PACKAGE LEAFLET: INFORMATION FOR THE USER

ISOTRETINOIN 5, 10, 20 & 40 mg SOFT CAPSULES

(isotretinoin)

Read all of this leaflet carefully before you start

taking this medicine.

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

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

•    This medicine has been prescribed for you personally and you should not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects becomes serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Isotretinoin is and what it is used for.

2.    Before you take Isotretinoin.

3.    How to take Isotretinoin.

4.    Possible side effects.

5.    How to store Isotretinoin.

6.    Further information.

1.    WHAT ISOTRETINOIN IS AND WHAT IT IS USED FOR

These capsules contain isotretinoin, which is a medicine related to vitamin A. Isotretinoin is used to treat severe types of acne that can cause permanent scarring, which has not improved after other anti-acne treatments. Isotretinoin can only be prescribed by a doctor who has specialised in the treatment of severe acne.

2.    BEFORE YOU TAKE ISOTRETINOIN

Do not take Isotretinoin - if you:

•    are pregnant, think you may be pregnant or are planning a pregnancy

•    are of a child-bearing age and you are not following the Pregnancy Prevention Plan (see box 'Pregnancy and breast-feeding, important' opposite)

•    are breast-feeding

•    are allergic (hypersensitive) to isotretinoin, or allergic to peanuts or soya (Isotretinoin contains soya oil) or any of the other capsule ingredients

•    are taking certain antibiotics called tetracyclines

•    are younger than 12 years of age

•    have a severe liver disease

•    have a high level of vitamin A in your body

•    have a high level of cholesterol or triglycerides in your blood.

Please tell your doctor if any of the above statements apply to you.

Take special care with Isotretinoin - tell your doctor if:

•    you have or have had depression or other mental health problems including previous experience of suicidal behaviour

•    you have problems with your kidneys or your liver

•    you are overweight

•    you regularly drink a lot of alcohol

•    you have diabetes, check your blood glucose levels more closely throughout the period of treatment

•    you experience dryness of the skin or lips - you can apply moisturising ointments or creams to your skin and use a lip balm to reduce this effect

•    your acne suddenly gets much worse - this usually occurs within 7 to 10 days, and usually does not require dose adjustment

•    you are allergic to peanuts or soya.

Before, during and after treatment you will have regular blood tests to check that there are no changes to your kidneys, liver, cholesterol and blood sugar levels. If there are changes, your doctor may decide to reduce the dose or stop treatment.

Avoid exposure to the sun as much as possible and do not use sun lamps and UV beds. If exposure to the sun is unavoidable, use a sunscreen of at least SPF 15. Reduce the amount of intensive physical exercise as pain in your joints or muscles may sometimes occur as part of your treatment.

You may find that your skin has become dry and fragile. Avoid the use of cosmetic skin treatments, for example do not apply anything that irritates the skin, like peeling cream.

Avoid wax depilation and cosmetic procedures designed to smooth your skin or to reduce scars or aging signs (for example dermabrasion or laser therapy) for at least 6 months after the end of treatment. These procedures may cause skin scarring, colour changes or peeling of the skin.

Your eyes may become sensitive and dry throughout the treatment. Wear glasses rather than contact lenses. You may need to wear sunglasses to protect your eyes from being dazzled.

Pregnancy and breast-feeding, important:

Isotretinoin may cause serious damage (malformations, such as a large head or no ears) to your unborn child if you become pregnant during treatment or during the 5 weeks after the end of treatment. This drug may also cause a miscarriage.

You must not take Isotretinoin if:

•    you are pregnant or if you intend to be pregnant during your treatment or up to 5 weeks after treatment ends

•    you are breast-feeding. The medicine is likely to pass into your milk and may harm your baby.

Before starting treatment women of child-bearing age must discuss and agree to the following points with the doctor:

•    you have understood why you must not become pregnant

•    you have received a pregnancy prevention brochure

•    you have agreed to use at least one effective method of contraception, and preferably two, including a barrier method (condom or cap):

*    at least 1 month before starting treatment

*    during ongoing treatment

*    for 5 weeks after treatment ends.

•    you must use contraception even if you are not sexually active or if you do not have menstrual periods

•    you understand and agree the need for monthly follow-up visits and for medically supervised pregnancy tests

*    1 month before starting treatment. The test is conducted during the first 3 days of the menstrual cycle (period)

*    each month during the treatment

*    5 weeks after stopping it.

The result of each test must be negative: You must not become pregnant at any time during treatment or up to 5 weeks following the end of treatment.

