Package leaflet: Information for the user

Neotigason, 10 mg, capsules
Neotigason, 25 mg, capsules
Acitretinum
WARNING
MAY CAUSE SEVERE HARM TO THE UNBORN CHILD
Women must use effective methods of contraception.
Do not use during pregnancy or if pregnancy is suspected.
Please read all of this leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents:

What Neotigason is and what it is used for
Important information before taking Neotigason
How to take Neotigason
Possible side effects
How to store Neotigason
Contents of the pack and other information

1. What Neotigason is and what it is used for

Neotigason contains an active substance called acitretin. It belongs to a group of medicines known as retinoids.
Neotigason is used in the treatment of severe skin disorders in which the skin becomes thickened and may peel or scale. These skin conditions include psoriasis, ichthyosis, pityriasis rubra pilaris, and follicular keratosis (Darier's disease). Acitretin helps restore normal skin growth.
Neotigason is usually prescribed under the supervision of a dermatologist (a doctor who specialises in skin disorders).

2. Important information before taking Neotigason

When not to take Neotigason:

If the patient is pregnant or breastfeeding.
If there is any risk that the patient may become pregnant, it is essential to follow the precautions outlined in the Pregnancy Prevention Programme; see section "Warnings and precautions".
If the patient is allergic to the active substance acitretin or to any of the other ingredients of this medicine (listed in section 6), or if the patient is taking other medicines known as retinoids.
If the patient has severe liver disease.
If the patient has severe kidney disease.
If the patient has high levels of lipids (fats) in the blood.
If the patient is taking medicines called tetracyclines (used to treat infections) or methotrexate (used in skin diseases, joint pain, or cancer); see also "Neotigason with other medicines".
If the patient is taking vitamin A or other retinoids (such as isotretinoin); see section "Neotigason with other medicines".

Talk to your doctor before taking Neotigason if you think any of the above warnings apply to you.

Warnings and precautions
Pregnancy Prevention Programme
Women who are pregnant must not take Neotigason.
This medicine can severely harm the unborn child (it has a "teratogenic" effect). It may cause serious malformations of the brain, face, ear, eyes, heart, and certain glands (thymus and parathyroid glands) of the fetus. It also increases the risk of miscarriage. These effects may occur even if Neotigason is taken for only a short time during pregnancy.

Do not take Neotigason if you are pregnant or suspect you may be pregnant.
Do not take Neotigason during breastfeeding. The medicine is likely to pass into breast milk and may harm the unborn child.
Do not take Neotigason if you could become pregnant during treatment.
Do not become pregnant for three years after stopping treatment, as the medicine may still remain in your body.

Neotigason may be prescribed to women of childbearing potential only if strict rules are followed.
This is due to the risk of severe birth defects in the unborn child.
The following conditions must be met:

The doctor must explain to the patient the risk of fetal damage (congenital malformations); the patient must understand why pregnancy must be avoided and how to prevent it.
The patient must discuss contraception (birth control methods) with the doctor. The doctor will provide information on effective contraceptive methods. The doctor may refer the patient to a specialist for contraceptive advice.
Before starting treatment, the doctor will request a pregnancy test. The test must confirm that the patient is not pregnant at the start of Neotigason treatment.

Women must use effective contraceptive methods before, during, and after treatment with Neotigason

The patient must agree to use at least one highly reliable method of contraception (e.g., intrauterine device or contraceptive implant), or two effective methods with different mechanisms (e.g., oral hormonal contraceptives and condoms). Discuss with your doctor which methods are most suitable for you.
The patient must use contraception for one month before starting Neotigason, throughout treatment, and for 3 years after stopping the medicine.
The patient must use contraception even if she is not menstruating or is not currently sexually active (unless the doctor determines it is unnecessary).

Women must agree to undergo pregnancy tests before, during, and after treatment with Neotigason

The patient must agree to regular follow-up visits with the doctor, ideally monthly.
The patient must agree to regular pregnancy testing, ideally monthly during treatment and every 1 to 3 months for 3 years after stopping Neotigason, as the medicine may still be present in the body (unless the doctor decides otherwise).
The patient must agree to additional pregnancy tests as recommended by the treating physician.
The patient must not become pregnant during treatment or for 3 years after stopping treatment, as the medicine may still be present in the body.
The treating physician will discuss all issues with the patient using a checklist and will ask the patient (or her parent or legal guardian) to sign it. This form confirms that the patient has been informed of the risks and agrees to follow the rules outlined above.

