PATIENT INFORMATION LEAFLET

AISOSKIN 10 mg soft capsules, 20 mg soft capsules

Isotretinoina
Equivalent 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
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, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Aisoskin is and what it is used for

Aisoskin contains the active substance isotretinoin and belongs to a class of medicines called retinoids.
Aisoskin is used for the treatment of severe forms of acne (such as conglobate, nodular acne, or acne with risk of permanent scarring) that have proven resistant to adequate courses of standard therapy with antibiotics and topical treatment.
Aisoskin should only be prescribed by, or under the supervision of, physicians experienced in the use of medicines for the treatment of severe acne, who fully understand the risks of treatment and the need for close patient monitoring.

2. What you need to know before using Aisoskin

Contact your doctor if you experience persistent pain in the lower back or buttocks during treatment with Aisoskin. These symptoms may be signs of sacroiliitis, a type of inflammatory back pain. Your doctor may discontinue therapy with Aisoskin 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 use Aisoskin

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 allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6)
if you are allergic to peanuts or soy. Aisoskin contains soybean oil and partially hydrogenated soybean oil
if you have liver problems (hepatic insufficiency)
if you have high levels of cholesterol or triglycerides in the blood (hypercholesterolemia, hypertriglyceridemia)
if you have high levels of vitamin A in your body (hypervitaminosis A)
if you are taking medicines called tetracyclines (see section “Other medicines and Aisoskin”)

Warnings and precautions
Pregnancy Prevention Programme
Pregnant women must not use Aisoskin
This medicine can severely harm the fetus (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 likely cause miscarriage. This can occur even if Aisoskin is used for only a short time during pregnancy.

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

Women who could become pregnant are prescribed Aisoskin 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 needed 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 instruct you to take a pregnancy test. The test must confirm that you are not pregnant when starting Aisoskin treatment.

Women must use effective contraception before, during, and after using Aisoskin

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 may be suitable for you.
You must use contraception for one month before starting Aisoskin, 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 Aisoskin

You must agree to regular check-ups, preferably monthly
You must agree to undergo regular pregnancy tests, preferably monthly during treatment and, since some medicines can remain in your body, for one month after stopping Aisoskin (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 treatment, as some medicines can 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 to you and that you agree to follow the above rules.

If you become pregnant while taking Aisoskin, 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 Aisoskin, 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 Aisoskin are too low to harm their partner's fetus. However, you must never share your medicines with anyone.

Additional precautions
Never give this medicine to anyone else. At the end of treatment, return any unused capsules to the pharmacist.
Do not donate blood during treatment with this medicine and for one month after stopping Aisoskin, as if a pregnant patient were to receive your blood, it could harm her fetus.

Talk to your doctor before taking Aisoskin:

if you have not 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 Aisoskin.
if your acne suddenly worsens in the early phase of treatment; this usually occurs within 7–10 days and resolves spontaneously without dose adjustment. See section “Observe the following precautions during treatment with Aisoskin” for further advice;
if you experience a sudden reduction in night vision (see section “Driving and use of machines” and “Possible side effects”); in this case, an ophthalmological examination may be advisable and your doctor may consider suspending treatment with Aisoskin;
if you engage in intense physical exercise, as you may experience muscle or joint pain and increased blood levels of enzymes indicating cardiac or muscular damage (creatine phosphokinase). In such cases, you should reduce the intensity of physical activity during treatment with Aisoskin;
if you experience symptoms and signs of increased intracranial pressure (intracranial hypertension), such as headache, nausea, vomiting, or visual disturbances, contact your doctor, who may instruct you to stop treatment immediately (see section “Possible side effects”);
if you have liver disease. Aisoskin may increase liver enzyme levels; therefore, your doctor will ask you to have periodic blood tests, and if levels do not return to normal, may recommend reducing the dose or stopping treatment;
if you have kidney disease, treatment may need to be started at a reduced dose (see section “How to take Aisoskin”);
if you have high levels of fats in the blood, such as triglycerides or cholesterol. Your doctor may consider modifying the dose or stopping treatment with Aisoskin, although often dietary changes may be sufficient. If these levels are too high or signs of pancreas inflammation (acute pancreatitis, which can sometimes be fatal) occur, treatment must be stopped;
if you have inflammatory bowel disease and develop severe episodes of bloody diarrhoea, contact your doctor, who will instruct you to stop treatment immediately;
if you are allergic to peanuts or soy, as you may experience allergic reactions, even severe ones, not limited to the skin. If you develop a severe allergic reaction, contact your doctor, who will discontinue therapy and provide appropriate monitoring;
if you have diabetes, your doctor will monitor your blood glucose levels more frequently throughout the treatment period;
if you are overweight, your doctor will monitor your blood lipid levels more frequently throughout the treatment period;
if you regularly drink large amounts of alcohol.

