PACKAGE LEAFLET

Package leaflet: Information for the user

Isotiorga 10 mg soft capsules, 20 mg soft capsules

Isotretinoin
Generic medicine
WARNING
CAN CAUSE SEVERE HARM TO 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 this leaflet carefully before taking this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult 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, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Isotiorga is and what it is used for

Isotiorga contains isotretinoin, an active substance similar to vitamin A, belonging to a
class of medicines known as retinoids (for the treatment of acne).
Isotiorga is indicated for the treatment of severe forms of acne (such as nodular acne and
conglobate acne or acne with risk of permanent scarring) in adults and adolescents aged 12 years and older,
and only after puberty. Isotiorga should be taken when acne does not improve with other anti-acne treatments,
including antibiotics and topical treatments.
Treatment with Isotiorga must be taken under the supervision of a dermatologist
(a doctor specialized in treating skin disorders).

2. What you need to know before taking Isotiorga

Do not take Isotiorga

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" section under "Warnings and precautions"
If you are allergic to isotretinoin, peanuts, soy or any of the other ingredients of this medicine (listed in section 6)
If you have liver disease
If you have high levels of lipids in the blood (cholesterol, triglycerides)
If you have excessively high levels of vitamin A in your body (hypervitaminosis A)
If you are taking tetracyclines (a type of antibiotic) (see "Other medicines and Isotiorga")

If any of these apply to you, contact your doctor before taking Isotiorga.
Warnings and precautions
Talk to your doctor before taking Isotiorga.

If you have ever suffered from any mental health problems, including depression, aggressive tendencies or mood swings. This also includes thoughts of self-harm or ending your life. This is because your mood may change while you are taking Isotiorga.

Pregnancy prevention programme
Women who are pregnant must not use Isotiorga
This medicine can seriously harm the unborn child (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 cause miscarriage. This can happen even if Isotiorga is
used for only a short time during pregnancy.

You must not use Isotiorga if you are pregnant or think you might be pregnant.
You must not use Isotiorga if you are breastfeeding. The medicine may pass into breast milk and harm the newborn.
You must not use Isotiorga if you could become pregnant during treatment.
You must not become pregnant for one month after stopping this treatment, as some medicines may remain in your body.

For women who could become pregnant, Isotiorga is prescribed under very strict rules.
This is due to the risk of harm to the unborn child.
These rules are:

Your doctor must explain the risk of harm to the unborn child – you must understand that you must not become pregnant and what is required to prevent pregnancy.
Your doctor must have discussed 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 instruct you to take a pregnancy test. The test must confirm that you are not pregnant when starting treatment with Isotiorga.

Women must use an effective method of contraception before, during and after using
Isotiorga

You must agree to use at least one highly reliable contraceptive method (for example an intrauterine device or contraceptive implant) or
two effective methods that work in different ways (for example 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 Isotiorga, during 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 tells you it is not necessary).

Women must agree to undergo pregnancy tests before, during and after using
Isotiorga

You must agree to attend regular check-ups, preferably every month.
You must agree to undergo regular pregnancy tests, preferably every month during treatment and, since some medicines may remain in your body, one month after stopping Isotiorga (unless your doctor decides this is not necessary in your case).
You must agree to perform additional pregnancy tests if requested by your doctor.
You must not become pregnant during treatment or within one month after stopping it, 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 you have been informed of the risks and that you will follow the rules outlined above.

If you become pregnant while taking Isotiorga, 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 Isotiorga, you must
contact your doctor. Your doctor may refer you to a specialist for consultation.
Your doctor has written information on pregnancy prevention for users of Isotiorga,
which should be provided to you.
A new prescription is required for further treatment. Each prescription is valid for 7 days.
Advice for men
Levels of oral retinoids in the semen of men taking Isotiorga are too low to harm their
partner's unborn child. 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
after treatment is completed.
Do not donate blood during treatment with this medicine and for 1 month after stopping
Isotiorga, as if a pregnant woman were to receive your blood, it could harm her unborn child.
Mental health problems
You may notice 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 notice these changes and
help you identify problems that need to be discussed with your doctor.
Advice for all patients

