Atomoxetine 60mg capsules

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Atomoxetine hydrochloride
Available from:
Genus Pharmaceuticals Ltd
ATC code:
N06BA09
INN (International Name):
Atomoxetine hydrochloride
Dosage:
60mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04040000; GTIN: 5011309006216

Package leaflet: Information for the user

Atomoxetine 10mg Hard Capsules

Atomoxetine 18mg Hard Capsules

Atomoxetine 25mg Hard Capsules

Atomoxetine 40mg Hard Capsules

Atomoxetine 60mg Hard Capsules

Atomoxetine 80mg Hard Capsules

Atomoxetine 100mg Hard Capsules

Atomoxetine (as hydrochloride)

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

The full name of this medicine is Atomoxetine 10mg, 18mg, 25mg, 40mg, 60mg, 80mg, 100mg

Hard Capsules but within the leaflet it will be referred to as Atomoxetine Capsules.

What is in this leaflet

What Atomoxetine Capsules are and what they are used for

What you need to know before you take Atomoxetine Capsules

How to take Atomoxetine Capsules

Possible side effects

How to store Atomoxetine Capsules

Contents of the pack and other information

1.

What Atomoxetine Capsules are and what they are used for

What it is used

for

Atomoxetine Capsules contain atomoxetine and is used to treat attention-deficit and hyperactivity

disorder

(ADHD). It is

used

in children over six years of

in young

people

adults

It is used only as a part of the total treatment of the disease which also requires treatments

which

not involve medicines, such as counselling and behavioural

therapy.

It is not for use as a treatment for ADHD in children under 6 years of age as it is not known if

drug works or is safe in this age group

In adults,

Atomoxetine Capsules are used to treat

ADHD when the symptoms are very

troublesome and

affect

your work or social life and when you have had symptoms of the disease as a

child.

How it

works

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Atomoxetine Capsules increases the amount of noradrenaline in the brain. This is a chemical that is

produced

naturally, and increases attention and decreases impulsiveness and hyperactivity in patients

with

ADHD. This medicine has been prescribed to help control the symptoms of ADHD.

This

medicine is not a stimulant and is therefore not

addictive.

It may take a few weeks after you start the medicine for your symptoms to fully

improve.

About

ADHD

Children and young people with ADHD find

hard to sit still

hard to

concentrate.

It is not their fault that they cannot do these things. Many children and young people struggle to

these things. However, with ADHD this can cause problems with everyday life. Children

young

people with ADHD may have difficulty learning and doing homework. They find it hard

behave

well at home, at school or in other places. ADHD does not affect the intelligence of

child or young

person.

Adults with ADHD find it difficult to do all the things that children find difficult; however

this

mean they have problems

with:

work

relationships

low self

esteem

education.

2.

What you need to know before you take Atomoxetine Capsules

Do not take Atomoxetine Capsules:

if you are allergic to atomoxetine or any of the other ingredients of this medicine

(listed in

section

if you took a medicine known as a monoamine oxidase inhibitor (MAOI), for

example

phenelzine,

in the last two weeks. An MAOI is sometimes used for depression and

other

mental-health problems; taking Atomoxetine Capsules with an MAOI could cause serious

side effects

be life-threatening. You also need to wait at least 14 days after you stop taking

Atomoxetine Capsules

before you take an

MAOI.

if you have an eye disease called narrow-angle glaucoma (increased pressure in your

eye).

if you have serious problems with your heart which may be affected by an increase in heart

rate

and/or blood pressure, as this may be an effect of

Atomoxetine Capsules.

if you have serious problems with the blood vessels in your brain - such as a stroke, swelling

weakening of part of a blood vessel (aneurysm) or narrow or blocked blood

vessels.

have a tumour of your adrenal gland

(phaeochromocytoma).

Do not take Atomoxetine Capsules if any of the above applies to you. If you are not sure, talk to your

doctor

pharmacist before you take Atomoxetine Capsules. This is because Atomoxetine Capsules

can make these problems

worse.

Warnings and precautions

Both adults and children should be aware of the following warnings and precautions. Talk to your

doctor or pharmacist before taking Atomoxetine Capsules if you

have:

thoughts about killing yourself or trying to kill

yourself.

problems with your heart (including heart defects) or an increased heartbeat. Atomoxetine

Capsules

increase your heart rate (pulse). Sudden death has been reported in patients with

heart defects.

high blood pressure. Atomoxetine Capsules can increase blood

pressure.

low blood pressure. Atomoxetine Capsules can cause dizziness or fainting in people with low

blood pressure.

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problems with sudden changes in your blood pressure or your heart

rate.

cardiovascular disease or past medical history of

stroke.

liver problems. You may need a lower

dose.

psychotic symptoms including hallucinations (hearing voices or seeing things which are

there), believing things that are not true or being

suspicious.

mania (feeling elated or over-excited, which causes unusual behaviour) and

agitation.

aggressive

feelings.

unfriendly and angry (hostility)

feelings.

a history of epilepsy or have had seizures for any other reason. Atomoxetine Capsules might

lead to

increase in seizure

frequency.

different moods than usual (mood swings) or feel very

unhappy.

hard-to-control, repeated twitching of any parts of the body or you repeat sounds and

words.

Tell your doctor or pharmacist if any of the above applies to you before starting treatment. This

because Atomoxetine Capsules can make these problems worse. Your doctor will want to monitor

medicine affects

you.

Checks that your doctor will make before you start to take

Atomoxetine Capsules

These checks are to decide if Atomoxetine Capsules is the correct medicine for

you.

Your doctor will measure

your

blood pressure and your heart rate (pulse) before and during the time you take

Atomoxetine

Capsules.

your height and weight if you are a child or teenager during the time you take

Atomoxetine

Capsules.

Your doctor will talk to you

about:

any other medicines you are

taking

whether there is any family history of sudden unexplained

death

any other medical problems (such as heart problems) you or your family may

have.

It is important that you provide as much information as you can. This will help your doctor

decide

Atomoxetine Capsules is the correct medicine for you. Your doctor may decide that other medical

tests

needed before you start taking this

medicine.

Other medicines and Atomoxetine Capsules

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other

medicines.

This includes non-prescription medicines. Your doctor will decide if you can

take

Atomoxetine

Capsules with your other medicines and in some cases your doctor may need to adjust your

dose

increase your dose much more

slowly.

Do not take Atomoxetine Capsules with medicines called MAOIs (monoamine oxidase inhibitors)

used

depression. See section 2 “Do not take

Atomoxetine Capsules”.

If you are taking other medicines, Atomoxetine Capsules may affect how well they work or may

cause

side

effects. If you are taking any of the following medicines, check with your doctor or

pharmacist

before taking

Atomoxetine Capsules:

medicines that increase blood pressure or are used to control blood

pressure

medicines such as antidepressants, for example imipramine, venlafaxine,

mirtazapine,

fluoxetine and

paroxetine

some cough and cold remedies which contain medicines that can affect blood pressure. It

important to check with your pharmacist when you buy any of these

products

some medicines used to treat mental health

conditions

medicines that are known to increase the risk of

seizures

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some medicines that cause Atomoxetine Capsules to stay in the body for longer than normal

(such

quinidine and

terbinafine)

salbutamol (a medicine to treat asthma) when taken by mouth or injected may make

feel as

if your heart is racing, but this will not make your asthma

worse.

The medicines below may lead to an increased risk of an abnormal rhythm of the heart

when

taken

with

Atomoxetine Capsules:

medicines used to control the rhythm of the

heart

medicines which change the concentration of salts in the

blood

medicines for malaria prevention and

treatment

some antibiotic medicines (such as erythromycin and

moxifloxacin).

If you are not sure about whether any medicines you are taking are included in the list above,

your doctor or pharmacist before taking

Atomoxetine Capsules.

Pregnancy and breast-feeding

It is not known if this medicine can affect an unborn baby or pass into breast

milk.

This medicine should not be used during pregnancy, unless your doctor has advised you to do

You should either avoid taking this medicine if you are breast-feeding or

discontinue

breastfeeding.

If you are pregnant or breast-

feeding,

thinking you may be pregnant or are planning to have a

baby,

ask your doctor or pharmacist for advice before taking

this medicine.

Driving and using

machines

You may feel tired, sleepy or dizzy after taking Atomoxetine Capsules. You should be careful if you

driving

a car or operating heavy machinery until you know how Atomoxetine Capsules affects

you. If you feel

tired,

sleepy or dizzy you should not drive or operate

machinery.

Important information about the content of the

capsules

Do not open Atomoxetine Capsules because the contents of the capsule can irritate the eye. If

contents of the capsules come into contact with the eye, the affected eye should be

flushed

immediately with water, and medical advice obtained. Hands and any other part of the body

that

have come into contact with the capsule contents should also be washed as soon as

possible.

3.

How to take Atomoxetine Capsules

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor

or pharmacist if you are not sure. This is usually one or two times a

(morning and late afternoon

or early

evening)

Children should not take this medicine without help from an adult.

If you are taking Atomoxetine Capsules once a day and experience sleepiness or feel sick, your

doctor

change your treatment schedule to twice a

day.

The capsules should be swallowed whole, either with or without

food.

