ISDIBEN: detailed information

Package leaflet: Information for the patient

Isdiben 5 mg, 10 mg, 20 mg, 40 mg soft capsules

isotretinoin
Equivalent medicine
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 side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read 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 other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Isdiben is and what it is used for

Isdiben contains isotretinoin.

Isotretinoin is related to vitamin A.
It belongs to a group of medicines called "retinoids".

Isotretinoin is used to treat severe forms of acne.

These forms of acne can cause permanent scarring.
These types of acne are also known as "nodular" acne or "conglobate" acne. Isotretinoin is used when your acne has not improved with other treatments, including antibiotics and topical skin treatments.

Your treatment must be carried out under the supervision of a specialist doctor, known as a "dermatologist", who specialises in treating skin disorders.

2. What you need to know before taking Isdiben

Contact your doctor if you experience persistent pain in the lower back or buttocks
during treatment with Isdiben. These symptoms may be signs of sacroiliitis, a type of
inflammatory back pain. Your doctor may discontinue Isdiben therapy and refer you
to a specialist for management of inflammatory back pain. Further evaluations may
be required, including imaging diagnostics such as magnetic resonance imaging (MRI).

Do not take Isdiben if:

you are allergic to peanuts or soybeans or to any of the other components of Isdiben. This medicine contains soybean oil, in addition to isotretinoin. See section 6 (Other information) at the end of this leaflet for a complete list of ingredients.
there is any possibility that you could become pregnant, you must follow the precautions outlined in the “Pregnancy Prevention Programme” in the section “Warnings and precautions”.
you are pregnant or breastfeeding
you have been diagnosed with liver problems
you have been diagnosed with very high levels of fats in the blood (such as elevated cholesterol or triglycerides)
you have been diagnosed with very high levels of vitamin A in the body (a condition known as “hypervitaminosis A”)
you are currently being treated with tetracyclines (a type of antibiotic) (see section “Other medicines and Isdiben”)

If any of the above apply to you, return to your doctor and do not take this medicine. Talk to your
doctor before taking it.

Use in adolescents over 12 years of age

Do not give this medicine to children under 12 years of age. Only give it to adolescents over 12 years of age if they have completed all pubertal changes.

Special precautions with Isdiben
Do not take this medicine if you are pregnant.

Pregnancy Prevention Programme
Pregnant women must not use Isdiben
This medicine can severely harm the fetus (it is said to be “teratogenic”), and may 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 occur even if Isdiben is used for only a short time during pregnancy.

Do not use Isdiben if you are pregnant or think you might be pregnant.
Do not use Isdiben if you are breastfeeding. The medicine can pass into breast milk and harm the newborn.
Do not use Isdiben 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.

Isdiben is prescribed to women of childbearing potential only 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 counseling.
Before starting treatment, your doctor will instruct you to take a pregnancy test. The test must confirm that you are not pregnant when starting Isdiben treatment. Women must use an effective method of contraception before, during, and after using Isdiben.
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 contraceptive pills and a condom). Discuss with your doctor which method may be suitable for you.
You must use contraception for one month before starting Isdiben, throughout treatment, and for one month after stopping treatment.
You must use contraception even if you do not have menstrual periods or are not sexually active (unless your doctor tells you it is not necessary).

Women must agree to undergo pregnancy testing before, during, and after using Isdiben

You must agree to regular follow-up visits, preferably every month.
You must agree to undergo regular pregnancy tests, preferably monthly during treatment and, since some medicines may remain in your body, one month after stopping Isdiben (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 explained to you and that you agree to follow the rules outlined above.

If you become pregnant while taking Isdiben, 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 Isdiben, you must contact your doctor. Your doctor may refer you to a specialist for consultation.
Your doctor will provide you with written information about pregnancy and contraception. If you have not received this information, ask your doctor.
Prescriptions for women of childbearing age are issued only for one month at a time. For prolonged treatment, a new prescription is required. You must present the prescription to the pharmacist within 7 days; if later, the pharmacist cannot dispense the medicine.

Advice for men
Levels of oral retinoids in the semen of men taking Isdiben are too low to harm the fetus of their partner. 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 the pharmacist.

Advice for all patients
Talk to your doctor before taking Isdiben:

if you have had mental health problems
including depression, aggressive tendencies, or mood changes
including thoughts of self-harm or suicide. This is because your mood may change while taking Isdiben. Also inform your doctor if you are taking any medicines for these conditions, as your mood may be affected while taking isotretinoin.

Mental health problems
You may notice changes in your mood and behavior, and 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.

