|
SIDE EFFECTS
During its premarketing assessment, multiple doses
of sertraline HCl were administered to approximately 3800
adult subjects as of June 30, 1995. The conditions and
duration of exposure to sertraline HCl 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 depression, OCD, and panic 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 be used to classify reported
adverse events. The frequencies presented, therefore,
represent the proportion of the approximately 3800 adult
individuals exposed to multiple doses of sertraline HCl
who experienced a treatment-emergent adverse event of
the type cited on at least one occasion while receiving
sertraline HCl. 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-Contolled Trials
TABLE 1 enumerates the most common treatment-emergent
adverse events associated with the use of sertraline HCl
(incidence of at least 5% for sertraline HCl and at least
twice that for placebo within at least one of the indications)
for the treatment of adult patients with depression/other*,
OCD, and panic disorder in placebo-controlled clinical
trials. Most patients received doses of 50 to 200 mg/day.
TABLE 2 enumerates treatement-emergent adverse events
that occurred in 2% or more of adult patients treated
with sertraline HCl and with incidence greater than placebo
who participated in controlled clinical trials comparing
sertraline HCl with placebo in the treatment of depression/other*,
OCD, and panic disorder. TABLE 2 provides combined date
for the pool of studies that are provided separately by
indication in TABLE 1
| TABLE
1 Most Common Treatment-Emergent Adverse Events: Incidence
in Placebo-Controlled Clinical Trials |
| |
Percentage
of Patients Reporting Event |
| |
Depression/Other* |
OCD |
Panic
Disorder |
| Body System/Adverse
Event |
Sertraline HCl (N=861) |
Placebo (N=853) |
Sertraline HCl (N=533) |
Placebo (N-373) |
Sertraline HCl (N=430) |
Placebo (N=275) |
| Autonomic
Nervous System Disorders |
Ejaculation
Failure (1) |
7 |
<1 |
17 |
2 |
19 |
1 |
Sweating
Increased |
8 |
3 |
6 |
1 |
5 |
1 |
| Central
& Periph. Nervous System Disorders |
| Somnolence |
13 |
6 |
15 |
8 |
15 |
9 |
| Tremor |
11 |
3 |
8 |
1 |
5 |
1 |
| Gastrointestinal
Disorders |
| Anorexia |
3 |
2 |
11 |
2 |
7 |
2 |
| Constipation |
8 |
6 |
6 |
4 |
7 |
3 |
Diarrhea/
Loose
Stools |
18 |
6 |
24 |
10 |
20 |
9 |
| Dyspepsia |
6 |
3 |
10 |
4 |
10 |
8 |
| Nausea |
26 |
12 |
30 |
11 |
29 |
18 |
| Psychiatric
Disorders |
| Agitation |
6 |
4 |
6 |
3 |
6 |
2 |
| Insomnia |
16 |
9 |
28 |
12 |
25 |
18 |
Libido
Decreased |
1 |
<1 |
11 |
2 |
7 |
1 |
| (1)
Primary ejaculatory delay. Denominator used was for
male patients only (N=271 sertraline HCl depression/other*;
N=271 placebo/depression/other*; N-296 sertraline
HCl OCD; N=219 placebo OCD; N = 216 sertraline HCl
panic disorder; N= 134 placebo panic disorder |
| *
Depression and other premarketing controlled trials. |
| TABLE
2 Treatment-Emergent Adverse Events: Incidence in
Placebo-Controlled Clinical Trials |
| |
Percentage
of Patients Reporting Event |
| |
Depression/Other*,
OCD, and Panic Disorder combined |
| Body
System/Adverse Event** |
Sertraline
HCl (N=1824) |
Placebo
(N=1501) |
| Autonomic
Nervous System Disorders |
| Ejaculation
Failure (1) |
14 |
1 |
| Mouth
Dry |
15 |
9 |
| Sweating
Increased |
7 |
2 |
| Central
& Periph. Nervous System Disorders |
| Somnolence |
14 |
1 |
| Dizziness |
13 |
8 |
| Headache |
26 |
23 |
| Paresthesia |
3 |
2 |
| Tremor |
9 |
2 |
| Disorders
of Skin and Appendages |
| Rash |
3 |
2 |
