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to reduce the frequency of early treatment

RX emergent side effects characteristic of panic
disorder.
SERTRALINE TABLETS
50MG Titration
Depression, OCD, Panic Disorder, Social
1.NAME OF THE MEDICINAL PRODUCT Anxiety Disorder and PTSD
Sertraline 50 mg film-coated tablets Patients not responding to a 50 mg dose may
2. QUALITATIVE AND QUANTITATIVE benefit from dose increases. Dose changes
COMPOSITION should be made in steps of 50 mg at intervals of
at least one week, up to a maximum of 200
Each film-coated tablet contains 50 mg mg/day. Changes in dose should not be made
sertraline (as sertraline hydrochloride). 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.
White capsule shaped, film coated tablets.
Maintenance
The tablet can be divided into equal doses.
Dosage during long-term therapy should be kept
4. CLINICAL PARTICULARS
at the lowest effective level, with subsequent
4.1 Therapeutic indications adjustment depending on therapeutic response.
Sertraline is indicated for the treatment of:
Depression
Major depressive episodes. Prevention of
Longer-term treatment may also be appropriate
recurrence of major depressive episodes.
for prevention of recurrence of major depressive
Panic disorder, with or without agoraphobia. episodes (MDE). In most of the cases, the
recommended dose in prevention of recurrence
Obsessive compulsive disorder (OCD) in adults of MDE is the same as the one used during
and paediatric patients aged 6-17 years. current episode. Patients with depression should
Social anxiety disorder. be treated for a sufficient period of time of at
least 6 months to ensure they are free from
Post traumatic stress disorder (PTSD) symptoms.
4.2 Posology and method of administration Panic disorder and OCD
Posology Continued treatment in panic disorder and OCD
Initial treatment should be evaluated regularly, as relapse
prevention has not been shown for these
Depression and OCD disorders.
Sertraline treatment should be started at a dose Elderly
of 50 mg/day.
Elderly should be dosed carefully, as elderly
Panic Disorder, PTSD, and Social Anxiety may be more at risk for hyponatraemia (see
Disorder section 4.4).
Therapy should be initiated at 25 mg/day. After Hepatic impairment
one week, the dose should be increased to 50 mg
once daily. This dosage regimen has been shown The use of sertraline in patients with hepatic
disease should be approached with caution. A
lower or less frequent dose should be used in previously prescribed dose may be considered.
patients with hepatic impairment (see section Subsequently, the physician may continue
4.4). Sertraline should not be used in cases of decreasing the dose, but at a more gradual rate.
severe hepatic impairment as no clinical data are
available (see section 4.4). 4.3 Contraindications
Hypersensitivity to the active substance or any
Renal impairment of the excipients listed in section 6.1.
No dosage adjustment is necessary in patients Concomitant treatment with irreversible
with renal impairment (see section 4.4). monoamine oxidase inhibitors (MAOIs) is
contraindicated due to the risk of serotonin
Paediatric population
syndrome with symptoms such as agitation,
Children and adolescents with obsessive tremor and hyperthermia. Sertraline must not be
compulsive disorder initiated for at least 14 days after discontinuation
of treatment with an irreversible MAOI.
Age 13-17 years: Initially 50 mg once daily. Sertraline must be discontinued for at least 7
Age 6-12 years: Initially 25 mg once daily. The days before starting treatment with an
dosage may be increased to 50 mg once daily irreversible MAOI (see section 4.5).
after one week. Concomitant intake of pimozide is
Subsequent doses may be increased in case of contraindicated (see section 4.5).
less than desired response in 50 mg increments 4.4 Special Warnings and precautions for use
over a period of some weeks, as needed. The
maximum dosage is 200 mg daily. However, the Serotonin Syndrome (SS) or Neuroleptic
generally lower body weights of children Malignant Syndrome (NMS)
compared to those of adults should be taken into The development of potentially life-threatening
consideration when increasing the dose from 50 syndromes like serotonin syndrome (SS) or
mg. Dose changes should not occur at intervals Neuroleptic Malignant Syndrome (NMS) has
of less than one week.
been reported with SSRIs, including treatment
Efficacy is not shown in paediatric major with sertraline. The risk of SS or NMS with
depressive disorder. SSRIs is increased with concomitant use of other
serotonergic drugs (including other serotonergic
No data is available for children under 6 years of antidepressants, triptans), with drugs which
age (see also section 4.4) impair metabolism of serotonin (including
Method of administration MAOIs e.g. methylene blue), antipsychotics and
other dopamine antagonists, and with opiate
Sertraline should be administered once daily, drugs. Patients should be monitored for the
either in the morning or evening. emergence of signs and symptoms of SS or
Sertraline tablet can be administered with or NMS syndrome (see section 4.3 ).
without food. Switching from Selective Serotonin Reuptake
Withdrawal symptoms seen on discontinuation Inhibitors (SSRIs), antidepressants or
of sertraline antiobsessional drugs
Abrupt discontinuation should be avoided. There is limited controlled experience regarding

