Sertraline Actavis

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Sertraline hydrochloride 55.95 mg equivalent to 50 mg Sertraline;  
Available from:
Teva Pharma (New Zealand) Limited
INN (International Name):
Sertraline hydrochloride 55.95 mg (equiv to 50 mg Sertraline)
Dosage:
50 mg
Pharmaceutical form:
Film coated tablet
Composition:
Active: Sertraline hydrochloride 55.95 mg equivalent to 50 mg Sertraline   Excipient: Calcium hydrogen phosphate Hyprolose Hypromellose Macrogol 400 Magnesium stearate Microcrystalline cellulose Polysorbate 80 Sodium starch glycolate Titanium dioxide
Prescription type:
Prescription
Manufactured by:
Mylan Laboratories Limited
Therapeutic indications:
Sertraline Actavis is indicated for the treatment of symptoms of depression, including depression accompanied by symptoms of anxiety, in patients with or without a history of mania. Following satisfactory response, continuation with sertraline therapy is effective in preventing relapse of the initial episode of depression or recurrence of further depressive episodes.
Product summary:
Package - Contents - Shelf Life: Blister pack, PVC/Aluminium - 30 tablets - 48 months from date of manufacture stored at or below 25°C protect from light - Blister pack, PVC/Aluminium - 90 tablets - 48 months from date of manufacture stored at or below 25°C protect from light
Authorization number:
TT50-9618
Authorization date:
2014-08-27

Read the complete document

New Zealand Consumer Medicine Information

SERTRALINE ACTAVIS

Sertraline hydrochloride

What is in this leaflet

This leaflet answers some common questions about SERTRALINE ACTAVIS.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits.

Your doctor has weighed the risks of you taking SERTRALINE ACTAVIS

against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or

pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What SERTRALINE ACTAVIS is used for

SERTRALINE ACTAVIS is used to treat depression and conditions called

obsessive compulsive disorder (OCD), panic disorder, post-traumatic stress

disorder (PTSD), social phobia (social anxiety disorder) and premenstrual

dysphoric disorder (PMDD).

PMDD affects some women in the days before their period. PMDD is different

from premenstrual syndrome (PMS). The mood symptoms (anger, sadness,

tension, etc) in PMDD are more severe than in PMS and affect the woman’s

daily activities and relationships with others.

SERTRALINE ACTAVIS belongs to a group of medicines called selective

serotonin reuptake inhibitors (SSRIs). They are thought to work by blocking

the uptake of a chemical called serotonin into nerve cells in the brain.

Serotonin and other chemicals called amines are involved in controlling mood.

Your doctor, however, may prescribe SERTRALINE ACTAVIS for another

purpose.

Ask your doctor if you have any questions about why SERTRALINE

ACTAVIS has been prescribed for you.

SERTRALINE ACTAVIS should not be used in children and adolescents

under the age of 18 years for the treatment of any medical condition other

than

obsessive

compulsive

disorder

(OCD).

safety

efficacy

SERTRALINE ACTAVIS for the treatment of medical conditions (other than

OCD) in this age group has not been satisfactorily established.

For the treatment of OCD, SERTRALINE ACTAVIS is not recommended for

use in children under the age of 6, as the safety and efficacy in children of this

age group has not been established.

This medicine is only available with a doctor's prescription.

There is no evidence that SERTRALINE ACTAVIS is addictive.

Before you take SERTRALINE ACTAVIS

When you must not take it

Do not take SERTRALINE ACTAVIS if:

you have ever had an allergic reaction to SERTRALINE ACTAVIS or

any of the ingredients listed at the end of this leaflet. Some of the

symptoms of an allergic reaction to SERTRALINE ACTAVIS may include

shortness of breath, wheezing or difficulty breathing, swelling of the face,

lips, tongue or other parts of the body, rash and itching or hives on the

skin.

2.

you have epilepsy not properly controlled by medication.

you are taking another medicine for depression called a monoamine

oxidase inhibitor (MAOI) or have been taking it within the last 14

days. Taking SERTRALINE ACTAVIS with a MAOI (eg moclobemide,

selegiline, phenelzine and tranylcypromine) may cause a serious reaction

with a sudden increase in body temperature, extremely high blood

pressure and convulsions (fits).

you are taking phentermine (used to help weight loss), tryptophan

(contained in protein-based foods or dietary proteins), medicines

used to treat migraine, eg sumatriptan, dextromethorphan (used as a

cough suppressant in cold and flu medications), methadone (used to

treat drug addiction) and medicines used to treat severe pain such as

tramadol, fentanyl or pethidine. These medicines can cause an

exaggerated response to SERTRALINE ACTAVIS.

5.

you are taking pimozide (used to treat disturbances in thinking,

feeling and behaviour).

Ask your doctor or pharmacist if you are not sure if you have been taking one

of these medicines.

Do not give SERTRALINE ACTAVIS to children or adolescents under the

age of 18 unless the doctor has prescribed it for the treatment of OCD.

Do not give SERTRALINE ACTAVIS to children under 6 years of age for

the treatment of OCD.

If

you

are

not

sure

whether

you

should

be

taking

SERTRALINE

ACTAVIS, talk to your doctor.

Do not take SERTRALINE ACTAVIS if:

the expiry date marked on the packaging has passed, even though the

tablets may look all right

the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to take it

Tell your doctor if you are allergic to any foods, dyes, preservatives or

any other medicines.

Tell your doctor if you have or have had any of the following medical

conditions:

any other mental illness

epilepsy or seizures

liver or kidney problems

heart conditions causing irregular heartbeats

a tendency to bleed more than normal

diabetes or high blood sugar

glaucoma, an eye condition.

Tell your doctor if you are pregnant or intend to become pregnant.

There have been reports that babies exposed to SERTRALINE ACTAVIS and

other antidepressants during the third trimester of pregnancy may develop

complications after birth.

Tell your doctor is you are breastfeeding or wish to breastfeed

SERTRALINE ACTAVIS passes into breast milk and may affect your baby.

Your

doctor

will

discuss

risks

benefits

using

SERTRALINE

ACTAVIS when pregnant or breastfeeding.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines

that you buy without a prescription from your pharmacy, supermarket or

health food shop.

You should also tell any health professional who is prescribing a new

medication for you that you are taking SERTRALINE ACTAVIS.

Some medicines may interfere with SERTRALINE ACTAVIS. These include:

other medicines for the treatment of depression called monoamine oxidase

inhibitors (MAOIs). Taking SERTRALINE ACTAVIS with, or within 14 days

of stopping a MAOI may cause a serious reaction with a sudden increase

in body temperature, extremely high blood pressure and convulsions

other

MAOI

medicines

such

linezolid,

antibiotic

used

treat

pneumonia and certain skin infections

other medicines for depression, panic disorder, social anxiety disorder or

obsessive

illnesses

dosulepin,

fluoxetine,

paroxetine,

citalopram,

venlafaxine)

lithium, a medicine used to treat mood swings

other medicine for premenstrual dysphoric disorder (eg fluoxetine)

tryptophan (contained in protein-based foods or dietary proteins)

phentermine (weight-reducing medicines)

dextromethorphan (used in cold and flu medicines to suppress cough)

medicines

strong

pain

management

(eg.

fentanyl,

tramadol

pethidine)

other medicines used to relieve pain, swelling and other symptoms of

inflammation, including arthritis (e.g. aspirin or NSAIDs such as ibuprofen

diclofenac)

pimozide (used to treat disturbances in thinking, feeling and behaviour)

St John's wort, a herbal remedy used to treat mood disorders

clozapine, a medicine used to treat schizophrenia

medicines for irregular heart beat (eg flecainide)

warfarin, or other medicines that stop the blood from clotting

phenytoin, a medicine used to treat epilepsy

sumatriptan, a medicine used to treat migraine

diazepam or other medicines that act on the brain or nervous system

cimetidine, a medicine used to treat reflux and ulcers

tolbutamide, a medicine used to treat diabetes

methadone, a medicine used to treat drug addiction

antibiotics.

These medicines may be affected by SERTRALINE ACTAVIS or may affect

how well it works. You may need different amounts of your medicine, or you

may need to take different medicines.

Your doctor or pharmacist has more information on medicines to be careful

with or avoid while taking SERTRALINE ACTAVIS.

How to take SERTRALINE ACTAVIS

Take SERTRALINE ACTAVIS exactly as your doctor has prescribed.

Follow all directions given to you by your doctor. They may differ from

the information contained in this leaflet.

How much to take

For Depression in Adults the usual starting dose of SERTRALINE ACTAVIS

is one 50 mg tablet each day. The dose can be increased gradually up to 200

mg a day if necessary

.