Inform your doctor if you have or have had any mental health disorders (including depression, suicidal behaviour or psychosis) or if you are taking medicines for any of these conditions.
Serious skin reactions (e.g. erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)) have been reported with the use of Isotiorga. Skin rash may progress to widespread blistering or skin peeling. Mouth, throat, nose, genital ulcers and conjunctivitis (red, swollen eyes) may also occur.
Rarely, Isotiorga can cause serious allergic reactions, some of which may affect the skin in the form of eczema, hives and bruising or red spots on arms and legs. If you develop an allergic reaction, stop taking Isotiorga, contact your doctor urgently and inform them that you are taking this medicine.
Reduce intense physical exercise. Isotiorga can cause muscle and joint pain, particularly in children and adolescents who engage in intense physical activity.
Contact your doctor if you experience persistent pain in the lower back or buttocks during treatment with Isotiorga. These symptoms may indicate sacroiliitis, a type of inflammatory back pain. Your doctor may stop treatment with Isotiorga and refer you to a specialist for management of inflammatory back pain. Further evaluations, including imaging diagnostics such as MRI, may be required.
Isotiorga has been associated with inflammatory bowel disease. Your doctor will discontinue Isotiorga if you develop severe bloody diarrhoea without a prior history of gastrointestinal disorders.
Isotiorga can cause dry eyes, intolerance to contact lenses and visual disturbances, including reduced night vision. Cases of dry eyes that did not resolve after discontinuation of therapy have been reported. Inform your doctor if you experience any of these symptoms. Your doctor may recommend using an eye ointment or artificial tears. If you wear contact lenses and develop intolerance, you may be advised to wear glasses during treatment. Your doctor may refer you to a specialist if you experience visual disturbances and may ask you to discontinue treatment with Isotiorga.
Benign intracranial hypertension has been reported with the use of Isotiorga, and in some cases with concomitant therapy of Isotiorga and tetracyclines (a type of antibiotic). Stop taking Isotiorga and contact your doctor immediately if you develop symptoms such as headache, nausea, vomiting or visual disturbances. Your doctor may refer you to a specialist to check for swelling of the optic disc (papilledema).
Isotiorga can increase liver enzyme levels. Your doctor will perform blood tests before, during and after treatment with Isotiorga to monitor liver function. If levels remain elevated, your doctor may reduce the dose or discontinue treatment with Isotiorga.
Isotiorga commonly increases blood lipid levels, such as cholesterol or triglycerides. Your doctor will monitor these levels before, during and after treatment with
Isotiorga. During treatment, it is recommended not to drink alcoholic beverages or at least reduce your usual intake. Inform your doctor if you have high blood lipid levels, if you have diabetes (high blood sugar), if you are overweight or if you are a heavy drinker. Your doctor may prescribe more frequent blood tests. If blood lipid levels remain high, your doctor may reduce the dose or discontinue treatment with Isotiorga.
Inform your doctor if you have kidney problems. Your doctor may start treatment with a lower dose of Isotiorga and then gradually increase it to the maximum tolerated dose.
Inform your doctor if you have fructose intolerance. Your doctor will not prescribe Isotiorga if you have been diagnosed with fructose or sorbitol intolerance.
Isotiorga can increase blood sugar levels. Rarely, new-onset diabetes has been reported. Your doctor may monitor blood sugar levels during treatment, especially if you already have diabetes, are overweight or are a heavy drinker.
Dry skin may occur. Use a moisturising ointment or cream and a lip balm during treatment. Avoid using exfoliating or anti-acne products to prevent skin irritation.
Avoid prolonged sun exposure and do not use sunlamps or tanning beds. Your skin may become more sensitive to sunlight. Before sun exposure, use a sunscreen with a high protection factor (SPF 15 or higher).
Avoid cosmetic dermatological procedures. Isotiorga may increase skin fragility. Avoid waxing (hair removal). Also avoid dermabrasion or laser treatments (removal of calloused skin or scars) during treatment and for at least 6 months after stopping treatment. These procedures may cause scarring, skin irritation or, rarely, changes in skin pigmentation. Children and adolescents Isotiorga is not recommended for children under 12 years of age. This is because it is not known whether it is safe or effective in this age group. Use in children over 12 years of age only after puberty. Other medicines and Isotiorga Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Do not take vitamin A supplements or tetracyclines (a type of antibiotic)
Do not use any anti-acne medicines during therapy with Isotiorga. Moisturising and emollient creams (creams or preparations that prevent water loss and soften the skin) may be applied. Pregnancy, breastfeeding and fertility If you are or think you may be pregnant, if you are breastfeeding or planning a pregnancy, consult your doctor before taking this medicine. For further information on pregnancy and contraception, see section 2 "Pregnancy prevention programme". Driving and using machines Night vision may be affected during treatment. This may occur without warning. In rare cases, this problem may persist after treatment ends. Dizziness and visual disturbances have been reported very rarely. If you experience these symptoms, you must not drive or operate machinery.
Isotiorga contains
Soybean seed oil. If you are allergic to peanuts or soy, do not use this medicine.
Sorbitol: sorbitol is a source of fructose. If your doctor has diagnosed (or you have been diagnosed) intolerance to certain sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, consult your doctor before taking (or before your child takes) this medicine.
Isotiorga 10 mg: this medicine contains up to 5 mg of sorbitol per soft capsule.
Isotiorga 20 mg: this medicine contains up to 7 mg of sorbitol per soft capsule.
Isotiorga 10 mg: Ponceau 4R. May cause allergic reactions.
Isotiorga 20 mg: Sunset Yellow FCF. May cause allergic reactions.