If a patient becomes pregnant while taking Neotigason, she must stop taking the medicine immediately
and contact her doctor. The doctor may refer the patient to a specialist for advice.
Additionally, a woman who becomes pregnant within 3 years after stopping Neotigason treatment
should contact her doctor. The doctor may refer her to a specialist for advice.

Advice for men
The amount of oral retinoids in the semen of men taking Neotigason is too low to harm their partner's unborn child. However, this medicine must never be shared with another person, especially with women.

Advice for all patients
Acitretin often increases blood levels of fats such as cholesterol and triglycerides, which has been associated with pancreatitis.
If you experience severe abdominal or back pain, inform your doctor immediately (these may be symptoms of pancreatitis).

Additional precautions
Never give this medicine to another person. All unused capsules must be returned to the pharmacist after treatment ends.
Before starting Neotigason, discuss the following with your doctor:

If you have diabetes. You may require more frequent blood sugar monitoring after starting Neotigason.
If you have high blood lipid levels or are overweight. Your doctor may order blood tests during Neotigason treatment to monitor your lipid levels.
If you have cardiovascular disorders. You may require more frequent monitoring by your doctor, e.g., blood pressure measurements.
If you consume large amounts of alcohol.
If you have impaired liver function.
If you have ever had mental health problems, including depression, aggression, mood swings, or psychotic symptoms (altered perception of reality, such as hearing voices or seeing things that are not there).

This is because Neotigason may affect your mood and mental health.

Mental health problems
You may not notice certain changes in your mood or behaviour, so it is important to inform your friends and family members that this medicine may cause changes in behaviour and mood. These individuals may notice such changes and help identify problems that need to be discussed with your doctor.

Other considerations during Neotigason treatment:

Neotigason may cause impaired night vision (see below "Driving and using machines" and section 4).
Neotigason may increase intracranial pressure. If symptoms of increased intracranial pressure occur—such as severe headaches, nausea, vomiting, or visual disturbances—contact your doctor immediately.
Neotigason may increase the skin's sensitivity to UV radiation. Before going into strong sunlight, protect exposed skin with a sunscreen containing a UV filter of at least SPF 15. Avoid using sunlamps (tanning beds) and excessive sun exposure.
Liver function and blood lipid levels should be checked before starting treatment and regularly during treatment. Your doctor may periodically monitor your bone health, as Neotigason may cause bone changes, especially in children and elderly patients undergoing long-term treatment.
High doses of Neotigason may cause mood changes (including irritability, aggression, and depression).
Very rarely, a severe condition (capillary leak syndrome/retinoic acid syndrome) has been reported, in which small blood vessels (capillaries) leak. This may lead to severe hypotension (low blood pressure), oedema (fluid accumulation causing swelling), and shock.
Very rarely, a severe skin reaction (exfoliative dermatitis) has been reported, with symptoms such as rash, blisters, and skin peeling. See section 4.
Due to the risk of fetal harm, this medicine must not be given to another person. Unused or expired capsules should be returned to a pharmacy for disposal.

Women of childbearing potential:
Neotigason causes developmental abnormalities in the unborn child. Pregnancy prevention and regular pregnancy testing are required during treatment and for 3 years after stopping Neotigason; see also "Pregnancy and breastfeeding". Women of childbearing potential must not consume alcohol during treatment and for 2 months after stopping treatment; see section "Neotigason and alcohol".

Blood donation:
Do not donate blood while taking this medicine or within 3 years after stopping Neotigason.
If a pregnant woman receives your blood, she may give birth to a child with congenital defects.

If any of the above warnings apply to you, contact your doctor or pharmacist before taking this medicine.

Neotigason with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Do not take methotrexate (used to treat skin diseases, joint inflammation, or cancer), tetracyclines (used to treat infections), or vitamin A and other retinoids (such as isotretinoin and tazarotene) together with Neotigason; see also section "When not to take Neotigason".
Before starting Neotigason, inform your doctor if you are taking phenytoin (used to treat epilepsy) or progestogen-only contraceptives (mini-pills) with low progesterone doses.

Neotigason and alcohol
Women of childbearing potential must not consume alcohol (in beverages, food, or medicines) during Neotigason treatment and for 2 months after stopping treatment. Concurrent alcohol consumption and Neotigason may form a compound called etretinate, which harms the fetus and is very slowly eliminated from the body. Effective contraception must be used for 3 years after stopping Neotigason treatment.

Effect on fertility, pregnancy, and lactation
Neotigason causes developmental abnormalities in the unborn child. The following instructions must be strictly followed, even if fertility problems exist.