For Obsessive Compulsive Disorder in Children (6-12 YEARS) the usual

starting dose of SERTRALINE ACTAVIS is 25 mg per day (half a 50 mg

tablet), increasing to one 50 mg tablet a day after one week.

For Obsessive Compulsive Disorder in Adults and Adolescents (13-17

years) the usual starting dose of SERTRALINE ACTAVIS is one 50 mg tablet

each day.

For Panic Disorder in Adults the usual starting dose of SERTRALINE

ACTAVIS is 25 mg per day, increasing to one 50 mg tablet a day after one

week.

For Post-Traumatic Stress Disorder in Adults the usual starting dose of

SERTRALINE ACTAVIS is 25 mg per day, increasing to one 50 mg tablet a

day after one week.

For Social Phobia (Social Anxiety Disorder) in Adults the usual starting

dose of SERTRALINE ACTAVIS is 25 mg per day, increasing to one 50 mg

tablet a day after one week.

maximum

recommended

dose

SERTRALINE

ACTAVIS

conditions listed above is 200 mg per day.

For Premenstrual Dysphoric Disorder (PMDD) the usual starting dose of

SERTRALINE ACTAVIS is one 50 mg tablet each day. If taking throughout

the menstrual cycle, the dose may be increased to a maximum of 150 mg a

day, increased in a step wise fashion. If taking in the last 14 days of the

menstrual cycle, the dose may be increased to a maximum of 100 mg a day.

Do not take more than the maximum doses recommended above for

PMDD.

How to take it

Swallow the tablet(s) with a glass of water.

Try to take your tablet(s) at the same time each day, either morning or

evening.

SERTRALINE ACTAVIS can be taken with or without food.

How long to take it

Most medicines for depression and obsessive illnesses take time to work, so

do not be discouraged if you do not feel better straight away.

take

weeks

even

longer

feel

full

benefit

SERTRALINE ACTAVIS.

Even when you feel well, you may need to take SERTRALINE ACTAVIS for

several months or longer. Continue taking SERTRALINE ACTAVIS until your

doctor tells you to stop.

If you have PMDD, your doctor may ask you to take this medicine only at

certain times of the month.

Do not stop taking SERTRALINE ACTAVIS, or change the dose, without

first checking with your doctor.

Occasionally the symptoms of depression or other psychiatric conditions may

include thoughts of harming yourself or committing suicide. It is possible that

these symptoms may continue or increase until the full anti-depressant effect

of your medicine becomes apparent (i.e. one to two months).

You or anyone close to you or caring for you should watch for these

symptoms and tell your doctor immediately or go to the nearest hospital

if you have any distressing thoughts or experiences during this initial

period or at any other time.

Contact your doctor if you experience any worsening of your depression

or other symptoms at any time during your treatment.

If you forget to take it

Do not take an extra dose to make up for the dose that you missed. Wait

until the next day and take your normal dose then.

If you are not sure what to do in this situation, ask your doctor or

pharmacist.

If

you

have

trouble

remembering

to

take

your

medicine,

ask

your

pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (0800

POISON or 0800 764 766) for advice, or go to Accident and Emergency at

your nearest hospital if you think you or anyone else may have taken

too

much

SERTRALINE

ACTAVIS,

even

if

there

are

no

signs

of

discomfort or poisoning. You may need urgent medical attention.

Keep telephone numbers for these places handy.

If you take too many tablets, it may make you feel drowsy, sick in the stomach

(nauseous), vomit, have fast or irregular heartbeats, tremors and feel agitated

or dizzy. Coma has been reported with overdose.

While you are taking SERTRALINE ACTAVIS

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you

are taking SERTRALINE ACTAVIS.

Tell

your

doctor

or

pharmacist

that

you

are

taking

SERTRALINE

ACTAVIS if you are about to be started on any new medicines.

Tell your doctor if you become pregnant while taking SERTRALINE

ACTAVIS.

If you are a woman of child-bearing age, you should avoid becoming pregnant

while taking SERTRALINE ACTAVIS.

Tell your doctor immediately if you have any suicidal thoughts or other

mental/mood changes.

A worsening of depressive symptoms including thoughts of suicide or self-

harm may occur in the first one or two months of you taking SERTRALINE

ACTAVIS or when the doctor changes your dose. These symptoms should be

controlled when the full effect of SERTRALINE ACTAVIS takes place.

Children, adolescents and young adults under 24 years of age are more likely

to experience these effects during the first few months of treatment.

Patients and caregivers should be alert and monitor for these effects.

Signs and symptoms of suicide include:

thoughts or talk of death or suicide

thoughts or talk of self-harm or harm to others

any recent attempts of self-harm

increase in aggressive behaviour, irritability or agitation

worsening of depression

All mention of suicide or violence must be taken seriously.

If you or someone you know is demonstrating these warning signs of

suicide while taking SERTRALINE ACTAVIS, contact your doctor or a

mental health professional right away.

Children

should

have

regular

checkups with

the

doctor

to

monitor

growth and development.

If you are going to have surgery, tell the surgeon or anaesthetist that

you are taking this medicine.

It may interact with other medicines used during surgery and cause unwanted

side effects.

If you are about to have any urine tests, tell your doctor that you are

taking this medicine.

It may interfere with the results of some tests.

Things you must not do

Do not stop taking SERTRALINE ACTAVIS, or change the dose, without

first checking with your doctor.

Do not let yourself run out of tablets over the weekend or on holidays.

Suddenly

stopping

SERTRALINE

ACTAVIS

cause

dizziness,

light

headedness, numbness, unusual tingling feelings or shakiness.

Do not give this medicine to anyone else, even if their symptoms seem

similar to yours.

Do not take SERTRALINE ACTAVIS to treat any other complaints unless

your doctor says to.

Things to be careful of

Be

careful

driving

or

operating

machinery

until

you

know

how

SERTRALINE ACTAVIS affects you.

Some medicines for depression may affect your ability to drive or operate

machinery or do things that could be dangerous if you are not alert.

Although drinking moderate amounts of alcohol is unlikely to affect your

response to SERTRALINE ACTAVIS, your doctor may suggest avoiding

alcohol while you are taking SERTRALINE ACTAVIS.

If you are feeling drowsy or are uncoordinated, be careful that you do

not fall over.

SERTRALINE ACTAVIS, like other medicines in this class, may increase your

risk of bone fracture.

You should wait at least 14 days after stopping SERTRALINE ACTAVIS

before starting medicines for depression or obsessive illnesses from the

MAOI

group,

such

as

moclobemide,

selegiline,

phenelzine,

tranylcypromine.

All of the above precautions are important even after you have stopped taking

SERTRALINE ACTAVIS.

The effects of SERTRALINE ACTAVIS may last for some days after you have

stopped taking it.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel

well while you are taking SERTRALINE ACTAVIS.

All medicines can have side effects. Sometimes they are serious, most of the

time they are not. You may need medical treatment if you get some of the

adverse effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if...

Tell your doctor or pharmacist if you notice any of the following and

they worry you:

headache, dizziness, shakiness, muscle stiffness or weakness, decrease

or loss of touch or other senses

dry mouth or excessive saliva, increased sweating, feeling sick, diarrhoea,

indigestion, vomiting, stomach pain, constipation, haemorrhoids

tiredness, hot flushes, fever, feeling unwell

weight increase or loss

sleeping difficulties, sexual problems, sleepiness

vision disturbance

menstrual irregularities

difficulty in passing urine, or increased frequency

unusually overactive, restlessness or difficulty sitting still

shaking or tremors

swollen or enlarged lymph glands

problem with swallowing

problem with speech.

Tell your doctor as soon as possible if...

Tell your doctor as soon as possible if you notice any of the following:

agitation,

nervousness,

anxiety,

frightening

dreams,

sleep

walking,

yawning, abnormal thinking, teeth grinding, loss of appetite, impaired

concentration, loss of memory, symptoms of agitation, anxiety, dizziness,

headache, nausea and tingling or numbness of the hands and feet after

stopping SERTRALINE ACTAVIS

uncontrollable muscle spasms affecting the eyes, head, neck and body

uncontrollable movements of the body, shuffling walk

palpitations, fainting or chest pain

irregular heartbeats

breathlessness

abnormal bleeding

sudden onset of severe headache.

Go to hospital if...

Tell your doctor immediately or go to Accident and Emergency at your

nearest hospital, if you notice any of the following:

fits or seizures

signs of allergy such as rash or hives, swelling of the face, lips or tongue,

wheezing or difficulty breathing

symptoms of sudden fever with sweating, fast heart beat and muscle

stiffness, which may lead to loss of consciousness

thoughts of suicide or attempting suicide or self harm.

