Package leaflet: Information for the user

Isotretinoina Difa Cooper 10 mg soft capsules, 20 mg soft capsules

Isotretinoin
Equivalent medicinal product
WARNING
CAN SERIOUSLY HARM THE FETUS
Women must use effective contraceptive methods
Do not use if you are or think you may be pregnant
This medicine is subject to additional monitoring. This will allow rapid
identification of new safety information. You can help by reporting any
adverse reactions you experience while taking this medicine.
See the end of section 4 for information on how to report adverse reactions.
Please read all of this leaflet carefully before taking this medicine
because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it may be harmful even if their symptoms are similar to yours.
If you experience any adverse reaction, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Isotretinoina Difa Cooper is and what it is used for
What you need to know before taking Isotretinoina Difa Cooper
How to take Isotretinoina Difa Cooper
Possible side effects
How to store Isotretinoina Difa Cooper
Contents of the pack and other information

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

Isotretinoin Difa Cooper contains the active substance isotretinoin, which is similar to Vitamin A. Isotretinoin acts against acne by reducing the activity of the sebaceous glands, preventing the formation of blackheads, and inhibiting skin inflammatory processes.
Isotretinoin Difa Cooper is used for the treatment of severe forms of acne (such as nodular acne, conglobate acne, or acne with risk of permanent scarring) that are resistant to standard appropriate therapies with oral antibiotics and topical treatment.

2. What you need to know before using Isotretinoin Difa Cooper

Treatment with Isotretinoin Difa Cooper must be prescribed and supervised by
a physician (preferably a specialist in skin disorders). The doctor provides all patients with an information guide and, in addition, for female patients, a guide on contraceptive methods. If these guides have not been provided or if the following precautionary measures have not been explained or fully understood, speak to your doctor before starting treatment.
Do not use Isotretinoin Difa Cooper

If you are pregnant or breastfeeding.
If there is any possibility you could become pregnant, you must follow the precautions outlined in the “Pregnancy Prevention Programme” in the section “Warnings and Precautions”.
If you are potentially fertile and do not meet all the conditions regarding contraception (birth control) (see “Warnings and precautions”).
If you have liver disease (hepatic insufficiency).
If you have excessively high levels of lipids in the blood.
If you have excessively high levels of vitamin A in the body (hypervitaminosis A).
If you are allergic to isotretinoin, soy, peanuts, the colouring Ponceau 4R (E124), or any of the excipients of this medicine (listed in section 6).
If you are taking tetracyclines (antibiotics).

Warnings and precautions
Pregnancy Prevention Programme
Pregnant women must not use Isotretinoin Difa Cooper
This medicine can severely harm the foetus (it is said to be “teratogenic”) – it can cause birth defects affecting the brain, face, ears, eyes, heart, and certain glands (thymus and parathyroid glands). It may also likely induce abortion. This can occur even if Isotretinoin Difa Cooper is used for only a short time during pregnancy.

Do not use Isotretinoin Difa Cooper if you are pregnant or think you might be pregnant.
Do not use Isotretinoin Difa Cooper if you are breastfeeding. The medicine may pass into breast milk and harm the newborn.
Do not use Isotretinoin Difa Cooper if you can become pregnant during treatment.
Do not become pregnant for one month after completing this treatment, as some medicines may remain in your body.

For women who could become pregnant, Isotretinoin Difa Cooper is prescribed
under very strict rules due to the risk of harm to the foetus.
These rules are:

Your doctor must explain the risk of foetal harm – you must understand that you must not become pregnant and what is required to prevent pregnancy.
Your doctor must discuss contraception (birth control) with you. Your doctor will provide information on how to avoid pregnancy and may refer you to a specialist for contraceptive counselling.
Before starting treatment, your doctor will instruct you to take a pregnancy test. The test must confirm that you are not pregnant when starting treatment with Isotretinoin Difa Cooper.

Women must use effective contraception before, during, and after using
Isotretinoin Difa Cooper

You must agree to use at least one highly reliable contraceptive method (e.g. an intrauterine device or contraceptive implant) or two effective methods that work in different ways (e.g. hormonal oral contraceptive and a condom). Discuss with your doctor which method may be suitable for you.
You must use contraception for one month before starting Isotretinoin Difa Cooper, throughout treatment, and for one month after stopping treatment.
You must use contraception even if you do not have periods or are not sexually active (unless your doctor advises otherwise).