Mental health issues
You may not notice certain changes in your mood and behaviour, so it is very important to inform your friends and family that you are taking this medicine. They may notice these changes and help you promptly identify problems that need to be discussed with your doctor.
Before, during, and after treatment, you must have regular blood tests to monitor kidney and liver function, cholesterol, and blood sugar levels. If abnormalities occur, your doctor may decide to adjust the dose or discontinue treatment.

Observe the following precautions during treatment with Aisoskin:

avoid prolonged exposure to sunlight or ultraviolet (UV) radiation. If necessary, use a high-protection sunscreen (SPF at least 15);
avoid cosmetic procedures for skin resurfacing (dermabrasion) or skin lesion reduction (laser therapy) for at least 5–6 months after stopping Aisoskin treatment. These procedures may cause scarring, skin discoloration (increased or decreased pigmentation), or skin irritation. Avoid using depilatory wax for at least 6 months after treatment due to the risk of skin tearing;
avoid using Aisoskin together with topical acne products that dissolve the skin's surface layers (keratolytic or exfoliating agents), as this may increase local irritation (see section “Other medicines and Aisoskin”);
if you experience dry skin or lips, apply a greasy ointment and lip balm from the start of treatment;
Isotretinoin may cause dry eyes, intolerance to contact lenses, and visual difficulties, including reduced night vision. Cases of persistent dry eyes after discontinuation of therapy have been reported. Inform your doctor if you experience any of these symptoms. Your doctor may recommend using lubricating 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 discontinue isotretinoin treatment.

Children and adolescents
Aisoskin is not indicated for the treatment of acne in prepubertal children, and its use is not recommended in children under 12 years of age.

Other medicines and Aisoskin
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not take Aisoskin together with the following medicines:

medicines containing vitamin A, as there is a risk of developing symptoms caused by high levels of vitamin A (hypervitaminosis A), such as severe headache, nausea or vomiting, drowsiness, irritability, and itching;
medicines used to treat bacterial infections such as tetracyclines. Cases of increased intracranial pressure (benign intracranial hypertension, pseudotumor cerebri) have been reported when Aisoskin is used with tetracyclines (see section “Warnings and precautions”);
topical acne medicines or other products used to dissolve the skin's surface layers (keratolytic or exfoliating agents), as this may increase local irritation (see section “Warnings and precautions – Observe the following precautions during treatment with Aisoskin”).

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Aisoskin must not be used under any circumstances during pregnancy (see section “What you need to know before using Aisoskin – Do not use Aisoskin”). Women must use effective contraception before, during, and after using Aisoskin. If, despite these precautions, pregnancy occurs during treatment with Aisoskin or within one month after, there is a high risk of severe and serious birth defects in your baby.
If pregnancy occurs during treatment with Aisoskin, stop treatment immediately and contact a specialist in congenital malformations (teratologist) for evaluation and consultation.
It is highly likely that this medicine passes into breast milk, causing harm to the baby. Therefore, Aisoskin is contraindicated in women who are breastfeeding.
For further information on pregnancy and contraception, see section 2 of the “Pregnancy Prevention Programme”.

Driving and use of machines
Exercise caution when driving or operating machinery, as Aisoskin may cause a sudden reduction in night vision, which rarely persists after treatment ends (see section “Warnings and precautions” and “Possible side effects”).
Treatment with Aisoskin may cause drowsiness, dizziness, and visual disturbances. Therefore, you should refrain from driving or engaging in any activity where reduced alertness could pose serious risks to yourself or others.

