Atomoxetine 100mg capsules

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Atomoxetine hydrochloride
Available from:
Macleods Pharma UK Ltd
ATC code:
N06BA09
INN (International Name):
Atomoxetine hydrochloride
Dosage:
100mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: ; GTIN: 18901463139117
Authorization number:
; PL 34771/0240

Read all of this leaflet carefully before you start taking this

medicine because it contains important information for you.



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.

Atomoxetine



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

Atomoxetine Macleods 10, 18,

25, 40, 60, 80 and 100 mg

capsules, hard

Package leaflet: Information for the user



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.

What is in this leaflet

These checks are to decide if Atomoxetine Macleods is the correct

medicine for you.

Checks that your doctor will make before you start to take

Atomoxetine Macleods

Tell your doctor or pharmacist if any of the above applies to you before

starting treatment. This is because Atomoxetine Macleods can make

these problems worse. Your doctor will want to monitor how the

medicine affects you.



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

repeat sounds and words.



different moods than usual (mood swings) or feel very unhappy.



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

Atomoxetine Macleods might lead to an increase in seizure frequency.



unfriendly and angry (hostility) feelings.



aggressive feelings.



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

behaviour) and agitation.



psychotic symptoms including hallucinations (hearing voices or

seeing things which are not there), believing things that are not true

or being suspicious.



liver problems. You may need a lower dose.



cardiovascular disease or past medical history of stroke.



problems with sudden changes in your blood pressure or your heart

rate.



low blood pressure. Atomoxetine Macleods can cause dizziness or

fainting in people with low blood pressure.



high blood pressure. Atomoxetine Macleods can increase blood

pressure.



problems with your heart (including heart defects) or an increased

heartbeat. Atomoxetine Macleods can increase your heart rate

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

defects.



thoughts about killing yourself or trying to kill yourself.

Both adult and children should be aware of the following warnings and

precautions. Talk to your doctor or pharmacist before taking

Atomoxetine Macleods if you have:

Warnings and precautions

Do not take Atomoxetine Macleods if any of the above applies to you.

If you are not sure, talk to your doctor or pharmacist before you take

Atomoxetine Macleods. This is because Atomoxetine Macleods can

make these problems worse.



have a tumour of your adrenal gland (phaeochromocytoma)



have serious problems with the blood vessels in your brain - such as

a stroke, swelling and weakening of part of a blood vessel

(aneurysm) or narrow or blocked blood vessels



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 Macleods



have an eye disease called narrow-angle glaucoma (increased

pressure in your eye)



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 Macleods with an MAOI could cause

serious side effects or be life-threatening. You also need to wait at

least 14 days after you stop taking Atomoxetine Macleods before

you take an MAOI



are allergic to atomoxetine or any of the other

ingredients of this medicine (listed in section 6).

Do NOT take Atomoxetine Macleods if you:

2.

What you need to know before you take

Atomoxetine Macleods



education



low self esteem



relationships



work

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

difficult; however this may mean they have problems with:

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.



hard to concentrate.



hard to sit still and

Children and young people with ADHD find it:

About ADHD

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

to fully improve.

Atomoxetine Macleods 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.

How it works

In adults, Atomoxetine Macleods is 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.

It 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 these people.

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

requires treatments which do not involve medicines, such as counselling

and behavioural therapy.



in adults



in young people



in children over six years of age

Atomoxetine Macleods contains atomoxetine and is used to treat

attention-deficit and hyperactivity disorder (ADHD). It is used

What it is used for

1.

What Atomoxetine Macleods is and what it is used for



Contents of the pack and other information



How to store Atomoxetine Macleods



Possible side effects



How to take Atomoxetine Macleods



What you need to know before you take Atomoxetine Macleods



What Atomoxetine Macleods is and what it is used for

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.

Adults



Atomoxetine Macleods should be started at a total daily dose of 40

mg for a minimum of 7 days. Your doctor may then decide to

increase this to the usual maintenance dose of 80 mg-100 mg daily.

The maximum daily dose your doctor will prescribe is 100 mg.

Pregnancy and breast-feeding



Body weight over 70 kg: a starting total daily dose of 40 mg for a

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

the usual maintenance dose of 80 mg daily. The maximum daily

dose your doctor will prescribe is 100 mg.



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

of body weight for a minimum of 7 days. Your doctor may then

decide to increase this to the usual maintenance dose of about 1.2

mg per kg of body weight daily.

