Sertraline Tablets SMPC Taj Pharmaceuticals

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Sertraline HCl Tablets 50mg Therapy should be initiated at 25mg/day. After

one week, the dose should be increased to 50mg
1. Name of the medicinal once daily. This dosage regimen has been shown
to reduce the frequency of early treatment
product emergent side effects characteristic of panic
disorder,
Sertraline HCl Tablets 50mg Taj Pharma
Titration
2. Qualitative and quantitative Depression, OCD, Panic Disorder, Social
composition Anxiety Disorder and PTSD
Each film-coated tablet contains: Patients not responding to a 50 mg dose may
Sertraline Hydrochloride USP benefit from dose increases. Dose changes
Equivalent to Sertraline 50mg should be made in steps of 50 mg at intervals of
Excipients q.s. at least one week, up to a maximum of 200
Colour: Indigo Carmine mg/day. Changes in dose should not be made
more frequently than once per week given the
For the full list of excipients, see section 6.1.
24-hour elimination half life of sertraline.
3. Pharmaceutical form The onset of therapeutic effect may be seen
within 7 days. However, longer periods are
Film-coated tablet.
usually necessary to demonstrate therapeutic
response, especially in OCD.
4. Clinical particulars
Maintenance
4.1 Therapeutic indications
Sertraline is indicated for the treatment of: Dosage during long-term therapy should be kept
at the lowest effective level, with subsequent
Major depressive episodes.Prevention of adjustments depending on therapeutic response.
recurrence of major depressive episodes.
Depression
Panic disorder, with or without agoraphobia.
Longer-term treatment may also be appropriate
Obsessive compulsive disorder (OCD) in adults for prevention of recurrence of major depressive
and paediatric patients aged 6-17 years. episodes (MDE). In most of the cases, the
Social anxiety disorder. recommended dose in prevention of recurrence
of MDE is the same as the one used during
Post traumatic stress disorder (PTSD) current episode. Patients with depression should
4.2 Posology and method of administration be treated for a sufficient period of time of at
Posology least 6 months to ensure they are free from
symptoms.
Initial treatment
Panic disorder and OCD
Depression and OCD
Continued treatment in panic disorder and OCD
Sertraline treatment should be started at a dose should be evaluated regularly, as relapse
of 50mg/day. prevention has not been shown for these
Panic Disorder, PTSD, and Social Anxiety disorders.
Disorder Elderly patients
Sertraline 50mg Tablets TajP harma : Uses , Side Effects , Interactions, Pi ctures, Warnings, Sertraline Dosage & Rx I nfo | Sert raline Uses, Side E ffe cts - Anti depras snt, Sertraline : Indi cations , Side Effects , Warning s, Sertraline - Drug Infor mation - TajPhar ma, Sertraline dose Taj phar maceuticals Sertraline interactions, Taj Phar mace utical Sertraline contraindications, S ertraline price, Sertraline TajPhar ma Antidepra ssnt Tablets S mPC - TajP harma Stay conne cted to all updated on Sertraline Taj Phar mace uticals Taj pharma ceutical s Mumbai. Patient I nfor mation Lea flets, SmP C.
Elderly should be dosed carefully, as elderly Withdrawal symptoms seen on discontinuation

