AXOTRET 20 mg Capsules

Contents of the leaflet

1. Leaflet attached to the packaging: information for the user
2. Axotret, 10 mg, soft capsules
3. Axotret, 20 mg, soft capsules
   1. WARNING
   2. You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.
   3. Table of contents of the leaflet
4. What is Axotret and what is it used for
   1. Indications
5. Important information before using Axotret
   1. When not to use Axotret:
   2. Warnings and precautions
   3. Women who are pregnant must not take Axotret.
   4. Axotret may be prescribed to female patients of childbearing potential only under strict conditions due to the risk of serious birth defects.
   5. Female patients must use effective methods of contraception before, during, and after treatment with Axotret
   6. Female patients must agree to have pregnancy tests before, during, and after treatment with Axotret
   7. Advice for men
   8. Additional precautions
   9. This medicinal product should never be given to another person. All unused capsules should be returned to the pharmacist after treatment has ended.
   10. Do not donate blood during treatment with this medicine or for a month after stopping Axotret. If the patient's blood is given to a pregnant woman, she may give birth to a child with birth defects.
   11. Axotret and other medicines
   12. Axotret with food and drink
   13. Pregnancy, breastfeeding, and fertility
   14. Driving and using machines
6. How to use Axotret
   1. Using a higher dose of Axotret than recommended
   2. Missing a dose of Axotret
   3. Stopping treatment with Axotret
7. Possible side effects
   1. Very common (may affect more than 1 in 10 people):
   2. Common (may affect up to 1 in 10 people):
   3. Rare (may affect up to 1 in 1,000 people):
   4. Very rare (may affect up to 1 in 10,000 people):
   5. If the patient experiences any of the above symptoms of mental disorders, they should
   6. Frequency not known (frequency cannot be estimated from the available data):
   7. Reporting side effects
8. How to store Axotret
9. Contents of the packaging and other information
   1. What Axotret contains
   2. What Axotret looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. Marketing authorization holder
   5. Manufacturer

Leaflet attached to the packaging: information for the user

Axotret, 10 mg, soft capsules

Axotret, 20 mg, soft capsules

Isotretinoin

WARNING

CAN CAUSE SERIOUS HARM TO THE UNBORN CHILD.
Women must use effective methods of contraception.
Do not use during pregnancy or suspected pregnancy.

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to you specifically. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Axotret and what is it used for
• 2. Important information before using Axotret
• 3. How to use Axotret
• 4. Possible side effects
• 5. How to store Axotret
• 6. Contents of the packaging and other information

1. What is Axotret and what is it used for

The active substance of Axotret is isotretinoin, which belongs to a group of medicines called retinoids.

Indications

Axotret is used to treat severe forms of acne (such as nodular or conglobate acne, or acne with a risk of permanent scarring) that have not responded to treatment with systemic antibacterial medicines and topical medicines.
Treatment with isotretinoin must be supervised by a dermatologist with experience in treating severe forms of acne with retinoids. Axotret is not used to treat acne before puberty or in children under 12 years of age.

2. Important information before using Axotret

When not to use Axotret:

• if the patient is pregnant or breastfeeding,
• if there is a risk that the patient may become pregnant, it is necessary to follow the precautions listed in the Pregnancy Prevention Program, see "Warnings and precautions",
• if the patient is allergic to isotretinoin, soybean oil (peanuts or soy) or any of the other ingredients of this medicine (listed in section 6),
• in patients with liver failure,
• in patients with significantly elevated lipid levels (cholesterol, triglycerides) in the blood,
• if the patient has a high level of vitamin A in the body (hypervitaminosis A),
• if the patient is taking antibiotics from the tetracycline group.

Warnings and precautions

Before starting treatment with Axotret, you should discuss it with your doctor or pharmacist:

• -If the patient has ever had mental health problems, including depression, aggression, or mood swings, as well as thoughts of self-harm or suicide. This is because Axotret may affect the patient's mood.

Pregnancy Prevention Program

Women who are pregnant must not take Axotret.

This medicine can seriously harm the unborn child (the medicine has a teratogenic effect). It can cause serious damage to the brain, face, ear, eyes, heart, and some glands (thymus and parathyroid) of the fetus. It also increases the risk of miscarriage. These effects can occur even if Axotret is taken for a short period during pregnancy.

