Axotret

Package leaflet: Information for the user

Axotret, 5 mg, soft capsules
Axotret, 40 mg, soft capsules
Isotretinoinum
WARNING
CAN CAUSE SEVERE BIRTH DEFECTS.
Women must use effective contraception.
Do not use during pregnancy or if pregnancy is suspected.
Please read 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 further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else 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.

Contents of the leaflet

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

1. What Axotret is and what it is used for

The active substance in Axotret is isotretinoin – a substance structurally similar to vitamin A, belonging to a group of medicines called retinoids (used in the treatment of acne).
Axotret is used to treat severe forms of acne (such as nodular or conglobate acne, or acne with risk of permanent scarring) in adult patients and adolescents above the age of 12, but only after puberty. Axotret is used when acne symptoms have not improved with other anti-acne treatments, including antibiotics and topical medications.
Treatment with isotretinoin must be supervised by a dermatologist (a doctor specialising in skin disorders).

2. Important Information Before Using Axotret

When not to use Axotret:

• if the patient is pregnant or breastfeeding,
• if there is any possibility that the patient could 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 isotretinoin, soybean oil (peanuts or soy), or any of the other ingredients of this medicine (listed in section 6),
• in patients with liver disease,
• in patients with significantly increased levels of lipids (cholesterol, triglycerides) in the blood,
• if the patient has high levels of vitamin A in the body (hypervitaminosis A),
• if the patient is concurrently taking tetracycline antibiotics (see section “Axotret and other medicines”).

If any of the above situations apply, consult a doctor before starting treatment with Axotret.
Warnings and precautions
Before starting treatment with Axotret, discuss this with your doctor or pharmacist:

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

Talk to your doctor if, during treatment with Axotret, the patient experiences persistent pain in the lower back or buttocks. These symptoms may indicate inflammation of the sacroiliac joints, a type of inflammatory back pain. The doctor may discontinue treatment with Axotret and refer the patient to a specialist for management of inflammatory back pain. Further evaluation, including imaging tests such as magnetic resonance imaging (MRI), may be necessary.
Pregnancy Prevention Programme
Women who are pregnant must NOT take Axotret
This medicine can severely harm the unborn child (it is “teratogenic”). It may cause serious malformations of the brain, face, ears, 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 Axotret is taken only for a short time during pregnancy.

• Do NOT take Axotret if the patient is pregnant or suspects she might be pregnant.
• Do NOT take Axotret during breastfeeding. The medicine is likely to pass into breast milk and may harm the infant.
• Do NOT take Axotret if the patient could become pregnant during treatment.
• The patient must NOT become pregnant for one month after stopping treatment, as the medicine may still be present in her body.

Axotret may be prescribed to women of childbearing potential only if they strictly comply with specific requirements due to the risk of severe birth defects.
The following conditions must be met:

• The doctor must explain to the patient the risk of fetal harm (birth defects); the patient must understand why she must not become pregnant and how to prevent it.
• The patient must discuss contraception (birth control methods) with her doctor. The doctor will provide information on contraceptive methods. The doctor may refer the patient to a specialist for contraceptive counselling.
• Before starting treatment, the doctor will request a pregnancy test. The test must confirm that the patient is not pregnant at the start of Axotret treatment.

Women must use effective contraception before, during, and after treatment with Axotret

• 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 that work in different ways (e.g., oral hormonal contraceptives and condoms). Discuss with the doctor which methods are most suitable for the patient.
• The patient must use contraception for one month before starting Axotret, throughout treatment, and for one month after stopping the medicine.
• The patient must use contraception even if she does not have periods 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 Axotret

• The patient must agree to regular follow-up visits with her doctor, ideally every month.
• The patient must agree to regular pregnancy tests, ideally every month during treatment and one month after stopping Axotret, as the medicine may still be present in her body (unless the doctor determines otherwise).
• The patient must agree to additional pregnancy tests as recommended by her treating physician.
• The patient must NOT become pregnant during or within one month after treatment, as the medicine may still be present in her body.
• The treating doctor will discuss all issues with the patient, using a checklist, and 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 above requirements.