The capsules should not be opened and the contents inside the capsules should not

removed

and taken in any other

way.

Taking the medicine at the same time each day may help you remember to take

Use in children and adolescents

If you are a child or teenager (6 years or

older):

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Your doctor will tell you how much Atomoxetine Capsules you should take and will calculate this

according

your weight. He/she will normally start you on a lower dose before increasing the

amount

Atomoxetine Capsules you need to take according to your body

weight.

Body weight up to 70kg: a starting total daily dose of 0.5mg per kg of body weight for

minimum of 7 days. Your doctor may then decide to increase this to the usual

maintenance

dose of about 1.2mg per kg of body weight

daily.

Body weight over 70kg: a starting total daily dose of 40mg for a minimum of 7 days.

Your

doctor may then decide to increase this to the usual maintenance dose of 80 mg daily.

maximum daily dose your doctor will prescribe is 100

Adults

Atomoxetine Capsules should be started at a total daily dose of 40mg for a minimum of 7 days.

Your

doctor may then decide to increase this to the usual maintenance dose of 80-100mg

daily.

The maximum daily dose your doctor will prescribe is 100

If you have problems with your liver your doctor may prescribe a lower

dose.

If you take more Atomoxetine Capsules than you should

Contact your doctor or the nearest hospital

casualty

department immediately and tell them how many

capsules you have taken. The most

commonly

reported symptoms accompanying overdoses are

gastrointestinal symptoms,

sleepiness,

dizziness, tremor, and abnormal

behaviour.

If you forget to take Atomoxetine Capsules

If you miss a dose, you should take it as soon as possible, but you should not take more than

your

total daily dose in any 24-hour period. Do not take a double dose to make up for a forgotten

dose.

If you stop taking Atomoxetine Capsules

If you stop taking Atomoxetine Capsules there are usually no side effects but your ADHD

symptoms

return. You should talk to your doctor first before you stop

treatment.

Things your doctor will do when you are on

treatment

Your doctor will do some

tests

before you start - to make sure that Atomoxetine Capsules is safe and will be of

benefit.

after you start - they will be done at least every 6 months, but possibly more

often.

They will also be done when the dose is changed. These tests will

include:

measuring height and weight in children and young

people

measuring blood pressure and heart

rate

checking whether you have any problems or if side effects have got worse while

taking

Atomoxetine Capsules.

Long-term

treatment

Atomoxetine Capsules does not need to be taken forever. If you take Atomoxetine Capsules for more

than a year, your

doctor

will review your treatment, to see if the medicine is still

needed.

If you have any further questions on the use of this medicine, ask your doctor or

pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Although

some people get

side effects most

people find that

Atomoxetine Capsules helps them.

Your doctor will talk

you about these side

effects.

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Some side effects could be serious. If you have any of the side effects below, see a

doctor

straight

away.

Uncommon (may affect up to 1 in 100

people)

feeling or having a very fast heartbeat, abnormal rhythms of the

heart

thinking about or feeling like killing

yourself

feeling

aggressive

feeling unfriendly and angry

(hostility)

mood swings or mood

changes

serious allergic reaction with symptoms

swelling of the face and

throat

difficulty

breathing

hives (small raised, itchy patches of

skin)

seizures

psychotic symptoms including hallucinations (hearing voices or seeing things which are

there), believing things that are not true or being

suspicious.

Children and adolescents aged under 18 have an increased risk of side effects such

as:

thinking about or feeling like killing

yourself (may affect up to 1 in 100 people)

mood swings or mood

changes (may affect up to 1 in 10 people).

Adults have a reduced risk (may affect up to 1 in 1,000 people) of side effects such

as:

seizures

psychotic symptoms including hallucinations (hearing voices or seeing things which are

there), believing things that are not true or being

suspicious.

Rare (may affect up to 1 in 1,000

people

)

liver

injury.

You should stop taking Atomoxetine Capsules and call your doctor immediately if you have any

of

the

following:

dark

urine

yellow skin or yellow

eyes

tummy pain which is sore when you press it (tenderness) on the right side just

below

your

ribs

a feeling of sickness (nausea) that is

unexplained

tiredness

itching

feeling that you are coming down with

flu.

Other side effects reported include the following. If they get serious, tell your doctor

or

pharmacist.

Children and adolescents over

6 years

Very Common (may affect more than 1 in 10

people)

headache

pain in the

stomach

decreased appetite (not feeling

hungry)

feeling or being

sick

sleepiness

increased blood

pressure

increased heart rate

(pulse).

These effects may disappear after a while

most

patients.

Common (may affect up to 1 in 10

people)

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being irritable or

agitated

problems sleeping including waking

early

depression

feeling sad or

hopeless

feeling

anxious

tics

large pupils (the dark centre of the

eye)

dizziness

constipation

loss of

appetite

upset stomach,

indigestion

swollen, reddened and itchy

skin

rash

feeling lazy

(lethargy)

chest

pain

tiredness

weight

loss.

Uncommon side effects (may affect up to 1 in 100

people)

fainting

tremor

migraine

blurred vision

abnormal skin sensation, such

burning, prickling, itching, or

tingling

tingling or numbness in the hands

or feet

seizure

(fits)

feeling or having a very fast

heartbeat

prolongation)

shortness of

breath

increased

sweating

itchy

skin

lack of strength or

energy.

Rare (may affect up to 1 in 1,000

people)

poor blood circulation which makes toes

fingers numb and pale (Raynaud’s

disease)

problems going to the toilet such as

frequent

or hesitant urinating, pain on

urinating

prolonged and painful

erections

groin pain in

males.

Adults

Very Common (may affect more than 1 in 10

people)

feeling

sick

mouth

headache

decreased appetite (not feeling

hungry)

problems getting to sleep, staying asleep

waking

early

increased blood

pressure

increased heart rate

(pulse).

Common (may affect up to 1 in 10

people)

feeling

agitated

decreased interest in

sleep

disturbance

depression

feeling sad or

hopeless

feeling

anxious

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dizziness

an abnormal taste or change in taste that

will

not go

away

tremor

tingling or numbness in the hands or

feet

sleepiness, drowsy, feeling

tired

constipation

stomach

ache

indigestion

wind

(flatulence)

being

sick

hot flush or

flushing

feeling or having a very fast

heartbeat

swollen, reddened and itchy

skin

increased

sweating

rash

problems going to the toilet such as not be

able

to urinate, frequent or hesitant urinating,

pain

urinating

inflammation of the prostate gland

(prostatitis)

groin pain in

failure to obtain an

erection

retarded

orgasm

difficulty maintaining an

erection

menstrual

cramps

lack of strength or

energy

tiredness

feeling lazy

(lethargy)

chills

feeling, irritable,

jittery

feeling

thirsty

weight

loss.

Uncommon (may affect up to 1 in 100

people)

restlessness

tics

fainting

migraine

blurred vision

heart rhythm abnormal (QT

prolongation)

feeling cold in fingers and

toes

chest

pain

shortness of

breath

raised red itchy rashes

(hives)

muscle

spasms

an urge to

urinate

abnormal or absence of

orgasm

irregular

menstruation

ejaculation

failure.

Rare (may affect up to 1 in 1,000

people)

poor blood circulation which makes toes

fingers numb and pale (Raynaud’s

disease)

prolonged and painful

erections.

Effects on

growth

Some children experience reduced growth (weight and height) when they start taking

Atomoxetine

Capsules.

However, with long-term treatment, children recover to the weight and height for their age

range.

Your doctor will watch your child’s height and weight over time. If your child is not growing

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gaining weight as expected, your doctor may change your child’s dose or decide to stop

Atomoxetine Capsules temporarily.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet. You can also report side effects directly via the

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

By reporting side effects you can help provide more information on the safety of this medicine.

5.

How to store Atomoxetine Capsules

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and blister after EXP.

The expiry date

refers

to the last day of that

month.

Tablet container:

Use within 6 months after first opening.

Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Atomoxetine Capsules contain

The active substance is atomoxetine hydrochloride. Each hard capsule contains atomoxetine

hydrochloride equivalent to either 10mg, 18mg, 25mg, 40mg, 60mg, 80mg or 100mg of

atomoxetine.

The other ingredients are:

Capsule content: co-processed maize starch (consisting of maize starch and pregelatinised

starch), dimethicone 350 cs, sodium starch glycolate (type A).

Capsule shell: gelatin, titanium dioxide (E171), black ink (which contains shellac, propylene

glycol, ammonia solution, black iron oxide (E172) and potassium hydroxide) and colourants*.

* The colourants are:

10mg: No additional colourant

18mg: Yellow iron oxide (E172)

25mg: and 40mg: Indigotine (E132) and black iron oxide (E172)

60mg: Indigotine (E132), black iron oxide (E172) and yellow iron oxide (E172)

80mg and 100mg: Yellow iron oxide (E172) and red iron oxide (E172).

What Atomoxetine Capsules look like and contents of the pack

10mg: Opaque white hard capsules, size 4 (14.3 mm x 5.31 mm), imprinted with “A910” in black ink.

18mg: Opaque gold (cap) and opaque white (body) hard capsules, size 3 (15.9mm x 5.82mm),

imprinted with “A918” in black ink.

