Toctino

Package leaflet: Information for the user

TOCTINO 10 mg soft capsules, 30 mg soft capsules

Alitretinoin
WARNING
CAN SERIOUSLY HARM THE UNBORN CHILD
Women must use effective contraception
Do not use if you are or think you may be pregnant
This medicine is under 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 using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4. Contents of this leaflet:
  1. What TOCTINO is and what it is used for
  2. What you need to know before taking TOCTINO
  3. How to take TOCTINO
  4. Possible side effects
  5. How to store TOCTINO
  6. Contents of the pack and other information

1. What TOCTINO is and what it is used for

The active substance of TOCTINO is alitretinoin. It belongs to a group of medicines known as retinoids, which are related to vitamin A. TOCTINO capsules are available in two strengths, containing 10 mg or 30 mg of alitretinoin.
TOCTINO is used to treat adults with severe chronic hand eczema that is resistant to other topical treatments, including steroids. Treatment with TOCTINO should be carried out under the supervision of a specialist skin doctor (dermatologist).

2. What you need to know before using TOCTINO

Do not use TOCTINO

• 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” described in the “Warnings and precautions” section.
• If you have liver disease
• If you have severe kidney disease
• If you have high levels of fats in your blood (such as high cholesterol or elevated triglycerides)
• If you have untreated thyroid disorders
• If you have very high levels of vitamin A in your body ( hypervitaminosis A )
• If you are allergic to alitretinoin, other retinoids (such as isotretinoin), peanuts or soy, or to any of the other ingredients of this medicine (listed in section 6)
• If you are taking tetracyclines (a type of antibiotic )

If any of these conditions apply to you, consult your doctor. Do not take TOCTINO.

Warnings and precautions
Pregnancy Prevention Programme
Pregnant women must not use TOCTINO
This medicine can seriously harm the unborn baby (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 TOCTINO
is used for only a short time during pregnancy.

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

TOCTINO is prescribed to women who could become pregnant only under very strict rules. This is due to
the risk of harm to the unborn baby.
These rules are:

• Your doctor must have explained to you the risk of harm to the unborn baby – 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 ask you to take a pregnancy test. The test must confirm that you are not pregnant when starting TOCTINO treatment.

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

• 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 TOCTINO, 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 otherwise).

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

• 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 TOCTINO (unless your doctor decides this is not necessary in your case).
• You must agree to undergo additional pregnancy tests if requested by your doctor.
• You must not become pregnant during treatment or in the month following 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 will confirm that you have been informed of the risks and that you agree to follow the above rules.

If you become pregnant while taking TOCTINO, 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 TOCTINO, you must 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 TOCTINO are too low to harm their partner’s unborn baby. However, you must never share your medicines with anyone else.
Additional precautions
Never give this medicine to anyone else. Return any unused capsules to the pharmacist at the end of treatment.
Do not donate blood during treatment with this medicine and for 1 month after stopping TOCTINO, as if a pregnant woman were to receive your blood, it could harm her unborn baby.
Talk to your doctor before using TOCTINO if:

• You have ever had mental health problems, including depression, aggressive tendencies, or mood changes. This also includes thoughts of self-harm or suicide. This is because your mood may change while taking TOCTINO.
• You have kidney disease. TOCTINO is not recommended for people with moderate kidney disease. If you have kidney disease, check with your doctor whether TOCTINO is suitable for you.
• You have high levels of fats in your blood, you may need more frequent blood tests. TOCTINO usually increases blood fats such as cholesterol or triglycerides. If blood fat levels remain high, your doctor may reduce the dose or stop TOCTINO treatment.
• If you have high blood sugar (diabetes), your blood sugar levels may need to be monitored more frequently, and your doctor may start TOCTINO therapy at a low dose.
• If you have ever had thyroid disorders. TOCTINO may lower thyroid hormone levels. If your thyroid hormone level is low, your doctor may prescribe replacement therapy.

During treatment, pay attention to the following:

• If you experience vision problems, inform your doctor immediately. It may be necessary to stop TOCTINO treatment and have an eye examination.
• If you develop persistent headache, nausea or vomiting (malaise), and blurred vision, these may be signs of a condition called benign intracranial hypertension. Stop taking the capsules immediately and contact your doctor as soon as possible.
• In case of hemorrhagic diarrhoea, stop taking the capsules immediately and contact your doctor as soon as possible.
• Minimise exposure to sunlight and avoid using sunbeds. Your skin may become more sensitive to sunlight. Before sun exposure, use a sunscreen product with a high protection factor (SPF 15 or higher). If your skin and lips become dry during treatment, use a moisturising lotion or cream and a lip balm.
• Reduce intense physical activity: alitretinoin may cause muscle and joint pain.
• In case of dry eyes, lubricating eye ointments or artificial tears may be helpful. If you wear contact lenses, you may need to wear glasses during alitretinoin treatment. Dry eyes and vision problems usually resolve after stopping treatment.
• TOCTINO may increase liver enzyme levels. Your doctor will perform blood tests during treatment to monitor these levels. If they remain elevated, your doctor may reduce the dose or stop TOCTINO treatment.