Women must agree to undergo pregnancy testing before, during, and after
using Isotretinoin Difa Cooper

You must agree to regular follow-up visits, preferably every month.
You must agree to regular pregnancy tests, preferably every month during treatment and, since some medicines may remain in your body, one month after stopping Isotretinoin Difa Cooper (unless your doctor decides this is not necessary in your case).
You must agree to additional pregnancy tests if requested by your doctor.
You must not become pregnant during treatment or within one month after stopping, as some medicines may remain in your body.
Your doctor will discuss all these points with you using a checklist and will ask you (or a relative/guardian) to sign it. This document confirms that the risks have been communicated and that you agree to follow the rules outlined above.

If you become pregnant while taking Isotretinoin Difa Cooper, stop taking this
medicine immediately and contact your doctor. Your doctor may refer you to a specialist for consultation.
Additionally, if you become pregnant within one month after stopping Isotretinoin Difa Cooper, you must contact your doctor. Your doctor may refer you to a specialist for consultation.
Advice for men
Levels of oral retinoids in the semen of men taking Isotretinoin Difa Cooper are too
low to harm their partner’s foetus. However, you must never share your medicine
with anyone.
Additional precautions
Never give this medicine to anyone else. Return any unused capsules to the
pharmacist at the end of treatment.
Do not donate blood during treatment with this medicine and for 1 month after
stopping Isotretinoin Difa Cooper, as if a pregnant woman were to receive your
blood, it could harm her foetus.
Talk to your doctor before taking Isotretinoin Difa Cooper

If you have a history of mental health problems, including depression, aggressive tendencies, or mood changes. This includes thoughts of self-harm or suicide. Your mood may change while taking Isotretinoin Difa Cooper.

Mental health problems
You may not notice certain changes in your mood and behaviour, so it is very important that you inform your friends and family that you are taking this medicine. They may observe these changes and help you promptly identify issues that need to be discussed with your doctor.

Skin Acne may sometimes worsen suddenly during the initial phase of treatment. However, this usually resolves within 7–10 days with continued treatment and generally does not require dose adjustment.
Avoid prolonged exposure to sunlight or UV radiation. If necessary, use adequate protective measures (long clothing, hats, a high sun protection factor sunscreen of at least 15). Avoid sunlamps and solariums.
Avoid aggressive dermabrasion (chemical or laser therapy) during treatment and for 5–6 months after treatment due to the risk of deep scarring, skin irritation, and inflammatory pigment changes (increased or decreased pigmentation).
Avoid using depilatory wax for at least 6 months after treatment due to the risk of skin tearing.
Avoid concomitant use of Isotretinoin Difa Cooper and any other anti-acne medicines with keratolytic or exfoliating action, as this may increase skin irritation (see “Other medicines and Isotretinoin Difa Cooper”). Use of a moisturising ointment or cream and a lip balm is recommended from the start of treatment, as treatment with Isotretinoin Difa Cooper may cause dryness of the skin and lips.
Eyes Night vision may be affected (night blindness), and this may occur without warning. Exercise caution when driving or operating machinery (see “Driving and use of machines”). An ophthalmological examination is recommended for patients experiencing any visual disturbances. It may be necessary to discontinue treatment with Isotretinoin Difa Cooper. Dry eyes, blurred vision, and corneal inflammation may also occur, which usually resolve after treatment ends. Dry eyes can be treated with lubricating eye ointments or artificial tears. Contact lens intolerance may occur, so patients wearing contact lenses may need to switch to glasses during treatment.
Musculoskeletal system Muscle and joint pain and increased blood levels of creatine phosphokinase may occur, especially in those who engage in intense physical activity (see section 4 “Possible side effects”). Caution and reduced physical activity are advised during treatment with Isotretinoin Difa Cooper.
Liver and biliary system Isotretinoin Difa Cooper may increase liver enzyme levels; your doctor will perform blood tests before, during, and after treatment to monitor liver function. If liver enzyme levels remain elevated, your doctor may reduce the dose or discontinue treatment with Isotretinoin Difa Cooper.
Blood lipid levels Inform your doctor if you have high blood lipid levels, as Isotretinoin Difa Cooper may increase levels of fats (such as triglycerides or cholesterol) in the blood. Your doctor will perform blood tests to monitor these levels before, during, and after treatment. Elevated blood lipid levels usually return to normal with dose reduction or discontinuation of treatment and may also resolve with dietary changes. Isotretinoin Difa Cooper must be discontinued if these levels become too high or if signs of pancreatitis occur.
Kidneys Inform your doctor if you have impaired kidney function, as dose adjustment may be necessary (see section 3 “How to use Isotretinoin Difa Cooper”).