25mg: Opaque blue (cap) and opaque white (body) hard capsules, size 3 (15.9mm x 5.82mm),

imprinted with “A925” in black ink.

40mg: Opaque blue hard capsules, size 2 (18mm x 6.35mm), imprinted with “A940” in black ink.

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60mg: Opaque blue (cap) and opaque gold (body) hard capsules, size 2 (18mm x 6.35mm),

imprinted with “A960” in black ink.

80mg: Opaque brown (cap) and opaque white (body) hard capsules, size 1 (19.4mm x 6.91mm),

imprinted with “A980” in black ink.

100mg: Opaque brown hard capsules, size 0 (21.7mm x 7.65mm), imprinted with “A900” in black

ink.

Atomoxetine 10mg, 18mg, 25mg, 40mg Hard Capsules are available in blister packs of 7’s, 28’s,

30’s, 56;s and 60’s.

Atomoxetine 60mg, 80mg, 100mg Hard Capsules are available in blister packs of 28’s, 30’s, 56’s

and 60’s.

Atomoxetine 10mg, 18mg,

25mg, 40mg, 60mg, 80mg, 100mg Hard Capsules are also available

in tablet containers of -28’s and 100’s.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

TEVA UK Limited, Eastbourne, BN22 9AG, United Kingdom

Manufacturer

Balkanpharma-Dupnitsa AD

3 Samokovsko Shosse Str., Dupnitsa

2600

Bulgaria

Actavis, Barnstaple, EX32 8NS, UK

This leaflet was last revised in 05/2018

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Atomoxetine 60mg Hard Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each hard capsule contains atomoxetine hydrochloride equivalent to 60 mg of

atomoxetine.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Hard capsule

Atomoxetine 60 mg capsules: hard capsule, size 2 (18 mm x 6.35 mm), opaque blue

(cap) and opaque gold (body), imprinted with “A960” in black ink.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Atomoxetine Capsules is indicated for the treatment of Attention-

Deficit/Hyperactivity Disorder (ADHD) in children of 6 years and older, in

adolescents and in adults as part of a comprehensive treatment programme. Treatment

must be initiated by a specialist in the treatment of ADHD, such as a paediatrician,

child/adolescent psychiatrist, or psychiatrist. Diagnosis should be made according to

current DSM criteria or the guidelines in ICD.

In adults, the presence of symptoms of ADHD that were pre-existing in childhood

should be confirmed. Third-party corroboration is desirable and Atomoxetine

Capsules should not be initiated when the verification of childhood ADHD symptoms

is uncertain. Diagnosis cannot be made solely on the presence of one or more

symptoms of ADHD. Based on clinical judgment, patients should have ADHD of at

least moderate severity as indicated by at least moderate functional impairment in 2

or more settings (for example, social, academic, and/or occupational functioning),

affecting several aspects of an individual’s life.

Additional information for the safe use of this product

A comprehensive treatment programme typically includes psychological, educational

and social measures and is aimed at stabilising patients with a behavioural syndrome

characterised by symptoms which may include chronic history of short attention span,

distractibility, emotional lability, impulsivity, moderate to severe hyperactivity, minor

neurological signs and abnormal EEG. Learning may or may not be impaired.

Pharmacological treatment is not indicated in all patients with this syndrome and the

decision to use the drug must be based on a very thorough assessment of the severity

of the patient’s symptoms and impairment in relation to the patient’s age and the

persistence of symptoms.

4.2

Posology and method of administration

Posology

Dosing of paediatric population up to 70 kg Body Weight

Atomoxetine Capsules should be initiated at a total daily dose of approximately 0.5

mg/kg. The initial dose should be maintained for a minimum of 7 days prior to

upward dose titration according to clinical response and tolerability. The

recommended maintenance dose is approximately 1.2 mg/kg/day (depending on the

patient’s weight and available dosage strengths of atomoxetine). No additional benefit

has been demonstrated for doses higher than 1.2 mg/kg/day. The safety of single

doses over 1.8 mg/kg/day and total daily doses above 1.8 mg/kg have not been

systematically evaluated. In some cases it might be appropriate to continue treatment

into adulthood.

Dosing of paediatric population over 70 kg Body Weight

Atomoxetine Capsules should be initiated at a total daily dose of 40 mg. The initial

dose should be maintained for a minimum of 7 days prior to upward dose titration

according to clinical response and tolerability. The recommended maintenance dose

is 80 mg. No additional benefit has been demonstrated for doses higher than 80 mg.

The maximum recommended total daily dose is 100 mg. The safety of single doses

over 120 mg and total daily doses above 150 mg have not been systematically

evaluated.

Dosing of Adults

Atomoxetine Capsules should be initiated at a total daily dose of 40 mg. The initial

dose should be maintained for a minimum of 7 days prior to upward dose titration

according to clinical response and tolerability. The recommended maintenance daily

dose is 80 mg to 100 mg. The maximum recommended total daily dose is 100 mg.

The safety of single doses over 120 mg and total daily doses above 150 mg have not

been systematically evaluated.

Additional information for the safe use of this product

Pre-treatment screening

Prior to prescribing it is necessary to take an appropriate medical history and conduct

a baseline evaluation of a patient’s cardiovascular status, including blood pressure

and heart rate (see sections 4.3 and 4.4).

Ongoing monitoring

Cardiovascular status should be regularly monitored with blood pressure and pulse

recorded after each adjustment of dose and then at least every 6 months. For

paediatric patients the use of a centile chart is recommended. For adults, current

reference guidelines for hypertension should be followed (see section 4.4).

Withdrawal of Treatment

In the study programme no distinct withdrawal symptoms have been described. In

cases of significant adverse effects, atomoxetine may be stopped abruptly; otherwise

the drug may be tapered off over a suitable time period.

Treatment with Atomoxetine Capsules need not be indefinite. Re-evaluation of the

need for continued therapy beyond 1 year should be performed, particularly when the

patient has reached a stable and satisfactory response.

Special Populations

Hepatic insufficiency

For patients with moderate hepatic insufficiency (Child-Pugh Class B), initial and

target doses should be reduced to 50% of the usual dose. For patients with severe

hepatic insufficiency (Child-Pugh Class C), initial dose and target doses should be

reduced to 25% of usual dose (see section 5.2).

Renal insufficiency

Subjects with end-stage renal disease had higher systemic exposure to atomoxetine

than healthy subjects (about a 65% increase), but there was no difference when

exposure was corrected for mg/kg dose. Atomoxetine Capsules can therefore be

administered to ADHD patients with end-stage renal disease or lesser degrees of renal

insufficiency using the usual dosing regimen. Atomoxetine may exacerbate

hypertension in patients with end-stage renal disease (see section 5.2).

Approximately 7% of Caucasians have a genotype corresponding to a non-functional

CYP2D6 enzyme (called CYP2D6 poor metabolisers). Patients with this genotype

have a several-fold higher exposure to atomoxetine when compared to patients with a

functional enzyme. Poor metabolisers are therefore at higher risk of adverse events

(see sections 4.8 and 5.2). For patients with a known poor metaboliser genotype, a

lower starting dose and slower up titration of the dose may be considered.

Elderly

The use of atomoxetine in patients over 65 years of age has not been systematically

evaluated.

Children under 6 years of age

The safety and efficacy of Atomoxetine Capsules in children under 6 years of age

have not been established. Therefore Atomoxetine Capsules should not be used in

children under 6 years of age (see section 4.4).

Method of administration

For oral use.

Atomoxetine Capsules can be administered as a single daily dose in the morning, with

or without food. Patients who do not achieve a satisfactory clinical response

(tolerability [e.g. nausea or somnolence] or efficacy) when taking Atomoxetine

Capsules as a single daily dose might benefit from taking it as twice daily evenly

divided doses in the morning and late afternoon or early evening.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section

6.1.

Atomoxetine should not be used in combination with monoamine oxidase inhibitors

(MAOIs). Atomoxetine should not be used within a minimum of 2 weeks after

discontinuing therapy with MAOI. Treatment with MAOI should not be initiated

within 2 weeks after discontinuing atomoxetine.

Atomoxetine should not be used in patients with narrow angle glaucoma, as in

clinical trials the use of atomoxetine was associated with an increased incidence of

mydriasis.

Atomoxetine should not be used in patients with severe cardiovascular or

cerebrovascular disorders (see section 4.4). Severe cardiovascular disorders may

include severe hypertension, heart failure, arterial occlusive disease, angina,

haemodynamically significant congenital heart disease, cardiomyopathies, myocardial

infarction, potentially life-threatening arrhythmias and channelopathies (disorders

caused by the dysfunction of ion channels). Severe cerebrovascular disorders may

include cerebral aneurysm or stroke.

Atomoxetine should not be used in patients with pheochromocytoma or a history of

pheochromocytoma (see section 4.4).

4.4

Special warnings and precautions for use

Suicide related behaviour

Suicide related behaviour (suicide attempts and suicidal ideation) has been reported in

patients treated with atomoxetine. In double blind clinical trials, suicide related

behaviours were uncommon but more frequently observed among children and

adolescents treated with atomoxetine compared to those treated with placebo, where

there were no events. In adult double blind clinical trials there was no difference in

frequency of suicide related behaviour between atomoxetine and placebo. Patients

who are being treated for ADHD should be carefully monitored for the appearance or

worsening of suicide related behaviour.