When stopping treatment with sertraline the the optimal timing of switching from SSRIs,
dose should be gradually reduced over a period antidepressants or antiobsessional drugs to
of at least one to two weeks in order to reduce sertraline. Care and prudent medical judgment
the risk of withdrawal reactions (see sections 4.4 should be exercised when switching, particularly
and 4.8). If intolerable symptoms occur from long-acting agents such as fluoxetine.
following a decrease in the dose or upon Other serotonergic drugs e.g. tryptophan,
discontinuation of treatment, then resuming the fenfluramine and 5-HT agonists
Co-administration of sertraline with other drugs general clinical experience that the risk of
which enhance the effects of serotonergic suicide may increase in the early stages of
neurotransmission such as tryptophan or recovery.
fenfluramine or 5-HT agonists, or the herbal
medicine, St John's Wort (hypericum Other psychiatric conditions, for which
perforatum), should be undertaken with caution sertraline is prescribed, can also be associated
and avoided whenever possible due to the with an increased risk of suicide-related events.
potential for a pharmacodynamic interaction. In addition, these conditions may be co-morbid
with major depressive disorder. The same
QTc Prolongation/Torsade de Pointes (TdP) precautions observed when treating patients with
major depressive disorder should therefore be
Cases of QTc prolongation and Torsade de observed when treating patients with other
Pointes (TdP) have been reported during post- psychiatric disorders.
marketing use of sertraline. The majority of
reports occurred in patients with other risk Patients with a history of suicide-related events,
factors for QTc prolongation/TdP. Therefore or those exhibiting a significant degree of
sertraline should be used with caution in patients suicidal ideation prior to commencement of
with risk factors for QTc prolongation. treatment are known to be at greater risk of
suicidal thoughts or suicide attempts, and should
Activation of hypomania or mania
receive careful monitoring during treatment. A
Manic/hypomanic symptoms have been reported meta-analysis of placebo-controlled clinical
to emerge in a small proportion of patients trials of antidepressant drugs in adult patients
treated with marketed antidepressant and with psychiatric disorders showed an increased
antiobsessional drugs, including sertraline. risk of suicidal behaviour with antidepressants
Therefore sertraline should be used with caution compared to placebo in patients less than 25
in patients with a history of mania/hypomania. years old.
Close surveillance by the physician is required. Close supervision of patients and in particular
Sertraline should be discontinued in any patient those at high risk should accompany drug
entering a manic phase. therapy especially in early treatment and
Schizophrenia following dose changes. Patients (and caregivers
of patients) should be alerted about the need to
Psychotic symptoms might become aggravated monitor for any clinical worsening, suicidal
in schizophrenic patients. behaviour or thoughts and unusual changes in
Seizures behaviour and to seek medical advice
immediately if these symptoms present.
Seizures may occur with sertraline therapy:
sertraline should be avoided in patients with Paediatric population
unstable epilepsy and patients with controlled Sertraline should not be used in the treatment of
epilepsy should be carefully monitored. children and adolescents under the age of 18
Sertraline should be discontinued in any patient years, except for patients with obsessive
who develops seizures. compulsive disorder aged 6-17 years old.
Suicide/suicidal thoughts/suicide attempts or Suicide-related behaviours (suicide attempt and
clinical worsening suicidal thoughts), and hostility (predominantly
aggression, oppositional behaviour and anger)
Depression is associated with an increased risk were more frequently observed in clinical trials
of suicidal thoughts, self harm and suicide among children and adolescents treated with
(suiciderelated events). This risk persists until antidepressants compared to those treated with
significant remission occurs. As improvement placebo. If, based on clinical need, a decision to
may not occur during the first few weeks or treat is nevertheless taken; the patient should be
more of treatment, patients should be closely carefully monitored for appearance of suicidal
monitored until such improvement occurs. It is symptoms. In addition only limited clinical
evidence is available concerning, long-term hallucination, syncope, seizure, coma,