The following patients have a higher risk of experiencing side effects
Patients with diabetes, overweight, high alcohol consumption, or lipid metabolism disorders should inform their doctor, as their health status must be closely monitored and frequent checks of blood lipid levels and/or blood glucose levels may be required.
During treatment with isotretinoin, fasting blood glucose levels may increase, and new-onset diabetes has been reported.
Children
Isotretinoin Difa Cooper is not indicated for the treatment of prepubertal acne and must not be taken by children under 12 years of age.
You must immediately stop treatment and promptly consult your doctor if you
experience any of the following symptoms:

Nausea, vomiting, upper abdominal pain, as these may be signs of pancreatitis
Headache, nausea, vomiting, visual disturbances, as these may be signs of increased intracranial pressure
Severe diarrhoea with blood, severe abdominal pain and/or cramps, as these may be signs of severe intestinal inflammation
Severe hypersensitivity reactions, such as rash, often accompanied by blue and red patches, itching, facial and limb swelling, breathing difficulties, circulatory symptoms, sometimes including collapse.

Other medicines and Isotretinoin Difa Cooper
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The following medicines must not be used during treatment with Isotretinoin Difa Cooper:

Vitamin preparations containing vitamin A due to the risk of overdose (see “Do not use Isotretinoin Difa Cooper”).
Tetracyclines (an antibiotic) due to the risk of increased intracranial pressure (see “Do not use Isotretinoin Difa Cooper”).
Other anti-acne medicines with keratolytic or exfoliating action on the skin surface, as this may increase skin irritation (see “Warnings and precautions”).

Isotretinoin Difa Cooper with food and drink
Capsules must be taken with food.
Pregnancy, breastfeeding and fertility

Isotretinoin Difa Cooper must not be taken during pregnancy
Isotretinoin Difa Cooper must not be taken during breastfeeding because isotretinoin probably passes into breast milk and may harm the infant.

For further information on pregnancy and contraception, see section 2 of the “Pregnancy Prevention Programme”.
Driving and use of machines
Night vision may be affected (night blindness), and this may occur without warning. In rare cases, this problem may persist after treatment ends. Exercise caution when driving or operating machinery. Very rarely, drowsiness, dizziness, and visual disturbances have been reported. If you experience these symptoms, you must not drive, operate machinery, or engage in other activities where these symptoms could endanger yourself or others (see “Warnings and precautions” and section 4 “Possible side effects”).
Isotretinoin Difa Cooper contains sorbitol
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Isotretinoin Difa Cooper contains Ponceau 4R (E124)
This medicine contains the colouring Ponceau 4R (E124), which may cause allergic reactions.

3. How to use Isotretinoin Difa Cooper

Always use this medicine exactly as directed by your doctor, who will determine how many capsules should be taken daily. If you have any doubts, consult your doctor or pharmacist.

Recommended dose

Dosing in adults, adolescents and elderly patients
The usual starting dose is 0.5 mg/kg per day. After several weeks, your doctor may adjust the dose depending on your response to treatment and the occurrence of adverse effects. For most patients, the dose ranges between 0.5 and 1.0 mg/kg per day.

Patients who do not tolerate Isotretinoin Difa Cooper at the recommended dose
In patients who do not tolerate the recommended dose, your doctor may decide to continue treatment at a reduced dose. In such cases, treatment duration will be longer and there may be a higher risk of relapse.