may be more at risk for hyponatraemia (see of sertraline
section 4.4).
Abrupt discontinuation should be avoided.
Patients with hepatic impairment When stopping treatment with sertraline the
dose should be gradually reduced over a period
The use of sertraline in patients with hepatic of at least one to two weeks in order to reduce
disease should be approached with caution. A the risk of withdrawal reactions (see sections 4.4
lower or less frequent dose should be used in and 4.8). If intolerable symptoms occur
patients with hepatic impairment (see section following a decrease in the dose or upon
4.4). Sertraline should not be used in cases of
discontinuation of treatment, then resuming the
severe hepatic impairment as no clinical data are previously prescribed dose may be considered.
available (see section 4.4). Subsequently, the physician may continue
Patients with renal impairment decreasing the dose, but at a more gradual rate.
No dosage adjustment is necessary in patients 4.3 Contraindications
with renal impairment (see section 4.4). Hypersensitivity to the active substance or any
of the excipients listed in section 6.1.
Paediatric population
Concomitant treatment with irreversible
Children and adolescents with obsessive monoamine oxidase inhibitors (MAOIs) is
compulsive disorder contraindicated due to the risk of serotonin
Age 13-17 years: Initially 50 mg once daily. syndrome with symptoms such as agitation,
tremor and hyperthermia. Sertraline must not be
Age 6-12 years: Initially 25 mg once daily. The initiated for at least 14 days after discontinuation
dosage may be increased to 50 mg once daily of treatment with an irreversible MAOI.
after one week. Sertraline must be discontinued for at least 7
Subsequent doses may be increased in case of days before starting treatment with an
less than desired response in 50 mg increments irreversible MAOI (see section 4.5).
over a period of some weeks, as needed. The Concomitant intake of pimozide is contra-
maximum dosage is 200 mg daily. However, the indicated (see section 4.5).
generally lower body weights of children
compared to those of adults should be taken into 4.4 Special warnings and precautions for use
consideration when increasing the dose from 50 Serotonin Syndrome (SS) or Neuroleptic
mg. Dose changes should not occur at intervals Malignant Syndrome (NMS)
of less than one week. The development of potentially life-threatening
Efficacy is not shown in paediatric major syndromes like serotonin syndrome (SS) or
depressive disorder. Neuroleptic Malignant Syndrome (NMS) has
been reported with SSRIs, including treatment
No data is available for children under 6 years of with sertraline. The risk of SS or NMS with
age (see also section 4.4) SSRIs is increased with concomitant use of other
Method of administration serotonergic drugs (including other serotonergic
antidepressants, amphetamines, triptans), with
Sertraline should be administered once daily, drugs which impair metabolism of serotonin
either in the morning or evening. (including MAOIs e.g. methylene blue),
antipsychotics and other dopamine antagonists,
Sertraline tablets can be administered with or
and with opiate drugs. Patients should be
without food,
monitored for the emergence of signs and Psychotic symptoms might become aggravated
symptoms of SS or NMS syndrome (see section in schizophrenic patients.
4.3).
Seizures
Switching from Selective Serotonin Reuptake
Inhibitors (SSRIs), antidepressants or anti- Seizures may occur with sertraline therapy:
obsessional drugs sertraline should be avoided in patients with
unstable epilepsy and patients with controlled
There is limited controlled experience regarding epilepsy should be carefully monitored.
the optimal timing of switching from SSRIs, Sertraline should be discontinued in any patient
antidepressants or anti-obsessional drugs to who develops seizures.
sertraline. Care and prudent medical judgement
should be exercised when switching, particularly Suicide / suicidal thoughts/suicide attempts or
from long-acting agents such as fluoxetine. clinical worsening
Depression is associated with an increased risk
Other serotonergic drugs e.g. tryptophan,
fenfluramine and 5-HT agonists of suicidal thoughts, self harm and suicide
(suicide-related events). This risk persists until
Co-administration of sertraline with other drugs significant remission occurs. As improvement
which enhance the effects of serotonergic may not occur during the first few weeks or
neurotransmission such as amphetamines, more of treatment, patients should be closely
tryptophan or fenfluramine or 5-HT agonists, or monitored until such improvement occurs. It is
the herbal medicine, St John's Wort general clinical experience that the risk of
(hypericumperforatum), should be undertaken suicide may increase in the early stages of
with caution and avoided whenever possible due recovery.
to the potential for a pharmacodynamic
interaction. Other psychiatric conditions for which sertraline
is prescribed can also be associated with an
QTc Prolongation/Torsade de Pointes (TdP) increased risk of suicide-related events. In
addition, these conditions may be co-morbid
Cases of QTc prolongation and Torsade de with major depressive disorder. The same
Pointes (TdP) have been reported during post- precautions observed when treating patients with
marketing use of sertraline. The majority of major depressive disorder should therefore be
reports occurred in patients with other risk observed when treating patients with other
factors for QTc prolongation/TdP. Therefore psychiatric disorders.
sertraline should be used with caution in patients
with risk factors for QTc prolongation. Patients with a history of suicide-related events
or those exhibiting a significant degree of
Activation of hypomania or mania
suicidal ideation prior to commencement of
Manic/hypomanic symptoms have been reported treatment are known to be at greater risk of
to emerge in a small proportion of patients suicidal thoughts or suicide attempts, and should
treated with marketed antidepressant and anti- receive careful monitoring during treatment. A
obsessional drugs, including sertraline. meta-analysis of placebo-controlled clinical
Therefore sertraline should be used with caution trials of antidepressant drugs in adult patients
in patients with a history of mania/hypomania. with psychiatric disorders showed an increased
Close surveillance by the physician is required. risk of suicidal behaviour with antidepressants
Sertraline should be discontinued in any patient compared to placebo in patients less than 25
entering a manic phase. years old.
Schizophrenia
Close supervision of patients and in particular (e.g. anticoagulants, atypical antipsychotics and
those at high risk should accompany drug phenothiazines, most tricyclic antidepressants,
therapy especially in early treatment and acetylsalicylic acid and non-steroidal anti-
following dose changes. Patients (and caregivers inflammatory drugs (NSAIDs)) as well as in
of patients) should be alerted about the need to patients with a history of bleeding disorders (see
monitor for any clinical worsening, suicidal section 4.5).
behaviour or thoughts and unusual changes in
Hyponatraemia
behaviour and to seek medical advice
immediately if these symptoms present. Hyponatraemia may occur as a result of
Paediatric population treatment with SSRIs or SNRIs including
sertraline. In many cases, hyponatraemia appears
Sertraline should not be used in the treatment of to be the result of a syndrome of inappropriate
children and adolescents under the age of 18 antidiuretic hormone secretion (SIADH). Cases
years, except for patients with obsessive of serum sodium levels lower than 110 mmol/l
compulsive disorder aged 6 – 17 years old. have been reported.
Suicide-related behaviours (suicide attempt and
Elderly patients may be at greater risk of
suicidal thoughts) and hostility (predominantly
developing hyponatraemia with SSRIs and
aggression, oppositional behaviour and anger)
were more frequently observed in clinical trials SNRIs. Also patients taking diuretics or who are
among children and adolescents treated with otherwise volume-depleted may be at greater
antidepressants compared to those treated with risk (see Use in elderly). Discontinuation of
placebo. If, based on clinical need, a decision to sertraline should be considered in patients with
treat is nevertheless taken; the patient should be symptomatic hyponatraemia and appropriate
medical intervention should be instituted. Signs
carefully monitored for appearance of suicidal
and symptoms of hyponatraemia include
symptoms. In addition only limited clinical
evidence is available concerning, long-term headache, difficulty concentrating, memory
impairment, confusion, weakness and
safety data in children and adolescents including
unsteadiness which may lead to falls. Signs and
effects on growth, sexual maturation and
cognitive and behavioural developments. A few symptoms associated with more severe and/or
cases of retarded growth and delayed puberty acute cases have included hallucination,
have been reported post-marketing. The clinical syncope, seizure, coma, respiratory arrest and
death.
relevance and causality are yet unclear (see
section 5.3 for corresponding preclinical safety Withdrawal symptoms seen on discontinuation
data). Physicians must monitor paediatric of sertraline treatment
patients on long-term treatment for
abnormalities in growth and development. Withdrawal symptoms when treatment is
discontinued are common, particularly if
Abnormal bleeding/Haemorrhage discontinuation is abrupt (see section 4.8). In
There have been reports of bleeding clinical trials, among patients treated with
abnormalities with SSRIs including cutaneous sertraline, the incidence of reported withdrawal
bleeding (ecchymoses and purpura) and other reactions was 23% in those discontinuing
sertraline compared to 12% in those who
haemorrhagic events such as gastrointestinal or
continued to receive sertraline treatment.
gynaecological bleeding, including fatal
haemorrhages. Caution is advised in patients The risk of withdrawal symptoms may be
taking SSRIs, particularly in concomitant use dependent on several factors including the
with drugs known to affect platelet function duration and dose of therapy and the rate of dose
reduction. Dizziness, sensory disturbances patients with severe hepatic impairment (see
(including paraesthesia), sleep disturbances section 4.2).
(including insomnia and intense dreams),
Renal impairment
agitation or anxiety, nausea and/or vomiting,
tremor and headache are the most commonly Sertraline is extensively metabolised, and
reported reactions. Generally these symptoms excretion of unchanged drug in urine is a minor
are mild to moderate; however in some patients route of elimination. In studies of patients with
they may be severe in intensity. They usually mild to moderate renal impairment (creatinine
occur within the first few days of discontinuing clearance 30-60 ml/min) or moderate to severe
treatment, but there have been very rare reports renal impairment (creatinine clearance 10-29
of such symptoms in patients who have ml/min), multiple dose pharmacokinetic
inadvertently missed a dose. Generally these parameters (AUC0-24 or Cmax) were not
symptoms are self-limiting and usually resolve significantly different compared with controls.
within 2 weeks, though in some individuals they Sertraline dosing does not have to be adjusted
may be prolonged (2 – 3 months or more). It is based on the degree of renal impairment.
therefore advised that sertraline should be
gradually tapered when discontinuing treatment Use in elderly
over a period of several weeks or months, Over 700 elderly patients (>65 years) have
according to the patient's needs (see section 4.2). participated in clinical studies. The pattern and
Akathisia/psychomotor restlessness incidence of adverse reactions in the elderly was
similar to that in younger patients.
The use of sertraline has been associated with
the development of akathisia, characterised by a SSRIs or SNRIs including sertraline have
subjectively unpleasant or distressing however been associated with cases of clinically
restlessness and need to move often significant hyponatraemia in elderly patients,
accompanied by an inability to sit or stand still. who may be a greater risk for this adverse event
This is most likely to occur within the first few (see Hyponatraemia in section 4.4).
weeks of treatment. In patients who develop Diabetes
these symptoms, increasing the dose may be
detrimental. In patients with diabetes, treatment with an SSRI
may alter glycaemic control. Insulin and/or oral
Hepatic impairment hypoglycaemic dosage may need to be adjusted.
Sertraline is extensively metabolised by the Electroconvulsive therapy
liver. A multiple dose pharmacokinetic study in
subjects with mild, stable cirrhosis demonstrated There are no clinical studies establishing the
a prolonged elimination half-life and risks or benefits of the combined use of ECT and
approximately three-fold greater AUC and sertraline.
Cmax in comparison to normal subjects. There Grapefruit juice
were no significant differences in plasma protein
binding observed between the two groups. The The administration of sertraline with grapefruit
use of sertraline in patients with hepatic disease juice is not recommended (see section 4.5).
must be approached with caution. If sertraline is
Interference with urine screening tests
administered to patients with hepatic
impairment, a lower or less frequent dose should False-positive urine immunoassay screening
be considered. Sertraline should not be used in tests for benzodiazepines have been reported in
patients taking sertraline. This is due to lack of
specificity of the screening tests. False-positive reversible MAO-inhibitor, a shorter withdrawal