safety data in children and adolescents including respiratory arrest, and death.
effects on growth, sexual maturation and
cognitive and behavioural developments. A few Withdrawal symptoms seen on discontinuation
of sertraline treatment
cases of retarded growth and delayed puberty
have been reported post-marketing. The clinical Withdrawal symptoms when treatment is
relevance and causality are yet unclear (see discontinued are common, particularly if
section 5.3 for corresponding preclinical safety discontinuation is abrupt (see section 4.8). In
data). Physicians must monitor paediatric clinical trials, among patients treated with
patients on long term treatment for abnormalities sertraline, the incidence of reported withdrawal
in growth and development. reactions was 23% in those discontinuing
Abnormal bleeding/Haemorrhage sertraline compared to 12% in those who
continued to receive sertraline treatment.
There have been reports of bleeding
abnormalities with SSRIs including cutaneous The risk of withdrawal symptoms may be
bleeding (ecchymoses and purpura) and other dependent on several factors including the
duration and dose of therapy and the rate of dose
haemorrhagic events such as gastrointestinal or
gynaecological bleeding, including fatal reduction. Dizziness, sensory disturbances
haemorrhages. Caution is advised in patients (including paraesthesia), sleep disturbances
taking SSRIs, particularly in concomitant use (including insomnia and intense dreams),
with drugs known to affect platelet function (e.g. agitation or anxiety, nausea and/or vomiting,
anticoagulants, atypical antipsychotics and tremor and headache are the most commonly
reported reactions. Generally these symptoms
phenothiazines, most tricyclic antidepressants,
are mild to moderate; however, in some patients
acetylsalicylic acid and non-steroidal anti-
inflammatory drugs (NSAIDs)) as well as in they may be severe in intensity. They usually
patients with a history of bleeding disorders (see occur within the first few days of discontinuing
section 4.5). treatment, but there have been very rare reports
of such symptoms in patients who have
Hyponatraemia inadvertently missed a dose. Generally these
symptoms are self-limiting and usually resolve
Hyponatraemia may occur as a result of within 2 weeks, though in some individuals they
treatment with SSRIs or SNRIs including may be prolonged (2-3 months or more). It is
sertraline. In many cases, hyponatraemia appears therefore advised that sertraline should be
to be the result of a syndrome of inappropriate gradually tapered when discontinuing treatment
antidiuretic hormone secretion (SIADH). Cases
over a period of several weeks or months,
of serum sodium levels lower than 110 mmol/l according to the patient's needs (see section 4.2).
have been reported. Elderly patients may be at
greater risk of developing hyponatraemia with Akathisia/psychomotor restlessness
SSRIs and SNRIs. Also patients taking diuretics
or who are otherwise volume-depleted may be at The use of sertraline has been associated with
greater risk (see Use in elderly). Discontinuation the development of akathisia, characterised by a
subjectively unpleasant or distressing
of sertraline should be considered in patients
restlessness and need to move often
with symptomatic hyponatraemia and
appropriate medical intervention should be accompanied by an inability to sit or stand still.
instituted. Signs and symptoms of This is most likely to occur within the first few
hyponatraemia include headache, difficulty weeks of treatment. In patients who develop
concentrating, memory impairment, confusion, these symptoms, increasing the dose may be
detrimental.
weakness and unsteadiness which may lead to
falls. Signs and symptoms associated with more Hepatic impairment
severe and/or acute cases have included
Sertraline is extensively metabolised by the
liver. A multiple dose pharmacokinetic study in
subjects with mild, stable cirrhosis demonstrated The administration of sertraline with grapefruit
a prolonged elimination half life and juice is not recommended (see section 4.5).
approximately threefold greater AUC and Cmax
Interference with urine screening tests
in comparison to normal subjects. There were no
significant differences in plasma protein binding False-positive urine immunoassay screening
observed between the two groups. The use of tests for benzodiazepines have been reported in
sertraline in patients with hepatic disease must patients taking sertraline. This is due to lack of
be approached with caution. If sertraline is specificity of the screening tests. False-positive
administered to patients with hepatic test results may be expected for several days
impairment, a lower or less frequent dose should following discontinuation of sertraline therapy.
be considered. Sertraline should not be used in Confirmatory tests, such as gas
patients with severe hepatic impairment (see chromatography/mass spectrometry, will
section 4.2). distinguish sertraline from benzodiazepines.
Renal impairment Angle-Closure Glaucoma
Sertraline is extensively metabolised, and SSRIs including sertraline may have an effect on
excretion of unchanged drug in urine is a minor pupil size resulting in mydriasis. This mydriatic
route of elimination. In studies of patients with effect has the potential to narrow the eye angle
mild to moderate renal impairment (creatinine resulting in increased intraocular pressure and
clearance 30-60 ml/min) or moderate to severe angle-closure glaucoma, especially in patients
renal impairment (creatinine clearance 10-29 pre-disposed. Sertraline should therefore be used
ml/min), multiple-dose pharmacokinetic with caution in patients with angle-closure
parameters (AUC0-24 or Cmax) were not glaucoma or history of glaucoma.
significantly different compared with controls.
Sertraline dosing does not have to be adjusted 4.5 Interaction with other medicinal products
based on the degree of renal impairment. and other forms of interaction
Use in elderly Contraindicated
Over 700 elderly patients (>65 years) have Monoamine Oxidase Inhibitors
participated in clinical studies. The pattern and Irreversible (non-selective) MAOIs (selegiline)
incidence of adverse reactions in the elderly was
similar to that in younger patients. Sertraline must not be used in combination with
irreversible MAOIs such as selegiline. Sertraline
SSRIs or SNRIs including sertraline have must not be initiated for at least 14 days after
however been associated with cases of clinically discontinuation of treatment with an irreversible
significant hyponatraemia in elderly patients, MAOI. Sertraline must be discontinued for at
who may be at greater risk for this adverse event least 7 days before starting treatment with an
(see Hyponatraemia in section 4.4). irreversibleMAOI (see section 4.3).
Diabetes Reversible, selective MAO-A inhibitor
In patients with diabetes, treatment with an SSRI (moclobemide)
may alter glycaemic control. Insulin and/or oral Due to the risk of serotonin syndrome, the
hypoglycaemic dosage may need to be adjusted. combination of sertraline with a reversible and
Electroconvulsive therapy selective MAOI, such as moclobemide, should
not be given. Following treatment with a
There are no clinical studies establishing the reversible MAO-inhibitor, a shorter withdrawal
risks or benefits of the combined use of ECT and period than 14 days may be used before
sertraline. initiation of sertraline treatment. It is
Grapefruit juice recommended that sertraline should be
discontinued for at least 7 days before starting
treatment with a reversible MAOI (see section Drugs that Prolong the QT Interval
4.3).
The risk of QTc prolongation and/or ventricular
Reversible, non-selective MAOI (linezolid) arrhythmias (e.g. TdP) may be increased with
concomitant use of other drugs which prolong
The antibiotic linezolid is a weak reversible and the QTc interval (e.g. some antipsychotics and
non-selective MAOI and should not be given to antibiotics) (see section 4.4).
patients treated with sertraline (see section 4.3).
Lithium
Severe adverse reactions have been reported in
patients who have recently been discontinued In a placebo-controlled trial in normal
from an MAOI (e.g. methylene blue) and started volunteers, the co-administration of sertraline
on sertraline, or have recently had sertraline with lithium did not significantly alter lithium
therapy discontinued prior to initiation of an pharmacokinetics, but did result in an increase in
MAOI. These reactions have included tremor, tremor relative to placebo, indicating a possible
myoclonus, diaphoresis, nausea, vomiting, pharmacodynamic interaction. When co-
flushing, dizziness, and hyperthermia with administering sertraline with lithium, patients
features resembling neuroleptic malignant should be appropriately monitored.
syndrome, seizures, and death.
Phenytoin
Pimozide
A placebo-controlled trial in normal volunteers
Increased pimozide levels of approximately 35% suggests that chronic administration of sertraline
have been demonstrated in a study of a single 200 mg/day does not produce clinically
low dose pimozide (2 mg). These increased important inhibition of phenytoin metabolism.
levels were not associated with any changes in Nonetheless, as some case reports have emerged
EKG. While the mechanism of this interaction is of high phenytoin exposure in patients using