• Do not take Axotret if you are pregnant or think you may be pregnant.
• Do not take Axotret during breastfeeding. The medicine is likely to pass into breast milk and may harm the baby.
• Do not take Axotret if you may become pregnant during treatment.
• The patient must not become pregnant for a month after stopping treatment, as the medicine may still be present in the patient's body.

Axotret may be prescribed to female patients of childbearing potential only under strict conditions due to the risk of serious birth defects.

The following conditions must be met:

• The doctor must explain to the patient the risk of birth defects and the patient must understand why they must not become pregnant and how to prevent it.
• The patient must discuss contraception (birth control methods) with the doctor. The doctor will provide the patient with information on birth control methods. The doctor may refer the patient to a specialist for advice on contraception.
• Before starting treatment, the doctor will ask the patient to have a pregnancy test. The test must show that the patient is not pregnant at the start of treatment with Axotret.

Female patients must use effective methods of contraception before, during, and after treatment with Axotret

• The patient must agree to use at least one highly effective method of contraception (e.g., an intrauterine device or contraceptive implant) or two effective methods that work in different ways (e.g., oral hormonal contraceptives and condoms). The patient should discuss with the doctor which methods are most suitable for them.
• The patient must use a contraceptive method for a month before taking Axotret, during treatment, and for a month after stopping treatment.
• The patient must use contraception even if they do not menstruate or are not currently sexually active (unless the doctor decides it is not necessary).

Female patients must agree to have pregnancy tests before, during, and after treatment with Axotret

• The patient must agree to have regular check-ups with the doctor, ideally every month.
• The patient must agree to have regular pregnancy tests, ideally every month during treatment and a month after stopping treatment with Axotret, as the medicine may still be present in the patient's body (unless the doctor decides it is not necessary for the patient).
• The patient must agree to have additional pregnancy tests as recommended by the doctor.
• The patient must not become pregnant during and for a month after stopping treatment, as the medicine may still be present in the patient's body.
• The doctor will discuss all these issues with the patient using a checklist and ask the patient (or their parent or guardian) to sign it. This form confirms that the patient has been informed of the risk and agrees to follow the above rules.

If the patient becomes pregnant while taking Axotret, they must stop taking
the medicineand contact their doctor immediately. The doctor may refer the patient to a specialist for advice.
Additionally, if the patient becomes pregnant within a month of stopping treatment with Axotret, they should contact their doctor. The doctor may refer the patient to a specialist for advice.
Prescriptions for women of childbearing potential are limited to a quantity sufficient for 30 days of treatment.
Continuation of treatment requires a new prescription, and each prescription is valid for only 7 days.

Advice for men

The amount of oral retinoids in the sperm of men taking Axotret is too small to harm the unborn child of their partner. However, this medicinal product should never be shared with anyone else, especially women.

Additional precautions

This medicinal product should never be given to another person. All unused capsules should be returned to the pharmacist after treatment has ended.

Do not donate blood during treatment with this medicine or for a month after stopping Axotret. If the patient's blood is given to a pregnant woman, she may give birth to a child with birth defects.