Mental health problems

• You may not notice changes in your mood or 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 identify problems that need to be discussed with your doctor.
• If you experience any mental health problems, including depression, aggressive tendencies, mood changes, thoughts of self-harm or suicide, stop taking TOCTINO immediately and contact your doctor as soon as possible.

Children and adolescents
TOCTINO is not recommended for people under 18 years of age. It is not known how it works in this age group.
Other medicines and TOCTINO
Do not take other retinoid medicines (for example, isotretinoin), vitamin A supplements, or tetracyclines (a type of antibiotic) while taking TOCTINO. This increases the risk of side effects.
Tell your doctor or pharmacist if:

• you are taking amiodarone (a medicine used to regulate heart rhythm). It is recommended not to take amiodarone together with TOCTINO.
• you are taking ketoconazole, fluconazole, miconazole (medicines used to treat infections). Your doctor may decide to reduce the dose of TOCTINO.
• you are taking simvastatin (a medicine used to lower cholesterol). TOCTINO may reduce the level of this medicine in your body.
• you are taking gemfibrozil (another medicine used to lower cholesterol) or oxandrolone (an anabolic steroid). Your doctor may decide to reduce the dose of TOCTINO.
• you are taking paclitaxel (used to treat cancer), rosiglitazone or repaglinide (used to treat diabetes). TOCTINO may increase the levels of these medicines in your body.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines and herbal products.
Pregnancy and breastfeeding
Do not take TOCTINO if you are breastfeeding

• This medicine may pass into breast milk and harm the newborn.

Do not take TOCTINO if you are pregnant
TOCTINO can seriously harm the unborn baby (it is said to be “teratogenic”). It may also increase the risk of miscarriage.

• Do not use TOCTINO if you are pregnant.
• Do not become pregnant during treatment with TOCTINO, or during the month following the end of treatment.

For further information on pregnancy and contraception, see section 2 “Pregnancy Prevention Programme”.
Driving and using machines
During treatment, you may experience reduced night vision. If this occurs, do not drive or operate machinery.
TOCTINO contains soybean oil and sorbitol
If you are allergic to peanuts or soy, do not use this medicine. If your doctor has diagnosed you with an intolerance to certain sugars, contact your doctor before taking TOCTINO.

3. How to use TOCTINO

When to take the capsules
The capsule should be taken with a main meal, preferably at the same time each day. The capsules must be swallowed whole and not chewed.
Dose
The dose is 10 or 30 mg once daily. In case of intolerance to the recommended dose of 30 mg, your doctor may prescribe the lower dose of 10 mg.
Always use TOCTINO exactly as directed by your doctor. If in doubt, consult your doctor or pharmacist.
How long to use the capsules
A treatment cycle usually lasts from 12 to 24 weeks, depending on the degree of improvement of the disease. If the first treatment cycle has been successful, your doctor may prescribe an additional cycle if symptoms reappear.
If you take more TOCTINO than you should
If you have taken too many capsules or if other people have accidentally taken your medicine, contact your doctor, pharmacist, or the nearest hospital immediately.
If you forget to take TOCTINO
If you forget to take a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for the forgotten capsule.

• 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.
Very common: may affect more than 1 in 10 people
Common: may affect from 1 to 10 in 100 people
Uncommon: may affect from 1 to 10 in 1,000 people
Rare: may affect from 1 to 10 in 10,000 people

Very common side effects

• Headache
• Increased blood fats: higher levels of fats (triglycerides) and cholesterol in the blood

Common side effects

• Blood cell disorders: increased number of platelets (cells that help blood clotting), decreased number of red blood cells and white blood cells in blood tests
• Thyroid disorders: decreased levels of thyroid hormones
• Eye disorders: inflammation of the eyes (conjunctivitis) and eyelids; sensation of dryness and irritation in the eyes
• Ask your pharmacist for a suitable eye drop. If you wear contact lenses and notice eye dryness, you may need to switch to glasses
• Ear disorders: persistent noises in the ears (tinnitus)
• Dizziness
• Blood and circulation: hot flushes, high blood pressure (hypertension)
• Stomach and intestinal disorders: feeling unwell (nausea), discomfort (vomiting), dry mouth
• Muscle and joint pain: muscle pain, joint pain, lack of energy (fatigue). Intense physical exercise may lead to high blood levels of muscle metabolism products
• Skin and hair disorders: dry skin, especially on the face, dry and inflamed lips, skin redness, itchy skin rash, inflamed skin, hair loss
• Liver disorders: increased liver enzymes in blood tests