The above list includes very serious side effects. You may need urgent

medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making

you feel unwell.

Other adverse effects not listed above may also occur in some patients. Tell

your doctor if you notice any other effects.

Some of these side effects (e.g., changes in thyroid function, liver function or

glucose control) can only be found when your doctor does tests from time to

time to check your progress.

Do not be alarmed by this list of possible adverse effects. You may not

experience any of them.

After taking SERTRALINE ACTAVIS

Storage

Keep your tablets where young children cannot reach them.

A locked cupboard at least 1½ metres above the ground is a good place to

store medicines.

Keep SERTRALINE ACTAVIS in a cool, dry place where the temperature

stays below 25°C. Protect from light. Do not store it or any other

medicine in the bathroom or near a sink.

Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep your tablets in their blister pack until it is time to take them.

Disposal

If your doctor tells you to stop taking SERTRALINE ACTAVIS, or the tablets

have passed their expiry date, ask your pharmacist what to do with any left

over.

Product description

What it looks like

SERTRALINE ACTAVIS tablets come in two strengths:

SERTRALINE

ACTAVIS

White

white,

capsule

shaped,

biconvex, film-coated tablets with break line on one side and “50” and “BL”

embossed on either side of the breakline.

SERTRALINE

ACTAVIS

White

off-white,

capsule

shaped,

biconvex, film coated tablets with “BL” and 100 embossed on one side.

A box contains 30 or 90 tablets.

Ingredients

SERTRALINE ACTAVIS contains either 50 mg or 100 mg of sertraline as the

active ingredient.

It also contains:

calcium hydrogen phosphate

hyprolose

microcrystalline cellulose

sodium starch glycollate

magnesium stearate.

The film coating contains hypromellose, macrogol, polysorbate and titanium

dioxide.

SERTRALINE ACTAVIS does not contain gluten, lactose or sugar.

Supplier

SERTRALINE ACTAVIS is distributed in New Zealand by:

Teva Pharma (New Zealand) Limited

PO Box 128 244

Remuera

Auckland 1541

Telephone: 0800 800 097

Date of preparation

4 May 2017

Read the complete document

New Zealand Data Sheet

Sertraline Actavis

Sertraline hydrochloride Tablets 50mg & 100mg

Presentation

Sertraline Actavis Tablets 50mg: White to off white, capsule shaped, biconvex,

film-coated tablets with “50” and “BL” embossed on either side of the breakline.

Sertraline Actavis Tablets 100mg: White to off- white, capsule shaped, biconvex,

film coated tablets with “100” and “BL” embossed on one side.

Sertraline Actavis tablets include the following inert ingredients: Calcium

hydrogen phosphate anhydrous, microcrystalline cellulose, hydroxypropyl

cellulose, sodium starch glycolate, magnesium stearate, hypromellose, macrogol

400, titanium dioxide, polysorbate – 80.

“Do not halve the Sertraline Actavis 100mg tablet. Dose equivalence when the

tablet is divided has not been established.”

Uses

Actions

Sertraline is a potent and selective inhibitor of neuronal serotonin (5-HT) uptake

in vitro, which results in the potentiation of the effects of 5-HT in animals. It has

only very weak effects on noradrenaline and dopamine neuronal reuptake. At

clinical doses, sertraline blocks the uptake of serotonin into human platelets. It is

devoid

stimulant,

sedative

anticholinergic

activity,

cardiotoxicity

animals. In controlled studies in normal volunteers, sertraline did not cause

sedation and did not interfere with psychomotor performance. In accord with its

selective

inhibition

5-HT

uptake,

sertraline

does

enhance

catecholaminergic activity. Sertraline has no affinity for muscarinic (cholinergic),

serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine

receptors. The chronic administration of sertraline in animals was associated with

downregulation of brain noradrenaline receptors as observed with other clinically

effective antidepressants and antiobsessional drugs.

Sertraline has not demonstrated potential for abuse. In a placebo-controlled,

double blind, randomised study of the comparative abuse liability of sertraline,

alprazolam and d-amphetamine in humans, sertraline did not produce positive

subjective effects indicative of abuse potential. In contrast, subjects rated both

alprazolam and d-amphetamine significantly greater than placebo on measures

of drug liking, euphoria and abuse potential. Sertraline did not produce either the

stimulation and anxiety associated with d-amphetamine or the sedation and

psychomotor impairment associated with alprazolam. Sertraline does not function

as a positive reinforcer in rhesus monkeys trained to self-administer cocaine, nor

does it substitute as a discriminative stimulus for either d-amphetamine or

pentobarbital in rhesus monkeys.

Pharmacokinetics

Sertraline exhibits dose proportional pharmacokinetics over the range of 50 to

200 mg. In man, following oral once daily dosing over the range of 50 to 200 mg

for 14 days, peak plasma concentrations (Cmax) of sertraline occur at about 4.5

to 8.4 hours post dosing. The pharmacokinetic profile in either adolescents or the

elderly is not significantly different from that in adults between 18 and 65 years.

The mean half-life of sertraline for young and elderly men and women ranges

from 22-36 hours. Consistent with the terminal elimination half-life, there is an

approximately two-fold accumulation up to steady state concentrations, which are

achieved

after

week

once

daily

dosing.

Approximately

circulating

drug

bound

plasma

proteins.

Animal

studies

indicate

that

sertraline has a large apparent volume of distribution. The pharmacokinetics of

sertraline in paediatric OCD patients have been shown to be comparable with

adults (although paediatric patients metabolise sertraline with slightly greater

efficiency). However, lower doses may be advisable for paediatric patients given

their lower body weights (especially 6-12 years), in order to avoid excessive

plasma levels.

Sertraline undergoes extensive first pass hepatic metabolism. The principal

metabolite in plasma, N-desmethylsertraline, is substantially less active (about 20

times) than sertraline in vitro, and there is no evidence of activity in in vivo

models of depression. The half-life of N-desmethylsertraline is in the range of 62-

hours.

Sertraline

N-desmethylsertraline

both

extensively

metabolised in man and the resultant metabolites excreted in faeces and urine in

equal amounts. Only a small amount (<0.2%) of unchanged sertraline is excreted

in the urine.

Food does not significantly change the bioavailability of sertraline tablets.

Major Depressive Disorder

study

conducted

which

involved

depressed

outpatients

responded by the end of an initial 8-week open treatment phase on sertraline 50-

200 mg/day. These patients (N=295) were randomised to continuation for 44

weeks

double-blind

sertraline

50-200

mg/day

placebo.

statistically

significantly

lower

relapse

rate

observed

patients

taking

sertraline

compared to those on placebo. The mean dose for completers was 70 mg/day.

Obsessive-Compulsive Disorder (OCD)

In a long-term study, patients meeting DSM-III-R criteria for OCD who had

responded

during

52-week

single-blind

trial

sertraline

50-200

mg/day

(n=224) were randomised to continuation of sertraline or to substitution of

placebo for up to 28 weeks of observation for discontinuation due to relapse or

insufficient clinical response. Patients receiving continued sertraline treatment

experienced

significantly

lower

rate

discontinuation

relapse

insufficient clinical response over the subsequent 28 weeks compared to those

receiving placebo. This pattern was demonstrated in male and female subjects.

Panic Disorder

In a long-term study, patients meeting DSM-III-R criteria for Panic Disorder who

had responded during a 52-week open trial on sertraline 50-200 mg/day (n=183)

were randomised to continuation of sertraline or to substitution of placebo for up

to 28 weeks of observation for discontinuation due to relapse or insufficient

clinical response. Patients receiving continued sertraline treatment experienced a

significantly lower rate of discontinuation due to relapse or insufficient clinical

response over the subsequent 28 weeks compared to those receiving placebo.

This pattern was demonstrated in male and female subjects.

Post-traumatic Stress Disorder (PTSD)

In a long-term study, patients meeting DSM-III-R criteria for PTSD who had

responded during a 24-week open trial on sertraline 50-200 mg/day (n=96) were

randomised to continuation of sertraline or to substitution of placebo for up to 28

weeks

observation

relapse.

Patients

receiving

continued

sertraline

treatment experienced significantly lower relapse rates over the subsequent 28

weeks compared to those receiving placebo. This pattern was demonstrated in

male and female subjects.

Social Phobia

In a social phobia relapse prevention study, patients who were responders at the

end of a 20 week, multicentre, flexible dose study that compared Sertraline (50-

200 mg/day) to placebo, were re-randomised for an additional 24 weeks to either

sertraline continuation treatment (within 50-200 mg/day) or placebo substitution,

while placebo responders remained on placebo. Patients receiving sertraline

continuation treatment experienced a statistically significantly lower relapse rate

over

this

week

study

than

patients

randomised

placebo

substitution

treatment.

