Fluoxetine 10mg capsules

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Fluoxetine hydrochloride
Available from:
DE Pharmaceuticals
ATC code:
N06AB03
INN (International Name):
Fluoxetine hydrochloride
Dosage:
10mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF:
Authorization number:
; PL 20117/0152

Eight important things you need to know about Fluoxetine

capsules

Fluoxetine treats depression and anxiety disorders. Like

all medicines it can have unwanted effects. It is therefore

important that you and your doctor weigh up the benefits

of treatment against the possible unwanted effects, before

starting treatment.

Fluoxetine won’t work straight away. Some people taking

antidepressants feel worse before feeling better. Your doctor

should ask to see you again a couple of weeks after you first

start treatment. Tell your doctor if you haven’t started feeling

better. See section 3, How to take Fluoxetine capsules.

Fluoxetine is not for use in children and adolescents

under 18. See Section 2, Children & adolescents aged 8 to

18 years.

Some people who are depressed or anxious think of

harming or killing themselves. If you start to feel worse, or

think of harming or killing yourself, see your doctor or go to

a hospital straight away. See Section 2, Thoughts of suicide

and worsening of your depression or anxiety disorder.

Don’t stop taking Fluoxetine without talking to your

doctor. If you stop taking Fluoxetine suddenly or miss a dose,

you may get withdrawal effects. See Section 3, If you stop

taking Fluoxetine capsules.

If you feel restless and feel like you can’t sit or stand still,

tell your doctor. Increasing the dose of fluoxetine may make

these feelings worse. See Section 4, Possible side-effects.

Taking some other medicines with Fluoxetine can cause

problems. You may need to talk to your doctor. See Section 2,

Other medicines and Fluoxetine capsules.

If you are pregnant or planning to get pregnant, talk to your

doctor. See section 2, Pregnancy, breast-feeding and fertility.

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.

What is in this leaflet:

1. What Fluoxetine capsules are and what they are used for

2. What you need to know before you take Fluoxetine capsules

3. How to take Fluoxetine capsules

4. Possible side effects

5. How to store Fluoxetine capsules

6. Contents of the pack and other information

What Fluoxetine capsules are and what they are used for

Fluoxetine is one of a group of medicine called selective serotonin

re-uptake inhibitors (SSRI) antidepressants.

Fluoxetine is used for the treatment of:

Adults:

Major depressive episodes

Obsessive-compulsive disorder

Bulimia Nervosa: Fluoxetine is used alongside psychotherapy

for the reduction of binge-eating and purging.

Children and adolescents aged 8 years and above:

Moderate to severe major depressive disorder, if the depression

does not respond to psychological therapy after 4-6 sessions.

Fluoxetine capsules should be offered to a child or young

person with moderate to severe major depressive disorder only

in combination with psychological therapy.

How Fluoxetine capsules work

Everyone has a substance called serotonin in their brain. People

who are depressed or have obsessive-compulsive disorder or

bulimia nervosa have lower levels of serotonin than others. It is

not fully understood how fluoxetine and other SSRIs work but they

may help by increasing the level of serotonin in the brain.

Treating these conditions is important to help you get better. If

it’s not treated, your condition may not go away and may become

more serious and more difficult to treat.

You may need to be treated for a few weeks or months to ensure

that you are free from symptoms.

What you need to know before you take Fluoxetine

capsules

Do not take Fluoxetine capsules

If you are allergic to fluoxetine or any of the other ingredients

of this medicine (listed in section 6). If you develop a rash or

other allergic reactions (like itching, swollen lips or face

or shortness of breath), stop taking the capsules straight

away and contact your doctor immediately.

If you are taking other medicines known as irreversible, non-

selective monoamine oxidase inhibitors (MAOIs), since serious

or even fatal reactions can occur (e.g. iproniazid used to treat

depression).

Treatment with Fluoxetine capsules should only be started at least

2 weeks after discontinuation of an irreversible, non-selective

MAOI.

Do not take any irreversible, non-selective MAOIs for at least

5 weeks after you stop taking Fluoxetine capsules.

If fluoxetine has been prescribed for a long period and/or at a high

dose, a longer interval needs to be considered by your doctor.

If you are taking metoprolol (to treat heart failure) since there is

an increased risk of your heart beat becoming too slow.

Warnings and precautions

Talk to your doctor or pharmacist before taking Fluoxetine

capsules if any of the following applies to you:

heart problems;

appearance of fever, muscle stiffness or tremor, changes in your

mental state like confusion, irritability and extreme agitation;

you may suffer from the so-called “serotonin syndrome” or

“neuroleptic malignant syndrome”. Although this syndrome

occurs rarely it may result in potentially life threatening

conditions; contact your doctor immediately, since Fluoxetine

capsules might need to be discontinued.

mania now or in the past; if you have a manic episode, contact

your doctor immediately because Fluoxetine capsules might

need to be discontinued;

history of bleeding disorders or appearance of bruises or

unusual bleeding;

ongoing treatment with medicines that thin the blood (see ‘Other

medicines and Fluoxetine capsules’);

epilepsy or fits. If you have a fit (seizures) or experience an

increase in seizure frequency, contact your doctor immediately;

Fluoxetine capsules might need to be discontinued;

ongoing ECT (electro-convulsive therapy);

ongoing treatment with tamoxifen (used to treat breast cancer)

(see ‘Other medicines and Fluoxetine capsules’);

starting to feel restless and cannot sit or stand still (akathisia).

Increasing your dose of Fluoxetine capsules may make this worse;

diabetes (your doctor may need to adjust your dose of insulin or

other antidiabetic treatment);

liver problems (your doctor may need to adjust your dosage);

low resting heart-rate and/or if you know that you may have

salt depletion as a result of prolonged severe diarrhoea and

vomiting (being sick) or usage of diuretics (water tablets);

ongoing treatment with diuretics (water tablets), especially if you

are elderly;

glaucoma (increased pressure in the eye).

Medicines like Fluoxetine capsules (so called SNRIs/SSRIs) may

cause symptoms of sexual dysfunction (see section 4). In some

cases, these symptoms have continued after stopping treatment.

Thoughts of suicide and worsening of your depression or

anxiety disorder

If you are depressed and/or have anxiety disorders you can

sometimes have thoughts of harming or killing yourself. These

may be increased when first starting antidepressants, since these

medicines all take time to work, usually about two weeks but

sometimes longer.

You may be more likely to think like this:

If you have previously had thoughts about killing or harming

yourself.

If you are a young adult. Information from clinical trials has

shown an increased risk of suicidal behaviour in adults aged

less than 25 years with psychiatric conditions who were

treated with an antidepressant.

If you have thoughts of harming or killing yourself at any time,

contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that

you are depressed or have an anxiety disorder, and ask them to

read this leaflet. You might ask them to tell you if they think your

depression or anxiety is getting worse, or if they are worried about

changes in your behaviour.

Children and adolescents (aged 8 to 18 years)

Patients under 18 have an increased risk of side-effects such as

suicide attempt, suicidal thoughts and hostility (predominantly

aggression, oppositional behaviour and anger) when they take

this class of medicines. Fluoxetine capsules should only be used

in children and adolescents aged 8 to 18 years for the treatment

of moderate to severe major depressive episodes (in combination

with psychological therapy) and it should not be used to treat other

conditions.

Additionally, only limited information concerning the

long-term safety of Fluoxetine capsules on growth, puberty,

mental, emotional and behavioural development in this age group

is available. Despite this, and if you are a patient under 18, your

doctor may prescribe Fluoxetine capsules for moderate to severe

major depressive episodes, in combination with psychological

therapy, because he/she decides that this is in your best interests.

If your doctor has prescribed Fluoxetine capsules for a patient

under 18 and you want to discuss this, please go back to your

doctor. You should inform your doctor if any of the symptoms

listed above develop or worsen when patients under 18 are taking

Fluoxetine capsules.