test results may be expected for several days period than 14 days may be used before
following discontinuation of sertraline therapy. initiation of sertraline treatment. It is
Confirmatory tests, such as gas recommended that sertraline should be
chromatography/mass spectrometry, will discontinued for at least 7 days before starting
distinguish sertraline from benzodiazepines. treatment with a reversible MAOI (see section
4.3).
Angle-Closure glaucoma
Reversible non-selective MAOI (linezolid)
SSRIs including sertraline may have an effect on
pupil size resulting in mydriasis. This mydriatic The antibiotic linezolid is a weak reversible and
effect has the potential to narrow the eye angle non-selective MAOI and should not be given to
resulting in increased intraocular pressure and patients treated with sertraline (see section 4.3).
angle-closure glaucoma, especially in patients
pre-disposed. Sertraline should therefore be used Severe adverse reactions have been reported in
with caution in patients with angle-closure patients who have recently been discontinued
glaucoma or history of glaucoma. from an MAOI (e.g. methylene blue) and started
on sertraline, or have recently had sertraline
Sexual dysfunction therapy discontinued prior to initiation of an
MAOI. These reactions have included tremor,
Selective serotonin reuptake inhibitors myoclonus, diaphoresis, nausea, vomiting,
(SSRIs)/serotonin norepinephrine reuptake flushing, dizziness and hyperthermia with
inhibitors (SNRIs) may cause symptoms of features resembling neuroleptic malignant
sexual dysfunction (see section 4.8). There have syndrome, seizures and death.
been reports of long-lasting sexual dysfunction
where the symptoms have continued despite Pimozide
discontinuation of SSRIs/SNRI.
Increased pimozide levels of approximately 35%
4.5 Interaction with other medicinal products have been demonstrated in a study of a single
and other forms of interaction low dose pimozide (2 mg). These increased
Contraindicated levels were not associated with any changes in
EKG. While the mechanism of this interaction is
Monoamine Oxidase Inhibitors
unknown, due to the narrow therapeutic index of
Irreversible MAOIs (e.g. selegiline) pimozide, concomitant administration of
sertraline and pimozide is contraindicated (see
Sertraline must not be used in combination with section 4.3).
irreversible MAOIs such as selegiline. Sertraline
must not be initiated for at least 14 days after Co-administration with sertraline is not
discontinuation of treatment with an irreversible recommended
MAOI. Sertraline must be discontinued for at CNS depressants and alcohol
least 7 days before starting treatment with an
irreversible MAOI (see section 4.3). The coadministration of sertraline 200 mg daily
did not potentiate the effects of alcohol,
Reversible, selective MAO-A inhibitor carbamazepine, haloperidol or phenytoin on
(moclobemide)
cognitive and psychomotor performance in
Due to the risk of serotonin syndrome, the healthy subjects; however, the concomitant use
combination of sertraline with a reversible and of sertraline and alcohol is not recommended.
selective MAOI, such as moclobemide, should Other serotonergic drugs
not be given. Following treatment with a
See section 4.4. There have been rare post-marketing reports

