Package Insert: Patient Information

Bexarotene Cipla 75 mg Soft Gelatin Capsules EFG

Read this entire package insert carefully before starting to take this medication because it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, report them to your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

The bexarotene, the active ingredient of this medication, belongs to a family of medications known as retinoids that are related to vitamin A.

This medication is administered to patients in advanced stages of cutaneous T-cell lymphoma (CTCL) whose disease has not responded to other therapies. CTCL is a condition in which certain cells of the body's lymphatic system, called T lymphocytes, become cancerous and affect the skin.

Do not take Bexaroteno Cipla:

• If you are allergic to bexarotene or any of the other components of this medication (listed in section 6).
• If you are pregnant or breastfeeding, or if you may become pregnant and are not using effective contraceptive measures.
• If you have had previous episodes of pancreatitis, if you have uncontrolled high levels of lipids (fats in the blood) (high cholesterol levels in the blood or high triglyceride levels in the blood), if you have hypervitaminosis A, uncontrolled thyroid disease, decreased liver function, or persistent systemic infection.

Warnings and precautions

Consult your doctor or pharmacist before starting to take this medication:

• If you have known hypersensitivity to retinoids (related to vitamin A), have liver disease, high levels of lipids in the blood, or are taking medications that may cause high levels of lipids in the blood, if you have uncontrolled diabetes mellitus, if you have had gallbladder or bile duct disease, or if you consume excessive amounts of alcohol.
• If you have ever had any mental health problems, such as depression, aggressive tendencies, or mood changes. This is because this medication may affect your mood.

Lipid level determinations in the blood should be performed in the fasting state before starting treatment and at weekly intervals, and subsequently at monthly intervals throughout the entire therapy with this medication.

Before starting treatment and throughout the treatment, blood tests will be performed to evaluate liver function and thyroid gland function and to check your white and red blood cell count.

Regular eye check-ups may be necessary if you experience visual difficulties while taking this medication.

Reduce your exposure to the sun as much as possible and avoid ultraviolet lamps.

Do not take more than 15,000 International Units per day of vitamin A supplements during treatment.

Mental health problems

You may notice some changes in your mood and behavior, so it is very important to tell your friends and family that this medication may affect your mood and behavior. They may notice these changes and help you identify any problems you need to discuss with your doctor.

Children and adolescents

This medication should not be administered to children or adolescents.

Other medications and Bexaroteno Cipla

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, such as:

• ketoconazole and itraconazole (used against fungal infections),
• erythromycin, clarithromycin, and rifampicin (used against bacterial infections),
• phenytoin and phenobarbital (used against seizures and other conditions),
• gemfibrozil (to reduce high levels of fat in the blood, such as triglycerides and cholesterol),
• vitamin A supplements, protease inhibitors (against viral infections),
• tamoxifen (against certain types of cancer),
• dexamethasone (for inflammatory conditions),
• insulin, medications that increase insulin secretion or insulin sensitivity (used for diabetes mellitus).

This is important, as taking multiple medications at the same time may enhance or reduce the effect of the medications.

Taking Bexaroteno Cipla with food and drinks

This medication should be taken with food (see section 3). If you regularly consume grapefruit or grapefruit juice, consult your doctor as these may potentially alter the body's response to this medication's therapy.

Pregnancy and breastfeeding

This medication may be harmful to a developing fetus. DO NOT use this medication if you are pregnant or breastfeeding. If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

If you may become pregnant, you should have a pregnancy test one week before starting treatment to confirm that you are not pregnant. You should use a reliable contraceptive method (birth control) that starts one month before starting treatment and continues for one month after stopping this medication. It is recommended to use two reliable forms of contraception together. You should consult your doctor if you are taking hormonal contraception (e.g., the birth control pill).

If you are a man and your partner is pregnant or may become pregnant, you should use condoms during sexual intercourse while taking this medication and for at least one month after the last dose.

Driving and operating machinery

The effect of this medication on your ability to drive a car or operate machinery is unknown. If you experience dizziness or visual problems during treatment, you should not drive vehicles or operate machinery.

Bexaroteno Cipla contains sorbitol

This medication contains 122,198 mg of sorbitol in each capsule. Sorbitol is a source of fructose. If your doctor has told you that you have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult your doctor before taking this medication.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Your doctor will prescribe a suitable dose for you.

The recommended dose is generally 4 to 10 capsules taken once a day. Take the prescribed number of capsules at the same time each day with a meal. Capsules can be taken immediately before, after, or during a meal, as preferred. Capsules should be swallowed whole, without chewing.