Fluoxetine capsules should not be used in the treatment of

children under the age of 8 years.

Other medicines and Fluoxetine capsules

Please tell your doctor or pharmacist if you are taking, have

recently taken or might take any other medicines.

Do not take Fluoxetine capsules with:

certain irreversible, non-selective monoamine oxidase

inhibitors (MAOIs), some used to treat depression.

Irreversible, non-selective MAOIs must not be used with

Fluoxetine capsules as serious or even fatal reactions (serotonin

syndrome) can occur (see section “Do not take Fluoxetine

capsules”). Treatment with Fluoxetine capsules should only be

started at least 2 weeks after discontinuation of an irreversible,

non-selective MAOI (for instance tranylcypromine). Do not take

any irreversible, non-selective MAOIs for at least 5 weeks after

you stop taking Fluoxetine capsules.

If Fluoxetine capsules have been prescribed for a long period

and/or at a high dose, a longer interval than 5 weeks may need

to be considered by your doctor.

metoprolol when used for heart failure; there is an increased

risk of your heart beat becoming too slow.

Fluoxetine capsules may affect the way the following medicines

work (interaction):

tamoxifen (used to treat breast cancer); because fluoxetine

may change the blood levels of this drug, resulting in the

possibility of a reduction in the effect of tamoxifen, your doctor

may need to consider prescribing a different antidepressant

treatment.

monoamine oxidase inhibitors A (MAOI-A) including

moclobemide, linezolid (an antibiotic) and methylthioninium

chloride (also called methylene blue, used for the treatment of

medicinal or chemical product induced methemoglobinemia):

due to the risk of serious or even fatal reactions (called

serotonin syndrome). Treatment with fluoxetine can be started

the day after stopping treatment with reversible MAOIs but the

doctor may wish to monitor you carefully and use a lower dose

of the MAOI-A drug.

mequitazine (for allergies); because taking this drug with

fluoxetine may increase the risk of changes in the electrical

activity of the heart.

phenytoin (for epilepsy); because fluoxetine may influence the

blood levels of this drug, your doctor may need to introduce

phenytoin more carefully and carry out check-ups when given

with Fluoxetine capsules.

lithium, selegiline, St. John’s Wort, tramadol (a painkiller),

triptans (for migraine) and tryptophan; there is an increased

risk of mild serotonin syndrome when these drugs are taken

with fluoxetine. Your doctor will carry out more frequent check-

ups.

medicines that may affect the heart’s rhythm, e.g. Class IA

and III antiarrhythmics, antipsychotics (e.g. phenothiazine

derivatives, pimozide, haloperidol), tricyclic antidepressants,

certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin,

erythromycin IV, pentamidine), anti-malaria treatment

particularly halofantrine or certain antihistamines (astemizole,

mizolastine), because taking one or more of these drugs with

fluoxetine may increase the risk of changes in the electrical

activity of the heart.

anti-coagulants (such as warfarin), NSAID (such as ibuprofen,

diclofenac), aspirin and other medicines which can thin

the blood (including clozapine, used to treat certain mental

disorders). Fluoxetine may alter the effect of these medicines

on the blood. If fluoxetine treatment is started or stopped when

you are taking warfarin, your doctor will need to perform certain

tests, adjust your dose and check on you more frequently.

cyproheptadine (for allergies); because it may reduce the

effect of Fluoxetine capsules.

drugs that lower sodium levels in the blood (including,

drug that causes increase in urination, desmopressin,

carbamazepine and oxcarbazepine); because these drugs may

increase the risk of sodium levels in the blood becoming too low

when taken with fluoxetine.

anti-depressants such as tricyclic anti-depressants, other

selective serotonin reuptake inhibitors (SSRIs) or bupropion,

mefloquine or chloroquine (used to treat malaria), tramadol

(used to treat severe pain) or anti-psychotics such as

phenothiazines or butyrophenones; because fluoxetine may

increase the risk of seizures when taken with these medicines.

flecainide, propafenone, nebivolol or encainide (for heart

problems), carbamazepine (for epilepsy), atomoxetine

or tricyclic antidepressants (for example imipramine,

desipramine and amitriptyline) or risperidone (for

schizophrenia); because fluoxetine may possibly change the

blood levels of these medicines, your doctor may need to lower

their dose when administered with Fluoxetine capsules.

Fluoxetine capsules with food, drink and alcohol

You can take Fluoxetine capsules with or without food, whatever

you prefer.

You should avoid alcohol while you are taking this medicine.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Fluoxetine

10mg Hard Capsules

Fluoxetine

Fluoxetine 10mg

Hard Capsules

Fluoxetine 10mg

Hard Capsules

FPO

FPO

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant

or are planning to have a baby, ask your doctor or pharmacist for

advice before taking this medicine.

Pregnancy

Talk to your doctor as soon as possible if you’re pregnant, if you

might be pregnant, or if you’re planning to become pregnant.

In babies whose mothers took fluoxetine during the first few

months of pregnancy, there have been some studies describing

an increased risk of birth defects affecting the heart. In the

general population, about 1 in 100 babies are born with a heart

defect. This increased to about 2 in 100 babies in mothers who

took fluoxetine.

When taken during pregnancy, particularly in the last 3 months

of pregnancy, medicines like fluoxetine may increase the risk

of a serious condition in babies, called persistent pulmonary

hypertension of the newborn (PPHN), making the baby breathe

faster and appear bluish. These symptoms usually begin during

the first 24 hours after the baby is born. If this happens to your

baby you should contact your midwife and/or doctor immediately.

It is preferable not to use this treatment during pregnancy unless

the potential benefit outweighs the potential risk. Thus, you

and your doctor may decide to gradually stop taking Fluoxetine

capsules while you are pregnant or before being pregnant.

However, depending on your circumstances, your doctor may

suggest that it is better for you to keep taking Fluoxetine capsules.

Caution should be exercised when used during pregnancy,

especially during late pregnancy or just before giving birth since

the following effects have been reported in new born children:

irritability, tremor, muscle weakness, persistent crying, and

difficulty in sucking or in sleeping.

Breast-feeding

Fluoxetine is excreted in breast milk and can cause side effects

in babies. You should only breast-feed if it is clearly necessary.

If breast-feeding is continued, your doctor may prescribe a lower

dose of fluoxetine.

Fertility

Fluoxetine has been shown to reduce the quality of sperm in

animal studies. Theoretically, this could affect fertility, but impact

on human fertility has not been observed as yet.

Driving and using machines

Psychotropic drugs such as fluoxetine may affect your judgment

or co-ordination. Do not drive or use machinery until you know

how Fluoxetine capsules affects you.

Important information about Fluoxetine capsules

Fluoxetine capsules contains less than 1 mmol sodium (23 mg)

per capsule, i.e. essentially ‘sodium-free’.

How to take Fluoxetine 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. Do not take more capsules than your doctor tells you.

Swallow the capsules with a drink of water. Do not chew the

capsules.

Adults:

The recommended dose is:

Depression: The recommended dose is 2 capsules (20 mg) daily.

Your doctor will review and adjust your dosage if necessary

within 3 to 4 weeks of the start of treatment.

If required, the dosage can be gradually increased up to a

maximum of 6 capsules (60 mg) daily. The dose should be

increased carefully to ensure that you receive the lowest

effective dose. You may not feel better immediately when you

first start taking your medicine for depression. This is usual

because an improvement in depressive symptoms may not

occur until after the first few weeks. Patients with depression

should be treated for at least 6 months.

Bulimia nervosa: The recommended dose is 6 capsules

(60 mg) daily.

Obsessive-compulsive disorder: The recommended dose is

2 capsules (20 mg) daily. Your doctor will review and adjust your

dosage if necessary after 2 weeks of treatment. If required, the

dosage can be gradually increased up to a maximum of

6 capsules (60 mg) daily.