| Gastrointestinal
Disorders |
| Anorexia |
6 |
2 |
| Constipation |
7 |
5 |
| Diarrhea/
Loose Stools |
20 |
9 |
| Dyspepsia |
8 |
4 |
| Flatulence |
3 |
2 |
| Nausea |
28 |
13 |
| Vomiting |
4 |
2 |
| General |
| Fatigue |
12 |
8 |
| Hot
Flushes |
2 |
1 |
| Psychiatric
Disorders |
| Agitation |
6 |
4 |
| Anxiety |
4 |
3 |
| Insomnia |
22 |
11 |
| Libido
Decreased |
5 |
1 |
| Nervousness |
6 |
4 |
| Special
Senses |
| Vision
Abnormal |
4 |
2 |
(1)
Primarily ejaculatory delay. Denominator used was
for male patients only (N=783
sertraline
HCl; N=624 placebo) |
| *
Depression and other premarketing controlled trials |
**
Included are events reported by at least 2% of patients
taking sertraline HCl except the
following
events, which had an incidence on placebo greater
than or equal to sertraline HCl:
abdominal
pain and pharyngitis. |
Associated with Discontinuation in Placebo-Controlled
Clinical Trials
TABLE 3 lists the adverse events associated with discontinuation
of sertraline HCl treatment (incidence at least twice that
for placebo an at least 1% for sertraline HCl in clinical
trials) in depression/other*, OCD, and panic disorder.
| TABLE
3 Most Common Adverse Events Associated with Discontinuation
in Placebo-Controlled Clinical Trials |
| Adverse
Event |
Depression/Other*,
OCD, and Panic Disorder combined (N=1824) |
Depression/Other*
(N=861) |
OCD
(N=533) |
Panic
Disorder (N=430) |
| Agitation |
1% |
1% |
-- |
3% |
| Anorexia |
-- |
-- |
-- |
1% |
| Anxiety |
-- |
-- |
-- |
1% |
| Concentration
Impaired |
-- |
-- |
-- |
1% |
| Depersonalization |
-- |
-- |
-- |
1% |
| Diarrhea |
3% |
2% |
2% |
4% |
| Dizziness |
-- |
-- |
1% |
2% |
| Dry
Mouth |
1% |
1% |
-- |
3% |
| Dyspepsia |
-- |
-- |
-- |
3% |
| Ejaculation
Failure (1) |
1% |
1% |
1% |
2% |
| Fatigue |
1% |
-- |
-- |
3% |
| Headache |
2% |
2% |
-- |
5% |
| Insomnia |
2% |
1% |
3% |
4% |
| Nausea |
4% |
4% |
3% |
6% |
| Nervousness |
1% |
-- |
-- |
3% |
| Paresthesia |
-- |
-- |
-- |
2% |
| Somnolence |
2% |
1% |
2% |
3% |
| Tremor |
1% |
2% |
-- |
-- |
| Vomiting |
-- |
-- |
-- |
1% |
(1)
Primary ejaculatory delay. Denominator used was for
male patients only (N=271
depression/other*;
N=296 OCD; N=216 panic disorder) |
| * Depression
and other premarketing controlled trials. |
Male and Female Sexual Dysfunction with SSRIs
Although changes in sexual desire, sexual performance, and
sexual satisfaction often occur as manifestations of a psychiatric
disorder, they may also be a consequence of pharmacologic
treatment. In particular, some evidence suggests that selective
serotonin reuptake inhibitors (SSRIs) can cause such untoward
sexual experiences. Reliable estimates of the incidence
and severity of untoward experiences involving sexual desire,
performance and satisfaction are difficult to obtain, however,
in part because patients and physicians may be reluctant
to discuss them. Accordingly, estimates of the incidence
of untoward sexual experience and performance cited in product
labeling, are likely to underestimate their actual incidence.
TABLE 4 displays the incidence of sexual side effects reported
by at least 2% of patients taking sertraline HCl in placebo-controlled
clinical trials.
| TABLE
4 |
| Treatment |
Ejaculation
Failure (Primarily Delayed Ejaculation) |
Decreased
Libido |
| |
N
(Males Only) |
Incidence |
N
(Males and Females) |
Incidence |
| Sertraline
HCl |
783 |
14% |
1824 |
5% |
| Placebo |
624 |
1% |
1501 |
1% |
There are no adequate and well-controlled studies examining
sexual dysfunction with sertraline treatment.
