Isoriac

Package leaflet: Information for the user

ISORIAC 10 mg soft capsules, 20 soft capsules

Isotretinoin
Generic medicine
WARNING
CAN CAUSE SEVERE HARM TO THE UNBORN CHILD.
Women must use effective contraception.
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 side effects you experience
while taking this medicine. See the end of section 4 for information on how to report
side effects.
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:
1 – What ISORIAC 10 mg, 20 mg soft capsules (hereinafter referred to as ISORIAC) is and what it is used for
2 – What you need to know before taking ISORIAC
3 – How to take ISORIAC
4 – Possible side effects
5 – How to store ISORIAC
6 – Contents of the pack and other information

1. What ISORIAC is and what it is used for

ISORIAC contains isotretinoin, which is the active substance and belongs to a class of
medicines known as retinoids.
ISORIAC is indicated 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 both standard
therapy with oral antibiotics and topical treatment (cream, gel, ointment, or lotion).
ISORIAC must be prescribed only by, or under the supervision of, physicians experienced in
the use and monitoring of retinoids for the treatment of severe acne.
ISORIAC is not indicated for the treatment of acne in prepubertal patients and is not
recommended for patients under 12 years of age.

2. What you should know before taking ISORIAC

Do not take ISORIAC

• If you are pregnant or breastfeeding.
• If there is any possibility that you could become pregnant, you must follow the precautions outlined in the “Pregnancy Prevention Programme”; see section “Warnings and precautions”.
• If you are allergic to isotretinoin or to any of the other ingredients of this medicine (listed in section 6), especially peanuts or soy.
• If you have hepatic insufficiency (severe liver disease).
• If you have hypervitaminosis A (very high levels of vitamin A in the body).
• If you have high levels of lipids in the blood (cholesterol, triglycerides).
• If you are taking an antibiotic belonging to the tetracycline family.
• If you are taking vitamin A or other retinoids (acitretin, alitretinoin).

Warnings and precautions
Talk to your doctor or pharmacist before taking ISORIAC:

• If you have had mental health problems, including depression, aggressive tendencies or mood changes, including thoughts of self-harm or ending your life. This is because your mood may change while taking ISORIAC.
• If you have kidney problems. Your doctor may adjust the isotretinoin dosage.
• If you are overweight or have diabetes mellitus, high cholesterol or triglyceride levels, or if you consume large amounts of alcohol. In these cases, increased levels of lipids and glycerides in the blood may occur. If any of these conditions apply, your doctor may prescribe periodic blood tests. Monitor your blood glucose levels closely throughout treatment if you have diabetes mellitus.
• If you have liver problems.

ISORIAC may increase transaminase levels (liver enzymes). Your doctor will order periodic blood tests before and during treatment to monitor liver function.
Persistently elevated enzyme levels may lead your doctor to reduce the dose of ISORIAC or discontinue treatment.

• If you have or have had intestinal disorders.

Stop treatment immediately and consult a doctor promptly if:

• You become pregnant during treatment or within one month after stopping treatment.
• You experience:
  • Difficulty breathing, itching and/or skin rash. These symptoms may indicate an allergic reaction.
  • Headache with nausea, vomiting or reduced vision.
  • Severe stomach pain, nausea or vomiting, or severe diarrhoea with blood in the stool.
  • Difficulty urinating or inability to urinate.
  • Reduced night vision and/or visual disturbances.
  • Mental health problems: particularly signs of depression (deep feelings of sadness or crying spells, thoughts of harming yourself (self-harm), or withdrawing (self-isolation) from family or friends).
• You may not notice certain changes in your mood or behaviour. It is very important to inform your friends and family that you are taking this medicine. They may observe these changes and help you identify problems that need to be discussed with your doctor.
• You notice yellowing of the eyes or skin, or feel dizzy.

Special warnings for female patients:
Pregnancy and breastfeeding, Important
Pregnancy Prevention Programme
Pregnant women must not take ISORIAC.
This medicine can severely harm the foetus (it is said to be “teratogenic”) – it may cause
birth defects affecting the brain, face, ears, eyes, heart, and certain glands (thymus and
parathyroid glands). It may also potentially cause miscarriage. This can occur
even if ISORIAC is taken for only a short time during pregnancy.