Do not take Neotigason if you are pregnant, suspect you may be pregnant, or could become pregnant during treatment or within 3 years after stopping treatment.
Do not take Neotigason if you are breastfeeding.
Birth control: If you are of childbearing age, you must use effective contraception continuously for at least 4 weeks before starting Neotigason, throughout treatment, and for 3 years after stopping acitretin. The primary contraceptive method should be a combination of an oral contraceptive or intrauterine device together with a condom or diaphragm. Progestogen-only contraceptives with low progesterone doses (mini-pills) are not recommended.
Pregnancy tests: Your doctor will require a mandatory pregnancy test up to 3 days before starting treatment. The test result must be negative. Neotigason treatment may begin only on the second or third day of the next menstrual period after a negative test. You will also be asked to perform regular pregnancy tests during treatment, every 28 days. Before each new prescription for Neotigason, your doctor will require proof of a negative pregnancy test performed no more than 3 days before the visit.
After stopping Neotigason, pregnancy tests should be performed every 1–3 months for 3 years after the last dose.
If you become pregnant or suspect pregnancy during treatment or within 3 years after stopping the medicine, contact your doctor immediately.
More information on pregnancy and contraception can be found in section 2, "Pregnancy Prevention Programme".
If you have any questions about the above instructions, discuss them with your doctor or pharmacist before taking Neotigason.

Driving and using machines
During Neotigason treatment, you may experience vision problems, especially at night. Exercise caution when driving, using tools, or operating machinery.

Neotigason contains glucose
If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.

Neotigason contains sodium
Neotigason contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered "sodium-free".

3. How to use Neotigason

This medicine should always be used according to the instructions given by your doctor or pharmacist. If in doubt, consult your doctor. Capsules are best taken once daily with food or with milk.
The usual dose for adult patients is 25 mg (i.e. 1 capsule containing 25 mg of acitretin) or 30 mg (3 capsules, each containing 10 mg of acitretin). Your doctor may adjust the dose depending on the disease and other factors, such as general health. The maximum recommended daily dose is 75 mg (i.e. 3 capsules, each containing 25 mg of acitretin).

Women of childbearing age
Treatment with Neotigason should only be started on the second or third day of the next menstrual period. At the beginning of treatment, your doctor will require a pregnancy test to be performed within 3 days prior to starting treatment and regular pregnancy testing during treatment and for 3 years after stopping treatment. Pregnancy test results must be negative. The patient must also use effective methods of contraception (birth control) continuously, without interruption, for at least 4 weeks before starting Neotigason, throughout the entire treatment period, and for 3 years after stopping acitretin treatment. See also section "Pregnancy and breastfeeding".

Use in children
Neotigason may be administered to children only when alternative treatment methods are inappropriate. The doctor will decide the dose, which depends, for example, on the condition being treated and the child's body weight.

Taking more Neotigason than recommended
If a patient or another person takes more Neotigason than recommended, contact a doctor or hospital immediately. Symptoms of overdose may include: headache, dizziness, nausea or vomiting, drowsiness, irritability, or skin itching.

Missed dose of Neotigason
Take the missed dose as soon as possible. However, if it is almost time for the next dose, skip the missed dose. Do not take a double dose to make up for a missed dose.

Stopping Neotigason
Do not stop taking Neotigason without consulting your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
You must stop taking Neotigason immediately and contact your doctor immediately
if any of the following adverse effects occur:

Severe headache, nausea, vomiting and visual disturbances. These may be symptoms of increased intracranial pressure ( very rare ).
Immediate allergic reactions, with symptoms such as rash, swelling or itching of the skin, redness and swelling of the eyes, severe swelling of the nasal mucosa, asthma or wheezing. These symptoms may range from mild to life-threatening ( frequency unknown ).
Yellowing of the skin and whites of the eyes – jaundice ( very rare ).
Jaundice and other symptoms such as loss of appetite, fever, general malaise, nausea, dark urine, abdominal discomfort. These may be symptoms of hepatitis ( uncommon ).
Severe condition (capillary leak syndrome/retinoic acid syndrome), during which small blood vessels (capillaries) leak. This may lead to severe hypotension, swelling due to fluid accumulation and shock (collapse). Symptoms include swelling or puffiness, difficulty breathing, stomach cramps, muscle pain, excessive thirst, general feeling of fatigue and weakness ( frequency unknown ).
Severe skin reaction with symptoms such as rash, blistering or exfoliative dermatitis ( frequency unknown ).