Priapism has been reported with all SSRIs.
While it is difficult to know the precise risk of sexual
dysfunction associated with the use of SSRIs, physicians
should routinely inquire about such possible side effects.
Other Adverse Events in Pediatric Patients
In approximately n=250 pediatric patients treated with sertraline
HCl, the overall profile of adverse events was generally
similar to that seen in adult studies, as shown in TABLE
1 and TABLE 2. However, the following adverse
events, not appearing in TABLE 1 and TABLE 2,
were reported at an incidence of at least 2% and occurred
at a rate at least twice the placebo rate in a controlled
trial (n=187): hyperkinesia, twitching, fever, malaise,
purpura, weight decrease, concentration impaired, manic
reaction, emotional lability, thinking abnormal, and epistaxis.
Other Events Observed During the Premarketing Evaluation
of Sertraline HCl
Following is a list of treatment-emergent adverse events
reported during premarketing assessment of sertraline HCl
in clinical trials (approximately 3800 adult subjects) except
those already listed in TABLE 1 and TABLE 2
or TABLE 3 or elsewhere in the prescribing information..
In 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 approximately 3800 adult individuals
exposed to multiple doses of sertraline HCl who experienced
an event of the type cited on at least one occasion while
receiving sertraline HCl. All events are included except
those already listed in TABLE 1 and TABLE 2
or TABLE 3 or elsewhere in the prescribing information,
those reported in terms so general as to be uninformative,
and those for which a causal relationship to sertraline
HCl treatment seemed remote. It is important to emphasize
that although the events reported occurred during treatment
with sertraline HCl, they were not necessarily caused by
it.
Events are further categorized by body system and listed
in order of decreasing frequency according to the following
definitions: frequent adverse events are those occurring
on one or more occasions in at least 1/100 patients: infrequent
adverse events are those occurring in 1/100 to 1/1000 patients;
rare events are those occurring in fewer than 1/1000 patients.
Events of major clinical importance are also described in
PRECAUTIONS.
Autonomic Nervous System Disorders: Frequent:
impotence; Infrequent: flushing, increased saliva,
cold clammy skin, mydriasis; Rare: pallor, glaucoma,
priapism, vasodilation.
Body as a Whole-General Disorders: Rare:
allergic reaction, allergy.
Cardiovascular: Frequent: palpitations,
chest pain; Infrequent: hypertension, tachycardia,
postural dizziness, postural hypotension, periorbital edema,
peripheral edema, hypotension, peripheral ischemia, syncope,
edema, dependent edema; Rare: precordial chest pain,
substernal chest pain, aggravated hypertension, myocardial
infarction, cerebrovascular disorder.
Central and Peripheral Nervous System Disorders:
Frequent: hypertonia, hypoesthesia; Infrequent:
twitching, confusion, hyperkinesia, vertigo, ataxia, migraine,
abnormal coordination, hyperesthesia, leg cramps, abnormal
gait, nystagmus, hypokinesia; Rare: dysphonia, coma,
dyskinesia, hypotonia, ptosis, choreoathetosis, hyporeflexia.
Disorders of the Skin and Appendages: Infrequent:
pruritus, acne, utricaria, alopecia, dry skin, erythematous
rash, photosensitivity reaction, maculopapular rash; Rare:
follicular rash, eczema, dermatitis, contact dermatitis,
bullous eruption, hypertrichosis, skin discoloration, pustular
rash.
Endocrine Disorders: Rare: exophthalmos,
gynecomastia.
Gastrointestinal Disorders: Frequent:
appetite increased; Infrequent: dysphagia, tooth
caries aggravated, eructation, esophagitis, gastroenteritis;
Rare: melena, glossitis, gum hyperplasia, hiccup,
stomatitis, tenesmus, colitis, diverticulitis, fecal incontinence,
gastritis, rectum hemorrhage, hemorrhagic peptic ulcer,
proctitis, ulcerative stomatitis, tongue edema, tongue ulceration.
General: Frequent: back pain, asthenia,
malaise, weight increase; Infrequent: fever, rigors,
generalized edema; Rare: face edema, aphthous stomatitis.