• Do not take ISORIAC if you are pregnant or think you might be pregnant.
• Do not take ISORIAC if you are breastfeeding. The medicine can pass into breast milk and harm the newborn.
• Do not take ISORIAC if you could 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, ISORIAC is prescribed under very strict rules
due to the risk of fetal harm.
These rules are:

• Your doctor must explain the risk of fetal 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. Your doctor may refer you to a specialist for contraceptive counselling.
• Before starting treatment, your doctor will require you to take a pregnancy test. The test must confirm that you are not pregnant when starting ISORIAC treatment.

Women must use an effective contraceptive method before, during, and after taking ISORIAC.

• 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 condom). Discuss with your doctor which method is suitable for you.
• You must use contraception for one month before starting ISORIAC, 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 tests before, during, and after taking ISORIAC.

• You must agree to regular follow-up visits, preferably monthly.
• You must agree to regular pregnancy tests, preferably monthly during treatment and for one month after stopping ISORIAC (unless your doctor decides otherwise in your case), as some medicines may remain in your body.
• 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 treatment, 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 explained to you and that you agree to follow the above rules.

If you become pregnant while taking ISORIAC, 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 ISORIAC, contact your doctor. Your doctor may refer you to a specialist for consultation.

Advice for men
The levels of oral retinoids in the semen of men taking ISORIAC 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. At the end of treatment, return any unused capsules to your pharmacist.
Do not donate blood during treatment with this medicine or for 1 month after stopping ISORIAC, as if a pregnant patient were to receive your blood, it could harm her foetus.

Children
Do not give this medicine to children under 12 years of age, as it is not known whether it is safe or effective in this age group and it is not indicated for prepubertal acne.

Other medicines and ISORIAC
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Do not take any medicine containing vitamin A or tetracyclines during therapy with ISORIAC.
Concomitant use of isotretinoin with topical keratolytics or anti-acne exfoliating agents should be avoided, as it may increase local irritation.

Pregnancy, breastfeeding and fertility
For further information on pregnancy and contraception, see section 2 of the “Pregnancy Prevention Programme”.

Driving and using machines
Be cautious when driving or operating machinery at night; night vision may be reduced during therapy, sometimes suddenly.
Visual disturbances rarely persist after discontinuation of therapy.

ISORIAC contains soybean oil:
If you are allergic to peanuts or soy, do not use this medicine.

Daily life advice:

• Apply moisturizing ointments or creams to the skin and use a lip balm during therapy if you experience dry skin or lips.
• In general, avoid applying irritating products to the skin (e.g. peeling creams) during therapy.
• Avoid excessive sun exposure: ISORIAC may increase sun sensitivity during treatment.
• However, if sun exposure cannot be avoided, apply a sunscreen cream (with a protection factor of at least 15).
• Do not use UV lamps, sunbeds or solariums.
• Avoid wax hair removal during treatment and for at least 6 months after stopping treatment. Also avoid surgical dermabrasion or laser therapy (cosmetic procedures intended to smooth the skin to reduce scars or signs of ageing). These procedures may cause skin scarring, hypo-/hyperpigmentation (decoloration or increased pigmentation of the skin), or epidermal detachment.
• Wear glasses instead of contact lenses during the entire treatment period if your eyes are very dry.
• You may need to wear sunglasses to protect your eyes from glare.
• Be cautious when driving vehicles or using machinery at night, as visual changes (reduced night vision) may occur suddenly.
• Avoid intense physical activity during treatment with ISORIAC, as joint or muscle pain may occasionally occur during therapy.

3. How to take ISORIAC

Dosage:
Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The usual starting dose is 0.5 mg per kilogram of body weight per day (0.5 mg/kg/day).
For most patients, the dose ranges between 0.5 and 1.0 mg/kg/day.
If you feel that the effect of ISORIAC is too strong or too weak, inform your doctor.
The capsules should be taken once or twice daily with meals. Swallow the capsules whole without chewing or sucking them.

Patients with severe renal impairment
In patients with severe renal impairment, treatment should start at a lower dose (e.g., 10 mg/day).

Use in children
ISORIAC is not indicated for the treatment of prepubertal acne and is not recommended for patients under 12 years of age.

Patients with intolerance
In patients who show severe intolerance to the recommended dose, the doctor may continue treatment at the highest tolerated dose.

A course of ISORIAC lasts from 16 to 24 weeks. Skin improvement may continue for up to 8 weeks after the end of treatment.
Therefore, wait at least this 8-week period before starting a new treatment course, if necessary. For most patients, a single course is sufficient.

If you take more ISORIAC than you should
If you have taken more ISORIAC than recommended, symptoms of hypervitaminosis A may occur, manifesting as severe headache, nausea or vomiting, drowsiness, irritability, and itching.
Contact your doctor, pharmacist, or the nearest hospital as soon as possible.