If the patient becomes pregnant while taking Axotret, she must IMMEDIATELY STOP
taking the medicine and contact her doctor. The doctor may refer her to a specialist for advice.
Additionally, a woman who becomes pregnant within one month after stopping Axotret should contact her treating doctor. The doctor may refer her to a specialist for advice.
Prescriptions for women of childbearing age are limited to a 30-day supply to ensure regular follow-up visits, including pregnancy testing and monitoring. Ideally, the pregnancy test, prescription issuance, and dispensing of isotretinoin should occur on the same day. Dispensing of isotretinoin should occur within a maximum of 7 days of the prescription date.
Advice for men
The amount of oral retinoids in the semen of men taking Axotret is too low to harm the unborn child of their partner. However, this medicine must never be shared with anyone else, especially women.
Additional precautions
Never pass this medicine to another person. All unused capsules must be returned to the pharmacist after treatment ends.
Do NOT donate blood while taking this medicine or within one month after stopping Axotret. If a pregnant woman receives the patient’s blood, she may give birth to a child with birth defects.
Information for all patients

• Discuss with your doctor if the patient has ever had mental health problems (including depression, suicidal behaviour, or psychosis) or is taking medication for any of these conditions. The patient may not notice certain changes in mood or behaviour, so it is very important to inform friends and family members about taking this medicine. They may notice such changes and help the patient quickly identify problems requiring discussion with the doctor.
• Severe skin reactions have been observed during isotretinoin treatment (e.g., erythema multiforme [EM], Stevens-Johnson syndrome [SJS], and toxic epidermal necrolysis [TEN]). Rashes may appear as widespread blistering or skin peeling. Also watch for mouth, throat, nose, or genital ulcers, and conjunctivitis (redness and swelling of the eyes).
  • In rare cases, Axotret may cause severe allergic reactions , which may include skin rash, hives, bruising, or red spots on the hands and feet. If an allergic reaction occurs, stop taking Axotret immediately, contact a doctor, and inform them about taking this medicine.
  • Limit intense physical exertion and exercise. Axotret may cause muscle and joint pain, particularly in children and adolescents engaging in intense physical activity.
  • Isotretinoin use has been associated with non-specific inflammatory bowel disease. If the patient develops severe bloody diarrhoea without a history of gastrointestinal disorders, the doctor will discontinue treatment with Axotret.
  • Axotret may cause dry eye syndrome, intolerance to contact lenses, and visual disturbances, including night vision impairment. Cases of persistent dry eye that did not resolve after treatment have been reported. Inform the doctor if any of these symptoms occur. The doctor may recommend lubricating eye ointments or artificial tears. If contact lens intolerance occurs, the doctor may advise wearing glasses during treatment. If visual disturbances occur, the doctor may refer the patient to a specialist for advice and may consider discontinuing Axotret.
  • Benign intracranial hypertension has been observed during isotretinoin treatment , sometimes when isotretinoin is taken concurrently with tetracyclines (a class of antibiotics used, for example, in acne treatment). If symptoms such as headache, nausea, vomiting, or visual disturbances occur, stop taking Axotret and contact a doctor immediately. The doctor may refer the patient to a specialist to check for papilledema (optic disc swelling).
  • Axotret may increase liver enzyme activity. The treating doctor will order appropriate blood tests before, during, and after treatment to monitor liver enzyme activity. If enzyme levels remain elevated, the doctor may reduce the dose or discontinue treatment with Axotret.
  • Isotretinoin often leads to increased blood lipid levels such as cholesterol or triglycerides. The doctor will check lipid levels before starting Axotret, during treatment, and after treatment ends. During treatment, it is best to avoid alcohol or at least reduce its consumption. Inform the doctor if the patient has high blood lipid levels, diabetes (high blood glucose), is overweight, or consumes large amounts of alcohol. More frequent blood tests may be necessary. If blood lipid levels remain high, the doctor may reduce the dose or discontinue treatment with Axotret.
  • Inform the doctor if the patient has any kidney disease. The doctor may start treatment with a lower dose of Axotret and gradually increase it to the maximum tolerated dose.
• Axotret may lead to increased blood glucose levels. In rare cases, diabetes has developed in patients. The doctor may monitor blood glucose levels during treatment, especially if the patient already has diabetes, is overweight, or consumes large amounts of alcohol.
• Skin dryness is likely to occur. During treatment, use a moisturizing cream or ointment and lip balm. To prevent skin irritation, avoid using peeling or anti-acne products.
• Avoid excessive sun exposure and using sunlamps or tanning beds. The skin may become more sensitive to sunlight. Apply sunscreen with a high UV protection factor (at least SPF 15) before going outdoors.
• Do not undergo any cosmetic skin procedures. Axotret may make the skin more sensitive. Do not wax, undergo dermabrasion, or laser treatments (to remove keratinized skin or scars) during treatment and for at least 6 months after treatment ends, as this may lead to scarring, skin irritation, or, rarely, skin discoloration.