If no improvement is noted within 10 weeks, your doctor will

reconsider your treatment.

Use in children and adolescents aged 8 to 18 years with

depression:

Treatment should be started and be supervised by a specialist.

The starting dose is 10mg/day. After 1 to 2 weeks, your doctor

may increase the dose to 20mg/day. The dose should be

increased carefully to ensure that you receive the lowest effective

dose. Lower weight children may need lower doses. If there is

a satisfactory response to treatment, your doctor will review the

need for continuing treatment beyond 6 months. If you have not

improved within 9 weeks, your doctor will reassess your treatment.

Elderly:

Your doctor will increase the dose with more caution and the daily

dose should generally not exceed 40 mg. The maximum dose is

6 capsules (60 mg) daily.

Liver impairment:

If you have a liver problem or are using other medication that

might affect fluoxetine, your doctor may decide to prescribe a

lower dose or tell you to take fluoxetine every other day.

If you take more Fluoxetine capsules than you should

If you have taken too many capsules, go to your nearest

hospital emergency department (or casualty) or tell your doctor

straight away.

Take the pack of Fluoxetine capsules with you if you can.

Symptoms of overdose include: nausea, vomiting, seizures,

heart problems (like irregular heart beat and cardiac arrest), lung

problems and change in mental condition ranging from agitation

to coma.

If you forget to take Fluoxetine capsules

If you miss a dose, do not worry. Take your next dose the next

day at the usual time. Do not take a double dose to make up for

a forgotten dose.

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

to remember to take it regularly.

If you stop taking Fluoxetine capsules

Do not stop taking Fluoxetine capsules without asking your

doctor first, even when you start to feel better. It is important

that you keep taking your medicine.

Make sure you do not run out of capsules.

You may notice the following effects (withdrawal effects) when you

stop taking Fluoxetine capsules: dizziness; tingling feelings like

pins and needles; sleep disturbances (vivid dreams, nightmares,

inability to sleep); feeling restless or agitated; unusual tiredness or

weakness; feeling anxious; nausea/vomiting (feeling sick or being

sick); tremor (shakiness); headaches.

Most people find that any symptoms on stopping Fluoxetine

capsules are mild and disappear within a few weeks. If you

experience symptoms when you stop treatment, contact your

doctor.

When stopping Fluoxetine capsules, your doctor will help you to

reduce your dose slowly over one or two week - this should help

reduce the chance of withdrawal effects.

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.

If you have thoughts of harming or killing yourself at any time,

contact your doctor or go to a hospital straight away (see

Section 2, Do not take Fluoxetine capsules).

If you get a rash or allergic reaction such as itching, swollen

lips/tongue or wheezing/shortness of breath, stop taking the

capsules straight away and tell your doctor immediately.

If you feel restless and cannot sit or stand still, you may have

akathisia; increasing your dose of Fluoxetine capsules may

make you feel worse. If you feel like this, contact your doctor.

Tell your doctor immediately if your skin starts to turn red or

you develop a varied skin reaction or your skin starts to blister

or peel. This is very rare.

Some patients have had:

a combination of symptoms (known as “serotonin syndrome”)

including unexplained fever with faster breathing or heart

rate, sweating, muscle stiffness or tremor, confusion, extreme

agitation or sleepiness (only rarely),

feelings of weakness, drowsiness or confusion mostly in elderly

people and in (elderly) people taking diuretics (water tablets),

prolonged and painful erection,

irritability and extreme agitation,

heart problems, such as fast or irregular heart rate, fainting,

collapsing or dizziness upon standing which may indicate

abnormal functioning of the heart rate.

If you have any of the above side effects, you should tell your

doctor immediately.

The following side effects have also been reported in patients

taking Fluoxetine capsules:

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

Difficulty or inability to sleep (insomnia),

Headache,

Diarrhoea, feeling sick (nausea),

Fatigue.

Common (may affect up to 1 in 10 people):

Not feeling hungry, weight loss,

Anxiety, nervousness,

Restlessness, poor concentration,

Feeling tense,

Decreased sex drive or sexual problems (including difficulty

maintaining an erection for sexual activity),

Sleep problems, unusual dreams, tiredness or sleepiness,

Dizziness,

Changes in taste,

Uncontrollable shaking movements,

Blurred vision,

Rapid and irregular heartbeat sensations,

Flushing,

Yawning,

Indigestion, vomiting,

Dry mouth,

Rash, urticaria, itching,

Excessive sweating,

Joint pain,

Passing urine more frequently,

Unexplained vaginal bleeding,

Feeling shaky or having chills.

Uncommon (may affect up to 1 in 100 people)

Feeling detached from yourself,

Strange thinking,

Abnormally high mood,

Orgasm problems,

Thoughts of suicide or harming yourself,

Grinding teeth,

Muscle twitching, involuntary movements or problems with

balance or co-ordination,

Becoming forgetful (memory impairment),

Enlarged (dilated) pupils,

Ringing in the ears,

Low blood pressure,

Shortness of breath,

Nose bleeds,

Difficulty swallowing,

Hair loss (alopecia),

Increased tendency to bruising,

Unexplained bruising or bleeding,

Cold sweat,

Difficulty passing urine,

Feeling cold or hot,

Abnormal liver test results.

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

Low levels of salt in the blood,

Reduction in blood platelets, which increases risk of bleeding

or bruising,

Reduction in white blood cell count,

Untypical wild behaviour,

Hallucinations,

Agitation,

Panic attacks,

Confusion,

Stuttering,

Aggression,

Fits,

Vasculitis (inflammation of a blood vessel))

Rapid swelling of the tissues around the neck, face, mouth

and/or throat,

Pain in the tube that takes food or water to your stomach,

Hepatitis,

Lung problems,

Sensitivity to sunlight,

Muscle pain,

Problems urinating,

Producing breast-milk.

Bone fractures - an increased risk of bone fractures has been

observed in patients taking this type of medicines.

Most of these side effects are likely to disappear with continued

treatment.

In children and adolescents (8-18 years):

In addition to the possible side effects listed above, Fluoxetine

capsules may slow growth or possibly delay sexual maturity.

Suicide-related behaviours (suicide attempt and suicidal

thoughts), hostility, mania and nose bleeds were also commonly

reported in children.

Reporting of side effects

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 the Yellow Card Scheme at:

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.

How to store Fluoxetine capsules

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

Do not store above 25°C.

Store in the original package in order to protect from moisture.

Do not use this medicine after the expiry date which is stated on

the carton after ‘EXP’. The expiry date refers to the last day of that

month.

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 Fluoxetine 10mg capsules contain

The active substance is fluoxetine hydrochloride equivalent to

10 mg fluoxetine.

The other ingredient is pre-gelatinised maize starch.

The capsule shell contains gelatin, brilliant blue (E133), titanium

dioxide (E171), yellow iron oxide (E172) and sodium laurilsulfate.

Printing ink components are shellac (E904), propylene glycol

(E1520), black iron oxide (E172) and potassium hydroxide

(E525).

What Fluoxetine 10mg capsules look like and contents of the

pack

Fluoxetine 10 mg capsules are green opaque hard gelatin

capsules with C28 marked on it and available in blister packs of

10, 14, 20, 30, 50, 70 or 100 capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Morningside Healthcare Ltd.

Unit C, Harcourt Way

Leicester

LE19 1WP

Manufacturer

Morningside Pharmaceuticals Ltd.

5 Pavilion Way

Loughborough

LE11 5GW

This leaflet was last revised in October 2019.

M0152LAMUKNA-S-002

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT

Fluoxetine 10mg hard capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains fluoxetine hydrochloride equivalent to 10mg of fluoxetine.