Sudden death and pre existing cardiac abnormalities

Sudden death has been reported in patients with structural cardiac abnormalities who

were taking atomoxetine at usual doses. Although some serious structural cardiac

abnormalities alone carry an increased risk of sudden death, atomoxetine should only

be used with caution in patients with known serious structural cardiac abnormalities

and in consultation with a cardiac specialist.

Cardiovascular effects

Atomoxetine can affect heart rate and blood pressure. Most patients taking

atomoxetine experience a modest increase in heart rate (mean <10 bpm) and/or

increase in blood pressure (mean <5 mm Hg) (see section 4.8).

However, combined data from controlled and uncontrolled ADHD clinical trials show

that approximately 8 12% of children and adolescents, and 6 10% adults experience

more pronounced changes in heart rate (20 beats per minute or greater) and blood

pressure (15 20 mmHg or greater). Analysis of these clinical trial data showed that

approximately 15 26% of children and adolescents, and 27 32% of adults

experiencing such changes in blood pressure and heart rate during atomoxetine

treatment had sustained or progressive increases. Long term sustained changes in

blood pressure may potentially contribute to clinical consequences such as

myocardial hypertrophy.

As a result of these findings, patients who are being considered for treatment with

atomoxetine should have a careful history and physical exam to assess for the

presence of cardiac disease, and should receive further specialist cardiac evaluation if

initial findings suggest such history or disease.

It is recommended that heart rate and blood pressure be measured and recorded

before treatment is started and, during treatment, after each adjustment of dose and

then at least every 6 months to detect possible clinically important increases. For

paediatric patients the use of a centile chart is recommended. For adults, current

reference guidelines for hypertension should be followed.

Atomoxetine should not be used in patients with severe cardiovascular or

cerebrovascular disorders (see section 4.3). Atomoxetine should be used with caution

in patients whose underlying medical conditions could be worsened by increases in

blood pressure and heart rate, such as patients with hypertension, tachycardia, or

cardiovascular or cerebrovascular disease.

Patients who develop symptoms such as palpitations, exertional chest pain,

unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease

during atomoxetine treatment should undergo a prompt specialist cardiac evaluation.

In addition, atomoxetine should be used with caution in patients with congenital or

acquired long QT or a family history of QT prolongation (see sections 4.5 and 4.8).

As orthostatic hypotension has also been reported, atomoxetine should be used with

caution in any condition that may predispose patients to hypotension or conditions

associated with abrupt heart rate or blood pressure changes.

Cerebrovascular effects

Patients with additional risk factors for cerebrovascular conditions (such as a history

of cardiovascular disease, concomitant medications that elevate blood pressure)

should be assessed at every visit for neurological signs and symptoms after initiating

treatment with atomoxetine.

Hepatic effects

Very rarely, spontaneous reports of liver injury, manifested by elevated hepatic

enzymes and bilirubin with jaundice, have been reported. Also very rarely, severe

liver injury, including acute liver failure, have been reported. Atomoxetine Capsules

should be discontinued in patients with jaundice or laboratory evidence of liver

injury, and should not be restarted.

Psychotic or manic symptoms

Treatment-emergent psychotic or manic symptoms, e.g., hallucinations, delusional

thinking, mania or agitation in patients without a prior history of psychotic illness or

mania can be caused by atomoxetine at usual doses. If such symptoms occur,

consideration should be given to a possible causal role of atomoxetine, and

discontinuation of treatment should be considered. The possibility that Atomoxetine

Capsules will cause the exacerbation of pre-existing psychotic or manic symptoms

cannot be excluded.

Aggressive behaviour, hostility or emotional lability

Hostility (predominantly aggression, oppositional behaviour and anger) was more

frequently observed in clinical trials among children, adolescents and adults treated

with atomoxetine compared to those treated with placebo. Emotional lability was

more frequently observed in clinical trials among children treated with atomoxetine

compared to those treated with placebo. Patients should be closely monitored for the

appearance or worsening of aggressive behaviour, hostility or emotional lability.

Possible allergic events

Although uncommon, allergic reactions, including anaphylactic reactions, rash,

angioneurotic oedema, and urticaria, have been reported in patients taking

atomoxetine.

Seizures

Seizures are a potential risk with atomoxetine. Atomoxetine should be introduced

with caution in patients with a history of seizure. Discontinuation of atomoxetine

should be considered in any patient developing a seizure or if there is an increase in

seizure frequency where no other cause is identified.

Growth and development

Growth and development should be monitored in children and adolescents during

treatment with atomoxetine. Patients requiring long-term therapy should be monitored

and consideration should be given to dose reduction or interrupting therapy in

children and adolescents who are not growing or gaining weight satisfactorily.

Clinical data do not suggest a deleterious effect of atomoxetine on cognition or sexual

maturation, however, the amount of available long-term data is limited. Therefore,

patients requiring long-term therapy should be carefully monitored.

New-onset or worsening of Comorbid Depression, Anxiety and Tics

In a controlled study of paediatric patients with ADHD and comorbid chronic motor

tics or Tourette’s Disorder, atomoxetine-treated patients did not experience worsening

of tics compared to placebo-treated patients. In a controlled study of adolescent

patients with ADHD and comorbid Major Depressive Disorder, atomoxetine-treated

patients did not experience worsening of depression compared to placebo-treated

patients. In two controlled studies (one in paediatric patients and one in adult patients)

of patients with ADHD and comorbid anxiety disorders, atomoxetine treated patients

did not experience worsening of anxiety compared to placebo- treated patients.

There have been rare post marketing reports of anxiety and depression or depressed

mood and very rare reports of tics in patients taking atomoxetine (see section 4.8).

Patients who are being treated for ADHD with atomoxetine should be monitored for

the appearance or worsening of anxiety symptoms, depressed mood and depression or

tics.

Paediatric population under six years of age

Atomoxetine Capsules should not be used in patients less than six years of age as

efficacy and safety have not been established in this age group.

Other therapeutic use

Atomoxetine Capsules is not indicated for the treatment of major depressive episodes

and/or anxiety as the results of clinical trials in adults in these conditions, where

ADHD is not present, did not show an effect compared to placebo (see section 5.1).

4.5

Interaction with other medicinal products and other forms of interaction

Effects of other drugs on atomoxetine

MAOIs

Atomoxetine should not be used with MAOIs (see section 4.3).

CYP2D6 inhibitors (SSRIs (e.g. fluoxetine, paroxetine), quinidine, terbinafine)

In patients receiving these drugs, atomoxetine exposure may be 6 to 8-fold increased

and C

ss max

3 to 4 times higher, because it is metabolised by the CYP2D6 pathway.

Slower titration and final lower dosage of atomoxetine may be necessary in patients

who are already taking CYP2D6 inhibitor drugs. If a CYP2D6 inhibitor is prescribed

or discontinued after titration to the appropriate atomoxetine dose has occurred, the

clinical response and tolerability should be re- evaluated for that patient to determine

if dose adjustment is needed.

Caution is advised when combining atomoxetine with potent inhibitors of cytochrome

P450 enzymes other than CYP2D6 in patients who are poor CYP2D6 metabolisers as

the risk of clinically relevant increases in atomoxetine exposure in vivo is unknown.

Salbutamol (or other beta

2

agonists)

Atomoxetine should be administered with caution to patients treated with high dose

nebulised or systemically administered salbutamol (or other beta

agonists) because

cardiovascular effects can be potentiated.

Contradictory findings regarding this interaction were found. Systemically

administered salbutamol (600

g i.v. over 2 hrs) in combination with atomoxetine

(60 mg twice daily for 5 days) induced increases in heart rate and blood pressure.

This effect was most marked after the initial co-administration of salbutamol and

atomoxetine but returned towards baseline at the end of 8 hours. However, in a

separate study the effects on blood pressure and heart rate of a standard inhaled dose

of salbutamol (200 µg) were not increased by the short term co-administration of

atomoxetine (80 mg once daily for 5 days) in a study of healthy Asian adults who

were extensive atomoxetine metabolisers. Similarly, heart rate after multiple

inhalations of salbutamol (800 µg) did not differ in the presence or absence of

atomoxetine.

Attention should be paid to monitoring heart rate and blood pressure, and dose

adjustments may be justified for either atomoxetine or salbutamol (or other beta

agonists) in the event of significant increases in heart rate and blood pressure during

co-administration of these drugs.

There is the potential for an increased risk of QT interval prolongation when

atomoxetine is administered with other QT prolonging drugs (such as neuroleptics,

class IA and III anti-arrhythmics, moxifloxacin, erythromycin, methadone,

mefloquine, tricyclic antidepressants, lithium, or cisapride), drugs that cause

electrolyte imbalance (such as thiazide diuretics) and drugs that inhibit CYP2D6.

Seizures are a potential risk with atomoxetine. Caution is advised with concomitant

use of medicinal drugs which are known to lower the seizure threshold (such as

tricyclic antidepressants or SSRIs, neuroleptics, phenothiazines or butyrophenone,

mefloquine, chloroquine, buproprion or tramadol) (see section 4.4). In addition,

caution is advised when stopping concomitant treatment with benzodiazepines due to

potential withdrawal seizures.