Hearing and Vestibular Disorders: Rare:
hyperacusis, labyrinthine disorder.
Hematopoietic and Lymphatic: Rare:
anemia, anterior chamber eye hemorrhage.
Liver and Biliary System Disorders: Rare:
abnormal hepatic function.
Metabolic and Nutritional Disorders: Infrequent:
thirst; Rare: hypoglycemia, hypoglycemia reaction.
Musculoskeletal System Disorders: Frequent:
myalgia; Infrequent: arthralgia, dystonia, arthrosis,
muscle cramps, muscle weakness.
Psychiatric Disorders: Frequent: yawning,
other male sexual dysfunction, other female sexual dysfunction;
Infrequent: depression, amnesia, paroniria, teeth-grinding,
emotional lability, apathy, abnormal dreams, euphoria, paranoid
reaction, hallucination, aggressive reaction, aggravated
depression, delusions; Rare: withdrawl syndrome,
suicide ideation, libido increased, somnambulism, illusion.
Reproductive: Infrequent: menstrual
disorder, dysmenorrhea, intermenstrural bleeding, vaginal
hemorrhage, amenorrhea, leukorrhea; Rare: female
breast pain, menorrhagia, balanoposthitis, breast enlargement,
atrophic vaginitis, acute female mastitis.
Respiratory System Disorders: Frequent:
rhinitis; Infrequent: coughing, dyspnea, upper respiratory
tract infection, epistaxis, bronchospasm, sinusitus; Rare:
hyperventilation, bradypnea, stridor, apnea, bronchitis,
hemoptysis, hypoventilation, laryngismus, laryngitis.
Special Senses: Frequent: tinnitus;
Infrequent: conjunctivitis, earache, eye pain, abnormal
accomodation; Rare: xerophthalmia, photophobia, diplopia,
abnormal lacrimation, scotoma, visual field defect.
Urinary System Disorders: Infrequent:
micturition frequency, polyuria, urinary retention, dysuria,
nocturia, urinary incontinence; Rare: cyctitis, oliguria,
pyelonephritis, hematuria, renal pain, strangury.
Laboratory Tests: In man, asymptomatic elevations
in serum transaminases (SGOT [or AST] and SGPT [or ALT])
have been reported infrequently (approximately 0.8%) in
association with sertraline HCl administration. These hepatic
enzyme elevations usually occurred within the first 1 to
9 weeks of drug treatment and promptly diminished upon drug
discontinuation.
Sertraline HCl therapy was associated with small mean increases
in total cholesterol (approximately 3%) and triglycerides
(approximately 5%), and a small mean decrease in serum uric
acid (approximately 7%) of no apparent clinical importance.
The safety profile observed with sertraline HCl treatment
in patients with depression, OCD and panic disorder is similar.
Other Events Observed During the Postmarketing Evaluation
of Sertraline HCl
Reports of adverse events temporarily associated with sertraline
HCl that have been received since market introduction, that
are not listed above and that may have no causal relationship
with the drug include the following: increased coagulation
times, bradycardia, AV block, atrial arrhythmias, hypothyroidism,
leukopenia, thrombocytopenia, hyperglycemia, priapism, galactorrhea,
hyperprolactinemia, neuroleptic malignant syndrome-like
events, psychosis, severe skin reactions, which potentially
can be fatal, such as Stevens-Johnson Syndrome, vasculitis,
photosensitivity and other severe cutaneous disorders, rare
reports of pancreatitis, and liver events-clinical features
(which in the majority of cases appeared to be reversible
with discontinuation of sertraline HCl) occurring in one
or more patients include: elevated enzymes, increased bilirubin,
hepatomegaly, hepatitis, jaundice, abdominal pain, vomiting,
liver failure and death. DRUG
ABUSE AND DEPENDENCE
Controlled Substance Class: Sertraline HCl
is not a controlled substance.
Physical and Psychological Dependence: Sertraline
HCl has not been systematically studied, in animals or humans,
for its potential for abuse, tolerance, or physical dependence.
However, the premarketing clinical experience with sertraline
HCl did not reveal any tendency for a withdrawal syndrome
or any drug-seeking behavior. As with any new CNS active
drug, physicians should carefully evaluate patients for
history of drug abuse and follow such patients closely,
observing them for signs of sertraline HCl misuse or abuse
(e.g., development of tolerance, incrementation of
dose, drug-seeking behavior).