If you are a child or teenager (6 years or older):

Important information about the content of the

capsules

Driving and using machines



Taking the medicine at the same time each day may help you

remember to take it



thinking that you may be pregnant or are planning to have a baby,

You may feel tired, sleepy or dizzy after taking

Atomoxetine Macleods. You should be careful if

you are driving a car or operating machinery until

you know how Atomoxetine Macleods affects you.

If you feel tired, sleepy or dizzy you should not

drive or operate machinery.

If you are:



pregnant or breast feeding,



You should either avoid taking this medicine if you are

breastfeeding or discontinue breastfeeding.

Do not open Atomoxetine Macleods capsules because the contents of

the capsule can irritate the eye. If the 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 may have come into contact with the capsule contents

should also be washed as soon as possible.

Your doctor will tell you how much Atomoxetine Macleods you should

take and will calculate this according to your weight. He/she will normally

start you on a lower dose before increasing the amount of Atomoxetine

Macleods you need to take according to your body weight.



whether there is any family history of sudden unexplained death



planning to breastfeed your baby

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

Macleods with your other medicines and in some cases your doctor may

need to adjust your dose or increase your dose much more slowly.

Do not take Atomoxetine Macleods with medicines called MAOIs

(monoamine oxidase inhibitors) used for depression. See section 2 “Do

not take Atomoxetine Macleods”.



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

injected may make you feel as if your heart is racing, but this will

not make your asthma worse



medicines that increase blood pressure or are used to control blood

pressure

It is important that you provide as much information as you can. This

will help your doctor decide if Atomoxetine Macleods is the correct

medicine for you. Your doctor may decide that other medical tests are

needed before you start taking this medicine.

Your doctor will talk to you about:

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

dose.



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

family may have



medicines such as antidepressants, for example imipramine,

venlafaxine, mirtazapine, fluoxetine and paroxetine



any other medicines you are taking



medicines that are known to increase the risk of seizures



medicines which change the concentration of salts in the blood

If you are taking other medicines, Atomoxetine Macleods 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 Macleods:



some cough and cold remedies which contain medicines that can

affect blood pressure. It is important to check with your pharmacist

when you get any of these products

Other medicines and Atomoxetine Macleods

How much to take

If you forget to take Atomoxetine Macleods

The medicines below may lead to an increased risk of an abnormal

rhythm of the heart when taken with Atomoxetine Macleods:



some medicines used to treat mental health conditions



medicines used to control the rhythm of the heart



If you are taking Atomoxetine Macleods once a day and experience

sleepiness or feel sick, your doctor may change your treatment

schedule to twice a day



Children should not take this medicine without the help from an

adult.



some medicines that cause Atomoxetine Macleods to stay in the

body for longer than normal (such as quinidine and terbinafine)



medicines for malaria prevention and treatment

3.  How to take Atomoxetine Macleods

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

breast milk.

If you take more Atomoxetine Macleods 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.



some antibiotic medicines (such as erythromycin and moxifloxacin)

ask your doctor or pharmacist for advice before taking this medicine.



The capsules should be swallowed whole, either with or without

food

If you are not sure about whether any medicines you are taking are

included in the list above, ask your doctor or pharmacist before taking

Atomoxetine Macleods.



The capsules should not be opened and the contents inside the

capsules should not be removed and taken in any other way



This medicine should not be used during pregnancy, unless your

doctor has advised you to do so.



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 day (morning and late afternoon

or early evening)



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

time you take Atomoxetine Macleods

Your doctor will measure your



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

you take Atomoxetine Macleods

Uncommon side effects (may affect up to 1 in 100 people)

CHILDREN and YOUNG

PEOPLE over 6 years

ADULTS

- fainting

- tremor

- migraine

- blurred vision

- abnormal skin sensation, such as

burning, prickling, itching, or

tingling

- tingling or numbness in the hands

or feet

- seizure (fits)

- feeling or having a very fast

heartbeat (QT prolongation)

- shortness of breath

- increased sweating

- itchy skin

- lack of strength or energy

- 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 side effects (may affect up to 1 in 1,000 people)

CHILDREN and YOUNG

PEOPLE over 6 years

ADULTS

- poor blood circulation which

makes toes and 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

- poor blood circulation which

makes toes and fingers numb and

pale (Raynaud’s disease)

- prolonged and painful erections

If you stop taking Atomoxetine Macleods there are

usually no side effects but your ADHD symptoms may

return. You should talk to your doctor first before you

stop treatment.

If you stop taking Atomoxetine Macleods



seizures



tiredness

Your doctor will do some tests

liver injury

Rarely

(may affect up to 1 in 1,000 people)



feeling aggressive



psychotic symptoms including hallucinations

(hearing voices or seeing things which are not

there), believing things that are not true or being

suspicious



difficulty breathing



dark urine

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

doctor or pharmacist.