For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM

Capsule, hard.

The capsules are green opaque and printed ‘C28’.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Adults:

Major depressive episodes.

Obsessive-compulsive disorder.

Bulimia nervosa: Fluoxetine is indicated as a complement of psychotherapy for the

reduction of binge-eating and purging activity.

Children and adolescents aged 8 years and above:

Moderate to severe major depressive episode if depression is unresponsive to

psychological therapy after 4–6 sessions. Antidepressant medication should be

offered to a child or young person with moderate to severe depression only in

combination with a concurrent psychological therapy.

4.2

Posology and method of administration

Posology

Adults

Major depressive episodes:

Adults and the elderly: The recommended dose is 20 mg daily. Dosage should be

reviewed and adjusted if necessary within 3 to 4 weeks of initiation of therapy and

thereafter as judged clinically appropriate. Although there may be an increased

potential for undesirable effects at higher doses, in some patients, with insufficient

response to 20 mg, the dose may be increased gradually up to a maximum of 60 mg

(see section 5.1). Dosage adjustments should be made carefully on an individual

patient basis, to maintain the patients at the lowest effective dose.

Patients with depression should be treated for a sufficient period of at least 6 months

to ensure that they are free from symptoms.

Obsessive-compulsive disorder:

Adults and the elderly: The recommended dose is 20 mg daily. Although there may

be an increased potential for undesirable effects at higher doses, in some patients, if

after 2 weeks there is insufficient response to 20 mg, the dose may be increased

gradually up to a maximum of 60 mg.

If no improvement is observed within 10 weeks, treatment with fluoxetine should be

reconsidered. If a good therapeutic response has been obtained, treatment can be

continued at a dosage adjusted on an individual basis. While there are no systematic

studies to answer the question of how long to continue fluoxetine treatment, OCD is a

chronic condition and it is reasonable to consider continuation beyond 10 weeks in

responding patients. Dosage adjustments should be made carefully, on an individual

patient basis, to maintain the patient at the lowest effective dose. The need for

treatment should be reassessed periodically. Some clinicians advocate concomitant

behavioural psychotherapy for patients who have done well on pharmacotherapy.

Long-term efficacy (more than 24 weeks) has not been demonstrated in OCD.

Bulimia nervosa:

Adults and the elderly: A dose of 60mg/day is recommended. Long-term efficacy

(more than 3 months) has not been demonstrated in bulimia nervosa.

All indications: The recommended dose may be increased or decreased. Doses above

80mg/day have not been systematically evaluated.

Paediatric population - Children and adolescents aged 8 years and above (Moderate

to severe major depressive episode):

Treatment should be initiated and monitored under specialist supervision. The starting

dose is 10 mg/day. Dose adjustments should be made carefully, on an individual

basis, to maintain the patient at the lowest effective dose.

After one to two weeks, the dose may be increased to 20 mg/day. Clinical trial

experience with daily doses greater than 20 mg is minimal. There is only limited data

on treatment beyond 9 weeks.

Lower weight children: Due to higher plasma levels in lower weight children, the

therapeutic effect may be achieved with lower doses (see Section 5.2).

For paediatric patients who respond to treatment, the need for continued treatment

after 6 months should be reviewed. If no clinical benefit is achieved within 9 weeks,

treatment should be reconsidered.

Elderly patients:

Caution

recommended

when

increasing

dose

daily

dose

should

generally not exceed 40mg. Maximum recommended dose is 60mg/day.

Hepatic impairment

A lower or less frequent dose (e.g., 20mg every second day) should be considered in

patients with hepatic impairment (see section 5.2), or in patients where concomitant

medication has the potential for interaction with Fluoxetine (see section 4.5).

Withdrawal symptoms seen on discontinuation of fluoxetine: Abrupt discontinuation

should be avoided. When stopping treatment with fluoxetine the dose should be

gradually reduced over a period of at least one to two weeks in order to reduce the

risk of withdrawal reactions (see section 4.4 and section 4.8). If intolerable symptoms

occur following a decrease in the dose or upon discontinuation of treatment, then

resuming

previously

prescribed

dose

considered.

Subsequently,

physician may continue decreasing the dose, but at a more gradual rate.

Method of administration

For oral administration.

Fluoxetine may be administered as a single or divided dose, during or between

meals.

When dosing is stopped, active drug substances will persist in the body for

weeks. This should be borne in mind when starting or stopping treatment.

4.3

Contraindications

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

6.1.

Fluoxetine is contra-indicated in combination with irreversible, non-selective

monoamine oxidase inhibitors (e.g. iproniazid) (see sections 4.4 and 4.5).

Fluoxetine is contra-indicated in combination with metoprolol used in cardiac

failure (see section 4.5).

4.4

Special warnings and precautions for use

Paediatric population - children and adolescents under 18 years of age

Suicide-related

behaviours

(suicide

attempt

suicidal

thoughts)

hostility

(predominantly aggression, oppositional behaviour and anger) were more frequently

observed in clinical trials among children and adolescents treated with antidepressants

compared to those treated with placebo. Fluoxetine should only be used in children

and adolescents aged 8 to 18 years for the treatment of moderate to severe major

depressive episodes and it should not be used in other indications. If, based on clinical

need, a

decision to treat

nevertheless taken, the

patient should

carefully

monitored

appearance

suicidal

symptoms.

addition,

only

limited

evidence

available

concerning

long-term

effect

safety

children

adolescents, including effects on growth, sexual maturation and cognitive, emotional

and behavioural developments (see section 5.3).

In a 19-week clinical trial decreased height and weight gain was observed in children

and adolescents treated with fluoxetine (see section 5.1). It has not been established

whether there is an effect on achieving normal adult height. The possibility of a delay

in puberty cannot be ruled out (see sections 5.3 and 4.8). Growth and pubertal

development (height, weight and TANNER staging) should therefore be monitored

during

after

treatment

with

fluoxetine.

either

slowed,

referral

paediatrician should be considered.

In paediatric trials, mania and hypomania were commonly reported (see section 4.8).

Therefore,

regular

monitoring

occurrence

mania/hypomania

recommended. Fluoxetine should be discontinued in any patient entering a manic

phase.

It is important that the prescribers discuss carefully the risks and benefits of treatment

with the child/young person and/or their parents.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm and

suicide (suicide-related events). This risk persists until significant remission occurs.

As improvement may not occur during the first few weeks or more of treatment,

patients should be closely monitored until such improvement occurs. It is general

clinical experience that the risk of suicide may increase in the early stages of

recovery.

Other psychiatric conditions for which fluoxetine is prescribed can also be associated

with an increased risk of suicide-related events. In addition, these conditions may be

co-morbid with major depressive disorder. The same precautions observed when

treating patients with major depressive disorder should therefore be observed when

treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, those exhibiting a significant degree

of suicidal ideation prior to commencement of treatment are known to be at a greater

risk of suicidal thoughts or suicide attempts, and should receive careful monitoring

during

treatment.

meta-analysis

placebo-controlled

clinical

trials

antidepressant drugs in adult patients with psychiatric disorders showed an increased

risk of suicidal behaviour with antidepressants compared to placebo in patients less

than 25 years old.

Close supervision of patients and in particular those at high risk should accompany

drug therapy especially in early treatment and following dose changes. Patients (and

caregivers of patients) should be alerted about the need to monitor for any clinical

worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to

seek medical advice immediately if these symptoms present.

Cardiovascular Effects

Cases of QT interval prolongation and ventricular arrhythmia including torsades de

pointes have been reported during the post-marketing period (see sections 4.5, 4.8 and

4.9).

