitor (MAOI). Symptoms of a drug
interaction between an SSRI and an MAOI include: hyperthermia, rigidity,
myoclonus, autonomic instability with possible rapid fluctuations of vital signs,
mental status changes that include confusion, irritability, and extreme agitation
progressing to delirium and coma. These reactions have also been reported in
patients who have recently discontinued an SSRI and have been started on an
MAOI. Some cases presented with features resembling neuroleptic malignant
syndrome. Therefore, sertraline HCl should not be used in combination with an
MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at
least 14 days should be allowed after stopping sertraline HCl before starting an
MAOI.
PRECAUTIONS
General
Activation of Mania/Hypomania: During premarketing testing, hypomania or mania
occurred in approximately 0.4% of sertraline HCl treated patients.
Weight Loss: Significant weight loss may be an undesirable result of treatment with
sertraline for some patients, but on average, patients in controlled trials had minimal, 1 to
2 pound weight loss, versus smaller changes on placebo. Only rarely have sertraline
patients been discontinued for weight loss.
Seizure: Sertraline HCl has not been evaluated in patients with a seizure disorder. These
patients were excluded from clinical studies during the product's premarket testing. No
seizures were observed among approximately 3000 patients treated with sertraline HCl in
the development program for depression. However, 4 patients out of approximately
1800 (220 < 18 years of age) exposed during the development program for
obsessive-compulsive disorder experienced seizures, representing a crude incidence of
0.2%. Three of these patients were adolescents, two with a seizure disorder and one with
a family history of seizure disorder, none of whom were receiving anticonvulsant
medication. Accordingly, sertraline HCl should be introduced with care in patients with a
seizure disorder.
Suicide: The possibility of a suicide attempt is inherent in depression and may persist until
significant remission occurs. Close supervision of high risk patients should accompany
initial drug therapy. Prescriptions for sertraline HCl should be written for the smallest
quantity of tablets consistent with good patient management, in order to reduce the risk of
overdose.
Because of the well-established comorbidity between both OCD and depression and
panic disorder and depression, the same precautions observed when treating patients
with depression should be observed when treating patients with OCD or panic disorder.
Weak Uricosuric Effect: Sertraline HCl is associated with a mean decrease in serum uric
acid of approximately 7%. The clinical significance of this weak uricosuric effect is
unknown, and there have been no reports of acute renal failure with sertraline HCl.
Use in Patients with Concomitant Illness: Clinical experience with sertraline HCl in
patients with certain concomitant systemic illness is limited. Caution is advisable in using
sertraline HCl in patients with diseases or conditions that could affect metabolism or
hemodynamic responses.
Sertraline HCl has not been evaluated or used to any appreciable extent in patients with a
recent history of myocardial infarction or unstable heart disease. Patients with these
diagnoses were excluded from clinical studies during the product's premarket testing.
However, the electrocardiograms of 774 patients who received sertraline HCl in
double-blind trials were evaluated and the data indicate that sertraline HCl is not
associated with the development of significant ECG abnormalities.
Sertraline HCl is extensively metabolized by the liver. In patients with chronic mild liver
impairment, sertraline clearance was reduced, resulting in increased AUC, Cmax, and
elimination half-life. The effects of sertraline in patients with moderate and severe hepatic
impairment have not been studied. The use of sertraline in patients with liver disease must
be approached with caution. If sertraline is administered to patients with liver impairment,
a lower or less frequent dose should be used (see CLINICAL PHARMACOLOGY and
DOSAGE AND ADMINISTRATION).
Since sertraline HCl is extensively metabolized, excretion of unchanged drug in urine is a
minor route of elimination. A clinical study comparing sertraline pharmacokinetics in
healthy volunteers to that in patients with renal impairment ranging from mild to severe
(requiring dialysis) indicated that the pharmacokinetics and protein binding are unaffected
by renal disease. Based on the pharmacokinetics results, there is no need for dosage
adjustment in patients with renal impairment (see CLINICAL PHARMACOLOGY).
Interference with Cognitive and Motor Performance: In controlled studies, sertraline
HCl did not cause sedation and did not interfere with psychomotor performance.
Hyponatremia: Several cases of hyponatremia have been reported and appeared to be
reversible when sertraline HCl was discontinued. Some cases were possibly due to the
syndrome of inappropriate antidiuretic hormone secretion. The majority of these
occurrences have been in elderly individuals, some in patients taking diuretics or who
were otherwise volume depleted.
Platelet Function: There have been rare reports of altered platelet function and/or
abnormal results from laboratory studies in patients taking sertraline HCl. While there
have been reports of abnormal bleeding or purpura in several patients taking sertraline
HCl, it is unclear whether sertraline HCl had a causative role.
Information for the Patient
Physicians are advised to discuss the following issues with patients for whom they
prescribe sertraline HCl:
Patients should be told that although sertraline HCl has not been shown to impair
the ability of normal subjects to perform tasks requiring complex motor and mental
skills in laboratory experiments, drugs that act upon the central nervous system
may affect some individuals adversely.
Patients should be told that although sertraline HCl has not been shown in
experiments with normal subjects to increase the mental and motor skill
impairments caused by alcohol, the concomitant use of sertraline HCl and alcohol
is not advised.