Indications

Children and Adolescents (6 – 17 yrs):

Sertraline Actavis is indicated for the treatment of paediatric patients (6 – 17

years of age) with OCD.

Adults:

Sertraline Actavis is indicated for the treatment of symptoms of depression,

including depression accompanied by symptoms of anxiety, in patients with or

without a history of mania. Following satisfactory response, continuation with

Sertraline therapy is effective in preventing relapse of the initial episode of

depression or recurrence of further depressive episodes.

Sertraline Actavis is indicated for the treatment of obsessive compulsive disorder

(OCD). Following initial response, sertraline has been associated with sustained

efficacy, safety and tolerability in up 2 years of treatment of OCD.

Sertraline Actavis is indicated for the treatment of panic disorder, with or without

agoraphobia.

Sertraline Actavis is indicated for the treatment of post-traumatic stress disorder

(PTSD).

Sertraline Actavis is indicated for the treatment of social phobia (social anxiety

disorder). Following satisfactory response, continuation with sertraline therapy is

effective in preventing relapse of the initial episode of social phobia.

Sertraline

Actavis

indicated

treatment

premenstrual

dysphoric

disorder (PMDD).

Dosage and Administration

Sertraline Actavis should be administered once daily, either in the morning or

evening.

Sertraline Actavis tablets can be administered with or without food.

“Do not halve the Sertraline Actavis 100mg tablet. Dose equivalence when the

tablet is divided has not been established.”

Initial Treatment in Adults

Depression and OCD

Sertraline treatment should be administered at a dose of 50 mg/day.

Panic Disorder, PTSD and Social Phobia

Therapy for panic disorder, PTSD and social phobia should be initiated at 25

mg/day. After one week, the dose should be increased to 50 mg once daily. This

dosage regimen has been shown to reduce the frequency of early treatment

emergent side effects characteristic of panic disorder.

Premenstrual Dysphoric Disorder

Sertraline treatment should be initiated with a dose of 50 mg/day, either daily

throughout the menstrual cycle or limited to the luteal phase of the menstrual

cycle, depending on physician assessment. Patients not responding to a 50

mg/day dose may benefit from dose increases (at 50 mg increments/menstrual

cycle) up to 150 mg/day when dosing daily throughout the menstrual cycle, or

100 mg/day when dosing during the luteal phase of the menstrual cycle. If a 100

mg/day dose has been established with luteal phase dosing, a 50 mg/day

titration step for three days should be utilized at the beginning of each luteal

phase dosing period.

Dosage adjustments, which may include changes between dosage regimens

(e.g., daily throughout the menstrual cycle versus during the luteal phase of the

menstrual cycle), may be needed to maintain the patient on the lowest effective

dosage and patients should be periodically reassessed to determine the need for

continued treatment.

Titration in Adults

For all indications other than PMDD

Patients not responding to a 50 mg dose may benefit from dose increases. Dose

changes should be made at intervals of at least one week, up to a maximum of

200 mg/day (refer to section above for details on dosage titration for PMDD).

The onset of therapeutic effect may be seen within 7 days. However, longer

periods are usually necessary to demonstrate therapeutic response, especially in

OCD.

Maintenance

Dosage during long-term therapy should be kept at the lowest effective level, with

subsequent adjustment depending on therapeutic response.

Use in Children

The safety and efficacy of sertraline has been established in paediatric OCD

patients aged 6 to 17. More than 250 paediatric OCD patients have been

exposed to sertraline in completed and ongoing studies. The safety profile of

sertraline in these paediatric studies is comparable to that observed in adult OCD

studies. The administration of sertraline to paediatric OCD patients (aged 13 to

17) should commence at 50 mg/day. Therapy for paediatric OCD patients (aged

6 to 12) should commence at 25 mg/day, increasing to 50 mg/day after one

week. Subsequent doses may be increased in case of lack of response in 50

mg/day increments, up to 200 mg/day, as needed. In a clinical trial in patients

aged 6 to 17 years with depression or OCD, sertraline appeared to have a similar

pharmacokinetic profile to that found in adults. However, the generally lower

body weights of children compared to those of adults should be taken into

consideration in advancing the dose from 50 mg, in order to avoid excessive

dosing.

The efficacy of sertraline in paediatric patients with depression or panic has not

been demonstrated in controlled trials. Safety and effectiveness in paediatric

patients below the age of 6 have not been established.

Titration in Children and Adolescents

Sertraline has an elimination half-life of approximately one day; dose changes

should not occur at intervals of less than one week.

Use in the Elderly

The same dose range as in younger patients may be used in the elderly. Over

700 elderly patients (>65 years) have participated in clinical studies which

demonstrated the efficacy of sertraline in this patient population. The pattern and

incidence of adverse reactions in the elderly was similar to that in younger

patients.

Use in Hepatic Impairment

The use of sertraline in patients with hepatic disease should be approached with

caution. A lower or less frequent dose should be used in patients with hepatic

impairment (see Warnings and Precautions).

Use in Renal Impairment

Sertraline is extensively metabolised. Excretion of unchanged drug in urine is a

minor route of elimination. As expected from the low renal excretion of sertraline,

sertraline dosing does not have to be adjusted based on the degree of renal

impairment (see Warnings and Precautions).

Contraindications

Sertraline Actavis is contraindicated in patients with a known hypersensitivity to

sertraline.

Concomitant

patients

taking

pimozide

contraindicated

(see

Interactions).

Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is

contraindicated (see Warnings and Precautions).

Warnings and Precautions

Monoamine Oxidase Inhibitors

Cases of serious reactions, sometimes fatal, have been reported in patients

receiving sertraline in combination with a monoamine oxidase inhibitor (MAOI),

including the selective MAOI, selegiline and the reversible MAOI, moclobemide

and the MAOI drugs, e.g., linezolid (an antibiotic which is a reversible non-

selective

MAOI)

methylene

blue.

Such

cases

presented

with

features

resembling serotonin syndrome, the symptoms of which include: hyperthermia,

rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital

signs, mental status changes that include confusion, irritability, and extreme

agitation progressing to delirium and coma. Therefore, sertraline should not be

used in combination with an MAOI or within 14 days of discontinuing treatment

with an MAOI. Similarly, at least 14 days should elapse after discontinuing

sertraline treatment before starting an MAOI (see Contraindications).

Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)

development

potentially

life-threatening

syndromes

like

serotonin

syndrome (SS) or Neuroleptic Malignant Syndrome (NMS) has been reported

with SSRIs, including treatment with sertraline. The risk of SS or NMS with

SSRIs is increased with concomitant use of serotonergic drugs (including triptans

fentanyl),

with

drugs

which

impair

metabolism

serotonin

(including

MAOIs), antipsychotics and other dopamine antagonists. SS symptoms may

include mental status changes (e.g. agitation, hallucinations, coma), autonomic

instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular

aberrations (e.g. hyperreflexia, incoordination) and/or gastrointestinal symptoms

(e.g. nausea, vomiting, diarrhoea). Some signs of SS, including hyperthermia,

muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs,

and mental status changes resemble NMS. Patients should be monitored for the

emergence

signs

symptoms

syndrome

(see

Contraindications).

Other Serotonergic Drugs

Coadministration of sertraline with other drugs which enhance the effects of

serotonergic neurotransmission, such as tryptophan, fenfluramine, fentanyl and

analogues,

tramadol,

5-HT

agonists,

dextromethorphan,

pethidine

methadone should be undertaken with caution and avoided whenever possible

due to the potential for pharmacodynamic interaction.

St John's Wort

Concomitant use of the herbal remedy St John's Wort (Hypericum perforatum) in

patients

receiving

SSRIs

should be

avoided

since there

is a possibility

serotonergic potentiation (see Interactions).

Switching

from

Selective

Serotonin

Reuptake

Inhibitors

(SSRIs),

Antidepressants or Antiobsessional Drugs

There is limited controlled experience regarding the optimal timing of switching

from SSRIs, antidepressants or antiobsessional drugs to sertraline.

Care

prudent

medical

judgment

should

exercised

when

switching,

particularly from long-acting agents such as fluoxetine. The duration of a washout

period for switching from one SSRI to another has not been established.

Use in Patients with Concomitant Illness

Caution is advisable in using sertraline in patients with diseases or conditions

that could affect metabolism or haemodynamic responses. Sertraline has not

been evaluated or used to any appreciable extent in patients with a recent history

of myocardial infarction or unstable heart disease. Patients with these diagnoses

were

excluded from clinical

studies during

the product's

premarket

testing.