3. How to take Isotiorga

Always take this medicine exactly as instructed by your doctor. If you have
any doubts, ask your doctor or pharmacist for advice.
The usual starting dose is 0.5 mg per kilogram of body weight per day (0.5
mg/kg/day). Therefore, if you weigh 60 kg, your starting dose will probably be 30 mg per day.
Take the capsules once or twice daily. Take the capsules with food.
Swallow the capsules whole, with liquid or food.
After a few weeks, your doctor may adjust the dose. This depends on your response to
treatment. For most patients, the dose ranges between 0.5 and 1.0 mg/kg per
day. If you feel that the effect of Isotiorga is too strong or too weak, inform your
doctor or pharmacist.
In patients with severe kidney problems, treatment usually starts with a reduced dose
(e.g. 10 mg/day), which will then be increased up to the maximum tolerated dose. In patients who
do not tolerate the recommended dose, your doctor may prescribe a reduced dose. In such cases,
treatment will last longer and there is a higher risk of relapse.
The duration of treatment is generally 16–24 weeks. Most patients require only a single
treatment cycle. Acne may continue to improve for up to 8 weeks after treatment ends.
Therefore, a new treatment cycle should not be started until at least this period has passed.
Some people may experience a worsening of acne during the first few weeks of
treatment. Usually, the condition improves with continued treatment.
If you take more Isotiorga than you should
If you take too many capsules or if someone accidentally takes this medicine, contact
your doctor or pharmacist immediately or go to the nearest hospital.
If you forget to take Isotiorga
If you miss a dose, take it as soon as possible. However, if it is almost time for your next
dose, skip the missed dose and continue your treatment as normal. Do not take a double dose
(two doses one after the other) to make up for a forgotten dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets 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, although some may persist after stopping therapy. Some side effects can be serious and require immediate medical attention. Your doctor can help you manage the situation.

Side effects requiring immediate medical treatment:

Skin problems
Frequency not known (cannot be estimated based on available data)

Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), which are potentially life-threatening and require immediate medical intervention. These initially appear as circular patches, often with blisters in the center, 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 Isotiorga and contact your doctor immediately.

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, and feelings of emotional distress.
Worsening of existing depression.
Becoming violent and aggressive.

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

Some people have had thoughts or intentions of self-harm or ending their life (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 Isotiorga. This may not be enough to stop the effects—you may need further help, and your doctor can ensure this is provided.