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 Macleods helps them. Your doctor will

talk to you about these side effects.

4.  Possible side effects

Children and young adults aged under 18 have an increased risk of

side effects such as:



thinking about or feeling like killing yourself



itching



mood swings or mood changes



measuring blood pressure and heart rate



feeling that you are coming down with flu

Adults have a reduced risk (

may affect up to 1 in 1,000 people

) of

side effects such as:



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

possibly more often.



serious allergic reaction with symptoms of

Long-term treatment



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

right side just below your ribs

seizures

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

include:

Atomoxetine Macleods does not need to be taken for ever. If you take

Atomoxetine Macleods for more than a year, your doctor will review

your treatment, to see if the medicine is still needed.



hives (small raised, itchy patches of skin)

You should stop taking Atomoxetine Macleods

and call your doctor immediately if you have any of the following:

Uncommon (

may affect up to 1 in 100 people

)

Some side effects could be serious

. If you have any of the side effects

below, see a doctor straight away.



swelling of the face and throat

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

tell your doctor or pharmacist.



mood swings or mood changes

(

may affect up to 1 in 10 people

)



thinking about or feeling like killing yourself

(

may affect up to 1 in

100 people

)



a feeling of sickness (nausea) that is unexplained



psychotic symptoms including hallucinations (hearing voices or

seeing things which are not there), believing things that are not true

or being suspicious



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

heart



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

worse while taking Atomoxetine Macleods



measuring height and weight in children and young people



before you start - to make sure that Atomoxetine Macleods is safe

and will be of benefit.



yellow skin or yellow eyes



feeling unfriendly and angry (hostility)

Things your doctor will do when you are on treatment

Do not store above 30°C.

Do not use this medicine after the expiry date stated on the carton and

blister after 'Exp'. The expiry date refers to the last day of that month.

5.  How to store Atomoxetine Macleods

Your doctor will watch your child's height and weight over time. If your

child is not growing or gaining weight as expected, your doctor may

change your child's dose or decide to stop Atomoxetine Macleods

temporarily.

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

includes any possible side effects not listed in this leaflet. You can also

report side effects directly via www.mhra.gov.uk/yellowcard or search

for MHRA Yellow Card in the Google Play or Apple App Store. By

reporting side effects you can help provide more information on the

safety of this medicine.

Reporting of side effects

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

start taking Atomoxetine Macleods. However, with long-term treatment,

children recover to the weight and height for their age range.

Effects on growth

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

18 mg: Gold cap/opaque white body size “3” capsules containing white to

off white powder, with 'I 24' on body imprinted with black ink

Iron oxide yellow (E172) (18 mg, 60 mg, 80 mg and

100 mg)

FD&C blue 2 (indigo carmine) (E132) (25 mg, 40 mg and 60 mg)

Titanium dioxide (E171) (10 mg, 18 mg, 25 mg, 40

mg, 60 mg, 80 mg and 100 mg)

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 to protect the environment.

What Atomoxetine Macleods 10, 18, 25, 40, 60, 80 and 100 mg

capsules contain

6.

Contents of the pack and other information

Iron oxide red (E172) (80 mg and 100mg)

Marketing Authorisation Holder

Macleods Pharma UK Limited

Wynyard Park House,

Wynyard Avenue, Wynyard,

100 mg: Opaque brown cap/opaque brown body size “1” capsules

containing white to off white powder, with 'I 29' on body imprinted with

black ink

Synoptis Industrial Sp. z o.o

62-020, Poland

ul. Rabowicka 15, Swarzędz,



The capsule shells contain sodium laurilsulfate

and gelatin. The capsule shell colourants are:

PL 34771/0234-0240

This leaflet was last approved in {03/2019}.

Manufacturer

60 mg: Opaque blue cap/gold body size “2” capsules containing white

to off white powder, with 'I 27' on body imprinted with black ink

40 mg: Opaque blue cap/opaque blue body size “3” capsules containing

white to off white powder, with 'I 26' on body imprinted with black ink

80 mg: Opaque brown cap/opaque white body size “2” capsules

containing white to off white powder, with 'I 28' on body imprinted with

black ink

10 mg: Opaque white cap/opaque white body size “3” capsules

containing white to off white powder, with 'I 23' on body imprinted with

black ink

Shellac (E904), Dehydrated alcohol (E1510), Isopropyl alcohol, Butyl

alcohol, Propylene glycol (E1520), Strong Ammonia solution (E527),

Black Iron Oxide (E172), Potassium hydroxide (E525).