Aisoskin 10 mg contains 3.717 mg of sorbitol per soft capsule.
Aisoskin 20 mg contains 11.89 mg of sorbitol per soft capsule.
Aisoskin contains less than 1 mmol (23 mg) of sodium per soft capsule, i.e., essentially ‘sodium-free’.
Aisoskin contains soybean oil and partially hydrogenated soybean oil. Aisoskin contains soy.
If you are allergic to peanuts or soy, do not use this medicine.
Aisoskin contains E 124 (Ponceau 4R). It may cause allergic reactions.

3. How to take Aisoskin

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The dosage will be calculated individually based on body weight and may be adjusted by your doctor during treatment.
The recommended starting dose is 0.5 mg/kg per day; however, your doctor will determine your individual needs.
For most patients, the dose ranges between 0.5 and 1.0 mg/kg per day.
The duration of treatment will depend on the individual daily dose.
The capsules should be taken once or twice daily during meals.
Complete healing from acne is generally achieved with a treatment course of 16–24 weeks.
In case of a confirmed relapse, your doctor will prescribe a new course of treatment with Aisoskin at the same daily dose and with the same cumulative dose.
Your skin may continue to improve for up to 8 weeks after completion of treatment; therefore, wait at least this 8-week period before starting a new course of treatment, if necessary.
If you are unable to tolerate the recommended dose, your doctor will reduce your dose, and the treatment will last longer.
If you have severe kidney problems, your doctor will prescribe a lower dosage (e.g., 10 mg/die). The dosage should then be increased up to 1 mg/kg/die or up to the maximum tolerated dose, according to your doctor's judgment.

Use in children
Aisoskin is not recommended for children under 12 years of age.

If you take more Aisoskin than you should
In case of accidental overdose, contact your doctor immediately or go to the nearest hospital.
If you take more capsules than prescribed by your doctor, you may experience symptoms caused by high levels of Vitamin A, including severe headache, nausea or vomiting, drowsiness, irritability, and itching. These symptoms are expected to be reversible and generally do not require treatment.

If you forget to take Aisoskin
Do not take a double dose to make up for the missed dose.
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 everybody gets them.
These effects often improve during treatment, or after stopping treatment, or after modifying the dose. In some cases, they may persist after discontinuation of treatment.

Serious side effects
Contact your doctor immediately if you experience any of the following serious side effects; urgent medical treatment may be required.

blurred vision, night blindness, reduced night vision, optic disc swelling (papilledema), visual disturbances;
severe allergic reactions (anaphylaxis) causing difficulty breathing, dizziness, collapse, shock, severe itching and/or swelling;
increased intracranial pressure (benign intracranial hypertension), seizures, drowsiness, dizziness;
severe damage to skeletal muscle (rhabdomyolysis).

The following serious side effects have a frequency that cannot be estimated from the available data:

severe forms of skin allergy (skin rash, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), which may be life-threatening and require immediate medical intervention. These initially appear as circular patches, often with central blisters, typically on the arms and hands or legs and feet. More severe rashes may include blistering on the chest and back. Severe forms can progress to widespread skin peeling, which may be life-threatening. These severe skin allergic reactions are often preceded by headache, fever, and body aches (flu-like symptoms). If you develop these skin symptoms, stop taking Aisoskin and contact your doctor immediately.

Other side effects
Other side effects are listed below by frequency:
Very common (occurs in at least 1 in 10 treated patients):

decrease in red blood cells (anaemia) and platelets (thrombocytopenia), increased platelet count (thrombocytosis), increased erythrocyte sedimentation rate;
inflammation of the eyelids (blepharitis) and of the inner mucous membrane of the eyeball (conjunctivitis), dry eyes, eye irritation;
increased levels of certain liver enzymes (transaminases) (see section “Warnings and precautions”);
dry lips (cheilitis), skin inflammation (dermatitis), dry skin, localized peeling, itching, erythematous rash, skin fragility (risk of friction injuries);
joint pain (arthralgia) and muscle pain (myalgia), back pain (particularly in children and adolescents);
increased triglycerides and reduced high-density lipoproteins.

Common (occurs in at least 1 in 100 and less than 1 in 10 treated patients):

decrease in neutrophils (neutropenia);
headache (cephalalgia);
nosebleeds (epistaxis), dry nose, inflammation of the nose and throat (rhinopharyngitis);
increased cholesterol and blood sugar levels (hypercholesterolemia and hyperglycaemia), presence of blood and protein in urine (haematuria and proteinuria).