describing patients with weakness,
Caution is also advised with fentanyl (used in hyperreflexia, incoordination, confusion, anxiety
general anaesthesia or in the treatment of and agitation following the use of sertraline and
chronic pain), other serotonergic drugs sumatriptan. Symptoms of serotonergic
(including other serotonergic antidepressants, syndrome may also occur with other products of
amphetamines, triptans), and with other opiate the same class (triptans). If concomitant
drugs.
treatment with sertraline and triptans is clinically
Special Precautions warranted, appropriate observation of the patient
is advised (see section 4.4).
Drugs that Prolong the QT Interval
Warfarin
The risk of QTc prolongation and/or ventricular
arrhythmias (e.g. TdP) may be increased with Co-administration of sertraline (200 mg daily)
concomitant use of other drugs which prolong with warfarin resulted in a small but statistically
the QTc interval (e.g. some antipsychotics and significant increase in prothrombin time, which
antibiotics) (see section 4.4). may in some rare cases unbalance the INR
value. Accordingly, prothrombin time should be
Lithium carefully monitored when sertraline therapy is
In a placebo-controlled trial in normal initiated or stopped.
volunteers, the co-administration of sertraline Other drug interactions, digoxin, atenolol,
with lithium did not significantly alter lithium cimetidine
pharmacokinetics but did result in an increase in
tremor relative to placebo, indicating a possible Co-administration with cimetidine caused a
pharmacodynamic interaction. When co- substantial decrease in sertraline clearance. The
administering sertraline with lithium patients clinical significance of these changes is
should be appropriately monitored. unknown. Sertraline had no effect on the beta-
adrenergic blocking ability of atenolol. No
Phenytoin interaction of sertraline 200 mg daily was
A placebo-controlled trial in normal volunteers observed with digoxin.
suggests that chronic administration of sertraline Drugs affecting platelet function
200 mg/day does not produce clinically
important inhibition of phenytoin metabolism. The risk of bleeding may be increased when
Nonetheless, as some case reports have emerged medicines acting on platelet function (e.g.
of high phenytoin exposure in patients using NSAIDs, acetylsalicylic acid and ticlopidine) or
sertraline, it is recommended that plasma other medicines that might increase bleeding
phenytoin concentrations be monitored risk are concomitantly administered with SSRIs,
following initiation of sertraline therapy, with including sertraline (see section 4.4).
appropriate adjustments to the phenytoin dose. Neuromuscular Blockers
In addition, co-administration of phenytoin may
cause a reduction of sertraline plasma levels. It SSRIs may reduce plasma cholinesterase activity
cannot be excluded that other CYP3A4 inducers, resulting in a prolongation of the neuromuscular
e.g. phenobarbital, carbamazepine, St John's blocking action of mivacurium or other
Wort, rifampicin may cause a reduction of neuromuscular blockers.
sertraline plasma levels.
Drugs Metabolized by Cytochrome P450
Triptans
Sertraline may act as a mild-moderate inhibitor 5.2). Interaction with strong inhibitors of
of CYP 2D6. Chronic dosing with sertraline 50 CYP2C19, e.g. omeprazole, lansoprazole,
mg daily showed moderate elevation (mean pantoprazole, rabeprazole, fluoxetine,
23%-37%) of steady-state desipramine plasma fluvoxamine cannot be excluded.
levels (a marker of CYP 2D6 isozyme activity).
Clinical relevant interactions may occur with 4.6 Fertility, pregnancy and lactation
Pregnancy
other CYP 2D6 substrates with a narrow
therapeutic index like class 1C antiarrhythmics There are no well controlled studies in pregnant
such as propafenone and flecainide, TCAs and women. However, a substantial amount of data
typical antipsychotics, especially at higher did not reveal evidence of induction of
sertraline dose levels. congenital malformations by sertraline. Animal
Sertraline does not act as an inhibitor of CYP studies showed evidence for effects on
3A4, CYP 2C9, CYP 2C19, and CYP 1A2 to a reproduction probably due to maternal toxicity
clinically significant degree. This has been caused by the pharmacodynamic action of the
confirmed by in-vivo interaction studies with compound and/or direct pharmacodynamic
action of the compound on the foetus (see
CYP3A4 substrates (endogenous cortisol,
section 5.3).
carbamazepine, terfenadine, alprazolam),
CYP2C19 substrate diazepam, and CYP2C9 Use of sertraline during pregnancy has been
substrates tolbutamide, glibenclamide and reported to cause symptoms, compatible with
phenytoin. In vitro studies indicate that sertraline withdrawal reactions, in some neonates, whose
has little or no potential to inhibit CYP 1A2. mothers had been on sertraline. This
Intake of three glasses of grapefruit juice daily phenomenon has also been observed with other
SSRI antidepressants. Sertraline is not
increased the sertraline plasma levels by
recommended in pregnancy, unless the clinical
approximately 100% in a cross-over study in
eight Japanese healthy subjects. Therefore, the condition of the woman is such that the benefit
of the treatment is expected to outweigh the
intake of grapefruit juice should be avoided
potential risk.
during treatment with sertraline (see section
4.4). Neonates should be observed if maternal use of
Based on the interaction study with grapefruit sertraline continues into the later stages of
juice, it cannot be excluded that the concomitant pregnancy, particularly the third trimester. The
administration of sertraline and potent CYP3A4 following symptoms may occur in the neonate
inhibitors, e.g. protease inhibitors, ketoconazole, after maternal sertraline use in later stages of
itraconazole, posaconazole, voriconazole, pregnancy: respiratory distress, cyanosis,
clarithromycin, telithromycin and nefazodone, apnoea, seizures, temperature instability, feeding
would result in even larger increases in exposure difficulty, vomiting, hypoglycaemia, hypertonia,
of sertraline. This also concerns moderate hypotonia, hyperreflexia, tremor, jitteriness,
irritability, lethargy, constant crying,
CYP3A4 inhibitors, e.g. aprepitant,
erythromycin, fluconazole, verapamil and somnolence and difficulty in sleeping. These
diltiazem. The intake of potent CYP3A4 symptoms could be due to either serotonergic
inhibitors should be avoided during treatment effects or withdrawal symptoms. In a majority of
with sertraline. instances the complications begin immediately
or soon (<24 hours) after delivery.
Sertraline plasma levels are enhanced by about
50% in poor metabolizers of CYP2C19 Epidemiological data have suggested that the
compared to rapid metabolizers (see section use of SSRIs in pregnancy, particularly in late
pregnancy, may increase the risk of persistent
pulmonary hypertension in the newborn occurred in 14% for sertraline vs 0% in placebo.