•    you must sign (yourself or the adult responsible for you) a consent form concerning treatment and contraception, confirming that:

*    you have been informed of the risks associated with Isotretinoin treatment

*    you agree to comply with the Pregnancy Prevention Plan.

Information for male patients - Isotretinoin treatment does not damage sperm. Isotretinoin and its metabolites are present in very low levels in your sperm. These levels are too low to harm the unborn baby of your female partner.

You must remember not to share your medication with anyone, particularly not females.

Do not donate blood - Do not donate blood during treatment and for 5 weeks after the end of treatment. If a pregnant woman were to receive your blood, her baby could be seriously damaged.

Taking other medicines - Please tell your doctor or your pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

It is very important to tell your doctor if you are taking any medicine containing vitamin A.

Driving and using machines - Be careful when driving or using machines at night because this treatment may affect your night vision. This can happen suddenly. It rarely continues once treatment has ended.

Important information about some ingredients of Isotretinoin - This drug contains soya-bean oil. Do not take this medicine if you are allergic to peanuts or soya.

3. HOW TO TAKE ISOTRETINOIN

Always take Isotretinoin as your doctor has told you. You should check with your doctor or your pharmacist if you are not sure. Your dosage is calculated individually based on your body weight and may be adjusted by your doctor during treatment.

The usual starting dose is 0.5 mg/kg per day, however your doctor will determine your individual requirements.

The capsules should be taken once or twice a day with food. Swallow the capsules whole without chewing or sucking them.

Normally treatment lasts from 16 to 24 weeks.

You should always complete your course of treatment. Your skin may continue to improve for up to 8 weeks after the end of treatment. Most patients only need one course of treatment.

Your doctor will review your dose after a few weeks of treatment to determine if an adjustment is required. Doses are usually within the range of 0.5 - 1.0 mg/kg per day. If you have problems with your kidneys then your doctor will give you a lower dose.

If your doctor wishes you to have further treatment, you should wait for a period of 8 weeks before beginning a new course of treatment.

If you are not able to tolerate the recommended dose, your doctor will reduce the dose you receive and your treatment will last longer.

If you take more Isotretinoin than you should -

If you have taken more capsules than you should, you may suffer from excessively high levels of vitamin A. The signs and symptoms include intense headaches, nausea or vomiting, sleepiness, irritability and itching. Contact your doctor, your pharmacist or the nearest hospital as soon as possible. Take the container and any remaining capsules with you.

If you forget to take Isotretinoin - Skip the missed dose and take the next dose as normal.

Do not take a double dose to make up for the forgotten dose.

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

4. POSSIBLE SIDE EFFECTS

Like all medicines, Isotretinoin can cause side effects, although not everybody experiences these.

These are rare but serious side effects. If any of the following happen, stop taking Isotretinoin and tell your doctor or seek medical advice immediately:

•    depression or worsening of depression (sadness, anxiety, becoming easily angered, aggression, irritability, loss of concentration, sleeping too much or too little, changes in weight or appetite, changes in mood or abnormal behaviour)

•    thinking about harming yourself or thinking about committing suicide

•    any other side effect related to your mental health (such as hearing voices or seeing things that are not there)

•    persistent headache with nausea, vomiting or visual disorders, drowsiness. This may occur commonly with certain antibiotics (tetracyclines)

•    violent pain in the abdomen, with or without bloody diarrhoea, nausea and vomiting

•    blurred vision or if you experience any difficulty in seeing

•    severe allergic reaction (anaphylaxis) causing difficulty breathing, dizziness, collapse, shock, severe itching and/or swelling

•    serious skin rash (erythema multiforme) appearing initially as circular patches often with a central blister usually on arms and hands or legs and feet but can affect any part of the body.

The other possible side effects are:

Very common (more than 1 in 10 patients):

•    dry or chapped skin, particularly on the face and lips

•    red and fragile skin, rash or mild itching or mild shedding of skin or a combination of these symptoms

•    dryness of the eyes, redness or dried crusts

•    eye irritation or conjunctivitis - causing itching and redness

•    swelling of the eyelids

•    back, muscle or joint pains

•    you may bruise or bleed more easily

•    change in liver function, which will be detected by blood tests given by your doctor

•    looking pale, feeling unusually tired

•    your blood tests show a decrease in high density lipoproteins (linked to cholesterol levels) or an increase of blood triglycerides.

Common (less than 1 in 10 patients):

•    headaches

•    nasal dryness, nosebleeds

•    symptoms of colds and flu, e.g. sore throat, runny nose, nasal congestion, sneezing and cough

•    increased levels of blood glucose with thirst and increased urination

•    increased levels of cholesterol (except HDL)

•    presence of proteins or blood in the urine

•    change in the number of white blood cells that can make you more prone to developing an infection.