Isotretinoin often increases blood fats, such as cholesterol and triglycerides. Your doctor will perform blood tests before, during, and after treatment with isotretinoin. It is best not to drink alcoholic beverages during treatment, or at least reduce your usual intake. Inform your doctor if you already have high blood fat levels, diabetes, are overweight, or have a tendency to drink excessive alcohol. You may need more frequent blood tests. If your blood fat levels remain high, your doctor may reduce the dose or discontinue this medicine.

Isotretinoin may affect your liver Your doctor will perform blood tests before, during, and after treatment with isotretinoin to monitor liver function. If your liver function is affected, your doctor may reduce the dose or discontinue this medicine.
Isotretinoin may increase blood sugar levels In rare cases, people may develop diabetes. Your doctor will monitor blood sugar levels during treatment, especially if you already have diabetes, are overweight, or drink excessive alcohol.
Your skin may become dry Use a moisturizer and lip balm. To prevent skin irritation, avoid using exfoliating products or other acne treatments that dry or peel the skin.
Severe skin reactions (e.g., erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)) have been reported with this medicine. Skin rashes may progress to blistering or skin peeling. Be alert also for mouth, throat, nose, or genital ulcers and conjunctivitis (red, swollen eyes).
Rarely, this medicine may cause severe allergic reactions, some of which may affect the skin as eczema, hives, bruising, or red spots on arms and legs. If you develop an allergic reaction, stop taking this medicine immediately, seek urgent medical advice, and inform the doctor that you are taking this medicine.
Avoid excessive sun exposure and do not use sunlamps or UV tanning beds. Your skin may become more sensitive to sunlight. Use a high-protection sunscreen (SPF 50 or higher) before sun exposure.
Avoid cosmetic skin treatments. Isotretinoin may make your skin more fragile. Avoid waxing, dermabrasion, or laser therapy (removal of skin layers or scars) during treatment and for at least 6 months after treatment. These may cause scarring, skin irritation, or, rarely, changes in skin color.
Isotretinoin has been associated with inflammatory bowel disease. Your doctor will discontinue isotretinoin if you develop severe diarrhea with blood, without prior gastrointestinal disorders.
Isotretinoin may cause dry eyes, intolerance to contact lenses, and visual difficulties, including reduced night vision. Cases of persistent dry eyes that did not resolve after stopping treatment 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. If you develop visual difficulties, your doctor may refer you to a specialist and may ask you to stop taking isotretinoin.
Benign intracranial hypertension has been reported with isotretinoin, and in some cases when isotretinoin was used together with tetracyclines (a class of antibiotics). Stop taking Isdiben and seek urgent medical advice 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 (papilloedema).
Reduce intense physical exercise. Isdiben may cause muscle and joint pain, especially in young people.
Do not take vitamin A supplements while taking this medicine. Concurrent use may increase the risk of adverse effects.
Inform your doctor if you have kidney problems. Your doctor may start with a lower dose of isotretinoin and gradually increase it to the maximum tolerated dose.
Do not donate blood during treatment with this medicine and for 1 month after stopping Isdiben, as if a pregnant woman were to receive your blood, it could harm the fetus.
Remember not to share your medicine with anyone else. Return any unused capsules at the end of treatment. Talk to your doctor or pharmacist about how to return the capsules.

Driving and using machines
During treatment, you may have eye problems and poor vision. This may occur suddenly. In rare cases, night vision problems have persisted after treatment ended. Very rarely, numbness and dizziness have been reported. If this happens to you, do not drive, ride a bicycle, or operate machinery.

Other medicines and Isdiben
Do not take vitamin A supplements or tetracyclines (a type of antibiotic), and do not use other acne treatments that may dry or peel the skin while taking Isdiben. It is advisable to use moisturizers and emollients (skin creams or preparations that prevent water loss and soften the skin).
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal products or over-the-counter medicines (including multivitamin supplements), or if you are using or have recently used any topical skin products.

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

Isdiben soft capsules contain soybean oil. If you are allergic to peanuts or soybeans, do not use this medicine.

3. How to take Isdiben

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
The usual starting dose is 0.5 mg per kg of body weight per day (0.5 mg/kg/day). If you weigh 60 kg, your starting dose will usually be 30 mg per day.
Take the capsules once or twice daily.
Take them during or after meals. Swallow the capsules whole with a drink or with a piece of food.
After a few weeks, your doctor may adjust the dose. This depends on how you respond to the medicine. For most people, the dose will be between 0.5 and 1 mg per kg of body weight per day. If you think the medicine is too strong or too weak, speak to your doctor or pharmacist.
If you have severe kidney problems, you will usually start with a lower dose (such as 10 mg per day), which will be increased gradually up to the maximum dose your body can tolerate. If your body cannot tolerate the recommended dose, a lower dose will be prescribed. This may mean that your treatment will last longer and that it is more likely your acne will return.
A course of treatment usually lasts from 4 to 6 months. Most people require only one course of treatment. Your acne may continue to improve for up to 8 weeks after the end of treatment. Another course is usually not started before this time.
Some people notice a worsening of acne during the first few weeks of treatment, but this usually improves with continued treatment.
If you take more Isdiben than you should
If you take too many capsules or if someone else accidentally takes your medicine, contact your doctor, pharmacist, or the nearest hospital immediately.
If you forget to take Isdiben
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take the next dose as usual. Do not take two doses at the same time.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Often side effects disappear or stop when treatment is discontinued. Your doctor can help you manage them.
Stop taking this medicine and contact your doctor immediately if you experience symptoms of any of
the following side effects. This may not be enough to stop the side effects. You may need further help, and your doctor can arrange this for you.