The active substance is atomoxetine hydrochloride. Each hard

capsule contains atomoxetine hydrochloride

equivalent to 10 mg, 18 mg, 25 mg, 40 mg, 60

mg, 80 mg or 100 mg of atomoxetine.

25 mg: Opaque blue cap/opaque white body size “3” capsules

containing white to off white powder, with 'I 25' on body imprinted with

black ink



The other ingredients are pregelatinized starch

and colloidal silicon dioxide.

Pack sizes: 7, 28 or 56 capsules.

Marketing Authorisation Holder & Manufacturer

Not all pack sizes may be marketed.

What Atomoxetine Macleods looks like and contents of the pack

Billingham, TS22 5TB

Printing ink:

The capsules are packed in Clear PVC/PVdC – Aluminium Blister.

United Kingdom

Very common side effects (may affect more than 1 in 10 people)

CHILDREN and YOUNG

PEOPLE over 6 years

ADULTS

- 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 in most patients.

- feeling sick

- dry mouth

- headache

- decreased appetite (not feeling

hungry)

- problems getting to sleep,

staying asleep

and waking early

- increased blood pressure

- increased heart rate (pulse)

Common side effects (may affect upto 1 in 10 people)

CHILDREN and YOUNG

PEOPLE over 6 years

ADULTS

- 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

- feeling agitated

- decreased interest in sex

- sleep disturbance

- depression

- feeling sad or hopeless

- feeling anxious

- 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 on

urinating

- inflammation of the prostate

gland (prostatitis)

- groin pain in men

- 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

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Atomoxetine Macleods 100 mg capsules, hard

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each hard capsule contains atomoxetine hydrochloride equivalent to 100 mg of

atomoxetine

For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM

Capsule, hard

Opaque brown cap/ opaque brown body size “1” capsules containing white to off

white powder, with ‘I 29’ on body imprinted with black ink.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Atomoxetine Macleods 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

Macleods 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

characterized 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

Atomoxetine Macleods can be administered as a single daily dose in the morning.

Patients who do not achieve a satisfactory clinical response (tolerability [e.g. nausea

or somnolence] or efficacy) when taking Atomoxetine Macleods 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.

Paediatric population:

Dosing of paediatric population up to 70 kg Body Weight:

Atomoxetine Macleods 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 Macleods should be initiated at a total daily dose of 40mg. 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 80mg. No additional benefit has been demonstrated for doses higher than 80mg.

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

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

evaluated.

Adults:

Atomoxetine Macleods 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 120mg 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 Macleods 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 Macleods

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 population: the use of atomoxetine in patients over 65 years of age has not

been systematically evaluated.

Paediatric population under six years of age: the safety and efficacy of Atomoxetine

Macleods in children under 6 years of age have not been established. Therefore

Atomoxetine Macleods should not be used in children under 6 years of age. (see

section 4.4)

Method of administration

For oral use. Atomoxetine Macleods can be administered with or without food.

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

(MAOI). 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 Special Warnings and Special Precautions

for Use – Cardiovascular Effects). 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 Special Warnings and Special Precautions for

Use – Cardiovascular Effects).

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

the 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. Longterm 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 Contraindications – Severe Cardiovascular

and Cerebrovascular

Disorders). 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 Macleods

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

Macleods 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 co morbid 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 co morbid 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 co-morbid anxiety disorders, atomoxetine-treated patients

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

There have been rare postmarketing 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 Macleods 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 Macleods 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).

Atomoxetine Macleods oral solution contains sorbitol. Patients with rare hereditary

problems of fructose intolerance should not take this medicine.

The capsules are not intended to be opened. Atomoxetine is an ocular irritant. In the

event of capsules content coming in contact with the eye, the affected eye should be

flushed immediately with water, and medical advice obtained. Hands and any

potentially contaminated surfaces should be washed as soon as possible.

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 Css 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 reevaluated 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 beta2 agonists

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

nebulised or systemically administered salbutamol (or other beta2 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 coadministration 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

g) were not increased by the short term coadministration 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

g) 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 beta2

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

coadministration 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 antiarrhythmics, 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 antihypertensive drugs. Because of a

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

antihypertensive drugs / drugs used to treat hypertension. Attention should be paid to

monitoring of blood pressure and review of treatment of atomoxetine or

antihypertensive 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/foetal 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 foetus.

Breast-feeding

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

Macleods 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

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

UK/H/5983/001-007/DC

8

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.

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

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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

UK/H/5983/001-007/DC

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

UK/H/5983/001-007/DC

15

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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