(PPHN). The observed risk was approximately 5 These undesirable effects are dose dependent
cases per 1000 pregnancies. In the general and are often transient in nature with continued
population 1 to 2 cases of PPHN per 1000 treatment.
pregnancies occur.
The undesirable effects profile commonly
Breast-feeding observed in double-blind, placebo-controlled
studies in patients with OCD, panic disorder,
Published data concerning sertraline levels in PTSD and social anxiety disorder was similar to
breast milk show that small quantities of that observed in clinical trials in patients with
sertraline and its metabolite N- depression.
desmethylsertraline are excreted in milk.
Generally negligible to undetectable levels were Table 1 displays adverse reactions observed
found in infant serum, with one exception of an from post-marketing experience (frequency not
infant with serum levels about 50% of the known) and placebo-controlled clinical trials
maternal level (but without a noticeable health (comprising a total of 2542 patients on sertraline
effect in this infant). To date, no adverse effects and 2145 on placebo) in depression, OCD, panic
on the health of infants nursed by mothers using disorder, PTSD and social anxiety disorder.
sertraline have been reported, but a risk cannot
be excluded. Use in nursing mothers is not Some adverse drug reactions listed in Table 1
recommended unless, in the judgment of the may decrease in intensity and frequency with
physician, the benefit outweighs the risk. continued treatment and do not generally lead to
cessation of therapy.
Fertility
Table 1: Adverse Reactions
Animal data did not show an effect of sertraline Frequency of adverse reactions observed
on fertility parameters (see section 5.3.). from placebo-controlled clinical trials in
Human case reports with some SSRIs have depression, OCD, panic disorder, PTSD and
shown that an effect on sperm quality is social anxiety disorder. Pooled analysis and
reversible. post-marketing experience.
Syste Very Comm Uncom Rare Freq
Impact on human fertility has not been observed m Com on mon (≥1/1000 uenc
so far. Organ mon (≥1/100 (≥1/100 0 to y
4.7 Effects on ability to drive and use Class (≥ to 0 to <1/1000) Not
machines 1/10) <1/10) <1/100) Kno
Clinical pharmacology studies have shown that wn
sertraline has no effect on psychomotor (can
performance. However, as psychotropic drugs not
may impair the mental or physical abilities be
required for the performance of potentially estim
hazardous tasks such as driving a car or ated
operating machinery, the patient should be from
cautioned accordingly. the
avail
4.8 Undesirable effects able
Nausea is the most common undesirable effect. data)
In the treatment of social anxiety disorder,
Infecti upper gastroen diverticuli
sexual dysfunction (ejaculation failure) in men
ons respirat teritis, tis§
and ory otitis and appetite mia,

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tions infectio on increas mellitus*,
n, disord ed hypoglyc
pharyn ers appetite aemia*,
gitis, * hyperglyc
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Neopla neoplas hyponatra
sms m emia*§
benign Psychi inso anxiety suicidal conversio
, atric mnia *, ideation/n
malign disord depress behavio disorder∗§
ant and ers ion*, ur, ,
unspec agitatio psychoti paroniria∗
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(includ libido disorder dependen
ing decreas *, ce, sleep
cysts ed*, thinking walking,
and nervous abnorma premature
polyps ness, l, ejaculatio
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Blood lymphade nalisati hallucin
and nopathy, on, ation*,
lymph thromboc nightm aggressi
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, bruxis euphoric
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ers a∗§ paranoia
Immun hyperse anaphylac Nervo Dizz tremor, amneisa, coma*,
e nsitivity toid us iness movem hypoaest akathisia
system *, reaction* system , ent hesia*, (see
disord seasonal disord head disorde muscle section
ers allergy* ers ache rs contracti 4.4),
*, (includi ons dyskinesi
Endocr hypothy hyperprol som ng involunt a,
ine roidism* actinaemi nole extrapy ary*, hyperaest
disord a*§, nce ramidal syncope hesia,
ers inappropr sympto *, cerebrova
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antidiureti such as esia*, spasm
c hyperki migraine (including
hormone nesia, *, reversible
secretion* hyperto convulsi cerebral
§
nia, on*, vasoconst
Metab decreas hyperchol dystoni dizzines riction
olism ed esterolae a, teeth s syndrome
grindin postural, and Call- hypertens

g or coordina Fleming ion,
gait tion syndrome rigidity
abnorm abnorma ) and
alities), l, speech ∗§,, psych tachycard
paraest disorder omotor ia§
hesia*, restlessne Eye visual mydriasi scotoma, macu
hyperto ss∗§ (see disord disturba s* glaucoma lopat
nia* section ers nce* , diplopia, hy
disturba 4.4), photopho
nce in sensory bia,
attentio disturban hyphaema
n, ce, *§, pupils
dysgeus choreoath unequal*§
ia etosis§, , vision
also abnormal§
reported , lacrimal
were disorder
signs and
Ear tinnitus ear pain
symptoms
and *
asscociate
labyrin
d with
th
serotonin
disord
syndrome
ers
* or
neurolepti Cardia palpitat tachycar myocardi
c c ions* dia*, al
malignant disord cardiac infarction
syndrome ers disorder *§,
: In some Torsade
cases de
associated Pointes*§
with (see
concomit section
ant use of 4.4 and
serotoner 4.5),
gic drugs bradycard
that ia, QTc
included prolongati
agitation, on* (see
confusion section
, 4.4 and
diaphores 4.5)
is, Vascul hot abnorma peripheral
diarrhoea, ar flush* l ischaemia
fever, disord bleeding
ers (such as, (including