Fluoxetine should be used with caution in patients with conditions such as congenital

long QT syndrome, a family history of QT prolongation or other clinical conditions

that predispose to arrhythmias (e.g., hypokalemia, hypomagnesemia, bradycardia,

acute myocardial infarction or uncompensated heart failure) or increased exposure to

fluoxetine (e.g., hepatic impairment), or concomitant use with medicinal products

known to induce QT prolongation and/or torsade de pointes (see section 4.5).

patients

with

stable

cardiac

disease

treated,

review

should

considered before treatment is started.

If signs of cardiac arrhythmia occur during treatment with fluoxetine, the treatment

should be withdrawn and an ECG should be performed.

Irreversible, non-selective monoamine oxidase inhibitors (e.g. iproniazid)

Some cases of serious and sometimes fatal reactions have been reported in patients

receiving an SSRI in combination with an irreversible, non-selective monoamine

oxidase inhibitor (MAOI).

These cases presented with features resembling serotonin syndrome (which may be

confounded with (or diagnosed as) neuroleptic malignant syndrome). Cyproheptadine

or dantrolene may benefit patients experiencing such reactions. Symptoms of a drug

interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic

instability with possible rapid fluctuations of vital signs, mental status changes that

include confusion, irritability and extreme agitation progressing to delirium and coma.

Therefore, fluoxetine is contra-indicated in combination with an irreversible, non-

selective MAOI (see section 4.3). Because of the two weeks-lasting effect of the

latter, treatment of fluoxetine should only be started 2 weeks after discontinuation of

an irreversible, non-selective MAOI. Similarly, at least 5 weeks should elapse after

discontinuing

fluoxetine

treatment

before

starting

irreversible,

non-selective

MAOI.

Serotonin syndrome or neuroleptic malignant syndrome-like events

On rare occasions, development of a serotonin syndrome or neuroleptic malignant

syndrome-like events have been reported in association with treatment of fluoxetine,

particularly when given in combination with other serotonergic (among others, L-

tryptophan) and/or neuroleptic drugs (see section 4.5). As these syndromes may result

potentially

life-threatening

conditions,

treatment

with

fluoxetine

should

discontinued

such

events

(characterised

clusters

symptoms,

such

hyperthermia,

rigidity,

myoclonus,

autonomic

instability

with

possible

rapid

fluctuations of vital signs, mental status changes including confusion, irritability,

extreme

agitation

progressing

delirium

coma)

occur

supportive

symptomatic treatment should be initiated.

Mania

Antidepressants

should

used

with

caution

patients

with

history

mania/hypomania. As with all antidepressants, fluoxetine should be discontinued in

any patient entering a manic phase.

Haemorrhage

There have been reports of cutaneous bleeding abnormalities, such as ecchymosis and

purpura with SSRI’s. Ecchymosis has been reported as an infrequent event during

treatment with fluoxetine. Other haemorrhagic manifestations (e.g. gynaecological

haemorrhages, gastro-intestinal bleedings and other cutaneous or mucous bleedings)

have been reported rarely. Caution is advised in patients taking SSRI’s, particularly in

concomitant use with oral anticoagulants, drugs known to affect platelet function (e.g.

atypical

antipsychotics

such

clozapine,

phenothiazines,

most

TCA’s,

aspirin,

NSAID’s), or other drugs that may increase risk of bleeding as well as in patients

with a history of bleeding disorders (see section 4.5).

Seizures

Seizures are a potential risk with antidepressant drugs. Therefore, as with other

antidepressants, fluoxetine should be introduced cautiously in patients who have a

history of seizures. Treatment should be discontinued in any patient who develops

seizures or where there is an increase in seizure frequency. Fluoxetine should be

avoided

patients

with

unstable

seizure

disorders/epilepsy

patients

with

controlled epilepsy should be carefully monitored (see section 4.5).

Electroconvulsive therapy (ECT)

There have been rare reports of prolonged seizures in patients on fluoxetine receiving

ECT treatment, therefore caution is advisable.

Tamoxifen

Fluoxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of

endoxifen, one of the most important active metabolites of tamoxifen. Therefore,

fluoxetine should whenever possible be avoided during tamoxifen treatment (see

section 4.5).

Akathisia / psychomotor restlessness

fluoxetine

been

associated

with

development

akathisia,

characterised by a subjectively unpleasant or distressing restlessness and need to

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

occur

within

first

weeks

treatment.

patients

develop

these

symptoms, increasing the dose may be detrimental.

Diabetes

patients

with

diabetes,

treatment

with

SSRI

alter

glycaemic

control.

Hypoglycaemia has occurred during therapy with fluoxetine and hyperglycaemia has

developed following discontinuation. Insulin and/or oral hypoglycaemic dosage may

need to be adjusted.

Hepatic/renal function

Fluoxetine is extensively metabolised by the liver and excreted by the kidneys. A

lower dose, e.g., alternate day dosing, is recommended in patients with significant

hepatic dysfunction. When given fluoxetine 20mg/day for 2 months, patients with

severe renal failure (GFR <10ml/min) requiring dialysis showed no difference in

plasma levels of fluoxetine or norfluoxetine compared to controls with normal renal

function.

Rash and allergic reactions

Rash,

anaphylactoid

events

and progressive

systemic

events,

sometimes

serious

(involving skin, kidney, liver or lung) have been reported. Upon the appearance of

rash or of other allergic phenomena for which an alternative aetiology cannot be

identified, fluoxetine should be discontinued.

Weight loss

Weight loss may occur in patients taking fluoxetine, but it is usually proportional to

baseline body weight.

Withdrawal symptoms seen on discontinuation of SSRI treatment

Withdrawal symptoms when treatment is discontinued are common, particularly if

discontinuation is abrupt (see section 4.8). In clinical trials, adverse events seen on

treatment

discontinuation

occurred

approximately

patients

both

fluoxetine and placebo groups. Of these adverse events, 17% in the fluoxetine group

and 12% in the placebo group were severe in nature.

The risk of withdrawal symptoms may be dependent on several factors, including the

duration and dose of therapy and the rate of dose reduction. Dizziness, sensory

disturbances (including paraesthesia), sleep disturbances (including insomnia and

intense dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor and

headache are the most commonly reported reactions. Generally, these symptoms are

mild to moderate; however, in some patients they may be severe in intensity. They

usually occur within the first few days of discontinuing treatment. Generally, these

symptoms are self-limiting and usually resolve within 2 weeks, although in some

individuals they may be prolonged (2-3 months or more). It is therefore advised that

fluoxetine should be gradually tapered when discontinuing treatment over a period of

least

weeks,

according

patient’s

needs

(see

“Withdrawal

symptoms seen on discontinuation of fluoxetine, section 4.2).

Mydriasis

Mydriasis has been reported in association with fluoxetine; therefore, caution should

be used when prescribing fluoxetine in patients with raised intraocular pressure or

those at risk of acute narrow-angle glaucoma.

Sexual dysfunction

Serotonin

norepinephrine

reuptake

inhibitors

(SNRIs)/serotonin

norepinephrine

reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section

4.8). There have been reports of long-lasting sexual dysfunction where the symptoms

have continued despite discontinuation of SSRIs/SNRI.

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say

essentially ‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

Half-life: The long elimination half-lives of both fluoxetine and norfluoxetine

should be borne in mind (see section 5.2) when considering pharmacodynamic

or pharmacokinetic drug interactions (e.g., when switching from fluoxetine to

other antidepressants).

Contra-indicated combinations

Irreversible, non-selective monoamine oxidase inhibitors (e.g. iproniazid):

Some cases of serious and sometimes fatal reactions have been reported in

patients receiving an SSRI in combination with an irreversible, non-selective

monoamine oxidase inhibitor (MAOI).

These cases presented with features resembling serotonin syndrome (which

may be confounded with [or diagnosed as] neuroleptic malignant syndrome).

Cyproheptadine

dantrolene

benefit

patients

experiencing

such

reactions.