Children and adolescents
Do not use Axotret in children under 12 years of age. It is not known whether the medicine is safe or effective in this age group.
Use in adolescents over 12 years of age is only possible after puberty.
Axotret and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.

• While taking Axotret, do NOT take products containing vitamin A or tetracyclines (an antibiotic used, for example, in acne treatment), or apply any anti-acne products to the skin. Moisturizers and emollients (creams or skin products that prevent water loss and soften the skin) may be used.
• While taking Axotret, avoid topical use of keratolytic or peeling anti-acne agents.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she might be pregnant, or plans to have a child, she should consult her doctor or pharmacist before using this medicine.
For more information on contraception, pregnancy, and breastfeeding, see section 2, “Pregnancy Prevention Programme”.
Driving and operating machinery
During isotretinoin treatment, impaired night vision may occur. This symptom may appear suddenly. Therefore, patients should exercise caution when driving or operating machinery.
Drowsiness, dizziness, and visual disturbances have been reported very rarely. If any of these symptoms occur, do not drive, operate machinery, or engage in other activities where the patient or others may be put at risk.
Axotret contains soybean oil (refined and hydrogenated)
Do not use if hypersensitivity to peanuts or soy has been diagnosed.
Axotret contains glycerol
The medicine may cause headache, gastrointestinal disturbances, and diarrhoea.
Axotret contains sorbitol
Sorbitol is a source of fructose.
Axotret 5 mg contains 5.85 mg of sorbitol per capsule.
Axotret 40 mg contains 14.43 mg of sorbitol per capsule.
Axotret (only the 40 mg strength) contains carmine red (E 124)
The medicine may cause allergic reactions.

3. How to use Axotret

This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult
your doctor or pharmacist.
The usual starting dose of Axotret is 0.5 mg per kilogram of body weight per day
(0.5 mg/kg bw per day). This means that if the patient's body weight is 60 kg, the usual starting
dose will typically be 30 mg per day.
Capsules should be taken once or twice daily.
The medicine should be taken with a full stomach. Capsules must be swallowed whole, with water
or taken together with food.
After a few weeks, the treating physician may adjust the dose. This will depend on how the
patient feels while taking the medicine. In most patients, the dose ranges from 0.5 mg/kg bw
per day to 1 mg/kg bw per day.
If the effect of Axotret seems too strong or too weak, consult your doctor or pharmacist.
If the patient has severe kidney disease, treatment with Axotret will be initiated by the doctor
at a lower dose (such as 10 mg per day), which will then be increased to the highest tolerated dose.
If the patient does not tolerate the recommended dose, the treating physician may continue treatment
with a lower dose, which may result in a longer treatment duration and a higher risk of disease recurrence.
The treatment cycle usually lasts from 16 to 24 weeks. Most patients will require only one treatment cycle.
Acne symptoms may continue to improve for up to 8 weeks after treatment ends. Therefore, a new treatment cycle should not be started before this period has passed.
In rare cases, acne symptoms may worsen during the first few weeks of treatment. Improvement is expected over time with continued treatment.
After treatment ends, any unused capsules should be returned to the pharmacist. They should be kept only if specifically instructed by the treating physician. Remember that this medicine was prescribed for a specific patient. Do not give it to others. It may harm them, even if their symptoms appear similar.
Taking more than the recommended dose of Axotret
If more than the recommended dose of Axotret is taken, or if the medicine is accidentally swallowed,
seek advice from your doctor, pharmacist, or nearest hospital immediately.
Missing a dose of Axotret
If a dose of Axotret is missed, take it as soon as possible. However, if it is almost time for the next dose,
do not take the missed dose; instead, continue with the next dose according to the regular schedule.
Do not take a double dose to make up for a missed dose.
Stopping treatment with Axotret
If you have any further doubts regarding the use of this medicine, consult your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Some adverse effects associated with isotretinoin use are dose-dependent.
Adverse effects usually resolve after dose adjustment or discontinuation of treatment, but some
may persist after treatment has ended. Some adverse effects may be severe
and require immediate medical attention.
Adverse effects requiring immediate medical attention: skin disorders
Frequency unknown (cannot be estimated based on available data)

• Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis), which may be life-threatening and require immediate medical attention. Initially, they appear as circular spots, often with centrally located blisters, usually on the hands and palms or feet and soles. More severe rashes may involve blistering on the chest and back. Additional symptoms may also occur, such as eye infection (conjunctivitis) or ulceration in the mouth, throat, or nose. Some types of rash may progress to widespread skin peeling, which may be life-threatening. The onset of these severe skin rashes is often preceded by headache, fever, and body aches (flu-like symptoms). If the patient develops a severe rash or any of the above skin symptoms, treatment with Axotret must be discontinued immediately and the doctor should be contacted without delay.

