Targretin 75 mg, soft capsules

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

TARGRETIN 75mg, soft capsules

Bexarotene

Read the entire leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, inform your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Targretin is and what it is used for

Bexarotene, the active substance in Targretin, belongs to a family of medicines known as retinoids, which are related to vitamin A.

Targretin capsules are given to patients with 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.

2. What you need to know before taking Targretin

Do not take Targretin:

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

Warnings and precautions

Talk to your doctor before starting Targretin

• if you have known hypersensitivity to retinoids (related to vitamin A), liver disease, high blood lipid levels, or are taking medicines that may cause high blood lipid levels; if you have uncontrolled diabetes mellitus; if you have had gallbladder or biliary tract 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 Targretin may affect your mood.

Fasting blood lipid levels should be measured before starting treatment and weekly thereafter, followed by monthly monitoring throughout Targretin therapy. Blood tests to assess liver and thyroid function, as well as white and red blood cell counts, should be performed before and during treatment.

Regular eye examinations may be necessary if you experience visual disturbances while taking this medicine.

Minimize sun exposure as much as possible and avoid ultraviolet lamps.

You must not consume more than 15,000 International Units per day of vitamin A supplements during treatment.

Mental health problems

You may experience changes in mood and behavior. It is very important to inform your friends and family that this medicine may affect your mood and behavior. They may notice these changes and help you identify any problems that need to be discussed with your doctor.

Children and adolescents

Targretin capsules should not be given to children or adolescents.

Other medicines and Targretin

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines such as:

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

This is important because taking more than one medicine at the same time may strengthen or weaken the effects of the medicines.

Taking Targretin with food and drink

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

Pregnancy and breastfeeding

Targretin may harm an unborn baby. DO NOT use Targretin if you are pregnant or breastfeeding. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, talk to your doctor before using this medicine.

If you could become pregnant, you must have a pregnancy test one week before starting treatment to confirm you are not pregnant. You must continuously use an effective method of contraception (birth control), starting one month before beginning treatment and continuing for at least one month after stopping Targretin. The use of two reliable forms of contraception together is recommended. You should discuss with your doctor if you are taking hormonal contraception (e.g., birth control pills).

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

Driving and using machines

It is unknown whether Targretin affects your ability to drive or operate machinery. If you experience dizziness or visual disturbances during therapy, you must not drive or operate machinery.

Targretin contains sorbitol and butylated hydroxyanisole

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

Butylated hydroxyanisole may cause irritation of mucous membranes; therefore, the capsules must be swallowed whole, without chewing.

3. How to take Targretin

Follow exactly the instructions for using this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

Your doctor will prescribe a dose suitable for you.

The recommended dose is generally 4 to 10 capsules taken once daily. You should take the prescribed number of capsules at the same time each day with a meal. The capsules may be taken immediately before or after the meal or during the meal, according to your preference. The capsules must be swallowed whole, without chewing.

Duration of Targretin therapy

Although some patients may notice improvement within the first few weeks of treatment, most patients require prolonged therapy of several months before improvement is noticed.

If you take more Targretin than you should

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

If you forget to take Targretin

If you forget to take a dose, take the prescribed daily dose with the next meal on the same day, and take your normal dose the following day. Do not take a double dose in one day to make up for a missed dose from the previous day.

If you stop taking Targretin

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

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

4. Possible adverse effects

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

If you notice any worsening of your condition while taking Targretin, 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 adverse effects have been reported in patients with CTCL treated with the recommended initial dose of capsules.

Very common (may occur in more than 1 in 10 treated patients):

Low white blood cell count.

Decreased levels of thyroid hormones.

Elevated blood lipids (triglycerides and cholesterol).

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

Headache, fatigue, pain.

Common (may occur in up to 1 in 10 treated patients):

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

Thyroid disorder.

Elevated liver enzymes, impaired kidney function, decreased serum proteins, weight gain.

Insomnia, dizziness, reduced skin sensation.

Dry eyes, deafness, eye discomfort including irritation and heaviness.

Swelling of arms and legs.

Nausea, diarrhea, dry mouth, dry lips, loss of appetite, constipation, excessive gas, abnormalities in liver function tests, vomiting.

Dry skin, skin disorder, 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 occur in up to 1 in 100 treated patients):

Blood disorders, blood coagulation disorders, eosinophilia, leukocytosis, lymphocytosis, purpura, platelet count higher or lower than normal.

Overactive thyroid.

Elevated bilirubin in blood, impaired kidney function, gout, reduced HDL cholesterol.

Agitation, difficulty maintaining balance, depression, increased skin sensitivity to touch, abnormal nerve sensations, dizziness.

Abnormal vision, blurred vision, eyelid inflammation, cataracts, inflammation of the white of the eye, corneal injury, ear disorder, visual field defects.

Swelling, bleeding, high blood pressure, rapid heartbeat, visible vein swelling, blood vessel dilation.

Gastrointestinal disorder, liver failure, pancreatitis.

Hair disorders, simple herpes, nail disorders, pustular rash, serous discharge, skin discoloration.

Muscle weakness.

Protein in urine, abnormal kidney function.

Back pain, skin infection, fever, parasitic infection, abnormal laboratory tests, mucosal disorders, tumors.

Other rare adverse effects include pancreatitis, cerebral hemorrhage, and liver failure.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Targretin

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

Do not use this medicine after the expiry date stated on the label. The expiry date is the last day of the month indicated.

Do not store above 30 °C. Keep the container tightly closed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Targretin

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

The capsules also contain the excipients macrogol, polysorbate, povidone, and butylated hydroxyanisole.

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

Nature of the product and pack contents

Targretin is available as soft capsules for oral use, supplied in a white plastic bottle containing 100 capsules.

Marketing Authorization Holder

H.A.C. Pharma
Péricentre 2
43 Avenue de la Côte de Nacre
14000 Caen
France

Manufacturer responsible for manufacturing

Creapharm Industry
29 rue Leon Faucher
51100 Reims
France

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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