unknown, due to the narrow therapeutic index of sertraline, it is recommended that plasma
pimozide, concomitant administration of phenytoin concentrations be monitored
sertraline and pimozide is contraindicated (see following initiation of sertraline therapy, with
section 4.3). appropriate adjustments to the phenytoin dose.
In addition, co-administration of phenytoin may
Co-administration with sertraline is not cause a reduction of sertraline plasma levels. It
recommended
cannot be excluded that other CYP3A4 inducers,
CNS depressants and alcohol e.g. phenobarbital, carbamazepine, St John´s
Wort, rifampicin may cause a reduction of
The co-administration of sertraline 200 mg daily sertraline plasma levels.
did not potentiate the effects of alcohol,
carbamazepine, haloperidol, or phenytoin on Triptans
cognitive and psychomotor performance in There have been rare post-marketing reports
healthy subjects; however, the concomitant use describing patients with weakness,
of sertraline and alcohol is not recommended. hyperreflexia, incoordination, confusion, anxiety
Other serotonergic drugs and agitation following the use of sertraline and
sumatriptan. Symptoms of serotonergic
See section 4.4. syndrome may also occur with other products of
Caution is also advised with fentanyl (used in the same class (triptans). If concomitant
general anaesthesia or in the treatment of treatment with sertraline and triptans is clinically
chronic pain), other serotonergic drugs warranted, appropriate observation of the patient
(including other serotonergic antidepressants, is advised (see section 4.4).
triptans), and with other opiate drugs. Warfarin
Special Precautions Co-administration of sertraline 200 mg daily
with warfarin resulted in a small but statistically
significant increase in prothrombin time, which phenytoin. In vitro studies indicate that sertraline
may in some rare cases unbalance the INR has little or no potential to inhibit CYP 1A2.
value. Accordingly, prothrombin time should be
carefully monitored when sertraline therapy is Intake of three glasses of grapefruit juice daily
initiated or stopped. increased the sertraline plasma levels by
approximately 100% in a cross-over study in
Other drug interactions, digoxin, atenolol, eight Japanese healthy subjects. Therefore, the
cimetidine intake of grapefruit juice should be avoided
during treatment withsertraline (see section 4.4).
Co-administration with cimetidine caused a
substantial decrease in sertraline clearance. The Based on the interaction study with grapefruit
clinical significance of these changes is juice, it cannot be excluded that the concomitant
unknown. Sertraline had no effect on the beta- administration of sertraline and potent CYP3A4
adrenergic blocking ability of atenolol. No inhibitors, e.g. protease inhibitors, ketoconazole,
interaction of sertraline 200 mg daily was itraconazole, posaconazole, voriconazole,
observed with digoxin. clarithromycin, telithromycin and nefazodone,
would result in even larger increases in exposure
Drugs affecting platelet function
of sertraline. This also concerns moderate
The risk of bleeding may be increased when CYP3A4 inhibitors, e.g. aprepitant,
medicines acting on platelet function (e.g. erythromycin, fluconazole, verapamil and
NSAIDs, acetylsalicylic acid and ticlopidine) or diltiazem. The intake of potent CYP3A4
other medicines that might increase bleeding inhibitors should be avoided during treatment
risk are concomitantly administered with SSRIs, with sertraline.
including sertraline (see section 4.4).
Sertraline plasma levels are enhanced by about
Neuromuscular Blockers 50% in poor metabolizers of CYP2C19
compared to rapid metabolizers (see section
SSRIs may reduce plasma cholinesterase activity 5.2). Interaction with strong inhibitors of
resulting in a prolongation of the neuromuscular CYP2C19, e.g. omeprazole, lansoprazole,
blocking action of mivacurium or other pantoprazole, rabeprazole, fluoxetine,
neuromuscular blockers. fluvoxamine cannot be excluded.
Drugs Metabolized by Cytochrome P450 4.6 Fertility, Pregnancy and lactation
Sertraline may act as a mild-moderate inhibitor Pregnancy
of CYP 2D6. Chronic dosing with sertraline 50
mg daily showed moderate elevation (mean There are no well controlled studies in pregnant
23%-37%) of steady-state desipramine plasma women. However, a substantial amount of data
levels (a marker of CYP 2D6 isozyme activity). did not reveal evidence of induction of
Clinical relevant interactions may occur with congenital malformations by sertraline. Animal
other CYP 2D6 substrates with a narrow studies showed evidence for effects on
therapeutic index like class 1C antiarrhythmics reproduction probably due to maternal toxicity
such as propafenone and flecainide, TCAs and caused by the pharmacodynamic action of the
typical antipsychotics, especially at higher compound and/or direct pharmacodynamic
sertraline dose levels. action of the compound on the foetus (see 5.3).
Sertraline does not act as an inhibitor of CYP Use of sertraline during pregnancy has been
3A4, CYP 2C9, CYP 2C19, and CYP 1A2 to a reported to cause symptoms, compatible with
clinically significant degree. This has been withdrawal reactions, in some neonates, whose
confirmed by in-vivo interaction studies with mothers had been on sertraline. This
CYP3A4 substrates (endogenous cortisol, phenomenon has also been observed with other
carbamazepine, terfenadine, alprazolam), SSRI antidepressants. Sertraline is not
CYP2C19 substrate diazepam, and CYP2C9 recommended in pregnancy, unless the clinical
substrates tolbutamide, glibenclamide and condition of the woman is such that the benefit
of the treatment is expected to outweigh the Clinical pharmacology studies have shown that
potential risk. sertraline has no effect on psychomotor
performance. However, as psychotropic drugs
Neonates should be observed if maternal use of may impair the mental or physical abilities
sertraline continues into the later stages of required for the performance of potentially
pregnancy, particularly the third trimester. The hazardous tasks such as driving a car or
following symptoms may occur in the neonate operating machinery, the patient should be
after maternal sertraline use in later stages of cautioned accordingly.
pregnancy: respiratory distress, cyanosis,
apnoea, seizures, temperature instability, feeding 4.8 Undesirable Effects
difficulty, vomiting, hypoglycaemia, hypertonia, Nausea is the most common undesirable effect.
hypotonia, hyperreflexia, tremor, jitteriness, In the treatment of social anxiety disorder,
irritability, lethargy, constant crying, sexual dysfunction (ejaculation failure) in men
somnolence and difficulty in sleeping. These occurred in 14% for sertraline vs 0% in placebo.
symptoms could be due to either serotonergic These undesirable effects are dose dependent
effects or withdrawal symptoms. In a majority of and are often transient in nature with continued
instances the complications begin immediately treatment.
or soon (<24 hours) after delivery.
The undesirable effects profile commonly
Epidemiological data have suggested that the observed in double-blind, placebo-controlled
use of SSRIs in pregnancy, particularly in late studies in patients with OCD, panic disorder,
pregnancy, may increase the risk of persistent PTSD and social anxiety disorder was similar to
pulmonary hypertension in the newborn that observed in clinical trials in patients with
(PPHN). The observed risk was approximately 5 depression.
cases per 1000 pregnancies. In the general
population 1 to 2 cases of PPHN per 1000 Table 1 displays adverse reactions observed
pregnancies occur. from postmarketing experience (frequency not
known) and placebo-controlled clinical trials
Breast-feedingPublished data concerning (comprising a total of 2542 patients on sertraline
sertraline levels in breast milk show that small and 2145 on placebo) in depression, OCD, panic
quantities of sertraline and its metabolite N- disorder, PTSD and social anxiety disorder.
desmethylsertraline are excreted in milk.
Generally negligible to undetectable levels were Some adverse drug reactions listed in Table 1
found in infant serum, with one exception of an may decrease in intensity and frequency with
infant with serum levels about 50% of the continued treatment and do not generally lead to
cessation of therapy.
maternal level (but without a noticeable health
effect in this infant). To date, no adverse effects Table 1: Adverse Reactions
on the health of infants nursed by mothers using
sertraline have been reported, but a risk cannot Frequency of adverse reactions observed from
be excluded. Use in nursing mothers is not placebo-controlled clinical trials in depression,
recommended unless, in the judgment of the OCD, panic disorder, PTSD and social anxiety
physician, the benefit outweighs the risk. disorder. Pooled analysis and postmarketing
experience (frequency not known).
Fertility
Very Common Uncommo Rare (≥1/1 Very Rare Frequency
Comm (≥1/100 to n 0000 to (<1/10000 not Known
Animal data did not show an effect of sertraline on <1/10) (≥1/1000 to <1/1000) ) (cannot be
on fertility parameters (see section 5.3.). Human (≥1/10) <1/100) estimated
from the
case reports with some SSRIs have shown that available
an effect on sperm quality is reversible. Impact data)
on human fertility has not been observed so far. Infections and Infestations
4.7 Effects on ability to drive and use Pharyngitis Upper Diverticulit