gastroint hepatitis,
estinal jaundice
bleeding and
)*, hepatic
hyperten failure)
sion*, Skin hyperhi periorbit rare
flushing, and drosis, aloedem reports of
haematu subcut rash*, a*, severe
ria* aneous urticaria cutaneous
Respir yawnin dyspnoe hypervent tissue *, adverse
atory, g* a, ilation, disord alopecia reactions
thoraci epistaxis interstitial ers *, (SCAR):
c and *, lung pruritus e.g.
medias broncho disease*§, *, Stevens-
tinal spasm* laryngosp purpura Johnson
disord asm, *, syndrome
ers dysphonia dermatit * and
, is, dry epidermal
stridor*§, skin, necrolysis
hypoventi face *§, skin
lation, oedema, reaction*§
hiccups cold ,
Gastro naus dyspeps melaena mouth sweat, photosens
intesti ea, ia, , tooth ulceration itivity§,
nal diarr constip disorder, , angioede
disord hoea ation* oesopha pancreatit ma, hair
ers , dry abdomi gitis, is*§, texture
mout nal glossitis, haematoc abnormal,
h pain* haemorr hezia, skin
vomitin hoids, tongue odour
g*, salivary ulceration abnormal
flatulen hypersec , dermatitis
ce retion, stomatitis bullous,
dysphag , rash
ia, follicular,
eructatio Muscu back osteoart rhabdomy trism
n, loskele pain, hritis, olysis*§, us*
tongue tal and arthralg muscle bone
disorder, connec ia*, twitchin disorder
Hepato hepatic tive myalgia g,
biliary function tissue muscle
disord abnormal, disord cramps*
ers serious ers ,
liver muscula
events r
weaknes nsferase results,

s increase semen
Renal pollakiu urinary d*, abnormal,
and ra, hesitation weight altered
urinary micturiti *, oliguria decrease platelet
disord on d*, function*
§
ers disorder,
urinary Injury, injury
retention poison
, urinary ing
incontin and
ence*, proced
polyuria ural
, compli
nocturia cations
Repro ejacu menstru sexual galactorrh Surgic vasodilati
ductiv latio ation dysfunct oea*, al and on
e n irregula ion, atrophic medica procedure
system failu r*, menorrh vulvovagi l
and re erectile agia, nitis, proced
breast dysfunc vaginal genital ures
disord tion haemorr discharge, * ADR identified post-marketing
ers hage, balanopos §
ADR frequency represented by the estimated
female thitis*§, upper limit of the 95% confidence interval using
sexual gynaecom “The Rule of 3”.
dysfunct astia*,
Withdrawal symptoms seen on discontinuation
ion priapism*
of sertraline treatment
,
Genera fatig malaise oedema hernia, Discontinuation of sertraline (particularly when
l ue* *,chest peripher drug abrupt) commonly leads to withdrawal
disord pain*, al*, tolerance symptoms. Dizziness, sensory disturbances
ers and astheni chills, decreased (including paraesthesia), sleep disturbances
admini a*, gait , (including insomnia and intense dreams),
stratio pyrexia disturba agitation or anxiety, nausea and/or vomiting,
n site * nce*, tremor and headache are the most commonly
conditi thirst reported. Generally these events are mild to
ons moderate and are self-limiting; however, in
some patients they may be severe and/or
Investi weight alanine blood
prolonged. It is therefore advised that when
gations increas aminotra cholestero
sertraline treatment is no longer required,
ed* nsferara l
gradual discontinuation by dose tapering should
se increased
be carried out (see sections 4.2 and 4.4).
increase *,
d*, abnormal Elderly population
aspartate clinical
aminotra laboratory SSRIs or SNRIs including sertraline have been
associated with cases of clinically significant
hyponatraemia in elderly patients, who may be Reporting suspected adverse reactions after
at greater risk for this adverse event (see section authorisation of the medicinal product is
4.4). important. It allows continued monitoring of the
benefit/risk balance of the medicinal product.
Paediatric population
4.9 Overdose
In over 600 paediatric patients treated with Toxicity
sertraline, the overall profile of adverse reactions
was generally similar to that seen in adult Sertraline has a margin of safety dependent on
studies. The following adverse reactions were patient population and/or concomitant
reported from controlled trials (n=281 patients medication. Deaths have been reported
treated with sertraline): involving overdoses of sertraline, alone or in
combination with other drugs and/or alcohol.
Very common (≥1/10): Headache (22%),
Therefore, any overdosage should be medically
insomnia (21%), diarrhoea (11%) and nausea treated aggressively.
(15%).
Symptoms
Common (≥1/100 to <1/10): Chest pain, mania,
pyrexia, vomiting, anorexia, affect lability, Symptoms of overdose include serotonin-
aggression, agitation, nervousness, disturbance mediated side-effects such as somnolence,
in attention, dizziness, hyperkinesia, migraine, gastrointestinal disturbances (e.g. nausea and
somnolence, tremor, visual disturbance, dry vomiting), tachycardia, tremor, agitation and
mouth, dyspepsia, nightmare, fatigue, urinary dizziness. Coma has been reported although less
incontinence, rash, acne, epistaxis, flatulence. frequently.
Uncommon (≥1/1000 to <1/100): ECG QT QTc prolongation/Torsade de Pointes has been
prolonged, suicide attempt, convulsion, reported following sertraline overdose;
extrapyramidal disorder, paraesthesia, therefore, ECG-monitoring is recommended in
depression, hallucination, purpura, all ingestions of sertraline overdoses.
hyperventilation, anaemia, hepatic function
Management
abnormal, alanine aminotransferase increased,
cystitis, herpes simplex, otitis externa, ear pain, There are no specific antidotes to sertraline. It is
eye pain, mydriasis, malaise, haematuria, rash recommended to establish and maintain an
pustular, rhinitis, injury, weight decreased, airway, and if necessary ensure adequate
muscle twitching, abnormal dreams, apathy, oxygenation and ventilation. Activated charcoal,
albuminuria, pollakiuria, polyuria, breast pain, which may be used with a cathartic, may be as
menstrual disorder, alopecia, dermatitis, skin or more effective than lavage, and should be
disorder, skin odour abnormal, urticaria, considered in treating overdose. Induction of
bruxism, flushing. emesis is not recommended. Cardiac (e.g. ECG)
Frequency not known: enuresis and vital signs monitoring is also recommended
along with general symptomatic and supportive
Class effects measures. Due to the large volume of
distribution of sertraline, forced diuresis,
Epidemiological studies, mainly conducted in dialysis, haemoperfusion and exchange
patients 50 years of age and older, show an transfusion are unlikely to be of benefit.
increased risk of bone fractures in patients
receiving SSRIs and TCAs. The mechanism 5. Pharmacological properties
leading to this risk is unknown.
5.1 Pharmacodynamic properties
Reporting of suspected adverse reactions
Pharmacotherapeutic group: Selective serotonin Clinical efficacy and safety