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

Dry, irritated or swollen eyes, which may lead to intolerance of contact lenses
Dryness, irritation or watery discharge from the nose, nosebleeds
Dry mouth, thirst
Dryness or inflammation of the lips, which can be relieved by applying a greasy ointment
Itching, hair loss, peeling of the skin on the hands or feet or even over the entire body
Changes in liver function (visible in blood tests)
Increased blood lipid levels (visible in blood tests).

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

Headache
Inflammation of the oral mucosa, abdominal pain, diarrhoea, nausea, vomiting
Sensitive skin, feeling of moist skin or rash, skin inflammation, abnormal hair structure, nail weakness, nail fold infection, skin redness
Joint pain, muscle pain
Swelling of the hands, ankles and feet.

Uncommon (may affect up to 1 in 100 people):

Dizziness
Blurred vision
Gingivitis
Cracks, fissures or erosions of the skin, e.g. around the mouth, skin blisters and skin inflammation (bullous dermatitis), increased sensitivity of the skin to sunlight (photosensitivity).

Rare (may affect up to 1 in 1000 people):

Peripheral nervous system damage, which may include symptoms such as muscle weakness, numbness and tingling of the feet, hands or burning, tearing or piercing pain.

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

Night blindness, inflammation of the cornea (corneal ulceration)
Bone pain, changes in bone growth.

Frequency unknown (cannot be estimated from available data):

Vaginal infections (also called candidiasis or fungal infection)
Mood changes, psychotic symptoms: altered perception of reality, such as hearing voices or seeing things that are not there
Hearing disorders, ringing in the ears (tinnitus)
Sudden flushing
Changes in taste sensation; bleeding from the rectum
Small, reddish nodules on the skin that may bleed easily (pyogenic granuloma), loss of eyelashes and eyebrows, skin swelling, skin rashes (causing itching and redness)
Skin thinning, exfoliative dermatitis
Improvement or worsening of glucose tolerance in patients with diabetes
Changes in voice quality (dysphonia).

At the beginning of treatment, a temporary worsening of psoriasis symptoms may sometimes occur.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed
in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported
directly to the Department of Monitoring Adverse Drug Reactions,
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309. Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder. By reporting
adverse effects, more information on the safety of this medicine can be collected.

5. How to store Neotigason

Keep this medicine out of sight and reach of children.
Store at a temperature not exceeding 25°C, in the original packaging.
Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the stated month.
Due to the risk of harmful effects on the unborn child, this medicine must not be passed on to other people. Unused or expired medicine must be returned to a pharmacy for disposal.

6. Contents of the package and other information

What Neotigason contains

The active substance is acitretin. Each capsule contains 10 mg or 25 mg of acitretin.
The other ingredients are:

Neotigason capsules, 10 mg:
gelatin, spray-dried liquid glucose, sodium ascorbate, microcrystalline cellulose
Capsule shell composition:
Capsule body: titanium dioxide (E 171), gelatin
Capsule cap: black iron oxide (E 172), yellow iron oxide (E 172), red iron oxide (E 172), titanium dioxide (E 171), gelatin
Printing ink: shellac, isopropyl alcohol, N-butyl alcohol, propylene glycol, ammonium hydroxide, black iron oxide (E 172)

Neotigason capsules, 25 mg:
gelatin, spray-dried liquid glucose, sodium ascorbate, microcrystalline cellulose
Capsule shell composition:
Capsule body: yellow iron oxide (E 172), titanium dioxide (E 171), gelatin
Capsule cap: black iron oxide (E 172), yellow iron oxide (E 172), red iron oxide (E 172), titanium dioxide (E 171), gelatin
Printing ink: shellac, isopropyl alcohol, N-butyl alcohol, propylene glycol, ammonium hydroxide, black iron oxide (E 172)

What Neotigason looks like and contents of the pack:
10 mg: capsules with a brown cap and a white body, printed with "10" in black ink on the body; size 4 capsules.
25 mg: capsules with a brown cap and a yellow body, printed with "25" in black ink on the body; size 1 capsules.
Each pack contains 30 or 100 capsules.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder:
Actavis Group PTC ehf.
Dalshraun 1
220 Hafnarfjörður
Iceland

Manufacturer:
CENEXI
52 rue Marcel et Jacques Gaucher
94120 Fontenay-sous-Bois
France

CENEXI
17 rue de Pontoise
95520 Osny
France

For more detailed information, please contact the representative of the marketing authorization holder:
Teva Pharmaceuticals Polska Sp. z o.o., Emilii Plater 53, 00-113 Warsaw, tel.: (22) 345 93 00.
Detailed and up-to-date information about this medicinal product is available by scanning with a smartphone
the QR code located on the Package Leaflet. The same information is also available on the website:
www.retinoidsteva.pl
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