Respiratory is,
machines Tract Gastroent
Infection, eritis, Dizziness with serotonin

Rhinitis Otitis Postural, syndrome or
Media Syncope, Neuroleptic
Neoplasms benign, malignant (including cysts and polyps) Migraine* Malignant
Syndrome: In
some cases
Neoplasm associated
† with
concomitant
Blood and lymphatic system disorders use of
serotonergic
drugs that
Lymphade Leucopaenia, included
nopathy Thrombocytop agitation,
aenia confusion,
diaphoresis,
Immune system disorders diarrhoea,
fever,
hypertension,
Hypersensit Anaphylac Allergy
rigidity and
ivity toid
tachycardia.
Reaction Akathisia and
Endocrine disorders psychomotor
restlessness
(see section
Hypothyroid Hyperprolactin 4.4).
ism aemia, Cerebrovascul
inappropriate ar Spasm
antidiuretic (including
hormone reversible
secretion cerebral
Metabolism and Nutrition Disorders vasconstriction
syndrome and
call-fleming
Decreased Diabetes Hyponatremia, syndrome)..
Appetite, mellitus, Hyperglycaemi Eye Disorders
Increased Hyperchol a
Appetite* esterolae
mia, Visual Mydriasis* Glaucoma, Vision
Hypoglyca Disturbance Lacrimal Abnormal,
emia Disorder, Pupils
Psychiatric Disorders Scotoma, Unequal
Diplopia,
Photophobi
Insomni Depression Hallucinatio Conversio Paroniria a,
a (19%) *, n*, n Hyphaema.
Depersonali Aggression Disorder, Ear and Labyrinth Disorders
sation, *, Euphoric Drug
Nightmare, Mood*, Dependen
Anxiety*, Apathy, ce, Tinnitus* Ear Pain
Agitation*, Thinking Psychotic
Nervousnes Abnormal disorder*,
s, Libido Paranoia, Cardiac Disorders
Decreased* Suicidal
, Bruxism Ideation/b
ehaviour** Palpitations Tachycard Myocardial QTc
*, Sleep * ia Infarction, prolongation,
Walking, Bradycardia Torsade de
Premature , Cardiac Pointes
Ejaculatio Disorder
n Vascular Disorders
Nervous System Disorders
Hot flush* Hypertensi Peripheral Abnormal

Dizzine Paraesthesi Convulsion* Coma*, Movement on*, Ischaemia, Bleeding (such
ss a*, Tremor, , Muscle Choreoath Disorders Flushing Haematuria as
(11%), Hypertonia, Contraction etosis, (including gastrointestina
Somnol Dysgeusia, s Dyskinesi extrapyramidal l bleeding)
ence Disturbance Involuntary* a, symptoms Respiratory, Thoracic, and Mediastinal Disorders
(13%), in Attention, , Hyperaest such as
Headac Coordinatio hesia, hyperkinesia,
he n Sensory hypertonia, Yawning* Bronchosp Laryngospa Interstitial
(21%)* Abnormal, Disturbanc dystonia,teeth asm*, sm, Lung Disease
Hyperkinesi e grinding or gait Dyspnoea, Hyperventil
a, Amnesia, abnormalities). Epistaxis ation,
Hypoaesthe Also reported Hypoventila
sia*, were signs tion,
Speech and symptoms Stridor,
Disorder, associated
Dysphonia, Ejaculat Erectile Vaginal Menorrhagi Gynaecoma