Axotret may cause an increase in the levels of certain fats, such as triglycerides or cholesterol, in the blood. Before, during, and after treatment, the doctor will perform tests to monitor the levels of these fats. The patient should inform the doctor about any previous high levels of lipids in the blood, diabetes, overweight, or alcoholism, as more frequent blood tests may be necessary.
Axotret may cause an increase in liver enzyme activity. Before, during, and after treatment, the doctor will perform blood tests to monitor this activity. If the elevated liver enzyme levels persist, the doctor may reduce the dose of Axotret or stop treatment with isotretinoin.
Axotret may cause an increase in blood sugar levels and, in rare cases, diabetes. The doctor may monitor blood sugar levels during treatment, especially if the patient has diabetes, is overweight, or is an alcoholic.
During treatment, the patient should use a moisturizing cream or balm for the skin, or lip balm, as dry skin or lips may occur during treatment with isotretinoin.
Mental health problems
There have been reports of depression, worsening of depressive symptoms, anxiety, aggression, mood changes, behavioral disorders, psychotic symptoms, and, rarely, suicidal thoughts, attempted suicide, and suicide.
The patient should inform the doctor if they have had mental health problems in the past, including depression, behavioral disorders, or psychosis.
The patient may not notice certain changes in their mood and behavior, so it is very important that they tell their friends and family that they are taking this medicine. These people may notice such changes and help the patient identify problems that need to be discussed with the doctor.
If the patient experiences an allergic reaction (skin redness, itching) or a severe anaphylactic reaction, they should stop treatment immediately and contact their doctor as soon as possible.
There have been very rare reports of mild intracranial hypertension associated with the use of Axotret. If the patient experiences persistent headache, nausea, vomiting, and vision disturbances, they should stop treatment immediately and contact their doctor as soon as possible.
In very rare cases, the use of Axotret has been associated with inflammatory bowel disease. If the patient experiences severe bloody diarrhea (e.g., blood in the stool), they should stop treatment immediately and contact their doctor as soon as possible.
Treatment with Axotret may cause impaired night vision. During treatment with isotretinoin, dry eyes or vision disturbances may occur, which usually resolve after treatment is stopped. There have been cases of dry eye that did not resolve after treatment was stopped. Always exercise caution when driving or operating machinery at night, as these vision disturbances can occur suddenly. If the patient wears contact lenses and experiences dry eyes, they may need to wear glasses during treatment. If the patient experiences any vision disturbances, they should contact their doctor immediately, as it may be necessary to stop using Axotret and have their vision examined.
The skin may be more sensitive to sunlight during treatment with Axotret. The patient should avoid prolonged exposure to sunlight and not use a sunlamp or tanning bed. Before going out in the sun, the patient should use a protective product with a high sun protection factor (SPF), at least SPF 15.
Axotret may cause the skin to become more sensitive. During and for at least 6 months after stopping treatment, the patient should avoid cosmetic procedures, such as dermabrasion or laser skin treatment (removing rough skin or scars) and wax depilation, due to the risk of scarring or skin irritation.
Due to the fact that muscle and joint pain have been observed during treatment with Axotret, the patient should reduce the intensity of physical exercise during treatment.
The patient should discuss with their doctor if they experience persistent back pain or pain in the buttocks during treatment. These symptoms may indicate inflammatory back pain. The doctor may stop treatment with Axotret and refer the patient to a specialist for treatment of back pain. Further evaluation, including imaging tests, such as an MRI, may be necessary.

Axotret and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or plan to take.
During treatment with Axotret, the patient should not take medicines containing vitamin A or antibiotics from the tetracycline group.
During treatment with Axotret, the patient should not take vitamin A supplements. Taking them together may increase the risk of side effects.

Axotret with food and drink

Axotret should be taken with food.

Pregnancy, breastfeeding, and fertility

More information on pregnancy and contraception can be found in section 2, "Pregnancy Prevention Program".
If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.

Driving and using machines

During treatment with Axotret, impaired night vision may occur. The onset of this symptom can be sudden. Therefore, patients should exercise caution when driving or operating machinery.
Drowsiness, dizziness, and vision disturbances have been reported very rarely. If these symptoms occur, the patient should not drive or engage in other activities that could put themselves or others at risk.
Axotret contains a small amount of ethanol (alcohol), less than 100 mg per dose.
Axotret contains soybean oil. The patient should not take Axotret if they are hypersensitive to peanuts or soy.

3. How to use Axotret

This medicine should always be used as directed by the doctor. If the patient is unsure, they should consult their doctor.
The usual dose of Axotret is 0.5 mg per kilogram of body weight per day (0.5 mg/kg/day).
After a few weeks, the doctor may adjust the dose. This will depend on how the patient feels while taking the medicine. In most patients, the dose is between 0.5 and 1 mg/kg/day.
If the patient feels that the effect of Axotret is too strong or too weak, they should consult their doctor or pharmacist.
The capsules should be taken with food, once or twice a day. The capsules should be swallowed whole, not chewed or sucked.
If the patient has severe kidney disease, the doctor will start treatment with a lower dose, such as 10 mg per day, and then increase it to the maximum tolerated dose.
If the patient does not tolerate the recommended dose, the doctor may continue treatment with a lower dose, which will be associated with a longer treatment duration and a higher risk of relapse of the disease.
In rare cases, the symptoms of acne may worsen during the first few weeks of treatment. Improvement should occur over time during continued treatment.
The treatment cycle usually lasts for 16 to 24 weeks. The symptoms of acne may resolve within 8 weeks after stopping treatment. Therefore, the patient should not start another treatment cycle until this time has passed. In most patients, only one treatment cycle is necessary.
After stopping treatment, the patient should return any unused capsules to the pharmacy. They should only be kept if the doctor recommends it. The patient should remember that the medicine was prescribed specifically for them. They should not give it to others. It may harm them, even if their symptoms seem the same.

