Prospect: Information for the User

TARGRETIN 75mg, soft capsules

Bexarotene

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, report them to your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

1.What Targretin is and for what it is used

2.What you need to know before starting to take Targretin

3.How to take Targretin

4.Possible adverse effects

5.Storage of Targretin

6.Contents of the package and additional information

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

Targretin capsules are 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 Targretin:

• If you are allergic to bexarotene or any of the other components of this medication (listed in section6).
• If you are pregnant, or breastfeeding, or if you can become pregnant and are not using effective birth control methods.
• 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 before starting to take Targretin

• 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. The reason is that Targretin may affect your mood.

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

Targretin capsules should not be administered to children or adolescents.

Other medications and Targretin:

Inform your doctor 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 weaken the effect of the medications.

Taking Targretin with food and drinks:

Targretin should be taken with food (see section3). If you regularly consume grapefruit or grapefruit juice, consult your doctor as these may potentially alter the body's response to Targretin therapy.

Pregnancy and breastfeeding:

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

If you can 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 birth control method that starts one month before starting treatment and continues for one month after stopping Targretin. It is recommended to use two reliable forms of birth control together. You should consult your doctor if you are taking hormonal birth control (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 Targretin and for at least one month after the last dose.

Driving and operating machinery:

The effect of Targretin 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.

Targretin contains sorbitol and butylhydroxyanisole:

Targretin contains a small amount of sorbitol (a type of sugar). If you have intolerance to certain sugars, consult your doctor before taking this medication.

Butilhydroxyanisole may cause mucous membrane irritation, so the capsules should be swallowed whole, without chewing.

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.You should take the prescribed number of capsules at the same time every day with a meal.The capsules can be taken immediately before, after, or during a meal, as you prefer.The capsules should be swallowed whole, without chewing.

Duration of Targretin 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 Targretin than you should

If you have taken more than the prescribed dose of Targretin, you should call your doctor.

If you forgot to take Targretin

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 Targretin treatment

Your doctor will determine for how long you should take Targretin and when you should stop treatment.Do not stop taking the medication until your doctor tells you to.

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 Targretin, tell your doctor. Sometimes it is necessary to adjust the dose or discontinue treatment. Your doctor will advise you what to do.

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

Very common (which may occur in more than one in 10patients treated):

Low white blood cell count.

Decreased thyroid hormone levels.

Elevated blood fats (triglycerides and cholesterol).

Skin reactions (itching, redness, irritation, skin peeling).

Headache, fatigue, pain.

Common (which may occur in up to one in 10patients treated):

Low red blood cell count, lymph node enlargement, worsening of lymphoma.

Thyroid disease.

Elevated 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 (which may occur in up to one in 100patients treated):

Blood disorders, blood clotting disorders, eosinophilia, leukocytosis, 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, dizziness.

Abnormal vision, blurred vision, eyelid inflammation, cataracts, corneal inflammation, ear disease, visual field defects.

Swelling, hemorrhage, high blood pressure, rapid heartbeat, visible vein swelling, vasodilation.

Gastrointestinal disease, liver insufficiency, pancreatitis.

Hair disease, herpes simplex, nail disease, pustular rash, serous supuration, skin discoloration.

Muscle weakness.

Protein in urine, abnormal renal function.

Back pain, skin infection, fever, parasitic infection, abnormal laboratory tests, mucous membrane disease, tumors.

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

Reporting side effects

If you experience any type of side effect, consultyour 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 of Pharmacovigilance of Medicines for Human Usewww.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 medicationafter the expiration date that appears on the label. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30?C. Keep the container perfectly closed.

Medicines should not be disposed of through drainsor in the trash. Ask your pharmacist how to dispose of the containers and medicines you no longer need. In this way, you will help protect the environment.

Composition ofTargretin

Each Targretin capsule contains 75mg of the active substance bexarotene.

The capsules also contain the components macrogol, polisorbate, povidone, and hydroxyisobutyl anisole.

The exterior of the capsule consists of gelatin, a special mixture of glycerin and sorbitol (glycerin, sorbitol, sorbitan anhydrides (1,4-sorbitan), mannitol, and water), titanium dioxide (E171), and printing ink (alcohol SDA 35A (ethanol and ethyl acetate), propylene glycol (E1520), iron oxide black (E172), polyvinyl acetate phthalate, purified water, isopropyl alcohol, macrogol 400, and ammonium hydroxide 28%).

Appearance of the product and contents of the package

Targretin is presented in soft gelatin capsules for oral use in a white plastic bottle with 100capsules.

Marketing Authorization Holder

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

e-mail: [email protected]

Responsible Person

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet:

Other sources of information

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.