Hiccups ion Dysfunction Haemorrh a, Atrophic stia
Failure age, Vulvuvagini
Gastrointestinal Disorders (14%) Sexual tis,
Dysfunctio Balanopost
n, Female hitis,
Diarrho Abdominal Oesophag Melaena, Pancreatitis Sexual Genital
ea Pain*, itis, Haematoch Dysfunctio Discharge,
(18%), Vomiting*, Dysphagia ezia, n, Priapism*,
Nausea Constipatio , Stomatitis, Menstruati Galactorrho
(24%), n*, Haemorrh Tongue on ea*
Dry Dyspepsia, oids, ulceration, irregular
Mouth Flatulence Salivary Tooth
General Disorders and Administration Site Conditions
(14%) Hypersecr Disorder,
etion, Glossitis,
Tongue Mouth
Fatigue Chest Oedema Hernia,
Disorder, Ulceration
(10%)* Pain*, Peripheral Drug
Eructation
Malaise , Chills, Tolerance
Hepatobiliary Disorders Pyrexia*, Decreased,
Asthenia*, Gait
Thirst Disturbance
Hepatic Serious liver
Function events
Abnormal (including
hepatitis,
jaundice and
Investigations
liver failure)
Skin and Subcutaneous Tissue Disorders
Alanine Semen Abnormal
Aminotran Abnormal, Clinical
Rash*, Periorbital Dermatitis, Rare sferase Blood Laboratory
Hyperhidro Oedema*, Dermatitis reports of Increased* cholesterol Results,
sis Face Bullous, severe , increased Altered
Oedema, Rash cutaneous Aspartate Platelet
Purpura*, Follicular, adverse Aminotran Function.
Alopecia*, Hair reactions sferase,
Cold Texture (SCAR): Increased*
Sweat, Abnormal, e.g. , Weight
Dry skin, Skin Odour Stevens- Decrease
Urticuria*, Abnormal Johnson d*, Weight
Pruritus syndrome Increased*
and
Injury and poisoning
epidermal
necrolysis,
Angioedem Injury
a,
Photosensit
ivity , Skin Surgical and medical procedures
Reaction.
Musculoskeletal and Connective Tissue Disorders
Vasodilatio
n
Arthralgia, Osteoarthr Bone Muscle Procedure
Myalgia itis, Disorder Cramps If adverse experience occurred in depression, OCD, panic disorder,
Muscular PTSD and social anxiety disorder, body term reclassified by depression
Weakness studies body term.
, Back † One case of neoplasm was reported in one patient receiving sertraline
Pain, compared with no cases in the placebo arm.
Muscle * these adverse reactions also occurred in postmarketing experience
Twitching ** the denominator uses the number of patients in that sex group-
Renal and Urinary Disorders combined: sertraline (1118 males, 1424 females) placebo (926 males,
1219 females) For OCD, short term, 1-12 week studies only
*** Cases of suicidal ideation and suicidal behaviours have been reported
Nocturia, Oliguria, during sertraline therapy or early after treatment discontinuation (see
Urinary Urinary section 4.4).
Retention* Hesitation
, Polyuria,
Pollakiura,
Micturition
disorder,
Withdrawal symptoms seen on discontinuation
Urinary of sertraline treatment
Incontinen
ce*
Discontinuation of sertraline (particularly when
Reproductive System and Breast Disorders**
abrupt) commonly leads to withdrawal
symptoms. Dizziness, sensory disturbances
(including paraesthesia), sleep disturbances
(including insomnia and intense dreams), Frequency not known: enuresis

agitation or anxiety, nausea and/or vomiting,
Class effects
tremor and headache are the most commonly
reported. Generally these events are mild to Epidemiological studies, mainly conducted in
moderate and are self-limiting; however, in patients 50 years of age and older, show an
some patients they may be severe and/or increased risk of bone fractures in patients
prolonged. It is therefore advised that when receiving SSRIs and TCAs. The mechanism
sertraline treatment is no longer required, leading to this risk is unknown.
gradual discontinuation by dose tapering should
be carried out (see sections 4.2 and 4.4). Reporting of suspected adverse reactions
Elderly population Reporting suspected adverse reactions after

authorisation of the medicinal product is
SSRIs or SNRIs including sertraline have been important. It allows continued monitoring of the
associated with cases of clinically significant benefit/risk balance of the medicinal product.
hyponatraemia in elderly patients, who may be
at greater risk for this adverse event (see section 4.9 Overdose
4.4). Toxicity
Paediatric population Sertraline has a margin of safety dependent on
In over 600 paediatric patients treated with patient population and/or concomitant
sertraline, the overall profile of adverse reactions medication. Deaths have been reported
was generally similar to that seen in adult involving overdoses of sertraline, alone or in
studies. The following adverse reactions were combination with other drugs and/or alcohol.
reported from controlled trials (n=281 patients Therefore, any overdosage should be medically
treated with sertraline): treated aggressively.
Very common (≥1/10): Headache (22%), Symptoms

insomnia (21%), diarrhoea (11%) and nausea Symptoms of overdose include serotonin-
(15%). mediated side effects such as somnolence,
Common (≥1/100 to <1/10): Chest pain, mania, gastrointestinal disturbances (such as nausea and
pyrexia, vomiting, anorexia, affect lability, vomiting), tachycardia, tremor, agitation and
aggression, agitation, nervousness, disturbance dizziness. Coma has been reported although less
in attention, dizziness, hyperkinesia, migraine, frequently.
somnolence, tremor, visual disturbance, dry QTc prolongation/Torsade de Pointes has been
mouth, dyspepsia, nightmare, fatigue, urinary reported following sertraline overdose;
incontinence, rash, acne, epistaxis, flatulence. therefore, ECG-monitoring is recommended in
Uncommon (≥1/1000 to <1/100): ECG QT all ingestions of sertraline overdoses.
prolonged, suicide attempt, convulsion, ManagementThere are no specific antidotes to
extrapyramidal disorder, paraesthesia, sertraline. It is recommended to establish and
depression, hallucination, purpura, maintain an airway and ensure adequate
hyperventilation, anaemia, hepatic function oxygenation and ventilation. Activated charcoal,
abnormal, alanine aminotransferase increased, which may be used with a cathartic, may be as
cystitis, herpes simplex, otitis externa, ear pain, or more effective than lavage, and should be
eye pain, mydriasis, malaise, haematuria, rash considered in treating overdose. Induction of
pustular, rhinitis, injury, weight decreased, emesis is not recommended. Cardiac (e.g. ECG)
muscle twitching, abnormal dreams, apathy, and vital sign monitoring is also recommended,
albuminuria, pollakiuria, polyuria, breast pain, along with general symptomatic and supportive
menstrual disorder, alopecia, dermatitis, skin measures. Due to the large volume of
disorder, skin odour abnormal, urticaria, distribution of sertraline, forced diuresis,
bruxism, flushing.
dialysis, haemoperfusion and exchange amphetamine or pentobarbital in rhesus