Mental health problems
You may notice some changes in your mood and behaviour, and 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 promptly that need to be discussed with your doctor.

Mental 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 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 thoughts), have attempted suicide, or have died by suicide. These people 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 problems. Your doctor may tell you to stop taking Isdiben. This may not be sufficient to stop the side effects: you may need further help, and your doctor can ensure this is provided.

Rashes and other skin symptoms
Frequency not known (frequency cannot be estimated from the available data)

This medicine can cause severe skin rashes, potentially life-threatening, requiring immediate medical attention. These often start as circular spots on the arms, hands, legs, or feet and may develop blisters. More severe rashes may appear as blisters on the chest and back. You may also have other symptoms, such as eye infection (conjunctivitis) or ulcers in the mouth, throat, or nose.
If a large area of skin begins to peel off, this is a dangerous sign and you must go to hospital immediately. Bring the medicine with you. Severe forms of skin rash can lead to widespread skin peeling, which may be life-threatening. If you have flu-like symptoms (headache, fever, aches), these may be followed by a rash, so monitor them closely and be ready to act quickly.

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

Dry skin, especially on the face and lips; red, sore skin; chapped and inflamed lips; rash, mild itching, and mild flaking. Using a moisturizing cream from the start of treatment may reduce the risk of these effects.
Skin may become redder and more fragile than usual, especially on the face.

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

Hair loss, which is usually temporary. Your hair will return to normal once treatment is completed.

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

Your acne may worsen during the first few weeks, but symptoms should improve over time.
Skin inflammation, swelling, and darkening, especially on the face.
Sensation of excessive sweating or itching.
Increased sensitivity to light.
Bacterial infections in the nail bed and other nail changes.
Swelling, discharge, pus.
Thicker scarring after surgical procedures.
Increased body hair.

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

Severe allergic reactions such as difficulty breathing or swallowing due to sudden swelling of the throat, face, lips, and mouth. Sudden swelling of hands, feet, and ankles may also occur. If you experience any allergic reaction, stop taking isotretinoin and contact your doctor immediately.
Skin allergic reactions such as rash, itching.

Other problems
Very common side effects ( may affect more than 1 in 10 people ):

Increased liver enzymes in blood tests.

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

Yellowing of the skin or eyes, feeling more tired than usual. These may be signs of hepatitis.
Difficulty urinating, swollen eyelids, feeling more tired than usual. These may be signs of kidney problems.
Severe abdominal pain, with or without bloody diarrhoea, malaise (nausea), and vomiting. These may be signs of serious intestinal conditions.
Persistent headache with nausea, vomiting, and vision changes, including blurred vision. These may be signs of benign intracranial hypertension, especially if isotretinoin is taken with antibiotics called tetracyclines.
Other vision problems, including blurred or distorted vision, cloudy surface of the eye (corneal opacity, cataract).
Dark or cola-coloured urine.
Muscle weakness that may be potentially life-threatening, possibly associated with difficulty moving arms or legs, painful or swollen areas of the body, bruising, dark urine, reduced or absent urine output, confusion, or dehydration. These are signs of muscle tissue breakdown that can lead to kidney failure (rhabdomyolysis). This may occur if you engage in intense physical activity while taking this medicine.

Stop taking this medicine and contact your doctor immediately if you experience symptoms of any of the
side effects listed above. This may not be sufficient to stop the side effects. You may need further help, which your doctor can arrange for you.
If you experience symptoms of any of the following side effects, contact your doctor immediately. Your
doctor may tell you to stop taking this medicine.

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

You may bleed or bruise more easily – if the number of blood clotting cells decreases.
Anaemia, weakness, dizziness, pale skin – if the number of red blood cells decreases.
Increased likelihood of infections with symptoms such as chills, sudden fever, sore throat, or flu-like symptoms – if the number of white blood cells (which help protect the body from infections and diseases) decreases.
Eye inflammation (conjunctivitis) and eyelid area inflammation; dry, irritated eyes. Ask your pharmacist for a suitable eye drop. If you have dry eyes and wear contact lenses, you may need to switch to glasses.
Back, muscle, or joint pain, especially in adolescents. To avoid worsening bone or muscle problems, reduce intense physical activity while taking isotretinoin.
Changes in blood fat levels (including HDL or triglycerides).