Anti-hypertensive drugs

Atomoxetine should be used cautiously with anti-hypertensive drugs. Because of a

possible increase in blood pressure, atomoxetine may decrease the effectiveness of

anti-hypertensive drugs/drugs used to treat hypertension. Attention should be paid to

monitoring of blood pressure and review of treatment of atomoxetine or

anti-hypertensive drugs may be justified in the case of significant changes of blood

pressure.

Pressor agents or drugs that increase blood pressure

Because of possible increase in effects on blood pressure, atomoxetine should be used

cautiously with pressor agents or medications that may increase blood pressure (such

as salbutamol). Attention should be paid to monitoring of blood pressure, and review

of treatment for either atomoxetine or pressor agents may be justified in the case of

significant change in blood pressure.

Drugs that affect noradrenaline

Drugs that affect noradrenaline should be used cautiously when co-administered with

atomoxetine because of the potential for additive or synergistic pharmacological

effects. Examples include antidepressants such as imipramine, venlafaxine and

mirtazapine, or the decongestants pseudoephedrine or phenylephrine.

Drugs that affect gastric pH

Drugs that elevate gastric pH (magnesium hydroxide/aluminum hydroxide,

omeprazole) had no effect on atomoxetine bioavailability.

Drugs Highly Bound to Plasma Protein

In vitro drug-displacement studies were conducted with atomoxetine and other highly

bound drugs at therapeutic concentrations. Warfarin, acetylsalicylic acid, phenytoin,

or diazepam did not affect the binding of atomoxetine to human albumin. Similarly,

atomoxetine did not affect the binding of these compounds to human albumin.

4.6

Fertility, Pregnancy and lactation

Pregnancy

Animal studies in general do not indicate direct harmful effects with respect to

pregnancy, embryonal/fetal development, parturition or postnatal development (see

section 5.3). For atomoxetine clinical data on exposed pregnancies are limited. Such

data are insufficient to indicate either an association or a lack of association between

atomoxetine and adverse pregnancy and/or lactation outcomes. Atomoxetine should

not be used during pregnancy unless the potential benefit justifies the potential risk to

the fetus.

Breastfeeding

Atomoxetine and/or its metabolites were excreted in the milk of rats. It is not known

if atomoxetine is excreted in human milk. Because of the lack of data, atomoxetine

should be avoided during breastfeeding.

4.7

Effects on ability to drive and use machines

Data on the effects on the ability to drive and use machines are limited. Atomoxetine

has a minor influence on the ability to drive and use machines. Atomoxetine has been

associated with increased rates of fatigue, somnolence, and dizziness relative to

placebo in paediatric and adult patients. Patients should be advised to use caution

when driving a car or operating hazardous machinery until they are reasonably certain

that their performance is not affected by atomoxetine.

4.8

Undesirable effects

Paediatric population

Summary of the safety profile

In paediatric placebo-controlled trials, headache, abdominal pain

and decreased

appetite are the adverse events most commonly associated with atomoxetine, and are

reported by about 19%, 18% and 16% of patients, respectively, but seldom lead to

drug discontinuation (discontinuation rates are 0.1% for headache, 0.2 % for

abdominal pain and 0.0% for decreased appetite). Abdominal pain and decreased

appetite are usually transient.

Associated with decreased appetite, some patients experienced growth retardation

early in therapy in terms of both weight and height gain. On average, after an initial

decrease in weight and height gain, patients treated with atomoxetine recovered to

mean weight and height as predicted by group baseline data over the long-term

treatment.

Nausea, vomiting and somnolence

can occur in about 10% to 11% of patients,

particularly during the first month of therapy. However, these episodes were usually

mild to moderate in severity and transient, and did not result in a significant number

of discontinuation from therapy (discontinuation rates

0.5%).

In both paediatric and adult placebo-controlled trials, patients taking atomoxetine

experienced increases in heart rate, systolic and diastolic blood pressure (see section

4.4).

Because of its effect on noradrenergic tone, orthostatic hypotension (0.2%) and

syncope (0.8%) have been reported in patients taking atomoxetine. Atomoxetine

should be used with caution in any condition that may predispose patients to

hypotension.

The following table of undesirable effects is based on adverse event reporting and

laboratory investigations from clinical trials and post marketing spontaneous reports

in children and adolescents:

Table: Adverse reactions

Frequency estimate: Very common (

1/10), common (

1/100 to <1/10), uncommon

1/1,000 to <1/100), rare (

1/10,000 to <1/1,000), very rare (<1/10,000), not known

(frequency cannot be estimated from the available data)

System Organ

Class

Very common

1/10

Common

1/100 to <1/10

Uncommon

1/1,000 to <1/100

Rare

1/10,000 to <1/1,000

Metabolism and

Nutrition Disorders

Appetite

decreased

Anorexia (loss

of appetite)

Public Assessment Report

Decentralised Procedure

Atomoxetine 10mg Hard Capsules

Atomoxetine 18mg Hard Capsules

Atomoxetine 25mg Hard Capsules

Atomoxetine 40mg Hard Capsules

Atomoxetine 60mg Hard Capsules

Atomoxetine 80mg Hard Capsules

Atomoxetine 100mg Hard Capsules

(Atomoxetine hydrochloride)

Procedure No: UK/H/5983/001-007/DC

UK Licence No: PL 30306/0659-0665

Actavis Group PTC ehf

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

2

LAY SUMMARY

Atomoxetine 10mg Hard Capsules

Atomoxetine 18mg Hard Capsules

Atomoxetine 25mg Hard Capsules

Atomoxetine 40mg Hard Capsules

Atomoxetine 60mg Hard Capsules

Atomoxetine 80mg Hard Capsules

Atomoxetine 100mg Hard Capsules

(atomoxetine hydrochloride)

The products Atomoxetine 10mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules may be

referred to as ‘Atomoxetine Hard Capsules’ in this report.

This is a summary of the Public Assessment Report (PAR) for Atomoxetine 10mg, 18mg, 25mg, 40mg,

60mg, 80mg and 100mg Hard Capsules (PL 30306/0659-0665; UK/H/5983/001-007/DC). It explains

how Atomoxetine Hard Capsules were assessed and their authorisation recommended, as well as their

conditions of use. It is not intended to provide practical advice on how to use Atomoxetine Hard

Capsules.

For practical information about using Atomoxetine Hard Capsules, patients should read the package

leaflet or contact their doctor or pharmacist.

What are Atomoxetine Hard Capsules and what are they used for?

Atomoxetine Hard Capsules are ‘generic’ medicines’. This means that Atomoxetine Hard Capsules are

similar to a ‘reference medicine’ already authorised in the UK called Strattera 10mg, 18 mg, 25 mg,

40 mg, 60 mg, 80 mg and 100 mg hard capsules (Eli Lilly and Company Limited, UK), which was first

authorised on 27 May 2004. Strattera 10mg, 18 mg, 25 mg, 40 mg, 60 mg, 80 mg and 100 mg hard

capsules may be referred to as ‘Strattera hard capsules’ in this report.

Atomoxetine Hard Capsules are used to treat attention-deficit and hyperactivity disorder (ADHD).The

capsules are used in:

- children over six years of age

- young people

- adults

Atomoxetine Hard Capsules are used only as a part of the comprehensive treatment of the disease which

also requires treatments which do not involve medicines, such as counselling and behavioural therapy.

This medicine is not for use as a treatment for ADHD in children under 6 years of age as it is not known

if the drug works or is safe in this age group.

In adults, Atomoxetine Hard Capsules are used to treat ADHD when the symptoms are very troublesome

and affect the patient’s work or social life and when the patient has had symptoms of the disease as a

child.

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

3

This medicine has been prescribed to help control the symptoms of ADHD. This medicine is not a

psycho-stimulant and there is no evidence to suggest that it has the potential to cause euphoria.

How do Atomoxetine Hard Capsules work?

Atomoxetine Hard Capsules contain the active substance atomoxetine (as atomoxetine hydrochloride),

which increases the amount of noradrenaline in the brain. This is a chemical that is produced naturally,

and increases attention and decreases impulsiveness and hyperactivity in patients with ADHD. It helps

to control the symptoms of ADHD.

About ADHD

Children and young people with ADHD find it hard to:

- sit still and

- concentrate.

It is not their fault that they cannot do these things. Many children and young people struggle to do these

things. However, with ADHD this can cause problems with everyday life. Children and young people

with ADHD may have difficulty learning and doing homework. They find it hard to behave well at

home, at school or in other places. ADHD does not affect the intelligence of a child or young person.

Adults with ADHD find it difficult to do all the things that children find difficult; however this may

mean they have problems with:

- work

- relationships

- low self esteem

- education.

How are Atomoxetine Hard Capsules used?

This medicine is available as a hard capsule and the capsules are taken by mouth.

The medicine should be taken exactly as advised by the patient’s doctor or pharmacist. This is usually

one or two times a day (morning and late afternoon or early evening). The patient should check with the

doctor or pharmacist if not sure.

Children should not take this medicine without help from an adult.