If you forget to take ISORIAC
Do not take a double dose to make up for the missed dose. Resume your regular dosing schedule with the next dose.

If you have further 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.
These effects often improve during treatment or after stopping or adjusting the dosage (consult your doctor). Your doctor can help you manage the situation.
Some side effects can be serious
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 distress
• Worsening of 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 lives (suicidal ideation), have 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 symptoms of any of these
mental health problems. Your doctor may tell you to stop taking ISORIAC. This may not be sufficient to stop the effects: you may need further help, and your doctor can ensure this is provided.

• Sudden life-threatening allergic reaction (anaphylactic reactions)
• Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), which may be life-threatening and require immediate medical attention. These initially appear as circular patches, often with blisters in the centre, usually on arms and hands or legs and feet. More severe rashes may include blistering on chest and back. Additional symptoms may include eye infections (conjunctivitis) or ulcers in the mouth, throat, or nose. Severe forms of skin rashes may progress to extensive skin peeling, which can be life-threatening. These serious rashes are often preceded by headache, fever, and body aches (flu-like symptoms).

If you develop a skin rash or these skin symptoms, stop treatment with Isoriac and contact your doctor immediately.
All other side effects are listed below by frequency.
Very common side effects: may affect more than 1 in 10 people

• Low red blood cell count (anaemia), decreased platelet count, increased platelet count.
• Increased erythrocyte sedimentation rate (an indicator of acute inflammation).
• Increased fatty acids (elevated triglycerides in blood), decreased protein component of lipoproteins (decreased high-density lipoproteins - HDL).
• Increased liver enzymes (elevated transaminases). In such cases, your doctor may need to order blood tests and take necessary measures.
• Red sores or deep cracks at the corners of the mouth or on the lips, skin inflammation, dry skin, localized peeling, itching, red skin rash, skin fragility.
• Eyelid infection, eye discharge with itching and crusted eyelids (conjunctivitis), eye irritation, and dry eyes.
• Back pain, muscle and joint pain. It is therefore advisable to reduce intense physical exercise during treatment. All these effects are reversible after stopping treatment.

Common side effects: may affect up to 1 in 10 people

• Increased blood glucose and a type of fat (cholesterol), presence of protein or blood in urine.
• Low white blood cell count, which may make you more susceptible to infections.
• Headache.
• Dry nose, nosebleeds, and nasopharyngitis.

Rare side effects: may affect up to 1 in 1,000 people

• Skin allergic reactions, hypersensitivity.
• Hair loss (alopecia).

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

• Inflammation of the pancreas, gastrointestinal bleeding, or inflammatory bowel disease. If you experience severe abdominal pain, with or without bloody diarrhoea, nausea, and vomiting, stop taking isotretinoin and contact your doctor as soon as possible.
• Liver diseases (hepatitis), including nausea, vomiting, loss of appetite, general malaise, fever, itching, yellowing of the skin and eyes.
• Kidney diseases, including severe fatigue, difficulty urinating or inability to urinate, and swollen eyelids. If you experience these symptoms while taking isotretinoin, stop treatment and contact your doctor.
• Blood sugar levels too high (diabetes), with symptoms including excessive thirst, passing a significantly increased amount of urine, increased appetite with weight loss, fatigue, drowsiness, weakness, depression, irritability, and general malaise. In this case, contact your doctor.
• Benign intracranial hypertension has occurred in patients receiving concomitant treatment with isotretinoin and certain antibiotics (tetracyclines). This hypertension presents with persistent headaches, nausea, vomiting, or blurred vision. Stop taking ISORIAC and consult your doctor as soon as possible.
• Seizures (convulsions).
• Narrowing or blockage of blood vessels.
• Worsening of acne in the first weeks of treatment with inflammatory skin lesions, severe form of acne (acne fulminans). However, in general, continuing treatment will lead to improvement of acne and other symptoms.
• Inflammation of the colon.
• Localized bacterial infections may occur.
• Facial erythema, skin rash.
• Hair disorders, abnormal hair growth, nail abnormalities, infected dandruff.
• Benign vascular lesions of the skin and mucous membranes.
• Increased sensitivity to sunlight (photosensitivity reaction, see advice for daily life in section 2). Increased pigmentation, excessive sweating.
• Enlarged lymph nodes.
• Elevated levels of uric acid in blood, which may cause gout.
• The medicine may impair night vision and sudden visual disturbances may occur. These effects rarely persist after treatment ends.
• Altered colour vision, severe eye irritation, corneal opacity, eye irritation or sensation of having something in the eye (keratitis), blurred vision, difficulty seeing (cataract), increased sensitivity to light, visual disturbances, and poor tolerance to contact lenses. You may need sunglasses to prevent glare. If the medicine causes even slight difficulty in seeing, inform your doctor promptly.
• Hearing impairment.
• Sudden chest tightness with shortness of breath and laboured breathing (bronchospasm), particularly in patients with asthma, voice changes (hoarseness).
• Dry throat, nausea.
• Malaise.
• Disease mainly affecting joints with pain and swelling, bone abnormalities, growth delay and reduced bone density, soft tissue calcification, tendon inflammation. Blood levels of an enzyme (creatine phosphokinase), released during muscle fibre breakdown, may be elevated during intense physical exertion in patients treated with isotretinoin, leading to muscle tissue damage which may cause kidney problems.
• Drowsiness, dizziness.