Psychiatric disorders
Rare adverse effects (may occur in less than 1 in 1,000 patients)

• Depression or depression-related disorders. Symptoms include: sadness, feelings of emptiness, mood changes, anxiety, crying spells, irritability, loss of pleasure, loss of interest in social or sports activities, too long or too short sleep, changes in body weight or appetite, reduced performance at school or work, or difficulty concentrating.
• Worsening of pre-existing depression.
• Tendency towards violence or aggression.

Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Some individuals have experienced thoughts or images of self-harm or suicide (suicidal thoughts), attempted suicide, or died by suicide. These individuals may not have shown symptoms of depression.
• Unusual behavior.
• Psychotic symptoms: loss of contact with reality, e.g., the patient hears voices or sees things that do not exist in reality.

If any of the psychiatric symptoms described above occur, contact the doctor immediately.
The doctor may recommend discontinuation of Axotret. Stopping the medication may not be sufficient for these symptoms to resolve; additional support may be needed, which the doctor can provide.
Allergic reactions
Rare adverse effects (may occur in less than 1 in 1,000 patients)

• Severe (anaphylactic) reactions: difficulty breathing or swallowing due to sudden swelling of the throat, face, lips, or mouth. Also sudden swelling of the hands, feet, and ankles.

Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Sudden chest tightness, shortness of breath, and wheezing, especially if the patient has asthma.

In case of a severe reaction, seek emergency department care immediately.
If any allergic reaction occurs, discontinue taking Axotret and contact your physician.
Musculoskeletal system
Frequency unknown (cannot be estimated based on available data)

• Muscle weakness, which may potentially be life-threatening, may be associated with difficulty moving arms or legs, pain, swelling, bruising of body parts, dark-colored urine, reduced urine output, or cessation of urine production, confusion, or dehydration. These are symptoms of rhabdomyolysis, i.e., breakdown of muscle tissue, which may lead to kidney failure. This may occur during intense physical activity while taking Axotret.

Liver and kidney function disorders
Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Yellowing of the skin or whites of the eyes and feeling tired. These may be symptoms of hepatitis.
• Difficulty urinating, swollen and puffy eyelids, feeling excessively tired. These may be symptoms of kidney inflammation. Treatment with Axotret must be discontinued immediately and the doctor should be contacted.

Nervous system disorders
Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Persistent headache accompanied by nausea, vomiting, and visual disturbances, including blurred vision. These may be symptoms of benign intracranial hypertension, particularly when Axotret is taken concomitantly with tetracycline antibiotics. Treatment with Axotret must be discontinued immediately and the doctor should be contacted.

Gastrointestinal disorders
Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Severe abdominal pain with bloody diarrhea, nausea, and vomiting, or without these symptoms. These may be symptoms of severe intestinal diseases. Treatment with Axotret must be discontinued immediately and the doctor should be contacted.

Eye disorders
Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Blurred vision. If blurred vision occurs, treatment with Axotret must be discontinued immediately and the doctor should be contacted. Any other changes in vision should prompt immediate contact with the doctor.

Other adverse effects
Very common adverse effects (may occur in more than 1 in 10 patients)

• Dry skin, especially around the lips and face, skin inflammation, chapped and inflamed lips, rash, mild itching, and slight peeling. A moisturizing cream should be used from the beginning of treatment.
• Skin more sensitive and redder than usual, especially on the face.
• Back pain, muscle pain, joint pain, particularly in children and adolescents. To avoid worsening any musculoskeletal or muscular complaints, intense physical activity should be limited during treatment with Axotret.
• Inflammation of the eyes (conjunctivitis) and eyelids, dryness and irritation of the eyes. Consult a pharmacist for appropriate eye drops. In case of dry eye syndrome, wearing glasses instead of contact lenses may be necessary.
• Increased liver enzyme activity in blood tests.
• Altered blood lipid levels (including HDL or triglycerides).
• Bruising, bleeding, or faster blood clotting—if the medicine has affected cells responsible for blood clotting.
• Anemia—weakness, dizziness, pale skin—if the medicine has affected red blood cells.