However, the electrocardiograms of 774 patients who received Sertraline in

double-blind trials were evaluated and the data indicate that Sertraline is not

associated with the development of significant ECG abnormalities.

QTc Prolongation/TdP

Cases of QTc prolongation and Torsades de Pointes (TdP) have been reported

during the post-marketing use of sertraline. The majority of reports occurred in

patients with other risk factors for QTc prolongation/TdP.

Sertraline should be used with caution in patients with risk factors for QTc

prolongation including congenital long QT syndrome, age >65 years, female sex,

structural heart disease/LV dysfunction, medical conditions such as renal or

hepatic disease, use of medicines that inhibit the metabolism of sertraline, and

the concomitant use of other QTc prolonging medicines (see Interactions).

Hypokalaemia and hypomagnesaemia should be corrected prior to treatment.

In high risk patients (e.g. congenital long QT syndrome or multiple risk factors),

an ECG should be performed prior to starting treatment, at steady state, after

dose increases or after starting any potentially interacting medicine. Electrolytes

should be monitored periodically and any abnormalities should be corrected prior

to starting sertraline. An ECG should be performed in all patients experiencing

symptoms that could be indicative of an arrhythmia (e.g. dizziness, palpitations,

syncope or new onset seizures).

Consideration should be given to stopping sertraline treatment or reducing the

dose if the QTc interval is >500 ms or increases by >60 ms during treatment.

Activation of Mania/Hypomania

During premarketing testing, hypomania or mania occurred in approximately

0.4% of sertraline treated patients. Activation of mania/hypomania has also been

reported in a small proportion of patients with major affective disorder treated

with other marketed antidepressant and antiobsessional drugs.

Hyperkinesia has been noted in paediatric patients treated with sertraline for

OCD, with an incidence of 8/53 (15.1%) for sertraline versus 3/54 (5.6%) for

placebo in 6 to 12 year olds, and 0/39 (0%) for sertraline versus 1/41 (2.4%) for

placebo in 13 to 17 year olds.

Weight Loss

Significant weight loss may be an undesirable result of treatment with sertraline

for some patients but, on average, patients in controlled trials had minimal 0.5 to

1 kg weight loss, versus smaller changes on placebo. Only rarely (< 0.1%) have

sertraline patients been discontinued for weight loss. In paediatric patients,

weight loss was seen in 2/53 (3.8%) versus 0/54 (0%) of 6 to 12 year old patients

and 3/39 (7.7%) versus 0/41 (0%) of 13 to 17 year olds treated with sertraline

versus placebo. It is recommended that paediatric patients receiving long-term

treatment should be monitored for weight and growth, consistent with good

medical care.

Seizures

Seizures are a potential risk with antidepressant and antiobsessional drugs.

Seizures were reported in approximately 0.08% of patients treated with sertraline

development program for depression.

seizures

were

reported in

patients treated with sertraline in the development program for panic. During the

development program for OCD, four out of approximately 1,800 patients exposed

to sertraline experienced seizures (approximately 0.2%). Three of these patients

were adolescents, two with a seizure disorder and one with a family history of

seizure disorder, none of whom were receiving anticonvulsant medication. In all

these cases, the relationship to sertraline therapy was uncertain. Since sertraline

has not been evaluated in patients with a seizure disorder, it should be avoided

in patients with unstable epilepsy and patients with controlled epilepsy should be

carefully

monitored.

Sertraline

should

discontinued

patient

develops seizures.

Clinical Worsening and Suicide Risk

The risk of a suicide attempt is inherent in depression and may persist until

significant remission occurs. This risk of suicide must be considered in all

depressed patients.

Because of the well-established comorbidity between OCD and depression,

panic disorder and depression, PTSD and depression, social phobia (social

anxiety

disorder)

depression,

PMDD

depression,

same

precautions observed when treating patients with depression should be observed

when treating patients with OCD, panic disorder, PTSD, social phobia or PMDD.

The risk of suicide attempts must be considered especially in depressed patients.

Patients

with

depression

experience

worsening

their

depressive

symptoms and/or the emergence of suicidal ideation and behaviours (suicidality)

whether or not they are taking antidepressant medications, and this risk may

persist until significant remission occurs. As improvement may not occur during

the first few weeks or more of treatment, patients should be closely monitored for

clinical worsening and suicidality, especially at the beginning of a course of

treatment, or at the time of dose changes, either increases or decreases.

Consideration should be given to changing the therapeutic regimen, including

possibly

discontinuing

medication,

patients

whose

depression

persistently worse or whose emergent suicidality is severe, abrupt in onset, or

was not part of the patient's presenting symptoms.

Patients (and caregivers of patients) should be alerted about the need to monitor

worsening

their

condition

and/or

emergence

suicidal

ideation/behaviour or thoughts of harming themselves and to seek medical

advice immediately if these symptoms present.

Patients with co-morbid depression associated with other psychiatric disorders

being treated with antidepressants should be similarly observed for clinical

worsening and suicidality.

Pooled analyses of 24 short-term (4 to 16 weeks), placebo-controlled trials of

nine

antidepressant

medicines

(SSRIs

others)

4400

children

adolescents with major depressive disorder (16 trials), obsessive compulsive

disorder (4 trials), or other psychiatric disorders (4 trials) have revealed a greater

risk of adverse events representing suicidal behaviour or thinking (suicidality)

during the initial treatment period (generally the first one to two months) in those

receiving antidepressants. The average risk of such events in patients treated

with an antidepressant was 4% compared with 2% of patients treated with

placebo. There was considerable variation in risk among the antidepressants, but

there was a tendency towards an increase for almost all antidepressants studied.

The risk of suicidality was most consistently observed in the major depressive

disorder trials, but there were signals of risk arising from trials in other psychiatric

indications (obsessive compulsive disorder and social anxiety disorder) as well.

No suicides occurred in these trials. It is unknown whether the suicidality risk in

children and adolescents patients extends to use beyond several months. The

nine

antidepressant

medicines

pooled

analyses

included

five

SSRIs

(citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRIs

(bupropion, mirtazapine, nefazodone, venlafaxine).

A further pooled analysis of short-term placebo-controlled trials of antidepressant

medicines (SSRIs and others) showed the increased risk of suicidal thinking and

behaviour (suicidality) during the initial treatment period (generally the first one to

two months) extend to young adults (ages 18-24) with major depressive disorder

(MDD) and other psychiatric disorders. These studies did not show an increase

in the risk of suicidality with antidepressants compared to placebo in adults

beyond age 24; there was a reduction in risk with antidepressants compared to

placebo in adults aged 65 and older.

Symptoms

anxiety,

agitation,

panic

attacks,

insomnia,

irritability,

hostility

(aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania,

and mania, have been reported in adults, adolescents and children being treated

with

antidepressants

major

depressive

disorder

well

other

indications, both psychiatric and non psychiatric. Although a causal link between

the emergence of such symptoms and either worsening of depression and/or

emergence of suicidal impulses has not been established, there is concern that

such symptoms may be precursors of emerging suicidality.

Families

caregivers

children

adolescents

being

treated

with

antidepressants

major

depressive

disorder

other

condition

(psychiatric or non psychiatric) should be informed about the need to monitor

these patients for the emergence of agitation, irritability, unusual changes in

behaviour, and other symptoms described above, as well as the emergence of

suicidality, and to report such symptoms immediately to health care providers. It

is particularly important that monitoring be undertaken during the initial few

months of antidepressant treatment or at times of dose increase or decrease.

Prescriptions for Sertraline Actavis should be written for the smallest quantity of

tablets consistent with good patient management, in order to reduce the risk of

overdose.

Akathisia/psychomotor restlessness

The use of sertraline has been associated with the development of akathisia,

characterized by a subjectively unpleasant or distressing restlessness and need

to move, often accompanied by an inability to sit or stand still. This is most likely

to occur within the first few weeks of treatment. In patients who develop these

symptoms, increasing the dose may be detrimental.

Weak Uricosuric Effect

Sertraline

associated

with

mean

decrease

serum

uric

acid

approximately 7%. The clinical significance of this weak uricosuric effect is

unknown, and there have been no reports of acute renal failure with sertraline.

Abnormal Bleeding/Haemorrhage

Bleeding abnormalities have been reported with the use of SSRIs (including

purpura, haematoma, epistaxis, vaginal bleeding, ecchymoses, gastrointestinal

bleeding and haemorrhage). This risk may be potentiated by concurrent use of

atypical antipsychotics and phenothiazines, most tricyclic antidepressants, non-

steroidal anti-inflammatory drugs (NSAIDs), aspirin or other medicines that affect

coagulation.