Using a higher dose of Axotret than recommended

If the patient takes a higher dose of Axotret than recommended or accidentally swallows the medicine, they should consult their doctor, pharmacist, or the nearest hospital.

Missing a dose of Axotret

If the patient misses a dose of Axotret, they should take it as soon as possible.
However, if it is almost time for the next dose, they should not take the missed dose, but take the next dose at the normal time. They should not take a double dose to make up for the missed dose.

Stopping treatment with Axotret

Stopping treatment may cause the symptoms to return.
If the patient has any further doubts about using this medicine, they should consult their doctor.

4. Possible side effects

Like all medicines, Axotret can cause side effects, although not everybody gets them.
These effects often resolve during continued treatment or after treatment is stopped. The doctor can help the patient deal with them.

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

• Blood disorders that affect various types of blood cells. There may be disorders of cells responsible for blood clotting, which means that bruising and bleeding may occur more easily. If there are disorders of red blood cells, anemia may occur. During treatment, blood will be regularly monitored.
• Inflammation of the eye (conjunctivitis) and the area around the eyelids (blepharitis).
• Dryness and mild irritation of the eyes. The patient should ask the pharmacist to recommend suitable eye drops that can help.
• Dry skin, particularly on the lips and face. There may be inflammatory skin conditions (dermatitis), flaking, and inflammation of the mouth (cheilitis), rash, itching, and peeling of the skin. This dryness can be reduced by regularly using good moisturizing creams from the start of treatment. In very common cases, the skin may become more delicate and redder than usual, especially on the face.
• Back pain. Due to the fact that muscle and joint pain are very common during treatment with Axotret, especially in children and adolescents, the patient should reduce the intensity of physical exercise during treatment.
• Increased liver enzyme activity, detected in blood tests performed throughout the treatment period.
• Increased levels of triglycerides in the blood, decreased levels of high-density lipoproteins.

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

• Neutropenia (reduced number of white blood cells - granulocytes, responsible for fighting infections).
• Headache.
• Dryness inside the nose, nosebleeds, and inflammation of the nasal passages.
• Increased levels of cholesterol in the blood, increased levels of glucose in the blood.
• Hematuria, proteinuria.

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

• Depression or related disorders. Symptoms include sadness, mood changes, anxiety, and emotional discomfort.
• Worsening of existing depression.
• Aggression or violent behavior.
• Allergic skin reactions, such as skin rash and itching, anaphylactic reactions, hypersensitivity. Severe allergic reactions (anaphylaxis) can cause chest tightness and difficulty breathing. If the patient experiences an allergic reaction, they should stop taking Axotret and contact their doctor.
• Hair loss. Hair should return to its normal state after treatment is stopped.
• Baldness.

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

• Some people have had thoughts or ideas about self-harmor suicide (suicidal thoughts), attempted suicide, or committed suicide. These people may not have shown symptoms of depression.
• Abnormal behavior.
• Psychotic symptoms: loss of contact with reality, e.g., the patient hears voices or sees things that do not exist.

If the patient experiences any of the above symptoms of mental disorders, they should

contact their doctor immediately. The doctor may advise stopping Axotret.
Stopping treatment may not be enough to resolve these effects; additional help may be necessary, and the doctor can provide it.