Common adverse effects (may occur in less than 1 in 10 patients)

• Headache.
• Higher blood cholesterol levels.
• Presence of protein or blood in urine.
• Increased susceptibility to infections, if the medicine has affected white blood cells.
• Drying of the nasal mucosa and formation of scabs leading to mild nosebleeds.
• Pain or inflammation of the throat and nasal cavity.
• Allergic reactions such as rash and itching. If any allergic reaction occurs, discontinue taking Axotret and contact your doctor.

Rare adverse effects (may occur in less than 1 in 1,000 patients)

• Hair loss (alopecia). Usually temporary. Should resolve after treatment ends.

Very rare adverse effects (may occur in less than 1 in 10,000
patients)

• Night vision impairment, color blindness, and reduced color perception may occur.
• Increased sensitivity to light may occur; wearing sunglasses may be necessary to protect the eyes from excessively bright light.
• Other visual disturbances, including blurred vision, image distortion, clouding of the eye surface (corneal clouding, cataract).
• Excessive thirst, frequent urination, blood test results indicating increased blood glucose levels. These may be symptoms of diabetes.
• During the first few weeks, acne may worsen, but symptoms should gradually improve over time.
• Skin inflamed, swollen, and darker than usual, especially on the face.
• Excessive sweating or itching.
• Joint inflammation; bone-related disorders (growth delay, excessive growth, and changes in bone density); may lead to inhibition of growth in developing bones.
• Calcium deposition in soft tissues, tendon pain, and elevated levels of muscle breakdown products in blood during intense physical activity.
• Increased light sensitivity.
• Bacterial infections at the base of nails, nail changes.
• Swelling, discharge, pus.
• Excessive scarring after surgical procedures.
• Increased body hair growth.
• Seizures, drowsiness, dizziness.
• Lymph node swelling may occur.
• Dry throat, hoarseness.
• Hearing deterioration.
• General malaise.
• High uric acid levels in blood.
• Bacterial infections.
• Blood vessel inflammation (sometimes with bruising or red spots).

Frequency unknown (cannot be estimated based on available data)

• Dark or dark brown urine.
• Difficulty achieving or maintaining erection.
• Reduced sexual drive.
• Breast swelling with or without tenderness in men.
• Vaginal dryness.
• Urethritis.
• Sacroiliitis, a type of inflammatory back pain causing pain in the lower back or buttocks.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to gather more information on the safety of the medicine.

5. How to store Axotret

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after the abbreviation:
"EXP". The expiry date refers to the last day of the stated month.
Store below 25°C.
Keep in the original packaging to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.
Return any remaining capsules to the pharmacist. Keep them only if advised by your doctor.

6. Contents of the pack and other information

What Axotret contains

• The active substance is isotretinoin. Axotret, 5 mg: One soft capsule contains 5 mg of isotretinoin.

Axotret, 40 mg: One soft capsule contains 40 mg of isotretinoin.

• Other ingredients are:
  Axotret, 5 mg: all-rac-α-tocopheryl acetate (E 307), hydrogenated vegetable oil (soya, type II), hydrogenated soya oil, refined soya oil, yellow beeswax;
  Capsule shell: gelatin, glycerol, liquid sorbitol, partially dehydrated, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172), purified water.
  Axotret, 40 mg: all-rac-α-tocopheryl acetate (E 307), hydrogenated vegetable oil (soya, type II), hydrogenated soya oil, refined soya oil, yellow beeswax;
  Capsule shell: gelatin, glycerol, liquid sorbitol, partially dehydrated, titanium dioxide (E 171), patent blue V (E 131), cochineal red (E 124), purified water.

What Axotret looks like and contents of the pack
Axotret, 5 mg: light orange, oval, soft capsules of size 2.
Axotret, 40 mg: purple, oval, soft capsules of size 12.
PVC/TE/PVDC/Aluminium blister pack in a cardboard carton.
Pack size:
Axotret, 5 mg: 30 soft capsules
Axotret, 40 mg: 30 soft capsules

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aristo Pharma Sp. z o.o.
Baletowa 30 Street
02-867 Warsaw
Tel.: +48 22 855 40 93
Fax: +48 22 855 40 95

Manufacturer
GAP SA
Agissilaou str. 46
173 41 Agios Dimitrios Attiki
Greece

Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (urpl.gov.pl)