If the patient is taking Atomoxetine Capsules once a day and experience sleepiness or feel sick, the

patient’s doctor may change the treatment schedule to twice a day.

The capsules should be swallowed whole, either with or without food.

The capsules should not be opened and the contents inside the capsules should not be removed and

taken in any other way.

Taking the medicine at the same time each day may help the patient to remember to take it.

Use in children and adolescents

If the patient is a child or teenager (6 years or older):

The patient’s doctor will tell him/her how much Atomoxetine Hard Capsules he/she should take and will

calculate this according to the patient’s weight. The doctor will normally start the patient on a lower

dose before increasing the amount of Atomoxetine Hard Capsules the patient you needs to take

according to his/her body weight.

Body weight up to 70kg: a starting total daily dose of 0.5mg per kg of body weight for a minimum of

7 days. The patient’s doctor may then decide to increase this to the usual maintenance dose of about

1.2mg per kg of body weight daily.

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

4

Body weight over 70kg: a starting total daily dose of 40mg for a minimum of 7 days. The patient’s

doctor may then decide to increase this to the usual maintenance dose of 80 mg daily. The maximum

daily dose the patient’s doctor will prescribe is 100mg.

Adults

Atomoxetine Hard Capsules should be started at a total daily dose of 40mg for a minimum of 7 days.

Your doctor may then decide to increase this to the usual maintenance dose of 80-100mg daily. The

maximum daily dose your doctor will prescribe is 100mg.

If the patient has problems with his/her liver, the patient’s doctor may prescribe a lower dose.

Please read section 3 of the package leaflet for detailed information on dosing recommendations, the

route of administration, and the duration of treatment.

Atomoxetine Hard Capsules can only be obtained with a prescription.

What benefits of Atomoxetine Hard Capsules have been shown in studies?

As Atomoxetine Hard Capsules are generic medicines, studies in patients have been limited to tests to

determine that Atomoxetine Hard Capsules are bioequivalent to the reference medicine, Strattera hard

capsules (Eli Lilly and Company limited, UK). Two medicines are bioequivalent when they produce the

same levels of the active substance in the body.

What are the possible side effects of Atomoxetine Hard Capsules

Because Atomoxetine Hard Capsules are generic medicines and are bioequivalent to the reference

medicine Strattera hard capsules (Eli Lilly and Company Limited, UK), the possible side effects are

taken as being the same as those of the reference medicine.

For the full list of all side effects reported with Atomoxetine Hard Capsules, see section 4 of the package

leaflet.

For the full list of restrictions, see the package leaflet.

Why are Atomoxetine Hard Capsules approved?

It was concluded that, in accordance with EU requirements, Atomoxetine Hard Capsules have been

shown to have comparable quality and to be bioequivalent to Strattera hard capsules (Eli Lilly and

Company Limited, UK). Therefore, the view was that, as for Strattera hard capsules (Eli Lilly and

Company Limited, UK), the benefits outweighs the identified risks.

What measures are being taken to ensure the safe and effective use of Atomoxetine Hard

Capsules?

A Risk Management Plan has been developed to ensure that Atomoxetine Hard Capsules are used as

safely as possible. Based on this plan, safety information has been included in the Summaries of Product

Characteristics and the package leaflet for Atomoxetine Hard Capsules, including the appropriate

precautions to be followed by healthcare professionals and patients.

Known side effects are continuously monitored. Furthermore new safety signals reported by patients and

healthcare professionals will be monitored and reviewed continuously as well.

Other information about Atomoxetine Hard Capsules

Austria, Bulgaria, the Czech Republic, Denmark, Ireland, Iceland, Malta, Romania, Sweden, the Slovak

and the UK agreed to grant Marketing Authorisations for Atomoxetine Hard Capsules on

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

5

14 February 2016. Marketing Authorisations were granted in the UK to Actavis Group PTC ehf on

09 March 2016.

The full PAR for Atomoxetine Hard Capsules follows this summary.

For more information about treatment with Atomoxetine Hard Capsules, read the package leaflet, or

contact your doctor or pharmacist.

This summary was last updated in April 2016.

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

6

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 7

Quality aspects

Page 8

Non-clinical aspects

Page 17

Clinical aspects

Page 18

User consultation

Page 21

Overall conclusion, benefit/risk assessment and

recommendation

Page 22

Annex 1 - Table of content of the PAR update for MRP and DCP

Page 23

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

UK/H/5983/001-007/DC

7

Scientific discussion

I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the Member States considered that the

applications for Atomoxetine 10mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

(PL 30306/0659-0665; UK/H/5983/001-007/DC) could be approved. The products may be collectively

referred to as Atomoxetine Hard Capsules. These are Prescription Only Medicines (POM) indicated for

the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children of 6 years and older, in

adolescents and in adults as part of a comprehensive treatment programme. Treatment must be initiated

by a specialist in the treatment of ADHD, such as a paediatrician, child/adolescent psychiatrist, or

psychiatrist. Diagnosis should be made according to current Diagnostic and Statistical Manual of Mental

Disorders (DSM) criteria or the guidelines in International Statistical Classification of Diseases and

Related Health Problems (ICD).

In adults, the presence of symptoms of ADHD that were pre-existing in childhood should be confirmed.

Third-party corroboration is desirable and Atomoxetine Hard Capsules should not be initiated when the

verification of childhood ADHD symptoms is uncertain. Diagnosis cannot be made solely on the

presence of one or more symptoms of ADHD. Based on clinical judgment, patients should have ADHD

of at least moderate severity as indicated by at least moderate functional impairment in 2 or more

settings (for example, social, academic, and/or occupational functioning), affecting several aspects of an

individual’s life.

Additional information for the safe use of the product:

A comprehensive treatment programme typically includes psychological, educational and social

measures and is aimed at stabilising patients with a behavioural syndrome characterised by symptoms

which may include chronic history of short attention span, distractibility, emotional lability, impulsivity,

moderate to severe hyperactivity, minor neurological signs and abnormal EEG. Learning may or may

not be impaired.

Pharmacological treatment is not indicated in all patients with this syndrome and the decision to use the

drug must be based on a very thorough assessment of the severity of the patient’s symptoms and

impairment in relation to the patient’s age and the persistence of symptoms.

These applications were submitted using the Decentralised Procedure (DCP), with the UK as Reference

Member State (RMS), and Austria, Bulgaria, the Czech Republic, Denmark, Ireland, Iceland, Malta,

Romania, Sweden and the Slovak Republic as Concerned Member States (CMS). The applications were

submitted under Article 10(1) of Directive 2001/83/EC, as amended, as generic applications. The

reference medicinal products for these applications are Strattera 10 mg, 18 mg, 25 mg, 40 mg, 60 mg

hard capsules (PL 0006/0375-0379) which were authorised to Eli Lilly and Company Limited, UK on

27 May 2004 and Strattera 80 mg and 100 mg hard capsules (PL 0006/0615-0616), which were

authorised to Eli Lilly and Company Limited, UK on 05 June 2008.

The active ingredient is atomoxetine (as atomoxetine hydrochloride). Atomoxetine is a highly selective

and potent inhibitor of the pre-synaptic noradrenaline transporter, its presumed mechanism of action,

without directly affecting the serotonin or dopamine transporters. Atomoxetine has minimal affinity for

other noradrenergic receptors or for other neurotransmitter transporters or receptors. Atomoxetine has

two major oxidative metabolites: 4-hydroxyatomoxetine and N-desmethylatomoxetine. 4-

hydroxyatomoxetine is equipotent to atomoxetine as an inhibitor of the noradrenaline transporter but,

unlike atomoxetine, this metabolite also exerts some inhibitory activity at the serotonin transporter.

However, any effect on this transporter is likely to be minimal, as the majority of 4-hydroxyatomoxetine

is further metabolised such that it circulates in plasma at much lower concentrations (1% of atomoxetine

concentration in extensive metabolisers and 0.1% of atomoxetine concentration in poor

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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metabolisers). N-desmethylatomoxetine has substantially less pharmacological activity compared with

atomoxetine. It circulates in plasma at lower concentrations in extensive metabolisers and at comparable

concentrations to the parent drug in poor metabolisers at steady-state.

Atomoxetine is not a psychostimulant and is not an amphetamine derivative. In a randomised, double-

blind, placebo-controlled, abuse-potential study in adults comparing effects of atomoxetine and placebo,

atomoxetine was not associated with a pattern of response that suggested stimulant or euphoriant

properties.

Two bioequivalence studies (conducted under fasting conditions) were submitted to support these

applications; one bioequivalence study comparing the applicant’s 40 mg strength test product versus the

reference product Strattera 40 mg capsules (Eli Lilly and Company Limited, UK) and the other

bioequivalence study comparing the applicant’s 60 mg strength test product versus the reference

Strattera 60 mg capsules (Eli Lilly and Company Limited, UK).The applicant has stated that the

bioequivalent studies were conducted in compliance with the International Conference on

Harmonisation Good Clinical Practice (GCP) guidelines and European guidelines

With the exception of the bioequivalence studies, no new non-clinical or clinical data were submitted,

which is acceptable given that the applications were based on being generic medicinal products of an

originator product that has been in clinical use for over 10 years.