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

Headache
The inside of the nose becomes dry and crusty, causing slight nosebleeds.
Sore throat or painful, inflamed nose.
Increased risk of infections, if white blood cells are affected.
Increased blood cholesterol levels
Presence of protein or blood in the urine
Allergic reactions such as skin rash, itching.

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

Seizures, numbness, dizziness
You may see less well at night, have blurred vision, colour blindness, or worsening of colour vision
You may become more sensitive to light; you may need to wear sunglasses to protect your eyes from strong sunlight
Lymph nodes (glands in the neck, armpits, and groin) may become swollen.
Dry throat, hoarseness
Sudden chest tightness, breathing difficulty, and wheezing, especially if you have asthma
Hearing difficulties
Intense thirst; frequent need to urinate; blood tests show increased blood sugar levels. These may be symptoms of diabetes.
General feeling of unwellness.
Increased blood uric acid levels.
Bacterial infections
Inflammation of blood vessels (sometimes with bruising, red spots)
Arthritis, bone changes (delayed growth, changes in bone density, abnormal bone growth); bone growth may stop.
Calcium deposits in soft tissues
Painful tendons
Increased blood creatine phosphokinase levels

Frequency not known (frequency cannot be estimated from the available data)

Problems achieving or maintaining an erection
Decreased libido (sex drive)
Breast enlargement with or without tenderness in men
Vaginal dryness
Sacroiliitis, a type of inflammatory back pain causing buttock or lower back pain
Urethritis (inflammation of the urethra)

Contact your doctor immediately if you experience symptoms of any of the side effects listed above. Your doctor may tell you to stop taking this medicine.
To avoid worsening bone or muscle problems, reduce intense physical activity while taking this medicine.
If you notice any side effect that concerns you, whether listed in this leaflet or not, speak with your doctor.

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 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 Isdiben

Keep this medicine out of the sight and reach of children.
Do not store above 25°C. Store in the original packaging.
Do not use this medicine after the expiry date stated on the carton and blisters after EXP. The expiry date refers to the last day of that month.
Return any unused capsules to the pharmacist at the end of treatment.
Keep this medicine only if your doctor tells you to do so.
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.

6. Pack contents and other information

What Isdiben 5 mg, 10 mg, 20 mg, 40 mg soft capsules contain
The active substance is isotretinoin.
Each 5 mg capsule contains 5 mg of isotretinoin.
Each 10 mg capsule contains 10 mg of isotretinoin.
Each 20 mg capsule contains 20 mg of isotretinoin.
Each 40 mg capsule contains 40 mg of isotretinoin.
The other components are: soybean seed oil, hydrogenated vegetable oil and yellow beeswax.
Composition of the capsule shell for 5 mg, 20 mg and 40 mg capsules: gelatin, glycerol, purified water, red iron oxide (E 172), yellow iron oxide (E 172) and titanium dioxide (E 171).
Composition of the capsule shell for 10 mg capsules: gelatin, glycerol, purified water and red iron oxide (E 172).

Description of the appearance of Isdiben 5 mg, 10 mg, 20 mg and 40 mg soft capsules and pack contents
Each Isdiben 5 mg soft capsule has an opaque, two-coloured red/brown and cream gelatin shell with a bright yellow/orange content. The oval capsule is printed in black ink on one side with the logo “5”.
Each Isdiben 10 mg soft capsule has an opaque red/brown gelatin shell with a bright yellow/orange content. The oval capsule is printed in black ink on one side with the logo “I 10”.
Each Isdiben 20 mg soft capsule has an opaque, two-coloured red/brown and cream gelatin shell with a bright yellow/orange content. The oval capsule is printed in black ink on one side with the logo “I 20”.
Each Isdiben 40 mg soft capsule has an opaque orange/brown gelatin shell with a bright yellow/orange content. The oval capsule is printed in black ink on one side with the logo “I 40”.
Isdiben is available in packs of 30, 50 or 100 capsules. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
ISDIN S.r.l., Via Tito Speri 8, 20154 Milano, Italy.

Manufacturers:
Catalent France Beinheim S.A., 74 rue Principale, 67930 Beinheim, France.
Catalent Germany Eberbach GmbH, Gammelsbacher Str. 2, 69412 Eberbach, Germany.
Catalent Germany Schorndorf GmbH, Steinbeisstrasse 2, 73614 Schorndorf, Germany.

You can get more information about this medicine from your doctor or pharmacist.