transfusion are unlikely to be of benefit. monkeys.
5. PHARMACOLOGICAL PROPERTIES Clinical efficacy and safety
5.1 Pharmacodynamic properties Major Depressive Disorder
Pharmacotherapeutic group: Selective serotonin A study was conducted which involved

reuptake inhibitors (SSRI), ATC code: N06 depressed outpatients who had responded by the
AB06 end of an initial 8-week open treatment phase on
sertraline 50-200 mg/day. These patients
Mechanism of action (n=295) were randomized to continuation for 44
weeks on double-blind sertraline 50-200 mg/day
Sertraline is a potent and specific inhibitor of
or placebo. A statistically significantly lower
neuronal serotonin (5 HT) uptake in vitro, which
relapse rate was observed for patients taking
results in the potentiation of the effects of 5-HT
sertraline compared to those on placebo. The
in animals. It has only very weak effects on mean dose for completers was 70 mg/day. The
norepinephrine and dopamine neuronal reuptake. % of responders (defined as those patients that
At clinical doses, sertraline blocks the uptake of
did not relapse) for sertraline and placebo arms
serotonin into human platelets. It is devoid of were 83.4% and 60.8%, respectively.
stimulant, sedative or anticholinergic activity or
cardiotoxicity in animals. In controlled studies in Post traumatic stress disorder (PTSD)
normal volunteers, sertraline did not cause
sedation and did not interfere with psychomotor Combined data from the 3 studies of PTSD in
performance. In accord with its selective the general population found a lower response
inhibition of 5-HT uptake, sertraline does not rate in males compared to females. In the two
enhance catecholaminergic activity. Sertraline positive general population trials, the male and
female sertraline vs. placebo responder rates
has no affinity for muscarinic (cholinergic),
were similar (females: 57.2% vs 34.5%; males:
serotonergic, dopaminergic, adrenergic,
53.9% vs 38.2%). The number of male and
histaminergic, GABA or benzodiazepine
female patients in the pooled general population
receptors. The chronic administration of
sertraline in animals was associated with down- trials was 184 and 430, respectively and hence
regulation of brain norepinephrine receptors as the results in females are more robust and males
observed with other clinically effective were associated with other baseline variables
antidepressants and antiobsessional drugs. (more substance abuse, longer duration, source
of trauma etc) which are correlated with
Sertraline has not demonstrated potential for decreased effect.
abuse. In a placebo-controlled, double-blind
randomized study of the comparative abuse Paediatric OCD
liability of sertraline, alprazolam and d- The safety and efficacy of sertraline (50-200
amphetamine in humans, sertraline did not mg/day) was examined in the treatment of non-
produce positive subjective effects indicative of depressed children (6-12 years old) and
abuse potential. In contrast, subjects rated both adolescent (13-17 years old) outpatients with
alprazolam and d-amphetamine significantly obsessive compulsive disorder (OCD). After a
greater than placebo on measures of drug liking, one week single blind placebo lead-in, patients
euphoria and abuse potential. Sertraline did not were randomly assigned to twelve weeks of
produce either the stimulation and anxiety flexible dose treatment with either sertraline or
associated with d-amphetamine or the sedation placebo. Children (6-12 years old) were initially
and psychomotor impairment associated with started on a 25 mg dose. Patients randomized to
alprazolam. Sertraline does not function as a sertraline showed significantly greater
positive reinforcer in rhesus monkeys trained to improvement than those randomised to placebo
self administer cocaine, nor does it substitute as on the Children's Yale-Brown Obsessive
a discriminative stimulus for either d- Compulsive Scale CY-BOCS (p =0.005) the
NIMH Global Obsessive Compulsive Scale Elimination