Symptoms

drug

interaction

with

MAOI

include:

hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid

fluctuations

vital

signs,

mental

status

changes

that

include

confusion,

irritability and extreme agitation progressing to delirium and coma.

Therefore, fluoxetine is contra-indicated in combination with an irreversible,

non-selective MAOI (see section 4.3). Because of the two weeks-lasting effect

of the latter, treatment of fluoxetine should only be started 2 weeks after

discontinuation of an irreversible, non-selective MAOI. Similarly, at least 5

weeks should elapse after discontinuing fluoxetine treatment before starting an

irreversible, non-selective MAOI.

Metoprolol used

in

cardiac

failure:

risk

metoprolol

adverse

events,

including excessive bradycardia, may be increased because of an inhibition of

its metabolism by fluoxetine (see section 4.3).

Not recommended combinations

Tamoxifen:

Pharmacokinetic

interaction

between

CYP2D6

inhibitors

tamoxifen, showing a 65-75 % reduction in plasma levels of one of the more

active

forms

tamoxifen,

i.e.

endoxifen,

been

reported

literature. Reduced efficacy of tamoxifen has been reported with concomitant

usage of some SSRI antidepressants in some studies. As a reduced effect of

tamoxifen

cannot

excluded,

co-administration

with

potent

CYP2D6

inhibitors (including fluoxetine) should whenever possible be avoided (see

section 4.4).

Alcohol: In formal testing, fluoxetine did not raise blood alcohol levels or

enhance the effects of alcohol. However, the combination of SSRI treatment

and alcohol is not advisable.

MAOI-A including linezolid and methylthioninium chloride (methylene blue):

Risk

serotonin

syndrome

including

diarrhoea,

tachycardia,

sweating,

tremor, confusion or coma. If the concomitant use of these active substances

with

fluoxetine

cannot

avoided,

close

clinical

monitoring

should

undertaken

concomitant

agents

should

initiated

lower

recommended doses (see section 4.4).

Mequitazine: risk of mequitazine adverse events (such as QT prolongation)

may be increased because of an inhibition of its metabolism by fluoxetine.

Combinations requiring caution

Phenytoin: Changes in blood levels have been observed when combined with

fluoxetine.

some

cases

manifestations

toxicity

have

occurred.

Consideration should be given to using conservative titration schedules of the

concomitant drug and to monitoring clinical status.

Serotonergic drugs (lithium, tramadol, triptans, tryptophan, selegiline (MAOI-

B), St. John's Wort (Hypericum perforatum)): There have been reports of mild

serotonin

syndrome

when

SSRIs

were

given

with

drugs

also

having

serotoninergic effect. Therefore, the concomitant use of fluoxetine with these

drugs should be undertaken with caution, with closer and more frequent

clinical monitoring (see section 4.4).

QT interval prolongation: Pharmacokinetic and pharmacodynamic studies

between fluoxetine and other medicinal products that prolong the QT interval

have not been performed. An additive effect of fluoxetine and these medicinal

products cannot be excluded. Therefore, co-administration of fluoxetine with

medicinal products that prolong the QT interval, such as Class IA and III

antiarrhythmics,

antipsychotics

(e.g.

phenothiazine

derivatives,

pimozide,

haloperidol),

tricyclic

antidepressants,

certain

antimicrobial

agents

(e.g.

sparfloxacin,

moxifloxacin,

erythromycin

pentamidine),

anti-malaria

treatment

particularly

halofantrine,

certain

antihistamines

(astemizole,

mizolastine), should be used with caution (see sections 4.4, 4.8 and 4.9).

Drugs affecting haemostasis (oral anticoagulants, whatever their mechanism,

platelets antiaggregants including aspirin and NSAIDs): risk of increased

bleeding. Clinical monitoring, and more frequent monitoring of INR with oral

anticoagulants, should be made. A dose adjustment during the fluoxetine

treatment and after its discontinuation may be suitable (see sections 4.4 and

4.8).

Cyproheptadine: There are individual case reports of reduced antidepressant

activity of fluoxetine when used in combination with cyproheptadine.

Drugs

inducing

hyponatremia:

Hyponatremia

undesirable

effect

fluoxetine.

combination

with

other

agents

associated

with

hyponatremia

(e.g.

diuretics,

desmopressin,

carbamazepine

oxcarbazepine) may lead to an increased risk (see section 4.8).

Drugs lowering the epileptogenic threshold: Seizures are an undesirable effect

of fluoxetine. Use in combination with other agents which may lower the

seizure

threshold

(for

example,

TCAs,

other

SSRIs,

phenothiazines,

butyrophenones, mefloquine, chloroquine, bupropion, tramadol) may lead to

an increased risk.

Other drugs metabolised by CYP2D6: Fluoxetine is a strong inhibitor of

CYP2D6 enzyme, therefore concomitant therapy with drugs also metabolised

by this enzyme system may lead to drug interactions, notably those having a

narrow therapeutic index (such as flecainide, propafenone and nebivolol) and

those that are titrated, but also with atomoxetine, carbamazepine, tricyclic

antidepressants and risperidone. They should be initiated at or adjusted to the

low end of their dose range. This may also apply if fluoxetine has been taken

in the previous 5 weeks.

4.6

Fertility, pregnancy and lactation

Pregnancy

Fluoxetine should not be used during pregnancy unless the clinical condition

of the woman requires treatment with fluoxetine and justifies the potential risk

to the foetus. Abrupt discontinuation of therapy should be avoided during

pregnancy (see section 4.2 “Posology and method of administration”). If

fluoxetine is used during pregnancy, caution should be exercised, especially

during late pregnancy or just prior to the onset of labour since some other

effects

have

been

reported

neonates:

irritability,

tremor,

hypotonia,

persistent crying, difficulty in sucking or in sleeping. These symptoms may

indicate either serotonergic effects or a withdrawal syndrome. The time to

occur and the duration of these symptoms may be related to the long half-life

of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days).

Epidemiological data have suggested that the use of SSRIs in pregnancy,

particular in late pregnancy, may increase the risk of persistent pulmonary

hypertension in the newborn (PPHN). The observed risk was approximately 5

cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN

per 1000 pregnancies occur.

Some epidemiological studies suggest an increased risk of cardiovascular

defects associated with the use of fluoxetine during the first trimester. The

mechanism is unknown. Overall the data suggest that the risk having an infant

with a cardiovascular defect following maternal fluoxetine exposure is in the

region

2/100

compared

with

expected

rate

such

defects

approximately 1/100 in the general population.

Breast-feeding

Fluoxetine and its metabolite, norfluoxetine, are known to be excreted in

human breast milk. Adverse events have been reported in breast-feeding

infants. If treatment with fluoxetine is considered necessary, discontinuation of

breast-feeding should be considered; however, if breast-feeding is continued,

the lowest effective dose of fluoxetine should be prescribed.

Fertility

Animal data have shown that fluoxetine may affect sperm quality (see section

5.3). Human case reports with some SSRI’s have shown that an effect on

PAR Fluoxetine 10mg Tablets

PL 20117/0152

1

Public Assessment Report

UKPAR

Fluoxetine 10mg hard capsules

(fluoxetine hydrochloride)

UK Licence Numbers: PL 20117/0152

Morningside Healthcare Ltd.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

2

LAY SUMMARY

Fluoxetine 10mg hard capsules

(fluoxetine hydrochloride, capsule, hard)

This is a summary of the Public Assessment Report (PAR) for Fluoxetine 10mg hard capsules (PL

20117/0152). It explains how Fluoxetine 10mg hard capsules was assessed and its authorisation

recommended, as well as its conditions of use. It is not intended to provide practical advice on how to

use Fluoxetine 10mg hard capsules.

The product will be referred to as Fluoxetine capsules throughout the remainder of this public

assessment report (PAR).

For practical information about using Fluoxetine capsules, patients should read the package leaflet or

contact their doctor or pharmacist.