Rare (occurs in at least 1 in 10,000 and less than 1 in 1,000 treated patients):

skin allergic reaction, hypersensitivity;
hair loss (alopecia).

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

bacterial infections (mucocutaneous) caused by Gram-positive bacteria;
abnormal growth of lymph nodes (lymphadenopathy);
diabetes mellitus, elevated blood uric acid levels (hyperuricaemia);
colour vision disturbances, cloudy lens of the eye (cataract), intolerance to contact lenses, corneal opacity, inflammation of the cornea (keratitis), excessive sensitivity to light (photophobia);
hearing loss;
inflammation of blood vessels (e.g. Wegener's granulomatosis, allergic vasculitis);
breathing difficulties, particularly in asthmatic patients (bronchospasm), voice changes (hoarseness);
inflammation of the intestine (colitis and ileitis), dry throat, gastrointestinal bleeding, diarrhoea and bleeding, nausea, inflammation of the pancreas (pancreatitis);
hepatitis;
fulminant acne (also known as febrile ulcerative acne, a severe form of acne that appears suddenly, particularly in males), worsening of acne (acne exacerbation), facial erythema, skin rashes (exanthema), changes in hair structure, abnormal hair growth (hirsutism), nail growth abnormalities (onychodystrophy), fingertip infections (paronychia), sun exposure-related allergies (photosensitivity reactions), red skin lesions (pyogenic granuloma), dark skin spots (cutaneous hyperpigmentation), increased sweating;
chronic joint inflammation (arthritis), calcification of ligaments and tendons (calcinosi), premature epiphyseal fusion, bone diseases (exostoses and hyperostoses), reduced bone density, tendinitis;
inflammatory kidney diseases (glomerulonephritis);
excessive formation of wound healing tissue, malaise;
increased blood levels of enzymes indicating cardiac and muscular damage (creatine phosphokinase).

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

difficulty achieving or maintaining erection
decreased libido
breast enlargement with or without tenderness in men
vaginal dryness
sacroiliitis, a type of inflammatory back pain causing buttock or lower back pain
urethritis.

Mental health problems
Rare 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 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 have 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 Aisoskin. This may not be enough to stop the effects—you may need further help, and your doctor can ensure that you receive it.

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 Aisoskin

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after Exp. The expiry date refers to the
last day of that month.
The expiry date indicated on the packaging applies to the product in its original, unopened packaging, correctly
stored.
Store at a temperature not exceeding 25 °C. Store in the original packaging and keep the blister in the outer
packaging to protect it from moisture and light.
Dispose of unused capsules at the end of treatment using the designated collection containers for pharmaceutical waste.
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. Contents of the pack and other information

What Aisoskin contains
The active substance in Aisoskin is: isotretinoin
Each Aisoskin 10 mg soft capsule contains: 10 mg of isotretinoin.
The other components are: soybean seed oil, -alpha-tocopherol, disodium edetate, butylhydroxyanisole, Lipodan
HP-100 (hydrogenated triglycerides Grindsted PS 101), yellow wax, partially hydrogenated soybean seed oil.
Components of the gelatin shell: gelatin, glycerol, sorbitol 70% (non-crystallizable), purified water,
Ponceau 4R (E 124), iron oxide black (E 172), titanium dioxide (E 171).
Each Aisoskin 20 mg soft capsule contains: 20 mg of isotretinoin.
The other components are: soybean seed oil, -alpha-tocopherol, disodium edetate, butylhydroxyanisole, Lipodan
HP-100 (hydrogenated triglycerides Grindsted PS 101), yellow wax, partially hydrogenated soybean seed oil.
Components of the gelatin shell: gelatin, glycerol, sorbitol 70% (non-crystallizable), purified water,
Ponceau 4R (E 124), indigotine (E 132), titanium dioxide (E 171).

Description of the appearance of Aisoskin and pack contents
Aisoskin is presented as soft capsules. The capsules are packaged in thermoformed blisters made of
PVC/PVDC and aluminum.
Each blister of Aisoskin 10 mg contains 30 soft capsules.
Each blister of Aisoskin 20 mg contains 30 soft capsules.

Marketing Authorization Holder and Manufacturer
Fidia Farmaceutici S.p.A.
Via Ponte della Fabbrica, 3/A
35031 Abano Terme (PD)