Allergic reactions
Rare side effects (may affect up to 1 in 1,000 people)

Severe (anaphylactic) reactions: difficulty breathing or swallowing due to sudden swelling of the throat, face, lips, or mouth. Sudden swelling of hands, feet, and ankles may also occur.

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

Sudden chest tightness with shortness of breath and dyspnea, particularly in patients with asthma.

If you experience a severe reaction, seek emergency medical help immediately. In case of an allergic reaction, stop taking Isotiorga and contact your doctor.

Bones and muscles
Frequency not known (cannot be estimated based on available data)

Potentially life-threatening muscle weakness, which may be associated with difficulty moving arms or legs, painful, swollen, or bruised areas of the body, dark urine, reduced or absent urination, confusion, or dehydration. These are signs of rhabdomyolysis, a muscle tissue injury that can lead to kidney failure. This may occur if you engage in intense physical activity during treatment with Isotiorga.

Liver and kidney problems
Very rare side effects (may affect up to 1 in 10,000 people)

Yellowing of the skin or eyes and drowsiness. These may be signs of hepatitis. Stop taking Isotiorga immediately and contact your doctor.
Difficulty urinating (passing urine), swollen eyelids, severe fatigue. These may be signs of kidney inflammation. Stop taking Isotiorga immediately and contact your doctor.

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

Persistent headache, accompanied by feeling unwell (nausea), being sick (vomiting), and changes in vision including blurred vision. These may be signs of benign intracranial hypertension, especially if Isotiorga is taken together with antibiotics called tetracyclines. Stop taking Isotiorga immediately and contact your doctor.

Intestinal and stomach problems
Very rare side effects (may affect up to 1 in 10,000 people)

Severe abdominal pain (stomach ache), with or without severe bloody diarrhoea, feeling unwell (nausea), and being sick (vomiting). These may be signs of serious intestinal disorders. Stop taking Isotiorga immediately and contact your doctor.

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

Blurred vision. If you experience blurred vision, stop taking Isotiorga immediately and contact your doctor. If your vision changes in any other way, contact a doctor as soon as possible.

Other side effects:

Very common side effects associated with Isotiorga: (may affect more than 1 in 10 people)

Dry skin, particularly of the lips and face, skin inflammation, chapped and inflamed lips, skin rash, mild itching, and mild peeling. Apply a moisturizing cream from the start of treatment.
Skin becomes more fragile and reddened than usual, especially on the face.
Back pain; muscle pain; joint pain, particularly in children and adolescents. To avoid worsening possible bone or muscle problems, reduce intense physical activity during treatment with Isotiorga.
Inflammation of the eye (conjunctivitis) and eyelid area; dry and irritated eyes. Ask your pharmacist for a suitable eye drop. If you suffer from dry eyes and wear contact lenses, you may need to wear glasses instead.
Increased liver enzymes observed in blood tests.
Altered blood lipid levels (including HDL or triglycerides).
Increased tendency to bruise, bleed, or clot—when platelets are affected.
Anaemia—weakness, dizziness, paleness—when red blood cells are affected.

Common side effects associated with Isotiorga: (may affect up to 1 in 10 people)

Headache.
Increased blood cholesterol.
Blood or protein in the urine.
Increased susceptibility to infections when white blood cells are affected.
Dry and crusty nasal mucosa, causing mild nosebleeds.
Irritation or inflammation of the throat and nose.
Allergic reactions such as skin rash, itching. In case of an allergic reaction, stop taking Isotiorga and contact your doctor.

Rare side effects associated with Isotiorga: (may affect up to 1 in 1,000 people)

Hair loss (alopecia). This is usually temporary. Hair should return to normal after treatment ends.