Uncommon side effects

• Vision disorders, including blurred vision, distorted vision, clouding of the eye surface (corneal opacity, cataract)
• If you experience these vision problems, stop using TOCTINO immediately and contact your doctor
• Skin disorders: itchy skin, skin peeling, skin rashes, eczema due to dry skin
• Ear, nose and throat disorders: nosebleeds
• Stomach and intestinal disorders: indigestion (dyspepsia)
• Bone disorders: abnormal bone growth, including a spinal disorder called ankylosing spondylitis

Rare side effects

• Persistent headache, accompanied by nausea, vomiting, and vision changes including blurred vision. These may be signs of benign intracranial hypertension
• If you experience these symptoms, stop using TOCTINO immediately and contact your doctor
• Blood and circulation: inflammation of blood vessels
• Skin and hair problems: nail disorders, increased sensitivity of the skin to sunlight, changes in hair structure

Other side effects
Other side effects have occurred in a very small number of people, but their exact frequency is unknown:
Severe allergic reactions
Symptoms include:

• Itchy skin rash (urticaria)
• Swelling, sometimes of the face or mouth (angioedema), causing difficulty in breathing
• Collapse
• If you have these symptoms, contact your doctor immediately. Stop taking TOCTINO.
• Stomach and intestinal problems: severe stomach (abdominal) pain, with or without bloody diarrhoea, feeling unwell and discomfort (vomiting)
• Stop taking TOCTINO immediately and contact your doctor. These may be signs of serious intestinal problems

Problems with night vision. Vision problems usually return to normal once treatment is stopped
Blood and circulation: swelling of the hands, lower legs and feet (peripheral oedema)

Side effects of other medicines in the same family as TOCTINO
These side effects have not been observed so far with TOCTINO, but their occurrence cannot be ruled out.
They are very rare and may affect fewer than 1 in 10,000 people.
Diabetes: excessive thirst; frequent need to urinate; blood tests show increased blood sugar levels. These may all be signs of diabetes
Bone disorders: arthritis; bone disorders (delayed growth, changes in bone density); bone growth may stop
Eye and vision disorders: colour blindness and worsening of colour vision; intolerance to contact lenses
Mental health problems

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

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

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

• Some people have had thoughts or intentions of harming themselves or ending their life (suicidal ideation), 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 any of these mental health symptoms. Your doctor may tell you to stop taking TOCTINO. This may not be enough to stop the effects; you may need further help, and your doctor can arrange for this

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 following website: “www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa”.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store TOCTINO

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

6. Package contents and other information

What TOCTINO contains
The active substance is alitretinoin.
Each soft capsule contains 10 mg of alitretinoin.
The other components are: soybean oil (refined), partially hydrogenated soybean oil, medium-chain triglycerides, yellow beeswax, all-rac-α-tocopherol, gelatin, glycerol, liquid sorbitol (non-crystallizing), purified water, iron oxide, red (E172), iron oxide, black (E172).
Each soft capsule contains 30 mg of alitretinoin.
The other components are: soybean oil (refined), partially hydrogenated soybean oil, medium-chain triglycerides, yellow beeswax, all-rac-α-tocopherol, gelatin, glycerol, liquid sorbitol (non-crystallizing), purified water, iron oxide, red (E172), iron oxide, yellow (E172).

Description of the appearance of TOCTINO and contents of the pack
TOCTINO 10 mg is presented as soft capsules. The capsules are approximately 11 mm long and 7 mm wide, oval-shaped, brown in colour, and marked with “A1”. The capsules are packed in blisters of 30 capsules.
TOCTINO 30 mg is presented as soft capsules. The capsules are approximately 13 mm long and 8 mm wide, oval-shaped, red-brown in colour, and marked with “A3”. The capsules are packed in blisters of 30 capsules.

Marketing Authorization Holder and Manufacturer
Stiefel Laboratories Legacy (Ireland) Ltd.
Finisklin Business Park
Sligo, Ireland
Legal representative: GlaxoSmithKline S.p.A., Via A. Fleming, 2 – 37135 Verona (Italy)

Manufacturer
SwissCaps GmbH,
Grassingerstrasse 9,
D-83043 Bad Aibling,
Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria, Denmark, Finland, France, Germany, Iceland, Italy, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, United Kingdom: Toctino
Greece: Cehado