The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in

place at all sites responsible for the manufacture, assembly and batch release of these products.

For manufacturing sites within the Community, the RMS has accepted copies of current manufacturing

authorisations issued by inspection services of the competent authorities as certification that acceptable

standards of GMP are in place at those sites.

For manufacturing sites outside the Community, the RMS has accepted copies of current GMP

Certificates of satisfactory inspection summary reports, ‘close-out letters’ or ‘exchange of information’

issued by the inspection services of the competent authorities (or those countries with which the EEA

has a Mutual Recognition Agreement for their own territories) as certification that acceptable standards

of GMP are in place at those non-Community sites.

The Member States considered that the applications could be approved at the end of procedure

(Day 210) on 14 February 2016. After a subsequent national phase, licences were granted in the UK to

Actavis group PTC ehf on 09 March 2016.

II

QUALITY ASPECTS

II.1

INTRODUCTION

The submitted documentation concerning the proposed product is of sufficient quality and meets the

current EU regulatory requirements.

The quality overall summary has been written by an appropriately qualified person and is a suitable

summary of the pharmaceutical aspects of the dossier.

Atomoxetine 10mg Hard Capsule are size 4 (14.3 mm x 5.31 mm), opaque white, hard capsules

imprinted with “A910” in black ink.

Atomoxetine 18mg Hard Capsules are size 3 (15.9 mm x 5.82 mm), opaque gold (cap) and opaque white

(body), hard capsules imprinted with “A918” in black ink.

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Atomoxetine 25mg Hard Capsules are size 3 (15.9 mm x 5.82 mm), opaque blue (cap) and opaque white

(body), hard capsules imprinted with “A925” in black ink.

Atomoxetine 40mg Hard Capsules are size 2 (18 mm x 6.35 mm), opaque blue, hard capsules imprinted

with “A940” in black ink.

Atomoxetine 60mg Hard Capsules are size 2 (18 mm x 6.35 mm), opaque blue (cap) and opaque gold

(body), hard capsules imprinted with “A960” in black ink.

Atomoxetine 80mg Hard Capsules are size 1 (19.4 mm x 6.91 mm), opaque brown (cap) and opaque

white (body) hard capsules imprinted with “A980” in black ink.

Atomoxetine 100mg Hard Capsules are size 0 (21.7 mm x 7.65 mm), opaque brown, hard capsules

imprinted with “A900” in black ink.

Each Atomoxetine 10mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsule contains

atomoxetine hydrochloride equivalent to 10mg,18mg, 25mg, 40mg, 60mg, 80mg and 100mg, of

atomoxetine, respectively.

The products also contain pharmaceutical excipients in the capsules and the capsule shells, namely

co-processed maize starch (consisting of maize starch and pregelatinised starch), dimethicone 350 cs,

sodium starch glycolate (type A), gelatin, titanium dioxide (E171), and printing ink. Printing ink

contains shellac, propylene glycol, ammonia solution, black iron oxide (E172), potassium hydroxide,

yellow iron oxide (E172; 18mg, 60mg, 80 mg and 100mg strength capsules only), black iron oxide

(E172; 25mg, 40mg and 60mg strengths), red iron oxide (E172; 80mg and 100mg strength capsules

only), indigotine (E132; 25mg and 40mg strength capsules only). Appropriate justification for the

inclusion of each excipient has been provided.

The products are packaged in:

opaque polyvinylchloride/polyvinylidine chloride/polyvinylchloride/aluminium blisters, in pack

sizes of 7 (10mg, 18mg, 25mg and 40mg strengths only), 28, 30, 56 and 60 hard capsules.

High-density polyethylene tablet containers, each with a polypropylene cap, in pack sizes of 28

and 100 hard capsules.

Not all pack sizes may be marketed.

Satisfactory specifications and Certificates of Analysis have been provided for all packaging

components. All primary packaging complies with current European regulations concerning materials in

contact with foodstuff.

II.2

DRUG SUBSTANCE

Atomoxetine hydrochloride

INN:

Atomoxetine hydrochloride

Chemical name:

R

N

-Methyl-3-(2-methylphenoxy)-3-phenylpropan-1-amine

hydrochloride

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Molecular formula:

ClNO

Structure:

291.8

Appearance:

White or almost white powder

Solubility:

Sparingly soluble in water, soluble in anhydrous ethanol and practically

insoluble in heptane

Polymorphism

Atomoxetine hydrochloride exhibits polymorphism.

Atomoxetine hydrochloride is the subject of a European Pharmacopoeia monograph.

All aspects of the manufacture and control of the active substance, atomoxetine hydrochloride, are

covered by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate of

Suitability.

II.3

MEDICINAL PRODUCT

Pharmaceutical Development

The objective of the development programme was to formulate safe, efficacious, stable hard capsules,

which were bioequivalent to Strattera hard capsules (Eli Lilly and Company Limited, UK).

Suitable pharmaceutical development data have been provided for these applications.

Comparative

in-vitro

dissolution and impurity profiles have been provided for the proposed and

reference products. The dissolution and impurity profiles were satisfactory.

With the exception of co-processed maize starch and the printing inks, all excipients comply with their

respective European Pharmacopoeia monographs. Co-processed maize starch and the printing inks are

controlled to suitable in house specifications.

With the exception of gelatin, none of the excipients contain materials of animal or human origin. The

suppliers of gelatin have provided Certificates of Suitability from the EDQM to show that it is

manufactured in line with current European guidelines concerning the minimising of risk of transmission

of Bovine Spongiform Encephalopathy/Transmissible Spongiform Encephalopathies (BSE/TSE).

No genetically modified organisms (GMO) have been used in the preparation of the excipients.

Manufacturing Process

Satisfactory batch formulae have been provided for the manufacture of the products, along with an

appropriate account of the manufacturing process. Based on pilot-scale batches, the manufacturing

process has been validated and has shown satisfactory results. The Marketing Authorisation holder has

committed to performing process validation on future production-scale batches.

Control of Finished Product

The finished product specifications are acceptable. Test methods have been described and have been

validated adequately. Batch data have been provided and comply with the release specifications.

Certificates of Analysis have been provided for all working standards used.

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Stability of the Product

Finished product stability studies were performed in accordance with current guidelines on batches of

finished product in the packaging proposed for marketing. Based on the results, a shelf life of 2 years

for the product packaged in blisters or stored in the unopened tablet containers, with the special storage

conditions ‘Do not store above 30°C’ has been accepted. The in-use shelf-life after first opening the

tablet containers is 6 months.

Suitable post approval stability commitments have been provided to continue stability testing on batches

of finished product.

Bioequivalence/Bioavailability

Satisfactory Certificates of Analysis have been provided for the test and reference batches used in the

bioequivalence studies. The bioequivalence studies are discussed in Section IV, Clinical Aspects.

II.4

Discussion on chemical, pharmaceutical and biological aspects

It is recommended that Marketing Authorisations are granted for Atomoxetine Hard Capsules, from a

quality point of view.

II.5

Summary of Product Characteristics (SmPCs), Patient Information Leaflet (PIL) and

Labels

The SmPCs, PILs and labelling text are satisfactory and in line with current guidance.

In accordance with Directive 2010/84/EU, the current version of the SmPCs and PIL are available on the

MHRA website.

The current labelling is presented below:

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Please find below representative labelling text for Atomoxetine 10mg Hard Capsules

(PL 30306/0659; UK/H/5983/001/DC). The labelling text for Atomoxetine 18mg, 25mg, 40mg,

60mg, 80mg and 100mg Hard Capsules (PL 30306/0660-0665; UK/H/5983/002-7/DC) is consistent

with the labelling text for Atomoxetine 10mg Hard Capsules (PL 30306/0659;

UK/H/5983/001/DC), with the exception of product name, marketing authorisation number and

pack size details. The MAH has committed to submitting mock-up livery to the relevant

regulatory authorities for approval before packs are marketed.

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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III.

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of atomoxetine are well-known,

no new non-clinical data are required and none have been provided.

The non-clinical overview has been written by an appropriately qualified person and is satisfactory,

providing an appropriate review of the relevant non-clinical pharmacology, pharmacokinetics and

toxicology.

III.2

Pharmacology

No new data have been submitted and none are required for applications of this type. Refer to Section

III.1, Introduction, above.

III.3

Pharmacokinetics

No new data have been submitted and none are required for applications of this type. Refer to Section

III.1, Introduction, above.

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III.4

Toxicology

No new data have been submitted and none are required for applications of this type. Refer to Section

III.1, Introduction, above.

III.5

Ecotoxicity/Environmental Risk Assessment (ERA)

The Marketing Authorisation Holder has provided adequate justification for not submitting an

Environment Risk Assessment (ERA). As the applications are for generic versions of an already

authorised product, it is not expected that environmental exposure will increase following approval of

the Marketing Authorisations for the proposed products. An Environmental Risk Assessment is therefore

not deemed necessary.

III.6

Discussion of the non-clinical aspects

No new non-clinical studies were conducted, which is acceptable given that the applications were based

on being generic medicinal products of an originator product that has been licensed for over 10 years.

It is recommended that Marketing Authorisations are granted for Atomoxetine Hard Capsules, from a

non-clinical point of view.

IV.