reuptake inhibitors (SSRI).
Major Depressive Disorder
Mechanism of action
A study was conducted which involved
Sertraline is a potent and specific inhibitor of depressed outpatients who had responded by the
neuronal serotonin (5-HT) uptake in vitro, which end of an initial 8-week open treatment phase on
results in the potentiation of the effects of 5-HT sertraline 50-200 mg/day. These patients
in animals. It has only very weak effects on (n=295) were randomized to continuation for 44
norepinephrine and dopamine neuronal reuptake. weeks on double-blind sertraline 50-200 mg/day
At clinical doses, sertraline blocks the uptake of or placebo. A statistically significantly lower
serotonin into human platelets. It is devoid of relapse rate was observed for patients taking
stimulant, sedative or anticholinergic activity or sertraline compared to those on placebo. The
cardiotoxicity in animals. In controlled studies in mean dose for completers was 70 mg/day. The
normal volunteers, sertraline did not cause % of responders (defined as those patients that
sedation and did not interfere with psychomotor did not relapse) for sertraline and placebo arms
performance. In accord with its selective were 83.4% and 60.8%, respectively.
inhibition of 5-HT uptake, sertraline does not
Post traumatic stress disorder (PTSD)
enhance catecholaminergic activity. Sertraline
has no affinity for muscarinic (cholinergic), Combined data from the 3 studies of PTSD in
serotonergic, dopaminergic, adrenergic, the general population found a lower response
histaminergic, GABA or benzodiazepine rate in males compared to females. In the two
receptors. The chronic administration of positive general population trials, the male and
sertraline in animals was associated with down- female sertraline vs. placebo responder rates
regulation of brain norepinephrine receptors as were similar (females: 57.2% vs 34.5%; males:
observed with other clinically effective 53.9% vs 38.2%). The number of male and
antidepressants and antiobsessional drugs. female patients in the pooled general population
Sertraline has not demonstrated potential for trials was 184 and 430, respectively and hence
the results in females are more robust and males
abuse. In a placebo-controlled, double-blind
randomized study of the comparative abuse were associated with other baseline variables
liability of sertraline, alprazolam and d- (more substance abuse, longer duration, source
amphetamine in humans, sertraline did not of trauma etc) which are correlated with
produce positive subjective effects indicative of decreased effect.
abuse potential. In contrast, subjects rated both Paediatric OCD
alprazolam and d-amphetamine significantly
greater than placebo on measures of drug liking, The safety and efficacy of sertraline (50-200
euphoria and abuse potential. Sertraline did not mg/day) was examined in the treatment of non-
produce either the stimulation and anxiety depressed children (6-12 years old) and
associated with d-amphetamine or the sedation adolescent (13-17 years old) outpatients with
and psychomotor impairment associated with obsessive compulsive disorder (OCD). After a
alprazolam. Sertraline does not function as a one week single blind placebo lead-in, patients
positive reinforcer in rhesus monkeys trained to were randomly assigned to twelve weeks of
self administer cocaine, nor does it substitute as flexible dose treatment with either sertraline or
a discriminative stimulus for either d- placebo. Children (6-12 years old) were initially
amphetamine or pentobarbital in rhesus started on a 25 mg dose. Patients randomized to
monkeys. sertraline showed significantly greater
improvement than those randomised to placebo
on the Children's Yale-Brown Obsessive multiple pathways including CYP3A4.