Frequency not known: cannot be estimated from available data

• Problems achieving or maintaining an erection
• Decreased libido
• Breast enlargement with or without tenderness in men.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ISORIAC

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Do not store above 25°C. Store in the original container. Keep the container tightly closed to protect the medicine from light.
After completion of treatment, return any remaining capsules to the pharmacist.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What ISORIAC contains
ISORIAC 10 mg, 20 mg, soft capsules

• The active substance is:
  For a 10 mg soft capsule: isotretinoin ..............................................10 mg
  For a 20 mg soft capsule: isotretinoin ..............................................20 mg
• The excipients are: refined soybean seed oil, hydrogenated vegetable oil, yellow beeswax.

Capsule shell composition of the 10 mg capsule: gelatin, glycerol, purified water,
iron oxide red (E172).
Capsule shell composition of the 20 mg capsule: gelatin, glycerol, purified water,
iron oxide red (E172), iron oxide yellow (E172), titanium dioxide 25% (E171) in glycerol.
Composition of the black ink: SDA 35 alcohol, propylene glycol, black iron oxide,
phthalic acid copolymer of polyvinyl acetate, water, isopropyl alcohol, polyethylene glycol, ammonium hydroxide.

Description of the appearance of ISORIAC and pack contents
This medicinal product is supplied as soft capsules in packs of 30.
Each 10 mg capsule has a red/brown gelatin shell with a bright yellow/orange contents and is printed on one side with the logo “I 10”.
Each 20 mg capsule has a two-coloured red/brown and cream gelatin shell with a bright yellow/orange contents and is printed on one side with the logo “I 20”.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
PIERRE FABRE ITALIA S.p.A.
Via G. Washington, 70
20146 Milan - Italy

Manufacturer
Catalent France Beinheim S.A.
74, rue Principale
67930 Beinheim, France
or
Catalent Germany Schorndorf GmbH
Steinbeisstrasse 2
73614 Schorndorf, Germany
or
Catalent Germany Eberbach GmbH
Gammelsbacher Str. 2
Eberbach, Baden-Wuerttemberg
69412, Germany

This medicinal product is authorised in the European Economic Area Member States
under the following names:

• Belgium: ISOCURAL
• Czech Republic: CURACNE
• France: CURACNE
• Greece: CURACNE
• Italy: ISORIAC
• Luxembourg: CURACNE
• Poland: CURACNE
• Slovakia: CURACNE
• Spain: ISOACNE

Prescription and distribution conditions:
ISORIAC is a prescription-only medicine; this is a medicine requiring special monitoring during treatment.

For women of childbearing potential:

• Prior to prescribing, the patient's consent to treatment and contraception must be obtained.
• The duration of the prescription is limited to one month of therapy. Continuation of treatment requires a new prescription.
• The treatment must be dispensed no later than 7 days after the date of prescription.
• The treatment will be dispensed only upon verification that the following mandatory declarations are present on the prescription:
  • For the first prescription:
    • Signature on the treatment and contraception consent form.
    • Use of at least one effective method of contraception, established at least one month prior.
    • Assessment of the patient's level of understanding.
    • Date of pregnancy test (plasma hCG).
  • For subsequent prescriptions:
    • Continued use of effective contraception.
    • Assessment of the patient's level of understanding.
    • Date of the last pregnancy test (plasma hCG).

For further information about ISORIAC, please consult your doctor or pharmacist.
Detailed and up-to-date information on this medicinal product is available by scanning the
QR code included in the PI with a smartphone. The same information is also available at the
following URL: http://www.aifa.gov.it/content/medicinali-base-di-retinoidi .