CLINICAL ASPECTS

IV.1

Introduction

The clinical pharmacology of atomoxetine is well-known. With the exception of data from the

bioequivalence studies detailed below, no new clinical data is provided or required for these

applications. The applicant’s clinical overview has been written by an appropriately qualified person and

is considered acceptable.

IV.2

Pharmacokinetics

With the exception of data from the bioequivalence studies detailed below, no new pharmacokinetic data

is provided or required for these applications.

The Marketing Authorisation Holder submitted the following bioequivalence studies to support the

applications:

Study 1

An open-label, randomised, three-treatment, three-period, three-sequence, three-way single-dose,

crossover, bioequivalence study comparing the test product Atomoxetine 40 mg IR (Immediate

Release) capsules (Actavis) versus the reference products Strattera 40 mg capsules (Eli Lilly and

Company Limited, UK) and Strattera 40 mg capsules (Eli Lilly Australia Pty, Australia) in

healthy human volunteers under fasting conditions.

Subjects were administered a single dose of either the test or reference product with 240 ml of water at

room temperature after at least a 10-hour overnight fast, according to the randomisation schedule. Blood

sampling was performed pre-dose and up to 48 hours post dose in each treatment period. A washout

period of 8 days was kept between each consecutive dosing period.

The three-way design was chosen in order to include a second reference product from the Australian

market. This is acceptable. Only the results pertaining to the test and European reference products are

discussed in this report as the pharmacokinetic results from the Australian product are not relevant to the

European Marketing Authorisation. The pharmacokinetic results are presented below:

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Table 1:_Summary of pharmacokinetic parameters (geometric means and arithmetic

means ± SD) for atomoxetine

Pharmacokinetic

parameter

Geometric mean

Arithmetic mean ±SD

Test (A)

Reference (B)

Test (A)

Reference (B)

(ng.h/mL)

1444.66

1392.3

1641.44±1091.592

1587.37±1124.699

(ng/mL)

289.54

282.40

303.07±95.136

297.24±101.173

area under the plasma concentration-time curve from time zero to t hours

maximum plasma concentration

standard deviation

Table 2: Ratios and 90% confidence intervals of Test Product (A) versus

Reference Product (B)

area under the plasma concentration-time curve from time zero to t hours

maximum plasma concentration

confidence interval

Ratios and 90% CI calculated from ln-transformed data

Conclusion of Study 1

The 90% confidence intervals of the test/reference ratio for AUC

and C

values lie within the

acceptable limits of 80.00% to 125.00%, in line with the ‘Guideline on the Investigation of

Bioequivalence

(CPMP/EWP/QWP/1401/98 Rev 1/Corr**). Thus, the data support the claim that the

applicant’s 40 mg strength test product is bioequivalent to the reference product Strattera 40 mg

capsules (Eli Lilly and Company Limited, UK) under fasting conditions.

Study 2

An open-label, randomised, , three-treatment, three-sequence, three-period, three-way,

single-dose, crossover, bioequivalence study comparing the test product Atomoxetine 60 mg IR

capsules (Actavis) versus the reference products Strattera 60 mg capsules (Eli Lilly and Company

Limited, UK) and Strattera 60 mg capsules (Eli Lilly Australia Pty, Australia) in healthy human

male subject under fasting conditions

The three-way design was chosen in order to include a second reference product from the Australian

market. This is acceptable. Only the results pertaining to the test and European reference products are

discussed in this report as the pharmacokinetic results from the Australian product are not relevant to the

European Marketing Authorisation. The pharmacokinetic results are presented below:

Atomoxetine 10 mg, 18mg, 25mg, 40mg, 60mg, 80mg and 100mg Hard Capsules

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Subjects were administered a single dose of either the test or reference product with 240 ml of water at

after at least a 10-hour overnight fast. Blood sampling was performed pre-dose and up to 48 hours post

dose in each treatment period. A washout period of 8 days was kept between each consecutive dosing

period. The pharmacokinetic results are presented below:

Table 3: Summary of pharmacokinetic parameters for atomoxetine

area under the plasma concentration-time curve from time zero to t hours

0-inf

area under the plasma concentration-time curve from time zero to infinity

maximum plasma concentration

time until C

is reached

Table 4: Bioequivalence of Test and reference Products

area under the plasma concentration-time curve from time zero to t hours

0-inf

area under the plasma concentration-time curve from time zero to infinity

confidence interval

coefficient of variation

time until C

is reached

Conclusion of Study 2

The 90% confidence intervals of the test/reference ratio for AUC and C

values lie within the

acceptable limits of 80.00% to 125.00%, in line with the ‘Guideline on the Investigation of

Bioequivalence

(CPMP/EWP/QWP/1401/98 Rev 1/Corr**). Thus, the data support the claim that the

applicant’s 60mg strength IR test product is bioequivalent to the reference product Strattera 60 mg

capsules (Eli Lilly, Spain) under fasting conditions.

Overall Bioequivalence Conclusion

Based on the results from the studies, bioequivalence has been demonstrated between the applicant’s

40mg and 60mg strength test products and the respective reference products Strattera 40 mg (Eli Lilly

and Company Limited, UK), and 60 mg capsules (Eli Lilly and Company Limited, UK), under fasting

conditions.

A biowaiver has been granted to the applicant’s 10mg, 18mg, 25mg, 80mg and 100mg strength products

based on data presented, in line with the current bioequivalence guideline.

IV.3

Pharmacodynamics

The clinical pharmacodynamic profile of atomoxetine is well-known. No new pharmacodynamic data

were submitted and none are required for applications of this type.

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IV.4

Clinical Efficacy

The efficacy of atomoxetine is well-known. No new efficacy data are presented for these applications

and none are required.

IV.5

Clinical Safety

With the exception of the data generated during the bioequivalence studies, no new safety data are

presented for these applications and none are required. No new or unexpected safety issues arose during

the bioequivalence studies.

IV.6

Risk Management Plan

The MAH has submitted a risk management plan, in accordance with the requirements of Directive

2001/83/EC as amended, describing the pharmacovigilance activities and interventions designed to

identify, characterise, prevent or minimise risks relating to atomoxetine hydrochloride

A summary of safety concerns in listed in the table below:

Routine pharmacovigilance is proposed for all safety concerns.

Routine risk minimisation is proposed for all safety concerns with the exception of ‘Increased blood

pressure and increased heart rate’.

Additional risk minimisation measures are proposed for the safety concerns of increased blood pressure

and increased heart rate as follows:

A prescriber pack will be provided which includes:

An introductory cover letter

A copy of the SmPC

Physicians guide including additional tools:

Checklist for actions to take before prescribing / dispensing or administering atamoxetine

Checklist for monitoring to manage cardiovascular risks with atomoxetine treatment

Measurements recording chart.

IV.7

Conclusion

It is recommended that Marketing Authorisations are granted for Atomoxetine Hard Capsules, from a

clinical point of view.

V.

USER CONSULTATION

The package leaflet has been evaluated via a user consultation study in accordance with the requirements

of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of user testing

the pack leaflet was English.

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The results show that the package leaflet meets the criteria for readability as set out in the Guideline on

the readability of the label and package leaflet of medicinal products for human use.

IV

OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND

RECOMMENDATION

QUALITY

The important quality characteristics of Atomoxetine Hard Capsules are well-defined and controlled.

The specifications and batch analytical results indicate consistency from batch to batch. There are no

outstanding quality issues that would have a negative impact on the benefit/risk balance.

NON-CLINICAL

No new non-clinical data were submitted. As the pharmacokinetics, pharmacodynamics and toxicology

of atomoxetine are well-known, no additional data were required.

No new non-clinical data were submitted and none are required for applications of this type.

EFFICACY

With the exception of the bioequivalence studies, no new data were submitted and none are required for

applications of this type.

Bioequivalence has been demonstrated between the applicant’s 40mg and 60mg strength test products

and their respective reference products Strattera 40 mg (Eli Lilly and Company Limited, UK, and

Strattera 60 mg capsules (Eli Lilly and Company, UK), under fasting conditions.

A biowaiver has been granted to the applicant’s 10mg, 18mg, 25mg, 80mg and 100mg strength products

based on data presented, in line with the current bioequivalence guideline.

SAFETY

With the exception of the safety data generated during the bioequivalence studies, no new data were

submitted and none are required for these applications. As the safety profile of is well known, no

additional safety data were required. No new or unexpected safety concerns arose from the

bioequivalence studies.

PRODUCT LITERATURE

The SmPCs, PIL and labelling text is satisfactory and in line with current guidance.

BENEFIT/RISK ASSESSMENT

The quality of the products is acceptable, and no new non-clinical or clinical safety concerns have been

identified. Extensive clinical experience with atomoxetine is considered to have demonstrated the

therapeutic value of the compound. The benefit/risk balance is therefore considered to be positive.

RECOMMENDATION

The grant of Marketing Authorisations is recommended.

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Annex 1

Table of content of the PAR update for MRP and DCP

Steps taken after the initial procedure with an influence on the Public Assessment Report

Scope

Procedure

number

Product

information

affected

Date of

start of the

procedure

Date of end

of

procedure

Approval/

non

approval

Assessment

report

attached

Y/N

(version)

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