Patients should be told that while no adverse interaction of sertraline HCl with
over-the-counter (OTC) drug products is known to occur, the potential for
interaction exists. Thus, the use of any OTC product should be initiated cautiously
according to the directions of use given for the OTC product.
Patients should be advised to notify their physician if they become pregnant or
intend to become pregnant during therapy.
Patients should be advised to notify their physician if they are breast-feeding an
infant.
Sertraline HCl oral concentrate is contraindicated with disulfuram (Antabuse) due to the
alcohol content of the concentrate.
Sertraline HCl contains 12% alcohol. Sertraline HCl oral concentrate must be diluted
before use. Just before taking, use the dropper provided to remove the required amount
of sertraline HCl oral concentrate and mix with 4 oz (½ cup) of water, gingerale,
lemon/lime soda, lemonade or orange juice ONLY. Do not mix sertraline HCl oral
concentrate with anything other than the liquids listed. The dose should be taken
immediately after mixing. Do not mix in advance. At times, a slight haze may appear after
mixing; this is normal. Note that caution should be exercised for persons with latex
sensitivity, as the dropper dispenser contains dry natural rubber.
Laboratory Tests
None.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Carcinogenesis: Lifetime carcinogenicity studies were carried out in CD-1 mice and
Long-Evans rats at doses up to 40 mg/kg/day. These doses correspond to 1 times (mice)
and 2 times (rats) the maximum recommended human dose (MRHD) on a mg/m2 basis.
There was a dose-related increase of liver adenomas in male mice receiving sertraline at
10-40 mg/kg (0.25-1.0 times the MRHD on a mg/m2 basis). No increase was seen in
female mice or in rats of either sex receiving the same treatments, nor was there an
increase in hepatocellular carcinomas. Liver adenomas have a variable rate of
spontaneous occurrence in the CD-1 mouse and are of unknown significance to humans.
There was an increase in follicular adenomas of the thyroid in female rats receiving
sertraline at 40 mg/kg (2 times the MRHD on a mg/m2 basis); this was not accompanied
by thyroid hyperplasia. While there was an increase in uterine adenocarcinomas in rats
receiving sertraline at 10-40 mg/kg (0.5-2.0 times the MRHD on a mg/m2 basis)
compared to placebo controls, this effect was not clearly drug related.
Mutagenesis: Sertraline had no genotoxic effects, with or without metabolic activation,
based on the following assays: bacterial mutation assay; mouse lymphoma mutation assay;
and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human
lymphocytes.
Impairment of Fertility: A decrease in fertility was seen in one of two rat studies at a
dose of 80 mg/kg (4 times the maximum recommended human dose on a mg/m2 basis).
Pregnancy Category C
Reproduction studies have been performed in rats and rabbits at doses up to 80
mg/kg/day and 40 mg/kg/day, respectively. These doses correspond to approximately 4
times the maximum recommended human dose (MRHD) on a mg/m2 basis. There was no
evidence of teratogenicity at any dose level. When pregnant rats and rabbits were given
sertraline during the period of organogenesis, delayed ossification was observed in fetuses
at doses of 10 mg/kg (0.5 times the MRHD on a mg/m2 basis) in rats and 40 mg/kg (4
times the MRHD on a mg/m2 basis) in rabbits. When female rats received sertraline
during the last third of gestation and throughout lactation, there was an increase in the
number of stillborn pups and in the number of pups dying during the first 4 days after
birth. Pup body weights were also decreased during the first 4 days after birth. These
effects occurred at a dose of 20 mg/kg (1 times the MRHD on a mg/m2 basis). The no
effect dose for rat pup mortality was 10 mg/kg (0.5 times the MRHD on a mg/m2 basis).
The decrease in pup survival was shown to be due to in utero exposure to sertraline
HCl. The clinical significance of these effects is unknown. There are no adequate and
well-controlled studies in pregnant women. Sertraline HCl should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
The effect of sertraline HCl 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 HCl is administered to a nursing woman.
Pediatric Use
The efficacy of sertraline HCl for the treatment of obsessive-compulsive disorder was
demonstrated in a 12-week, multicenter, placebo-controlled study with 187 outpatients
ages 6-17 (see CLINICAL STUDIES). The effectiveness of sertraline HCl in pediatric
patients with depression or panic disorder has not been systematically evaluated.
Sertraline pharmacokinetics were evaluated in 61 pediatric patients between 6 and 17
years of age with depression or OCD and revealed similar drug exposures to those of
adults when plasma concentration was adjusted for weight (see CLINICAL
PHARMACOLOGY, Pharmacokinetics).
More than 250 patients with depression or OCD between 6 and 17 years of age have
received sertraline HCl in clinical trials. The adverse event profile observed in these
patients was generally similar to that observed in adult studies with sertraline HCl (see
ADVERSE REACTIONS). As with other SSRIs, decreased appetite and weight loss
have been observed in association with the use of sertraline HCl. Consequently, regular
monitoring of weight and growth is recommended if treatment of a child with an SSRI is
to be continued long term. Safety and effectiveness in pediatric patients below the age of
6 have not been established.
The risks, if any, that may be associated with sertraline's extended use in children and
adolescents with OCD have not be 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 relatively short-term clinical studies and from 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.
Geriatric Use
Several hundred elderly patients have participated in clinical studies with sertraline HCl.
The pattern of adverse reactions in the elderly was similar to that in younger patients.