What are Fluoxetine capsules

and what is it used for?

Fluoxetine capsules are a ‘hybrid generic medicine’. This means that it is similar to a reference medicine

containing the same active substance but is available at a lower strength (10 mg).

The reference medicine for this product is Prozac 20 mg hard capsules (Eli Lily and Company Limited).

This medicine is used for the treatment of:

Adults:

Depression

Obsessive-compulsive disorder

Bulimia nervosa (compulsive eating/purging).

Children and adolescents aged 8 years and above:

Moderate to severe major depressive disorder, if the depression does not respond to psychological

therapy after 4-6 sessions. Fluoxetine capsules should be offered to a child or young person with

moderate to severe major depressive disorder only in combination with psychological therapy.

The patient’s doctor may also prescribe this medicine for a different purpose and/or at a different dosage

from that given in the package leaflet. The patient must always follow the doctor’s prescription and the

instructions given on the label of the pack.

How do Fluoxetine capsules medicine work?

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant that influences the central

nervous system.

How are Fluoxetine capsules used?

The pharmaceutical form of this medicine is a hard capsule. The route of administration of this medicine

is oral (by mouth).

The patient must always take this medicine exactly as their doctor has told them. The patient must check

with their doctor or pharmacist if they are not sure.

Fluoxetine can be taken as a single dose or divided into several doses.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

3

The recommended dose in adults with depression is 20 mg daily. A doctor will review and adjust the

dosage if necessary within 3 to 4 weeks of the start of treatment. If required, the dosage can be gradually

increased up to a maximum of 60 mg daily.

The recommended dose in adults with bulimia nervosa is 60 mg daily. A doctor will review the need for

continuing treatment beyond 6 months (3 months for bulimia), and treatment will be reassessed if no

improvement is seen.

The recommended dose in adults with obsessive-compulsive disorder is 20 mg daily. A doctor will

review and adjust the patient’s dose if necessary after 2 weeks of treatment. If required, the dosage can

be gradually increased up to a maximum of 60 mg daily. If no improvement is noted within 10 weeks,

the patient’s doctor will reconsider their treatment.

The starting dose in children and adolescents aged 8 to 18 years with depression is 10 mg/day. After 1 to

2 weeks, a doctor may increase the dose to 20 mg/day. Lower weight children may need lower doses.

Treatment should be started and supervised by a specialist.

In older people, the patient’s doctor will increase the dose with more caution and the daily dose should

generally not exceed 40 mg.

If the patient has a liver problem, or is using other medication that might affect fluoxetine, the patient’s

doctor may decide to prescribe a lower dose or tell them to take fluoxetine every other day.

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

route of administration, and the duration of treatment.

This medicine can only be obtained with a prescription.

What benefits of Fluoxetine capsules have been shown in studies?

The Company provided data from studies to determine that Fluoxetine 20mg Capsules, hard (PL

20117/0151) which is already marketed by the same Company (Morningside Healthcare Limited) as this

application (PL 20017/0152), is bioequivalent to Prozac 20 mg hard capsules (Eli Lily and Company

Limited). Two medicines are bioequivalent when they produce the same levels of the active substance in

the body.

What are the possible side effects of this medicine?

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

The most common side effects with Fluoxetine capsules (which may affect more than 1 in 10 people) are

Difficulty or inability to sleeping (insomnia)

Headache

Diarrhoea, feeling sick (nausea)

Fatigue.

The most common side effects with Fluoxetine capsules (which may affect up to 1 in 10 people) are:

Not feeling hungry, weight loss

Anxiety, nervousness

Restlessness, poor concentration

Feeling tense

Decreased sex drive or sexual problems (including difficulty maintaining an erection for sexual

activity)

Sleep problems, unusual dreams, tiredness or sleepiness

PAR Fluoxetine 10mg Tablets

PL 20117/0152

4

Dizziness

Changes in taste

Uncontrollable shaking movements

Blurred vision

Rapid irregular heartbeat sensations

Flushing

Indigestion, vomiting

Dry mouth

Rash, urticaria, itching

Excessive sweating

Joint pain

Passing urine more frequently

Unexplained vaginal bleeding

Feeling shaky or having chills

For the full list of all side effects reported with this medicine, see section 4 of the package leaflet

available on the MHRA website.

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

Why was this medicine approved?

The MHRA decided that this medicine’s benefits are greater than its risks and recommended that it be

approved for use.

What measures are being taken to ensure the safe and effective use of Fluoxetine capsules?

A risk management plan (RMP) has been developed to ensure that Fluoxetine capsules are used as safely

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

Characteristics and the package leaflet for Fluoxetine 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/healthcare professionals will be monitored/reviewed continuously.

Other information about this medicine

The MHRA agreed to grant a marketing Authorisation for Fluoxetine capsules on 04 November 2015.

The full PAR for this medicine follows this summary.

For more information about treatment with this medicine, read the package leaflet, or contact your

doctor or pharmacist.

This summary was last updated in December 2015.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

5

TABLE OF CONTENTS

Introduction

Page 6

Quality aspects

Page 7

Non-clinical aspects

Page 8

Clinical aspects

Page 9

User consultation

Page 13

Overall conclusion, benefit/risk assessment and

recommendation

Page 13

PAR Fluoxetine 10mg Tablets

PL 20117/0152

6

I

INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the Medicines and Healthcare products

Regulatory Agency (MHRA) granted Morningside Healthcare limited, a marketing authorisation for the

medicinal product Fluoxetine capsules (PL 20117/0152). The product is a prescription-only medicine

(POM) indicated for:

Adults:

Major depressive episodes.

Obsessive-compulsive disorder.

Bulimia nervosa: Fluoxetine is indicated as a complement of psychotherapy for the reduction of

binge-eating and purging activity

.

Children and adolescents aged 8 years and above:

Moderate to severe major depressive episode if depression is unresponsive to psychological

therapy after 4–6 sessions. Antidepressant medication should be offered to a child or young

person with moderate to severe depression only in combination with a concurrent psychological

therapy.

This application was submitted under Article 10(3) of Directive 2001/83/EC, as amended, as a hybrid

application, cross-referring to Prozac 20 mg hard capsules which was originally licenced on 25

November 1988 to Eli Lily and Company Limited, UK (PL 00006/0195).

The Applicant (Morningside Healthcare Limited) already has a higher strength (20 mg) of this product

approved and marketed (Fluoxetine 20mg Capsules, hard; PL 20117/0151) and since a 10 mg reference

product has not been licenced in the EEA previously, the Applicant conducted a clinical study using

Fluoxetine 20mg Capsules, hard as the test product against Prozac 20 mg hard capsules (Eli Lily and

Company Limited, UK) as the reference product. This is acceptable.

Fluoxetine is a selective inhibitor of serotonin reuptake, and this probably accounts for the mechanism of

action. Fluoxetine has practically no affinity to other receptors such as α1-, α2-, and β-adrenergic;

serotonergic; dopaminergic; histaminergic1; muscarinic; and GABA receptors.

One bioequivalence study was submitted to support this application comparing the applicant’s higher

strength test product Fluoxetine 20mg Capsules, hard (Morningside Healthcare Limited; PL

20117/0151) with the reference product Prozac 20 mg hard capsules (Eli Lily and Company Limited,

UK) under fasting conditions. The Applicant has requested a biowaiver for the 10 mg strength. This is

acceptable since the pharmacokinetics of fluoxetine hydrochloride is linear over the therapeutic dose

range up to 40 mg. As the requirements for a biowaiver specified in the guideline on the investigation of

bioequivalence (CPMP/QWP/EWP/1401/98 Rev. 1/Corr**) have been met, the claim for a biowaiver for

the 10 mg strength capsules is justified and accepted. The applicant has stated that the bioequivalence

study was conducted in compliance with the study protocol and Good Clinical Practices (GCP)

guidelines.