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

Night vision may be impaired, worsening of colour blindness and colour vision.
Increased sensitivity to light; you may need to wear sunglasses to protect your eyes from strong sunlight.
Other vision problems, including blurred vision, distorted vision, cloudy eye surface (corneal opacity, cataract).
Excessive thirst; frequent need to urinate; blood tests show increased blood sugar levels. These may be signs of diabetes.
Worsening of acne in the first few weeks, but symptoms should improve over time.
Skin inflammation, swelling, and increased pigmentation, especially on the face.
Excessive sweating or itching.
Arthritis; bone disorders (growth delay, excessive growth, and changes in bone density); growth may stop in developing bones.
Calcium deposits in soft tissues, tendon pain, high levels of muscle breakdown products in the blood during intense physical activity.
Increased sensitivity to light.
Bacterial infections at the base of the nail, nail changes.
Swelling, discharge, pus.
Thickening of scars after surgery.
Increased body hair.
Seizures, drowsiness, dizziness.
Lymph nodes may swell.
Dryness of the throat, hoarseness.
Hearing impairment.
Feeling of general malaise.
High levels of uric acid in the blood.
Bacterial infections.
Inflammation of blood vessels (sometimes with bruising, red spots).

Frequency not known: Frequency not known (cannot be estimated based on available data)

Dark or tea-coloured urine.
Problems achieving or maintaining an erection.
Decreased libido.
Breast enlargement with or without tenderness in men.
Vaginal dryness.
Sacroiliitis, a type of inflammatory back pain causing pain in the buttocks or lower back.
Urethritis (inflammation of the urethra).

Reporting of side effects
If you experience any side effect, 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 Isotiorga

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

Do not use this medicine after the expiry date stated on the packaging next to EXP. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any damage or signs of tampering with the packaging.
Do not store above 25 °C.
Store in the original packaging and keep the blister in the box to protect it from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. Return unused capsules to the pharmacist. Keep only on the advice of your doctor.

6. Package contents and other information

What Isotiorga contains
The active substance is isotretinoin.
The other ingredients are: all-rac-alpha-tocopheryl acetate, hydrogenated vegetable oil (type II), hydrogenated soybean oil, yellow beeswax, refined soybean oil, gelatin, glycerol, partially dehydrated liquid sorbitol, titanium dioxide (E-171), patent blue V (E-131) and ponceau 4R (E-124) for the 10 mg capsule; sunset yellow FCF (E-110) for the 20 mg capsule, and purified water.

Description of the appearance of Isotiorga and contents of the pack
Isotiorga is available in soft capsules containing 10 mg or 20 mg of isotretinoin.
Isotiorga 10 mg: purple, oval soft capsules, size 3. The capsule is approximately 11.1 mm long and 6.8 mm wide.
Isotiorga 20 mg: white-cream, oval soft capsules, size 6. The capsule is approximately 13.8 mm long and 8.1 mm wide.
Blister packs made of PVC/TE/PVdC / orange aluminum foil.
Soft capsules 10 mg
Pack sizes: 30, 50, 60 and 100 capsules
Soft capsules 20 mg
Pack sizes: 30, 50, 60 and 100 capsules
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Laboratoires Bailleul S.A.
10-12 Avenue Pasteur
L-2310 Luxembourg
LUXEMBOURG

Manufacturer
GAP S.A.
46, Agissilaou str.,
173 41 Agios Dimitrios, Attiki,
Greece

This medicinal product is authorized in the European Economic Area Member States
under the following names:
Austria Isotiorga 10 mg, 20 mg, 40 mg Weichkapseln
Belgium Isotiorga 10 mg, 20 mg soft capsules/Weichkapseln/zachte capsules
Czech Republic Asotiorga
Estonia Isotiorga
Germany Isotiorga 10 mg, 20 mg Weichkapseln
Greece Isotretinoin/Bailleul 20 mg, 40 mg καψάκιο, μαλακό
Hungary Isotiorga 20 mg lágy kapszula
Italy Isotiorga
Luxembourg Isotiorga 20 mg soft capsules
Portugal Isotiorga 10 mg, 20 mg cápsulas molles
Romania Isotiorga 10 mg, 20 mg caps moi
Slovak Republic Isotiorga 20 mg mäkké kapsuly
Spain Isotiorga 20 mg, 40 mg cápsulas blandas