Rare (less than 1 in 1,000 patients):

•    hair loss (your hair should become normal again when treatment is over)

•    allergic skin reactions causing rash, itching and swelling.

Very rare (less than 1 in 10,000 patients):

•    sudden chest tightness and possible difficulty breathing (bronchospasm), particularly in patients with asthma

•    dry throat which may cause hoarseness

•    slight hearing loss

•    inflammation of the kidneys - difficulty urinating or even inability to urinate together with swollen eyelids and severe tiredness

•    increased levels of blood sugar

•    high levels of uric acid in the blood

•    increased levels of blood creatine phosphokinase

•    dark urine, pale stools, yellowing of the eyes and the skin, nausea, fever and severe tiredness (Hepatitis)

•    swelling of lymph glands

•    your acne may get worse at the beginning of treatment. However, this should improve as you continue treatment

•    increased skin pigmentation

•    skin inflamed, swollen and darker than usual, especially on the face

•    increased sensitivity to the sun during treatment

•    excessive sweating

•    bacterial infections at the base of the nails, with swelling, redness or a discharge of pus

•    nail changes

•    increased body hair

•    changes in the texture of your hair, thickening of the hair. Your hair should become normal again when treatment is over

•    poor night vision. This can happen quite suddenly

•    changes in colour vision

•    intense eye irritation, swelling of the cornea (keratitis) and cataracts

•    irritation while wearing contact lenses

•    abnormal sensitivity to light. You may need sunglasses to protect your eyes from being dazzled

•    redness, pain, swelling of blood vessels

•    convulsions or seizures

•    diabetes (causing increased level of blood glucose with thirst and increased urination)

•    blurred vision, difficulty seeing, headaches and even a loss of vision

•    severe acne

•    a rash or abnormal reddening on the face

•    widespread rash

•    small, dull, red skin growths in the mouth and nose

•    arthritis, bone changes (for example, delayed growth, changes to bone density, abnormal bone growths)

•    swelling of tendons and ligaments. Symptoms include stiffness, swelling, ache, pain of the joint.

If you experience pain in your joints or muscles, reduce the amount of physical activity and exercise you do during your treatment.

If any of the side effects gets serious, or if you notice any side effect not listed in this leaflet, please tell your doctor or pharmacist.

5.    HOW TO STORE ISOTRETINOIN

Keep out of the reach and sight of children.

Do not use after the expiry date stated on the box. This is given after the letters 'EXP'. The expiry date refers to the last day of that month. Do not store above 25°C. Store in the original packaging. When you have finished your treatment, you must return all the remaining capsules to your pharmacist. Do not dispose yourself via wastewater or household waste. These measures will help to protect the environment.

6.    FURTHER INFORMATION

What Isotretinoin 5 mg, 10 mg, 20 mg, 40 mg soft capsules contain - The active substance is:

For a soft capsule of 5 mg: isotretinoin 5 mg For a soft capsule of 10 mg: isotretinoin 10 mg For a soft capsule of 20 mg: isotretinoin 20 mg For a soft capsule of 40 mg: isotretinoin 40 mg. The other ingredients are: soya-bean oil, hydrogenated vegetable oil and beeswax yellow. Composition of the capsule shell of 5 mg, 20 mg and 40 mg: gelatin, glycerol, purified water, red iron oxide (E172), yellow iron oxide (E172) and titanium dioxide (E171).

Composition of the capsule shell of 10 mg: gelatin, glycerol, purified water and red iron oxide (E172).

What Isotretinoin 5 mg, 10 mg, 20 mg, 40 mg soft capsules look like and contents of the pack -

Each Isotretinoin 5 mg soft capsule has a bi-coloured opaque red/brown and cream gelatin shell, with a bright yellow/orange fill. The capsule is printed on one side in black ink with the logo '5'.

Each Isotretinoin 10 mg soft capsule has a red/brown gelatin shell, with a bright yellow/orange fill. The capsule is printed on one side in black ink with the logo 'I 10'.

Each Isotretinoin 20 mg soft capsule has a bi-coloured opaque red/brown and cream gelatin shell, with a bright yellow/orange fill. The capsule is printed on one side in black ink with the logo 'I 20'.

Each Isotretinoin 40 mg soft capsule has an orange/brown opaque gelatin shell, with a bright yellow/orange fill. The capsule is printed on one side in black ink with the logo 'I 40'.

There are 30 capsules in each box.

Marketing Authorisation Holder: Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom.

Manufacturer: Catalent France Beinheim S.A.,

74 rue Principale, 67930 Beinheim, France.

This leaflet was last approved in: 10/2010    286355 10002619