Compulsive Scale CY-BOCS (p=0.005) the CYP2C19 (see section 4.5) and CYP2B6.
NIMH Global Obsessive Compulsive Scale Sertraline and its major metabolite
(p=0.019), and the CGI Improvement (p=0.002) desmethylsertraline are also substrate of P-
scales. In addition, a trend toward greater glycoprotein in-vitro.
improvement in the sertraline group than the
Elimination
placebo group was also observed on the CGI
Severity scale (p=0.089). For CY-BOCs the The mean half-life of sertraline is approximately
mean baseline and change from baseline scores 26 hours (range 22-36 hours). Consistent with
for the placebo group was 22.25 ± 6.15 and -3.4 the terminal elimination half-life, there is an
± 0.82, respectively, while for the sertraline approximately two-fold accumulation up to
group, the mean baseline and change from steady state concentrations, which are achieved
baseline scores were 23.36 ± 4.56 and -6.8 ± after one week of once-daily dosing. The half
0.87, respectively. In a post-hoc analysis, life of N-desmethylsertraline, is in the range of
responders, defined as patients with a 25% or 62 to 104 hours. Sertraline and N-
greater decrease in the CY-BOCs (the primary desmethylsertraline are both extensively
efficacy measure) from baseline to endpoint, metabolized in man and the resultant metabolites
were 53% of sertraline-treated patients excreted in faeces and urine in equal amounts.
compared to 37% of placebo-treated patients Only a small amount (<0.2%) of unchanged
(p=0.03). sertraline is excreted in the urine.
Long term safety and efficacy data are lacking Linearity/non-linearity
for this paediatric population.
Sertraline exhibits dose proportional
Paediatric population pharmacokinetics in the range of 50 to 200 mg.
No data is available for children under 6 years of Pharmacokinetics in specific patient groups
age.
Paediatric population with OCD
5.2 Pharmacokinetic properties
Absorption Pharmacokinetics of sertraline was studied in 29
paediatric patients aged 6-12 years old, and 32
In man, following an oral once-daily dosage of adolescent patients aged 13-17 years old.
50 to 200 mg for 14 days, peak plasma Patients were gradually uptitrated to a 200 mg
concentrations of sertraline occur at 4.5 to 8.4 daily dose within 32 days, either with 25 mg
hours after the daily administration of the drug. starting dose and increment steps, or with 50 mg
Food does not significantly change the starting dose or increments. The 25 mg regimen
bioavailability of sertraline tablets. and the 50 mg regimen were equally tolerated.
Distribution In steady state for the 200 mg dose, the
sertraline plasma levels in the 6-12 year old
Approximately 98% of the circulating drug is group were approximately 35% higher compared
bound to plasma proteins. to the 13-17 year old group, and 21% higher
compared to adult reference group. There were
Biotransformation
no significant differences between boys and girls
Sertraline undergoes extensive first-pass hepatic regarding clearance. A low starting dose and
metabolism. titration steps of 25 mg are therefore
recommended for children, especially with low
Based on clinical and in-vitro data, it can be bodyweight. Adolescents could be dosed like
concluded that sertraline is metabolized by adults.
Adolescents and elderly 21 through 56 (at doses of 10, 40, or 80

mg/kg/day) with a nondosing recovery phase up
The pharmacokinetic profile in adolescents or to Postnatal Day 196. Delays in sexual
elderly is not significantly different from that in maturation occurred in males and females at
adults between 18 and 65 years.
different dose levels (males at 80 mg/kg and
Hepatic impairment females at ≥10 mg/kg), but despite this finding
there were no sertraline-related effects on any of
In patients with liver damage, the half life of the male or female reproductive endpoints that
sertraline is prolonged and AUC is increased were assessed. In addition, on Postnatal Days 21
three fold (see sections 4.2 and 4.4). to 56, dehydration, chromorhinorrhea, and
Renal impairment reduced average body weight gain was also
observed. All of the aforementioned effects
In patients with moderate-severe renal attributed to the administration of sertraline were
impairment, there was no significant reversed at some point during the nondosing
accumulation of sertraline. recovery phase of the study. The clinical
Pharmacogenomics relevance of these effects observed in rats
administered sertraline has not been established.
Plasma levels of sertraline were about 50%
higher in poor metabolizers of CYP2C19 versus 6. Pharmaceutical particulars
extensive metabolizers. The clinical meaning is
not clear, and patients need to be titrated based 6.1 List of excipients
on clinical response. Tablet core:
5.3 Preclinical safety data Cellulose, Microcrystalline, Calcium Hydrogen

Preclinical data does not indicate any special Phosphate Dihydrate, Silica, Colloidal
hazard for humans based on conventional Anhydrous Sodium Starch Glycolate,
studies of safety pharmacology, repeated dose Hydroxypropyl cellulose, Magnesium Stearate.
toxicity, genotoxicity and carcinogenesis. Tablet Coating:
Reproduction toxicity studies in animals showed
no evidence of teratogenicity or adverse effects Titanium dioxide, Hypromellose, Macrogol,
on male fertility. Observed foetotoxicity was Polysorbate.
probably related to maternal toxicity. Postnatal 6.2 Incompatibilities
pup survival and body weight were decreased Not applicable
only during the first days after birth. Evidence
was found that the early postnatal mortality was 6.3 Shelf life
due to in-utero exposure after day 15 of 3 years
pregnancy. Postnatal developmental delays
6.4 Special precautions for storage
found in pups from treated dams were probably
This medicinal product does not require any
due to effects on the dams and therefore not
special storage conditions.
relevant for human risk.
6.5 Nature and contents of container
Animal data from rodents and non-rodents does
Aluminium foil/PVC blisters.
not reveal effects on fertility.
Pack Size: 7, 14, 28, 30, 50, 60, 90, 100 and
Juvenile animal studies
500 tablets.
A juvenile toxicology study in rats has been
Not All Packs May Be Marketed.
conducted in which sertraline was administered
orally to male and female rats on Postnatal Days
6.6 Special precautions for disposal and other

handling
No special requirements.
7. Manufactured In India By:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai - 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-
222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m.
EST
E-mail: tajgroup@tajpharma.com

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Sertraline 50mg Tablets TajP harma : Uses , Side Effects , Interactions, Pi ctures, Warnings, Sertraline Dosage & Rx I nfo

Sertraline HCl Tablets 50mg Therapy should be initiated at 25mg/day. After

Elderly should be dosed carefully, as elderly Withdrawal symptoms seen on discontinuation

specificity of the screening tests. False-positive reversible MAO-inhibitor, a shorter withdrawal

See section 4.4. There have been rare post-marketing reports

pulmonary hypertension in the newborn occurred in 14% for sertraline vs 0% in placebo.

and ory otitis and appetite mia,

grindin postural, and Call- hypertens

ers (such as, (including

weaknes nsferase results,

Pharmacotherapeutic group: Selective serotonin Clinical efficacy and safety

on the Children's Yale-Brown Obsessive multiple pathways including CYP3A4.

Adolescents and elderly 21 through 56 (at doses of 10, 40, or 80

5.3 Preclinical safety data Cellulose, Microcrystalline, Calcium Hydrogen

6.6 Special precautions for disposal and other

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