DRUG INTERACTIONS
Potential Effects
of Coadministration of Drugs Highly Bound to Plasma Proteins:
Because sertraline is tightly bound to plasma protein, the
administration of sertraline HCl to a patient taking another
drug which is tightly bound to protein, (e.g., warfarin,
digitoxin) may cause a shift in plasma concentrations potentially
resulting in an adverse effect. Conversely, adverse effects
may result from displacement of protein bound sertraline
HCl by other tightly bound drugs.
In a study comparing prothrombin time AUC (0-120 hr) following
dosing with warfarin (0.75 mg/kg) before and after 21 days
of dosing with either sertraline HCl (50-200 mg/day) or
placebo, there was a mean increase in prothrombin time of
8% relative to baseline for sertraline HCl compared to a
1% decrease for placebo (p<0.02). The normalization of
prothrombin time for the sertraline HCl group was delayed
compared to the placebo group. The clinical significance
of this change is unknown. Accordingly, prothrombin time
should be carefully monitored when sertraline HCl therapy
is initiated or stopped.
Cimetidine: In a study assessing disposition
of sertraline HCl (100 mg) on the second of 8 days of cimetidine
administration (800 mg daily), there were significant increases
in sertraline HCl mean AUC (50%), Cmax (24%)
and half-life (26%) compared to the placebo group. The clinical
significance of these changes is unknown.
CNS Active Drugs: In a study comparing the
disposition of intravenously administered diazepam before
and after 21 days of dosing with either sertraline HCl (50
to 200 mg/day escalating dose) or placebo, there was a 32%
decrease relative to baseline in diazepam clearance for
the sertraline HCl group compared to a 19% decrease relative
to baseline for the placebo group (p<0.03). There was
a 23% increase in Tmax for desmethyldiazepam
in the sertraline HCl group compared to a 20% decrease in
the placebo group (p<0.03). The clinical significance
of these changes is unknown.
In a placebo-controlled trial in normal volunteers, the
administration of two doses of sertraline HCl did not significantly
alter steady-state lithium levels or the renal clearance
of lithium.
Nonetheless, at this time, it is recommended that plasma
lithium levels be monitored following initiation of sertraline
HCl therapy with appropriate adjustments to the lithium
dose. In a controlled study of a single dose (2 mg) of pimozide,
200 mg sertraline (q.d.) co-administration to steady state
was associated with a mean increase in pimozide AUC and
Cmax of about 40%, but was not associated with any changes
in EKG. Since the highest recommended pimozide dose (10
mg) has not been evaluated in combination with sertraline,
the effect on QT interval and PK parameters at doses higher
than 2 mg at this time are not known. While the mechanism
of this interaction is unknown, due to the narrow therapeutic
index of pimozide and due to the interaction noted at a
low dose of pimozide, concomitant administration of Zoloft
and pimozide should be contraindicated (see CONTRAINDICATIONS).
The risk of using sertraline HCl in combination with other
CNS active drugs has not been systematically evaluated.
Consequently, caution is advised if the concomitant administration
of sertraline HCl and such drugs is required.
There is limited controlled experience regarding the optimal
timing of switching from other antidepressants to sertraline
HCl. Care and prudent medical judgement should be exercised
when switching, particularly from long-acting agents. The
duration of an appropriate washout period which should intervene
before switching from one selective serotonin reuptake inhibitor
(SSRI) to another has not been established.
Monoamine Oxidase Inhibitors: See CONTRAINDICATIONS
and WARNINGS.
Drugs Metabolized by Cytochrome P450 3A4:
In two separate in vivo interaction studies, sertraline
was co-administered with cytochrome P450 3A4 substrates,
terfenadine or carbamazepine, under steady-state conditions.
The results of these studies demonstrated that sertraline
co-administration did not increase plasma concentrations
of terfenadine or carbamazepine. These data suggest that
sertraline HCl's extent of inhibition of P450 3A4 is not
likely to be of clinical significance. In three separate
in vivo interaction studies, sertraline was co-administered
with cytochrome P450 3A4 substrates, terfenadine, carbamazepine,
or cisapride under steady-state conditions. The results
of these studies indicated that sertraline did not increase
plasma concentrations of terfenadine, carbamazepine, or
cisapride. These data indicate that sertraline’s extent
of inhibition of P450 3A4 activity is not likely to be of
clinical significance. Results of the interaction study
with cisapride indicate that sertraline 200 mg (q.d.) induces
the metabolism of cisapride (cisapride AUC and Cmax were
reduced by about 35%).