Sertraline

should

therefore

used

with

caution

patients

concomitantly treated with medicines that increase the risk of bleeding or in

patients with a past history of abnormal bleeding or those with predisposing

conditions. Pharmacological gastroprotection should be considered for high risk

patients.

Hyponatremia

Hyponatremia

occur

result

treatment

with

SSRIs

(Selective

Serotonin Reuptake Inhibitors) or SNRIs (Serotonin and Noradrenaline Reuptake

Inhibitors) including sertraline. In many cases, hyponatremia appears to be the

result of a syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Cases of serum sodium levels lower than 110 mmol/L have been reported.

Elderly patients may be at greater risk of developing hyponatremia with SSRIs

and SNRIs. Also patients taking diuretics or who are otherwise volume-depleted

may be at greater risk (see Warnings and Precautions – Use in the Elderly).

Discontinuation of sertraline should be considered in patients with symptomatic

hyponatremia and appropriate medical intervention should be instituted. Signs

symptoms

hyponatremia

include

headache,

difficulty

concentrating,

memory impairment, confusion, weakness and unsteadiness which may lead to

falls. Signs and symptoms associated with more severe and/or acute cases have

included hallucination, syncope, seizure, coma, respiratory arrest, and death.

Bone Fractures

Epidemiological studies show an increased risk of bone fractures in patients

receiving serotonin reuptake inhibitors (SRIs) including sertraline. The

mechanism leading to this risk is not fully understood.

Diabetes/Loss of Glycaemic Control

Cases of new onset diabetes mellitus have been reported in patients receiving

SSRIs

including

sertraline.

Loss

glycaemic

control

including

both

hyperglycaemia and hypoglycaemia has also been reported in patients with and

without pre-existing diabetes. Patients should therefore be monitored for signs

and symptoms of glucose fluctuations. Diabetic patients especially should have

their glycaemic control carefully monitored since their dosage of insulin and/or

concomitant oral hypoglycaemic drug may need to be adjusted.

Angle-Closure Glaucoma

SSRIs including sertraline may have an effect on pupil size resulting in mydriasis.

This mydriatic effect has the potential to narrow the eye angle resulting in

increased

intraocular

pressure

angle-closure

glaucoma,

especially

patients

pre-disposed.

Sertraline

should

therefore

used

with

caution

patients with angle-closure glaucoma or history of glaucoma.

Symptoms associated with discontinuation

During marketing of sertraline and other SSRIs and SNRIs (Serotonin and

Norepinephrine Reuptake Inhibitors), there have been spontaneous reports of

adverse events occurring upon discontinuation of these drugs, particularly when

abrupt, including the following: dysphoric mood, irritability, agitation, dizziness,

sensory disturbances (e.g. paresthesias such as electric shock sensations),

anxiety,

confusion,

headache,

lethargy,

emotional

lability,

insomnia,

hypomania. While these events are generally self-limiting, some have been

reported to be severe.

Patients should be monitored for these symptoms when discontinuing treatment

with sertraline. A gradual reduction in the dose rather than abrupt cessation is

recommended whenever possible. If intolerable symptoms occur following a

decrease in the dose or upon discontinuation of treatment, then resuming the

previously prescribed dose may be considered. Subsequently, the physician may

continue decreasing the dose but at a more gradual rate (see Adverse Effects,

Warnings

and

Precautions

Lactation

Dosage

and

Administration).

Electroconvulsive Therapy

There are no clinical studies establishing the risks or benefits of the combined

use of electroconvulsive therapy (ECT) and sertraline

Effects on Fertility

A decrease in fertility was seen in one of two rat studies at a dose of 80 mg/kg

(giving rise to plasma drug exposure levels similar to or slightly higher than that

achieved following the maximum recommended human dose of 200 mg).

Use in Pregnancy (Category C)

Reproduction studies have been performed in rats and rabbits at doses up to

approximately

times

maximum

daily

human

mg/kg

dose

respectively. There was no evidence of teratogenicity at any dose level.

At the dose level corresponding to approximately 2.5 to 10 times the maximum

daily human mg/kg dose, however, sertraline was associated

with delayed

ossification processes in foetuses, probably secondary to effects on the dams.

There was decreased neonatal survival following maternal administration of

sertraline at doses of approximately 5 times the maximum human mg/kg dose.

Similar effects on neonatal survival have been described for other antidepressant

drugs. The clinical significance of these effects is unknown.

There are no adequate and well controlled studies in pregnant women. Because

animal

reproduction

studies

always

predictive

human

response,

sertraline

should

used

during

pregnancy

only

perceived

benefits

outweigh the risks, taking into account the risks of untreated depression.

Neonates exposed to Sertraline, other SSRIs or SNRIs late in the third trimester

have developed complications requiring prolonged hospitalization, respiratory

support and tube feeding. Such complications can arise immediately upon

delivery. Reported clinical findings have included respiratory distress, cyanosis,

apnoea,

seizures,

temperature

instability,

feeding

difficulty,

vomiting,

hypoglycaemia,

hypotonia,

hyperreflexia,

tremor,

jitteriness,

irritability,

constant crying. These features are consistent with either a direct toxic effect of

SSRIs and SNRIs or, possibly, a drug discontinuation syndrome.

Exposure during late pregnancy to SSRIs may have an increased risk for

persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2

per 1,000 live births in the general population and is associated with substantial

neonatal morbidity and mortality. In a retrospective case-control study of 377

women whose infants were born with PPHN and 836 women whose infants were

born healthy, the risk for developing PPHN was approximately six-fold higher for

infants exposed to SSRIs after the 20

week of gestation compared to infants

who had not been exposed to antidepressants during pregnancy. A study of

831,324 infants born in Sweden in 1997-2005 found a PPHN risk ratio of 2.4

(95% CI 1.2-4.3) associated with patient-reported maternal use of SSRIs "in early

pregnancy" and a PPHN risk ratio of 3.6 (95% CI 1.2-8.3) associated with a

combination of patient-reported maternal use of SSRIs "in early pregnancy" and

an antenatal SSRI prescription "in later pregnancy."

Epidemiological

studies

have

suggested

increased

risk

congenital

abnormalities associated with use of SSRIs and SNRIs in pregnancy. The

relevance for sertraline treatment remains unknown.

Epidemiological data suggests that the use of SSRIs and SNRIs in pregnancy

may be associated with a small but statistically significant increase in pre-term

delivery.

Women

childbearing

potential

should

employ

adequate

method

contraception if taking sertraline.

Use in Lactation

Isolated studies in small numbers of nursing mothers and their infants indicated

negligible or undetectable levels of sertraline in infant serum, although levels in

breast milk were more concentrated than in maternal serum. Use in nursing

mothers is not recommended unless, in the judgment of the physician, the benefit

outweighs the risk.

If sertraline is used during pregnancy and/or lactation, the physician should be

aware of post-marketing reports of symptoms, including those compatible with

withdrawal reactions, in some neonates whose mothers had been on SSRI

antidepressants, including sertraline.

Paediatric Use

A total of 225 paediatric patients have completed OCD trials with sertraline. The

safety profile of Sertraline in these paediatric studies is comparable to that

observed in the adult OCD studies.

Only limited clinical evidence is available concerning long-term safety data in

children and adolescents, including effects on growth, sexual maturation and

cognitive and behavioural developments. Physicians must monitor paediatric

patients on long term treatment for abnormalities in growth and development.

Safety and effectiveness in paediatric patients below the age of 6 have not been

established.

Sertraline should not be used in children and adolescents below the age of 18

years for the treatment of major depressive disorder. The efficacy and safety of

sertraline has not been satisfactorily established for the treatment of major

depressive disorder in this age group.

Geriatric Use

Several hundred elderly patients have participated in clinical studies with

Sertraline. The pattern of adverse reactions in the elderly was similar to that in

younger patients.

Use in Hepatic Impairment

Sertraline

extensively

metabolised

liver.

multiple

dose

pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a

prolonged elimination half-life and approximately three-fold greater AUC and

in comparison to normal subjects. There were no significant differences in

plasma protein binding observed between the two groups. The use of sertraline

in patients with hepatic disease should be approached with caution. A lower or

less frequent dose should be used in patients with hepatic impairment.

Use in Renal Impairment

Sertraline is extensively metabolised. Excretion of unchanged drug in urine is a

minor route of elimination. In studies of patients with mild to moderate renal

impairment (creatinine clearance 30-60 mL/min) or moderate to severe renal

impairment (creatinine clearance 10-29 mL/min), multiple dose pharmacokinetic

parameters (AUC

0-24

or C

) were not significantly different compared with

controls.