(p=0.019), and the CGI Improvement (p =0.002)
scales. In addition, a trend toward greater The mean half-life of sertraline is approximately
improvement in the sertraline group than the 26 hours (range 22-36 hours). Consistent with
placebo group was also observed on the CGI the terminal elimination half-life, there is an
Severity scale (p=0.089). For CY-BOCs the approximately two-fold accumulation up to
mean baseline and change from baseline scores steady state concentrations, which are achieved
after one week of once-daily dosing. The half-
for the placebo group was 22.25 ± 6.15 and -3.4
life of N-desmethylsertraline is in the range of
± 0.82, respectively, while for the sertraline
group, the mean baseline and change from 62 to 104 hours. Sertraline and N-
baseline scores were 23.36 ± 4.56 and -6.8 ± desmethylsertraline are both extensively
0.87, respectively. In a post-hoc analysis, metabolized in man and the resultant metabolites
responders, defined as patients with a 25% or excreted in faeces and urine in equal amounts.
greater decrease in the CY-BOCs (the primary Only a small amount (<0.2%) of unchanged
sertraline is excreted in the urine.
efficacy measure) from baseline to endpoint,
were 53% of sertraline-treated patients Linearity/non-linearity
compared to 37% of placebo-treated patients
(p=0.03). Sertraline exhibits dose proportional
pharmacokinetics in the range of 50 to 200 mg.
Long term safety and efficacy data are lacking
for this paediatric population. Pharmacokinetics in specific patient groups
Paediatric population Paediatric population with OCD
No data is available for children under 6 years of Pharmacokinetics of sertraline was studied in 29
age. paediatric patients aged 6-12 years old, and 32
adolescent patients aged 13-17 years old.
5.2 Pharmacokinetic properties Patients were gradual uptitrated to a 200 mg
Absorption daily dose within 32 days, either with 25 mg
starting dose and increment steps, or with 50 mg
In man, following an oral once-daily dosage of starting dose or increments. The 25 mg regimen
50 to 200 mg for 14 days, peak plasma and the 50 mg regimen were equally tolerated.
concentrations of sertraline occur at 4.5 to 8.4 In steady state for the 200 mg dose, the
hours after the daily administration of the drug. sertraline plasma levels in the 6-12 year old
Food does not significantly change the group were approximately 35% higher compared
bioavailability of sertraline tablets. to the 13-17 year old group, and 21% higher
compared to adult reference group. There were
Distribution
no significant differences between boys and girls
Approximately 98% of the circulating drug is regarding clearance. A low starting dose and
bound to plasma proteins. titration steps of 25 mg are therefore
recommended for children, especially with low
Biotransformation bodyweight. Adolescents could be dosed like
Sertraline undergoes extensive first-pass hepatic adults.
metabolism. Adolescents and elderly
Based on clinical and in-vitro data, it can be The pharmacokinetic profile in adolescents or
concluded that sertraline is metabolized by elderly is not significantly different from that in
multiple pathways including CYP3A4, adults between 18 and 65 years.
CYP2C19 (see section 4.5) and CYP2B6.
Sertraline and its major metabolite Hepatic impairment
desmethylsertraline are also substrate of P-
glycoprotein in-vitro.
In patients with liver damage, the half life of reduced average body weight gain was also
sertraline is prolonged and AUC is increased observed. All of the aforementioned effects
three fold (see sections 4.2 and 4.4). attributed to the administration of sertraline were
reversed at some point during the nondosing
Renal impairment
recovery phase of the study. The clinical
In patients with moderate-severe renal relevance of these effects observed in rats
impairment, there was no significant administered sertraline has not been established.
accumulation of sertraline.
6. PHARMACEUTICAL PARTICULARS
Pharmacogenomics
6.1 List of excipients
Plasma levels of sertraline were about 50% Core tablets:
higher in poor metabolizers of CYP2C19 versus
extensive metabolizers. The clinical meaning is Calcium hydrogen phosphate dihydrate
not clear, and patients need to be titrated based Cellulose microcrystalline
on clinical response.
Hydroxypropylcellulose
5.3 Preclinical safety data
Sodium starch glycolate (Type A)
Preclinical data does not indicate any special
hazard for humans based on conventional Magnesium stearate
studies of safety pharmacology, repeated dose
toxicity, genotoxicity and carcinogenesis. Film coating:
Reproduction toxicity studies in animals showed Opadry White OY-S-7355 containing –
no evidence of teratogenicity or adverse effects
on male fertility. Observed foetotoxicity was Titanium dioxide (E171)
probably related to maternal toxicity. Postnatal Hypromellose
pup survival and body weight were decreased
only during the first days after birth. Evidence Macrogol 400
was found that the early postnatal mortality was Polysorbate-80
due to in-utero exposure after day 15 of
pregnancy. Postnatal developmental delays 6.2 Incompatibilities
found in pups from treated dams were probably Not applicable.
due to effects on the dams and therefore not
6.3 Shelf life
relevant for human risk.
For PVC-Aluminium Blister packs: 4 years
Animal data from rodents and non-rodents does
For PVC/PVdC- Aluminium Blister packs: 3
not reveal effects on fertility.
years
Juvenile animal studies
6.4 Special precautions for storage
A juvenile toxicology study in rats has been Store in the original package.
conducted in which sertraline was administered
This medicinal product does not require any
orally to male and female rats on Postnatal Days
special storage conditions
21 through 56 (at doses of 10, 40, or 80
mg/kg/day) with a nondosing recovery phase up 6.5 Nature and contents of container
to Postnatal Day 196. Delays in sexual
maturation occurred in males and females at White opaque PVC – Aluminium blister or
different dose levels (males at 80 mg/kg and white opaque PVdC – PVC Aluminium blisters
females at ≥10 mg/kg), but despite this finding Packs of 10, 14, 15, 20, 28, 30, 42, 50, 56, 60,
there were no sertraline-related effects on any of 84, 98 and 100 film-coated tablets
the male or female reproductive endpoints that
were assessed. In addition, on Postnatal Days 21 Not all pack sizes may be marketed.
to 56, dehydration, chromorhinorrhea, and
6.6 Special precautions for disposal and other

handling
Any unused medicinal product or waste material
should be disposed off in accordance with local
requirements.
7. MANUFACTURER:
Manufactured in India by:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
At:388/34, Changodar Industrial Estate
Changodar- 382 210
Dist- Ahmedabad. Gujarat (India)
MFG. LIC NO: G/25A/4795-A

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Sertalin 50mg Tablets SMPC, Taj Pharma ce uticals

to reduce the frequency of early treatment

3. PHARMACEUTICAL FORM The onset of therapeutic effect may be seen

Abrupt discontinuation should be avoided. There is limited controlled experience regarding

evidence is available concerning, long-term hallucination, syncope, seizure, coma,

Use in elderly Contraindicated

4.7 Effects on ability to drive and use Pharyngitis Upper Diverticulit

Infection, eritis, Dizziness with serotonin

Hot flush* Hypertensi Peripheral Abnormal

Dysphonia, Ejaculat Erectile Vaginal Menorrhagi Gynaecoma

(including insomnia and intense dreams), Frequency not known: enuresis

Elderly population Reporting suspected adverse reactions after

Very common (≥1/10): Headache (22%), Symptoms

dialysis, haemoperfusion and exchange amphetamine or pentobarbital in rhesus

Pharmacotherapeutic group: Selective serotonin A study was conducted which involved

NIMH Global Obsessive Compulsive Scale Elimination

Paediatric population Paediatric population with OCD

6.6 Special precautions for disposal and other

Manufactured in India by:

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