Drugs Metabolized by P450 2D6: Many antidepressants
(e.g., the SSRIs) including sertraline, and most
tricyclic antidepressants inhibit the biochemical activity
of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin
hydroxylase), and thus, may increase the plasma concentrations
of co-administered drugs that are metabolized by P450 2D6.
The drugs for which this potential interaction is of greatest
concern are those metabolized primarily by 2D6 and which
have a narrow therapeutic index (e.g., the tricyclic
antidepressants and the type 1C antiarrhythmics propafenone
and flecainide). The extent to which this interaction is
an important clinical problem depends on the extent of the
inhibition of P450 2D6 by the antidepressant and the therapeutic
index of the co-administered drug. There is variability
among the antidepressants in the extent of clinically important
2D6 inhibition, and in fact sertraline at lower doses has
a less prominent inhibitory effect on 2D6 than some others
in the class. Nevertheless, even sertraline has the potential
for clinically important 2D6 inhibition. Consequently, concomitant
use of a drug metabolized by P450 2D6 with sertraline HCl
may require lower doses than usually prescribed for the
other drug. Furthermore, whenever sertraline is withdrawn
from co-therapy, an increased dose of the co-administered
drug may be required (see Tricyclic Antidepressants
- below).
Tricyclic Antidepressants (TCAs): The extent
to which SSRI TCA interactions may pose clinical problems
will depend on the degree of inhibition and the pharmacokinetics
of the SSRI involved. Nevertheless, caution is indicated
in the co-administration of TCAs with sertraline HCl, because
sertraline HCl may inhibit TCA metabolism. Plasma TCA concentrations
may need to be monitored, and the dose of TCA may need to
be reduced, if a TCA is co-administered with sertraline
HCl (see Drugs Metabolized by P450 2D6 - above).
Sumatriptan: There have been rare postmarketing
reports describing patient with weakness, hyperreflexia,
and incoordination following the use of a selective serotonin
reuptake inhibitor (SSRI) and sumatriptan. If concomitant
treatment with sumatriptan and an SSRI (e.g., citalopram,
fluoxetine, fluvoxamine, paroxetine, sertraline) is clinically
warranted, appropriate observation of the patient is advised.
Hypoglycemic Drugs: In a placebo-controlled
trial in normal volunteers, administration of sertraline
HCl for 22 days (including 200 mg/day for the final 13 days)
caused a statistically significant 16% decrease from baseline
in the clearance of tolbutamide following an intravenous
1000 mg dose. Sertraline HCl administration did not noticeably
change either the plasma protein binding or the apparent
volume of distribution of tolbutamide, suggesting that the
decreased clearance was due to a change in the metabolism
of the drug. The clinical significance of this decrease
in tolbutamide clearance is unknown.
Atenolol: Sertraline HCl (100 mg) when administered
to 10 healthy male subjects had no effect on the beta-adrenergic
blocking ability of atenolol.
Digoxin: In a placebo-controlled trial in
normal volunteers, administration of sertraline HCl for
17 days (including 200 mg/day for the last 10 days) did
not change serum digoxin levels on digoxin renal clearance.
Microsomal Enzyme Induction: Preclinical studies
have shown sertraline HCl to induce hepatic microsomal enzymes.
In clinical studies, sertraline HCl was shown to induce
hepatic enzymes minimally as determined by a small (5%)
but statistically significant decrease in antipyrine half-life
following administration of 200 mg/day for 21 days. This
small change in antipyrine half-life reflects a clinically
insignificant change in hepatic metabolism.
Electroconvulsive Therapy: There are no clinical
studies establishing the risks or benefits of the combined
use of electroconvulsive therapy (ECT) and sertraline HCl.
Alcohol: Although sertraline HCl did not potentiate
the cognitive and psychomotor effects of alcohol in experiments
with normal subjects, the concomitant use of sertraline
HCl and alcohol in depressed patients or OCD patients is
not recommended.
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