Half-lives were similar and there were no differences in plasma protein binding in

all groups studied. This study indicates that, as expected from the low renal

excretion of sertraline, sertraline dosing does not have to be adjusted based on

the degree of renal impairment.

Alcohol

As with other psychotropic drugs patients should be advised to avoid alcohol use

while taking sertraline.

Driving/Use of Machinery

Clinical pharmacology studies have shown that sertraline has no effect on

psychomotor performance. However, as psychotropic drugs may impair the

mental or physical ability required for the performance of potentially hazardous

tasks such as driving a car or operating machinery, the patient should be

cautioned accordingly.

Laboratory Tests

False-positive urine immunoassay screening tests for benzodiazepines have

been reported in patients taking sertraline. This is due to lack of specificity of the

screening tests. False positive test results may be expected for several days

following discontinuation of sertraline therapy. Confirmatory tests, such as gas

chromatography/mass

spectrometry,

will

distinguish

sertraline

from

benzodiazepines.

Adverse Effects

Clinical Trial Data:

Side effects that occurred significantly more frequently with sertraline than with

placebo in multiple dose studies for depression were:

Gastrointestinal Disorders: Diarrhoea/loose stools, dry mouth, dyspepsia and

nausea.

Metabolism and Nutrition Disorders: Anorexia

Nervous System Disorders: Dizziness, somnolence and tremor.

Psychiatric Disorders: Insomnia

Reproductive System and Breast Disorders: Sexual dysfunction (principally

ejaculatory delay in males).

Skin and Subcutaneous Tissues Disorders: Increased sweating

The side effect profile commonly observed in double-blind, placebo-controlled

studies in patients with OCD, panic disorder, PTSD, social phobia and PMDD

was similar to that observed in clinical trials in patients with depression.

No weight gain was observed in controlled clinical trials with sertraline treatment

for depression or OCD; some patients may experience a reduction in body

weight with sertraline.

Post-Marketing Data

Voluntary reports of adverse events in patients receiving sertraline since market

introduction have been received. They include the following:

Blood and Lymphatic System Disorders: Leucopenia, lymphadenopathy and

thrombocytopenia.

Cardiac Disorders: Palpitations, myocardial infarction, bradycardia, tachycardia,

QTc prolongation and Torsades de Pointes.

Ear and Labyrinth Disorders: Tinnitus.

Endocrine Disorders: Hyperprolactinaemia, hypothyroidism and syndrome of

inappropriate ADH secretion (SIADH).

Eye Disorders: Mydriasis, scotoma, glaucoma and vision abnormal.

Gastrointestinal

Disorders:

abdominal

pain,

constipation,

haemorrhoids,

pancreatitis, salivary hypersecretion, tongue disorder, dysphagia, oesophagitis

and vomiting.

General Disorders and Administration Site Conditions: Asthenia, chest pain,

oedema peripheral, fatigue, fever and malaise.

Hepatobiliary Disorders: Serious liver events (including hepatitis, jaundice and

liver failure) and asymptomatic elevations in serum transaminases (SGOT and

SGPT).

Immune

System

Disorders:

Allergic

reactions,

allergy

anaphylactoid

reaction.

Injury, Poisoning and Procedural Complications: Bone fracture.

Investigations: Abnormal clinical laboratory results, altered platelet function,

increased

serum

cholesterol,

weight

decrease

weight

increase

electrocardiogram QT prolonged.

Metabolism

and

Nutrition

Disorders:

Appetite

increased,

hyponatremia,

diabetes mellitus, hyperglycaemia and hypoglycaemia.

Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia, back

pain, and muscle cramps.

Nervous

System

Disorders:

Coma,

convulsions,

cerebrovascular

spasm

(including

reversible

cerebral

vasconstriction

syndrome

Call-Fleming

syndrome), headache, migraine, movement disorders (including extrapyramidal

symptoms such as akathisia, dystonia, hyperkinesia, hypertonia, teeth grinding or

gait abnormalities), muscle contractions involuntary, dyskinesia, paraesthesia

hypoaesthesia,

coordination

abnormal,

amnesia,

speech

disorder,

tongue

disorders, dysphagia and syncope. Also reported were signs and symptoms

associated with serotonin syndrome: In some cases associated with concomitant

serotonergic

drugs,

that

included

agitation,

confusion,

diaphoresis,

diarrhoea, fever, hypertension, rigidity and tachycardia.

Psychiatric

Disorders:

Agitation,

aggressive

reaction,

anxiety,

depressive

symptoms, euphoria, hallucination, libido decreased-female, libido decreased-

male,

paroniria,

depersonalisation,

nightmare,

nervousness,

apathy,

thinking

abnormal, sleep walking, disturbance in attention and psychosis.

Renal

and

Urinary

Disorders:

Urinary

incontinence,

urinary

retention

enuresis.

Reproductive System and Breast Disorders: Galactorrhoea, gynaecomastia,

menstrual irregularities, premature ejaculation and priapism.

Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm, dyspnoea,

hiccups, dysphonia and yawning.

Skin

and

Subcutaneous

Tissue

Disorders:

Alopecia,

angiooedema,

face

oedema, periorbital oedema, photosensitivity skin reaction, pruritus, dermatitis,

rash (including rare reports of serious exfoliative skin disorders: e.g. Stevens-

Johnson syndrome and epidermal necrolysis) and urticaria.

Vascular

Disorders:

Peripheral

ischaemia,

flushes,

hypertension

abnormal bleeding (predominantly of the skin and mucous membranes, including

purpura,

epistaxis,

haematomas,

haemorrhoids,

vaginal

bleeding

gastrointestinal bleeding).

Discontinuation

symptoms:

Symptoms

following

discontinuation

sertraline

have

been

reported

included

agitation,

anxiety,

dizziness,

headache, nausea and paraesthesia.

Adverse Reactions from Clinical Trials in Paediatric MDD

In clinical trials in children and adolescents aged 6 to 17 years with major

depressive disorder the following adverse events were reported at a frequency of

at least 2% of subjects and occurred at a rate of at least twice that of placebo:

diarrhoea (9.5% vs 1.6%), agitation (6.3% vs 1.1%), anorexia (5.3% vs 1.1%),

vomiting (4.2% vs 1.1%) hyperkinesia (2.6% vs 0.5%), dry mouth (2.1% vs

0.5%),

tremor

(2.1%

urinary

incontinence

(2.1%

0%).

incidence of discontinuation due to adverse events was 9% (n=17) with sertraline

and 2.1 (n=4) with placebo. The most common reasons for discontinuation due to

adverse events, whether or not related to sertraline, were aggressive reaction

(1.6%), agitation (1.6%), suicidal ideation (1.6%), hyperkinesia (1.1%), suicide

attempt (1.1%) and aggravated depression (1.1%).

In the safety analysis, suicide attempt was reported in the same number of

patients in sertraline (2/189, 1.1%) and placebo (2/184, 1.1%) with an incidence

of suicide attempts in sertraline-treated subjects of 1.1% (2 attempts in 2/189

subjects) versus 1.6% in placebo-treated subjects (3 attempts in 2/184 subjects).

Suicidal ideation was reported by 3 sertraline-treated patients (1.6%) and no

placebo treated patients. This difference is not statistically significant. Note that

sertraline should not be used in children and adolescents to treat MDD (see

Precautions).

Interactions

Monoamine Oxidase Inhibitors

See Contraindications and Warnings and Precautions.

Pimozide

Increased pimozide levels have been demonstrated in a study of single low dose

pimozide (2 mg) with sertraline coadministration.

These increased levels were not associated with any changes in EKG. While the

mechanism of this interaction is unknown, due to the narrow therapeutic index of

pimozide,

concomitant

administration

sertraline

pimozide

contraindicated.

Medicines that Prolong the QTC Interval

The risk of QTc prolongation and/or ventricular arrhythmias (e.g. Torsades de

Pointes) is increased with concomitant use of other medicines which prolong the

QTc interval (e.g. some antipsychotics and antibiotics). Please check the data

sheets of other medicines administered for information on their effects on the

QTc interval (see Warnings and precautionsQTc Prolongation/Tdp).

CNS Depressants and Alcohol

The co-administration of sertraline 200 mg daily did not potentiate the effects of

alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor

performance in healthy subjects; however, the concomitant use of sertraline and

alcohol is not recommended.

Lithium

placebo-controlled

trials

normal

volunteers,

co-administration

sertraline with lithium did not significantly alter lithium pharmacokinetics, but did

result

increase

tremor

relative

placebo,

indicating

possible

pharmacodynamic

interaction.