The duration of Bexaroteno Cipla therapy

Although some patients notice improvement after the first few weeks of treatment, most patients require a longer therapy of several months before noticing improvement.

If you take more Bexaroteno Cipla than you should

If you have taken more than the prescribed dose of this medication, contact your doctor.

If you forgot to take Bexaroteno Cipla

If you forgot to take a dose, take the daily dose with the next meal on the same day, and take the normal dose the next day. Do not take a double dose on a single day to compensate for the missed doses from the previous day.

If you interrupt treatment with Bexaroteno Cipla

Your doctor will determine for how long you should take this medication and when to discontinue treatment. Do not stop taking the medication until your doctor instructs you to do so.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

If you notice any worsening of your condition while taking this medicine, inform your doctor. Sometimes it is necessary to adjust the dose or discontinue treatment. Your doctor will advise you on what to do.

The following side effects were reported in patients with LCCT treated with the recommended initial dose of capsules.

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

• Low white blood cell count.
• Decrease in thyroid hormone levels.
• Elevation of blood fats (triglycerides and cholesterol).
• Skin reactions (itching, redness, irritation, skin peeling).
• Headache, fatigue, pain.

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

• Low red blood cell count, lymph node enlargement, worsening of lymphoma.
• Thyroid disease.
• Elevation of liver enzymes, impaired renal function, decreased serum proteins, weight gain.
• Insomnia, dizziness, decreased skin sensation.
• Dry eyes, hearing loss, eye discomfort, including irritation and heaviness.
• Swelling of arms and legs.
• Nausea, diarrhea, dry mouth, dry lips, loss of appetite, constipation, gas, abnormalities in liver function tests, vomiting.
• Dry skin, skin disease, hair loss, skin ulcers, acne, skin thickening, skin nodules, increased sweating.
• Joint pain, bone pain, muscle pain.
• Chills, abdominal pain, allergic reaction, infection.

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

• Blood disorders, eosinophilia, leucocytosis, lymphocytosis, purpura, elevated or decreased platelet count.
• Hyperactive thyroid.
• Elevated bilirubin in the blood, impaired renal function, gout, decreased HDL cholesterol.
• Restlessness, difficulty maintaining balance, depression, increased skin sensation, abnormal nerve sensations, vertigo.
• Abnormal vision, blurred vision, conjunctival inflammation, cataracts, corneal injury, ear disease, visual field defects.
• Swelling, hemorrhage, high blood pressure, rapid heartbeat, visible venous swelling, vasodilation.
• Gastrointestinal disease, liver insufficiency, pancreatitis.
• Hair disease, herpes simplex, nail disease, pustular eruption, serous supuration, skin discoloration.
• Muscle weakness.
• Protein in urine, abnormal renal function.
• Back pain, skin infection, fever, parasitic infection, abnormal laboratory tests, mucosal disease, tumors.

Other rare side effects include pancreatitis, cerebral hemorrhage, and liver insufficiency.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label after ‘EXP’. The expiration date is the last day of the month indicated.

Store below 25?°C. Keep the bottle perfectly closed.

Medicines should not be disposed of through drains or in the trash. Dispose of containers and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Bexaroteno Cipla

The active substance is bexaroteno. Each capsule contains 75 mg of bexaroteno.

The other components are:

• Content of the capsules: macrogol 400, polisorbate 20, povidone, and butylhydroxyanisole (E320).
• Capsule coating:gelatin, special mixture of sorbitol and glycerin (glycerin, sorbitol, sorbitan anhydrides (1,4-sorbitan), mannitol, and water), and titanium dioxide (E171).

Appearance of the product and contents of the packaging

Bexaroteno Cipla 75 mg hard capsules EFG are soft gelatin capsules of oval shape, opaque white to off-white in color, and filled with a white to off-white suspension.

Bexaroteno Cipla 75 mg hard capsules EFG are presented in a high-density polyethylene bottle with a child-resistant safety closure, containing 100 capsules.

Marketing authorization holder and responsible manufacturer

Cipla Europe NV

De Keyserlei 58-60, Box 19,

2018, Antwerp

Belgium

Local representative

Cipla Europe NV C/Guzmán el Bueno, 133 Edif Britannia-

28003- Madrid

Spain

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Germany: Bexaroten Cipla 75 mg Weichkapsel

Spain: Bexaroteno Cipla 75 mg hard capsules EFG

France: Bexarotène Cipla 75 mg, capsule molle

Italy: Bexarotene Cipla

Last review date of this leaflet: October 2021

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).