Patients with severe renal impairment
In patients with severe kidney problems, treatment with Isotretinoin Difa Cooper should be initiated at a reduced dose, for example 10 mg/day. The dose should then be increased up to the maximum dose tolerated by the patient.

Method of administration
The capsules should be taken once or twice daily with food. Swallow the capsules whole; do not chew or suck them.

Duration of treatment
The duration of treatment depends on the daily dose and is generally 16–24 weeks.
Acne may continue to improve for up to 8 weeks after the end of treatment. Therefore, a new treatment cycle should not be started until at least this period has passed. Most patients require only a single course of treatment.

If you take more Isotretinoin Difa Cooper than you should
If you take too many capsules or if someone accidentally takes this medicine, contact your doctor, pharmacist or the nearest hospital immediately.

If you forget to take Isotretinoin Difa Cooper
If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten dose.

If you stop using Isotretinoin Difa Cooper
Do not stop treatment without consulting your doctor, as acne may recur.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects,
although not everyone experiences them.
Some of the side effects associated with isotretinoin use are dose-related. Side effects are generally reversible after dose adjustment or discontinuation of treatment; however, some may persist after stopping therapy.
The following symptoms are the most commonly reported side effects of isotretinoin:
dry skin, dryness of mucous membranes such as lips (cheilitis), nasal mucosa (nosebleeds), and eyes (conjunctivitis).
Side effects are listed below according to their frequency of occurrence:

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

Anaemia, increased erythrocyte sedimentation rate, increase or decrease in platelet count
Eye inflammation (conjunctivitis) and eyelid area inflammation (blepharitis), dry eyes, eye irritation
Increased liver enzyme levels (transaminases) (see section 2 “Warnings and precautions”)
Inflammation of lips and skin, dry skin, peeling of skin and mucous membranes, itching, skin redness, increased skin susceptibility to injury (risk of friction trauma)
Muscle or joint pain, back pain (particularly in children and adolescent patients) (see section 2 “Warnings and precautions”)
Increased blood lipid levels, reduced HDL cholesterol

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

Decreased white blood cell count (neutropenia)
Headache
Nosebleeds, dry nose, inflammation of nose and throat
Increased blood cholesterol, increased blood sugar levels, presence of blood or protein in urine

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

Skin allergic reactions, hypersensitivity reactions, including occasionally shock (anaphylactic reactions)
Increased hair loss

Very rare (may affect up to 1 in 10,000 people):

Skin and mucosal infections caused by certain bacteria (Gram-positive)
Swollen lymph nodes (lymphadenopathy)
Diabetes mellitus, increased blood uric acid
Increased pressure in the brain (benign intracranial hypertension) (see section 2 “Warnings and precautions”), seizures, drowsiness, dizziness
Blurred vision, cataract, colour blindness (difficulty seeing colours), intolerance to contact lenses, corneal opacity, night blindness, corneal inflammation, optic nerve swelling (papilledema, which may be associated with visual disturbances as a sign of increased brain pressure), light sensitivity, visual disturbances
Hearing impairment
Inflammation of blood vessels (e.g. Wegener's granulomatosis, allergic vasculitis)
Sudden chest tightness with shortness of breath and dyspnoea (bronchospasm, particularly in asthmatic patients) (see section 2 “Warnings and precautions”), hoarseness
Inflammatory bowel diseases (colon, ileum), dry throat, gastrointestinal tract bleeding, bloody diarrhoea, nausea, pancreatitis (see section 2 “Warnings and precautions”)
Liver inflammation (hepatitis)
Severe acne (acne fulminans), worsening of acne, inflammatory skin changes (skin redness (facial), rash), hair changes, increased body hair, nail changes, inflammation of tissue surrounding the nails, photosensitivity, development of skin nodules (pyogenic granuloma), skin hyperpigmentation, increased sweating
Joint inflammation, calcium deposition in ligaments and tendons, premature epiphyseal fusion, bone overgrowth (exostoses), reduced bone density, tendon inflammation, muscle weakness
Kidney disorders (glomerulonephritis)
Increased connective tissue formation (granulation tissue), feeling unwell
Increased blood creatine phosphokinase levels

Not known (frequency cannot be estimated from available data):

Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) which are potentially life-threatening and require immediate medical attention. These symptoms initially appear as circular spots, often with central blisters, usually on arms and hands or legs and feet; more severe rashes may include blisters on chest and back. Additional symptoms may include eye infections (conjunctivitis) or ulcers in mouth, throat or nose. Severe forms of rash may progress to widespread skin peeling, which can be fatal. These are often preceded by headache, fever, muscle pain (flu-like symptoms). If you develop a rash or these skin symptoms, stop treatment with Isotretinoina Difa Cooper and contact your doctor immediately.
Difficulty achieving or maintaining an erection
Decreased libido
Breast enlargement with or without tenderness in men

Mental health problems
Rare side effects (may affect up to 1 in 1,000 people):

Depression or related disorders. Symptoms include sadness or mood changes, anxiety, feelings of emotional discomfort
Worsening of pre-existing depression
Becoming violent or aggressive

Very rare side effects (may affect up to 1 in 10,000 people):

Some people have had thoughts or intentions of harming themselves or ending their life (suicidal ideation), attempted suicide, or died by suicide. These individuals may not appear depressed.
Unusual behaviour.
Signs of psychosis: loss of contact with reality, such as hearing voices or seeing things that are not there.

Contact your doctor immediately if you experience any of these mental health symptoms. Your doctor may advise you to stop taking Isotretinoina Difa Cooper. This may not be sufficient to stop the effects: you may need further help, which your doctor can provide.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. Side effects can also be reported directly via the national reporting system at the website
www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-
avversa.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Isotretinoin Difa Cooper

Do not store above 30°C. Keep in the original packaging to protect the medicine from moisture and light.
Keep this medicine out of the sight and reach of children.
Return unused capsules to the pharmacist.
Do not use this medicine after the expiry date stated on the outer carton and blister. The expiry date refers to the last day of that month.

6. Package contents and other information

What Isotretinoin Difa Cooper contains
The active substance is isotretinoin.
10 mg strength
Each soft capsule contains 10 mg of isotretinoin.
20 mg strength
Each soft capsule contains 20 mg of isotretinoin.
The excipients are:
Capsule contents: Refined soybean seed oil, DL-alpha-tocopherol, disodium edetate, butylated hydroxyanisole, hydrogenated vegetable oil, partially hydrogenated soybean seed oil, yellow wax.
Capsule shell
10 mg strength: gelatin, glycerol 98–101%, sorbitol 70%, purified water, Ponceau 4R (E 124), black iron oxide (E 172) and titanium dioxide (E 171).
20 mg strength: gelatin, glycerol 98–101%, sorbitol 70%, purified water, Ponceau 4R (E 124), indigo carmine (E 132) and titanium dioxide (E 171).

Description of the appearance of Isotretinoin Difa Cooper and package contents:
10 mg strength: elongated soft purple capsules containing an opaque yellow/orange viscous liquid. The soft capsule is 10 mm long.
20 mg strength: elongated soft brown capsules containing an opaque yellow/orange viscous liquid. The soft capsule is 12 mm long.
Pack sizes: 20, 30, 50, 60 or 100 soft capsules.

Marketing Authorization Holder
Difa Cooper S.p.A.
Via Milano 160
21042 Caronno Pertusella (Varese)
Italy

Manufacturer

Merckle GmbH, Graf-Arco Strasse 3, D-89079 Ulm, Germany
Merckle GmbH, Ludwing Merckle Strasse 3, D-89143 Blaubeuren, Germany
TOLL MANUFACTURING SERVICES, S.L., Aragoneses 2, 28108, Alcobendas, Madrid, Spain
Industrial Farmacéutica Cantabria, S.A., C/ Pirita, 9, 28850 Torrejón de Ardoz (Madrid), Spain

This medicinal product is authorized in the European Economic Area countries under the following names:
10 mg strength
Denmark Isotretinoin Teva
Germany Isotretinoin-ratiopharm 10 mg Weichkapseln
Italy Isotretinoina Difa Cooper 10 mg soft capsules
20 mg strength
Denmark Isotretinoin Teva
Germany Isotretinoin-ratiopharm 20 mg Weichkapseln
Italy Isotretinoina Difa Cooper 20 mg soft capsules