When

co-administering

sertraline

with

medications, such as lithium, which may act via serotonergic mechanisms,

patients should be appropriately monitored.

Phenytoin

placebo-controlled

trial

normal

volunteers

suggests

that

chronic

administration of sertraline 200 mg/day does not produce clinically important

inhibition of phenytoin metabolism. Nonetheless, it is recommended that plasma

phenytoin concentrations be monitored following initiation of sertraline therapy,

with appropriate adjustments to the phenytoin dose. In addition, co-administration

of phenytoin may cause a reduction of sertraline plasma levels.

Coadministration of Medicines with Serotonergic Action

Sumatriptan

There have been rare post-marketing reports describing patients with weakness,

hyperreflexia, incoordination, confusion, anxiety and agitation following the use of

sertraline

sumatriptan.

concomitant

treatment

with

sertraline

sumatriptan is clinically warranted, appropriate observation of the patient is

advised (see Warnings and Precautions: Other Serotonergic Drugs).

Other Serotonergic Drugs

See Warnings and Precautions.

St John's Wort

See Warnings and Precautions.

Protein Bound Drugs

Since sertraline is bound to plasma proteins, the potential of sertraline to interact

with other plasma protein bound drugs should be borne in mind.

However, in three formal interaction studies with diazepam, tolbutamide, and

warfarin, respectively, sertraline was not shown to have significant effects on the

protein binding of the substrate (see subsections Warfarin, CNS Active Drugs

and Hypoglycaemic Drugs).

Warfarin

Co-administration of sertraline 200 mg daily with warfarin resulted in a small but

statistically significant increase in prothrombin time, the clinical significance of

which is unknown. Accordingly, prothrombin time should be carefully monitored

when sertraline therapy is initiated or stopped.

Medicines that interfere with haemostasis (NSAIDs, aspirin, warfarin, etc)

Serotonin release by platelets plays an important role in haemostasis. There is

an association between use of psychotropic drugs that interfere with serotonin

reuptake and the occurrence of abnormal bleeding. Concurrent use of an NSAID,

aspirin or warfarin potentiates the risk. Thus, patients should be cautioned about

using such medicines concurrently with Sertraline Actavis.

Cimetidine

Co-administration of sertraline with cimetidine caused a substantial decrease in

sertraline clearance. The clinical significance of this change is unknown.

CNS active drugs

Co-administration of sertraline 200 mg daily with diazepam resulted in small,

statistically significant changes in some pharmacokinetic parameters. The clinical

significance of these changes is unknown.

Hypoglycaemic drugs

Co-administration of sertraline 200 mg daily with tolbutamide resulted in small,

statistically significant changes in some pharmacokinetic parameters. The clinical

significance of these changes is unknown.

Sertraline 200 mg daily did not affect the pharmacokinetics of glibenclamide.

Patients receiving biguanides should monitor their blood glucose carefully when

sertraline is introduced.

Atenolol

Sertraline had no effect on the beta-adrenergic blocking ability of atenolol.

Digoxin

Sertraline 200 mg daily did not change serum digoxin levels or digoxin renal

clearance.

Drugs Metabolised by Cytochrome P450 (CYP) 2D6

There is variability among antidepressants in the extent to which they inhibit the

activity

isozyme

cytochrome

2D6.

clinical

significance

this

depends on the extent of the inhibition and the therapeutic index of the co-

administered drug. CYP 2D6 substrates with a narrow therapeutic index include

TCAs and class 1C antiarrhythmics such as propafenone and flecainide. In

formal interaction studies, chronic dosing with sertraline 50 mg daily showed

minimal elevation (mean 23-37%) of steady state desipramine plasma levels (a

marker of CYP 2D6 isoenzyme activity).

Drugs Metabolised by Other CYP Enzymes (CYP 3A3/4, CYP 2C9, CYP

2C19, CYP 1A2)

CYP

3A3/4

In

vivo

interaction

studies

have

demonstrated

that

chronic

administration of sertraline 200 mg daily does not inhibit the CYP 3A3/4 mediated

6-β hydroxylation of endogenous cortisol or the metabolism of carbamazepine or

terfenadine. In addition, the chronic administration of sertraline 50 mg daily does

not inhibit the CYP 3A3/4 mediated metabolism of alprazolam. The data suggest

that sertraline is not a clinically relevant inhibitor of CYP 3A/34.

CYP 2C9 - The apparent lack of clinically significant effects of the chronic

administration

sertraline

daily

plasma

concentrations

tolbutamide, phenytoin and warfarin suggests that sertraline is not a clinically

relevant

inhibitor

2C9.

(see

subsections

Hypoglycaemic

Drugs,

Phenytoin and Warfarin).

CYP 2C19 - The apparent lack of clinically significant effects of the chronic

administration of sertraline 200 mg daily on plasma concentrations of diazepam

suggests that sertraline is not a clinically relevant inhibitor of CYP 2C19. (see

subsection CNS Active Drugs).

CYP 1A2 - In vitro studies indicate that sertraline has little or no potential to

inhibit CYP 1A2.

Microsomal Enzyme Induction

Preclinical studies have shown Sertraline to induce hepatic microsomal enzymes.

In clinical studies, Sertraline was shown to induce hepatic enzymes minimally as

determined by a small (5%) but statistically significant decrease in antipyrine half-

life following administration of 200 mg/day for 21 days.

Overdosage

On the evidence available, sertraline has a wide margin of safety in overdose. An

overdose of sertraline alone of up to 13.5 g has been reported. Deaths have

been reported involving overdoses of sertraline, primarily in combination with

other

drugs

and/or

alcohol.

Therefore,

overdosage

should

treated

aggressively.

Symptoms of overdose include serotonin-mediated side effects such as QYc

prolongation, Torsades de Pointes, somnolence, gastrointestinal disturbances

(such as nausea and vomiting), tachycardia, tremor, agitation and dizziness.

Less frequently reported was coma.

There are no specific antidotes to sertraline. Establish and maintain an airway

ensure

adequate

oxygenation

ventilation,

necessary.

Activated

charcoal, which may be used with a cathartic, may be as or more effective than

lavage, and should be considered in treating overdose. Induction of emesis is not

recommended. Cardiac and vital sign monitoring is recommended along with

general symptomatic and supportive measures. Due to the large volume of

distribution of sertraline, forced diuresis, dialysis, hemoperfusion, and exchange

transfusion are unlikely to be of benefit.

Contact the National Poisons Centre on 0800 764 766 or 0800 POISON.

Pharmaceutical Precautions

Storage

Store below 25°C. Store in the original package. Protect from light and heat.

Shelf- life

4 years when stored below 25°C.

Medicine Classification

Prescription Medicine

Package Quantities

Blister Packs of 30 and 90 tablets

Further Information

Preclinical Safety Data

Extensive chronic safety evaluation studies in animals show that sertraline is

generally well tolerated at doses that are appreciable multiples of those that are

clinically effective. Sertraline has also been shown to be devoid of mutagenic

effects.

Carcinogenicity

The carcinogenic potential of sertraline has not been fully elucidated. Lifetime

carcinogenicity studies were carried out in CD-1 mice and Long-Evans rats (at

doses up to 40 mg/kg), giving rise to plasma drug exposure levels similar to or

slightly higher than that achieved following the maximum recommended human

dose of 200 mg. There was a dose-related increase in the incidence of liver

adenomas in male mice receiving sertraline at 10-40 mg/kg. No increase was

seen in female mice or in rats of either sex receiving the same treatments, nor

was there an increase in hepatocellular carcinomas. Liver adenomas have a

variable rate of spontaneous occurrence in the CD-1 mouse and are of unknown

significance to humans. There was an increase in follicular adenomas of the

thyroid in female rats receiving sertraline at 40 mg/kg; this was not accompanied

by thyroid hyperplasia. While there was an increase in uterine adenocarcinomas

in rats receiving sertraline at 10-40 mg/kg compared to placebo controls, this

effect was not clearly drug related.

Genotoxicity

Sertraline had no genotoxic effects, with or without metabolic activation, based

on the following assays; bacterial mutation assay; mouse lymphoma mutation

assay; and tests for cytogenetic aberrations in vivo in mouse bone marrow and in

vitro in human lymphocytes.

Sertraline

hydrochloride

naphthylamine

derivative,

having

following

chemical

name:

(1S,cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-

naphthalenamine hydrochloride. It has a molecular weight of 342.7.

Name and Address

Teva Pharma (New Zealand) Limited

PO Box 128 244

Remuera

Auckland 1541

Telephone: 0800 800 097

Date of Preparation

28 April 2017

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