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

which is acceptable given that this application was based on the product being shown to be bioequivalent

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

No new or unexpected safety concerns arose during the review of information provided by the

Marketing Authorisation Holder and it was, therefore, judged that the benefits of taking Fluoxetine

capsules outweigh the risks and a Marketing Authorisation was granted.

PAR Fluoxetine 10mg Tablets

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II

QUALITY ASPECTS

II.1

Introduction

Each capsule contains fluoxetine hydrochloride equivalent to 10 mg fluoxetine.

Other ingredients consist of the pharmaceutical excipients

pregelatinised maize starch and the capsule

shell comprised of the following components:

Capsule body and cap:

FD & C Blue 1 (E133), Yellow iron oxide (E 172), titanium dioxide (E

171), gelatin and sodium lauryl sulfate.

Printing ink:

Shellac (E904), propylene glycol (E1520), black iron oxide (E172) and potassium

hydroxide (E525).

The product is packed into PVC/aluminium blisters and is available in pack sizes of 10, 14, 20, 30, 50,

70 or 100 capsules. Not all pack sizes may be marketed. Satisfactory specifications and Certificates of

Analysis have been provided for all packaging components.

II.2.

Drug Substance

INN:

Fluoxetine hydrochloride

Chemical name:

RS

)-N-Methyl-3-phenyl-3-[4-(trifluoromethyl) phenoxy] propan-1-amine,

hydrochloride

Structural formula:

Molecular formula:

NO.HCl

Molecular mass:

345.8

Appearance:

A white or almost white, crystalline powder.

Solubility:

Sparingly soluble in water, freely soluble in methanol and sparingly soluble in

methylene chloride.

Fluoxetine hydrochloride is the subject of a European Pharmacopoeia monograph.

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

by the 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 a safe, efficacious, stable capsule

containing 10 mg fluoxetine (as hydrochloride) that is dose proportional to the formulation of the

Applicant’s approved product, Fluoxetine 20mg Capsules, hard (Morningside Healthcare Limited; PL

20117/0151) and comparable in performance to the reference product Prozac 20 mg hard capsules (Eli

Lily and Company Limited, UK).

A satisfactory account of the pharmaceutical development has been provided.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

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The excipient, pregelatinised maize starch, complies with its European Pharmacopoeia monograph and

the capsule shell is controlled to suitable in-house specifications. Satisfactory Certificates of Analysis

have been provided for all excipients. Suitable batch analysis data have been provided for each

excipient.

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 European Directorate for the

Quality of Medicines (EDQM) to show that they are 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 this product.

Manufacture of the product

A satisfactory batch formula has been provided for the manufacture of the product, along with an

appropriate account of the manufacturing process. The manufacturing process has been validated at

commercial-scale batch size and shown satisfactory results.

Finished Product Specification

The finished product specification proposed is acceptable. Test methods have been described that have

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

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

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. The data from these studies support a

shelf-life of 2 years with the storage conditions. ‘Do not store above 25ºC. Store in the original package

in order to protect from moisture.’

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

of finished product.

II.4

Discussion on chemical, pharmaceutical and biological aspects

There are no objections to the approval of this application from a pharmaceutical viewpoint.

III

NON-CLINICAL ASPECTS

III.1

Introduction

As the pharmacodynamic, pharmacokinetic and toxicological properties of fluoxetine hydrochloride are

well-known, no new non-clinical studies are required and none have been provided. An overview based

on the literature review is, thus, appropriate.

The MAH’s non-clinical expert report 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

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

9

III.3

Pharmacokinetics

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.4

Toxicology

Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.

III.5

Ecotoxicity/environmental risk assessment (ERA)

Since Fluoxetine capsules are intended for generic substitution, this will not lead to an increased

exposure to the environment. An environmental risk assessment is therefore not deemed necessary.

III.6

Discussion on the non-clinical aspects

No new non-clinical studies were conducted or necessary for this type of application.

There are no objections to the approval of this application from a non-clinical viewpoint.

IV

CLINICAL ASPECTS

IV.1

Introduction

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

the bioequivalence study detailed below, no new pharmacodynamics or pharmacokinetic data are

provided or are required for this application.

The Applicant submitted one bioequivalence study on a higher strength capsule (20 mg) to support this

application to demonstrate bioequivalence with the reference product. Based on linear pharmacokinetics

and dissolution data the Applicant has requested a biowaiver for the 10 mg strength. This is acceptable.

No new efficacy or safety studies have been performed and none are required for this type of

application. A comprehensive review of the published literature has been provided by the applicant,

citing the well-established clinical pharmacology, efficacy and safety of fluoxetine hydrochloride.

Based on the data provided, Fluoxetine 20mg Capsules, hard can be considered bioequivalent to Prozac

20 mg hard capsules (Eli Lily and Company Limited, UK).

IV.2

Pharmacokinetics

In support of this application, the Applicant submitted the following bioequivalence study:

STUDY

An open label, randomised, two-period, two-treatment, single dose, crossover study to compare

the

pharmacokinetics

of

the

applicant’s

test

product

Fluoxetine

20mg

Capsules,

hard

(Morningside Healthcare Limited; PL 20117/0151) versus the reference product,

Prozac 20 mg

hard capsules (Eli Lily and Company Limited, UK), in healthy adult subjects under fasting

conditions.

The subjects were administered a single dose (20 mg) of either the test or the reference product under

fasting conditions. Blood samples were collected for plasma levels before dosing and up to and

including 168 hours after each administration. The washout period between the treatment phases was 45

days. The pharmacokinetic results are presented below:

PAR Fluoxetine 10mg Tablets

PL 20117/0152

10

Table: Summary of geometric means and 90% confidence intervals for test and reference product for

fluoxetine.

Table: 90% Confidence interval for fluoxetine (log transformed data):

PAR Fluoxetine 10mg Tablets

PL 20117/0152

11

Conclusion

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

values for fluoxetine for the

20 mg strength 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 20 mg test product is bioequivalent to the reference product Prozac 20 mg hard

capsules (Eli Lily and Company Limited, UK).

As the 10 mg and 20 mg strength test products meet the biowaiver criteria specified in the current

bioequivalence guidance, the results and conclusions of the bioequivalence study with the 20 mg capsule

strength can be extrapolated to the 10 mg strength capsule.

IV.3

Pharmacodynamics

No new pharmacodynamic data were submitted and none were required for an application of this type.

IV.4

Clinical efficacy

No new efficacy data were submitted and none were required for an application of this type.

IV.5

Clinical safety

No new safety data were submitted and none were required for this application.

IV.6

Risk Management Plan (RMP)

The marketing authorisation holder (MAH) has submitted a risk management plan (RMP), 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 fluoxetine

hydrochloride.

A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are

listed below:

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PL 20117/0152

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Summary table of safety concerns:

PAR Fluoxetine 10mg Tablets

PL 20117/0152

13

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

IV.7

Discussion on the clinical aspects

No new clinical studies were conducted or necessary for this type of application.

There are no objections to the approval of this application from a clinical viewpoint

.

The grant of a marketing authorisation is recommended for this application.

V

User consultation

A user consultation with target patient groups on the package information leaflet (PIL) has been

performed on the basis of a bridging report making reference to Fluoxetine 20mg Capsules, hard (PL

20117/0151). The bridging report submitted by the Applicant has been found acceptable.

VI

Overall conclusion, benefit/risk assessment and recommendation

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

identified. Extensive clinical experience with fluoxetine hydrochloride is considered to have

demonstrated the therapeutic value of the compound. The benefit-risk is, therefore, considered to be

positive.

PAR Fluoxetine 10mg Tablets

PL 20117/0152

14

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

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPC) and Patient

Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for Fluoxetine capsules is presented below:

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