• Seizures, drowsiness, dizziness.
• Vasculitis.
• Lymphadenopathy (enlargement of the lymph nodes).
• Mild intracranial hypertension, especially when isotretinoin is used with certain antibiotics (tetracyclines). If the patient experiences persistent headache, nausea, vomiting, and vision disturbances, they should stop treatment and contact their doctor immediately.
• Due to dry eyes during treatment, people who wear contact lenses may need to wear glasses.
• Impaired night vision caused by the medicine, which can make it harder to see in the dark. The medicine can also cause color blindness and some patients may have reduced ability to distinguish colors. The patient may become more sensitive to light and may need to wear sunglasses to protect their eyes from too much sunlight.
• Vision disturbances, such as blurred vision, corneal clouding, and cataracts (clouding of the lens of the eye). If the patient experiences any vision disturbances, they should contact their doctor immediately, as it may be necessary to stop using Axotret and have their vision examined.
• Hearing problems (worsening of hearing).
• Severe gastrointestinal disorders, such as pancreatitis, gastrointestinal bleeding, colitis, and inflammatory bowel disease. If the patient experiences severe abdominal pain with bloody diarrhea or without, nausea, and vomiting, they should stop treatment and contact their doctor immediately.
• Kidney inflammation. Symptoms include excessive fatigue, difficulty urinating, and swollen and puffy eyelids. If the patient experiences these symptoms, they should stop treatment and contact their doctor.
• Bacterial infections of the skin and mucous membranes. Local bacterial infections of the tissue around the nail, swelling with pus discharge, nail changes, thickening of scars after surgical procedures, and increased body hair.
• Diabetes, with symptoms including excessive thirst and frequent urination. Blood tests often showed elevated blood sugar levels.
• Increased levels of uric acid in the blood (hyperuricemia).
• Excessive sweating.
• Bronchospasm, especially in patients with asthma, hoarseness.
• Worsening of acne symptoms.
• The skin may appear inflamed and swollen, with increased pigmentation on the face, and there may be skin rashes, hair disorders.
• Arthritis, bone disorders (including delayed bone growth, bone spurs, and decreased bone density), calcification of tendons and ligaments, rare cases of tendon pain, and abnormal levels of muscle breakdown products in the blood, if the patient engages in intense physical exercise during treatment. Bones that have not yet finished growing may stop growing prematurely.
• Severe liver disorders (hepatitis). If the patient experiences yellowing of the skin or eyes with fatigue, they should stop treatment and contact their doctor immediately.
• Increased activity of creatine phosphokinase in the blood.
• Excessive granulation, malaise.

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

• Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), which can be life-threatening and require immediate medical attention. At the beginning, they appear as round spots, often with centrally located blisters, usually on the arms and hands or legs and feet, and more severe rashes may be accompanied by blisters on the chest and back. Additional symptoms may include eye inflammation (conjunctivitis) or oral, throat, or nasal ulcers. Severe skin rashes can cause widespread skin peeling, which can be life-threatening. These severe skin rashes are often preceded by headache, fever, and flu-like symptoms. If a rash develops or the above skin changes occur, the patient should stop treatment with Axotret and contact their doctor immediately.
• Difficulty achieving or maintaining an erection.
• Reduced libido.
• Breast tenderness or swelling, occurring in men,
• Vaginal dryness.
• Sacroiliitis, a type of back pain with an inflammatory cause, causing pain in the lower back or buttocks.
• Urethritis.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products:
Aleje Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309
e-mail: [email protected]
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, it is possible to gather more information on the safety of the medicine.

5. How to store Axotret

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of that month.
Store in a temperature below 25°C.
Store in the original packaging.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Axotret contains

• The active substance of Axotret is isotretinoin. One soft capsule contains 10 mg or 20 mg of isotretinoin.
• The other ingredients are: hydrogenated soybean oil, hydrogenated vegetable oil, white beeswax, disodium edetate, butylhydroxyanisole, refined soybean oil. Coating(only for Axotret, 10 mg): gelatin, glycerol, iron oxide red (E 172), titanium dioxide (E 171), purified water. Coating(only for Axotret, 20 mg): gelatin, glycerol, allura red (E 129), brilliant blue (E 133), titanium dioxide (E 171), purified water. Printing ink: shellac, iron oxide black (E 172), n-butanol, propylene glycol, isopropanol, ammonium hydroxide.

What Axotret looks like and contents of the pack

Axotret is a soft capsule.
Axotret, 10 mg: light pink opaque gelatin capsules of oval shape, with 'RR' printed in ink, containing an orange-yellow oily liquid.
Axotret, 20 mg: brown opaque gelatin capsules of oval shape, with 'RR' printed in ink, containing an orange-yellow oily liquid.
Axotret is available in blisters containing 30 or 60 soft capsules, packed in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Aristo Pharma Sp. z o.o.
Baletowa 30
02-867 Warsaw

Manufacturer

Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132JH Hoofddorp
Netherlands
GAP SA
46, Agissilaou str.
Agios Dimitrios Attiki, 173 41
Athens
Greece
Date of last revision of the leaflet:January 2024

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