TARGRETIN 75 mg SOFT GEL CAPSULES

Introduction

Package Leaflet: Information for the User

TARGRETIN 75mg, soft capsules

Bexarotene

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Targretin and what is it used for

Bexarotene, the active ingredient of 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 you take 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, or during breast-feeding, 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 elevated lipid levels (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 Targretin

• if you have known hypersensitivity to retinoids (related to vitamin A), if you have liver disease, high lipid levels in the blood, or are taking medications that may cause high lipid levels 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 levels in the blood should be determined before starting treatment and at weekly intervals, and then at monthly intervals during the entire duration of Targretin therapy. Before starting treatment and throughout treatment, you will have blood tests to evaluate your liver and thyroid function and to check your white and red blood cell count.

Regular eye exams may be necessary if you experience vision problems while taking this medicine.

Reduce 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 that you tell your friends and family that this medicine 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 given to children or adolescents.

Other medicines and Targretin

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

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

This is important because taking more than one medicine at the same time can enhance or weaken the effect of the medicines.

Taking Targretin with food and drinks

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

Pregnancy and breast-feeding

Targretin may harm a developing fetus. DO NOT use Targretin if you are pregnant or breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

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 contraceptive method continuously (birth control) that starts one month before initiating treatment and continues until one month after stopping Targretin. It is recommended to use two reliable forms of contraception together. You should consult your doctor if you are taking hormonal contraceptives (e.g., birth control pills).

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 using machines

It is not known if Targretin affects your ability to drive or use machines. If you experience dizziness or vision problems during therapy, you should not drive vehicles or use 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 medicine.

Butylhydroxyanisole may cause irritation to the mucous membranes; therefore, the capsules should be swallowed whole, without chewing.

3. How to take Targretin

Follow the instructions for administration of this medicine exactly 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 each day with a meal. The capsules can be taken immediately before, after, or during the meal, as you prefer. The capsules should be swallowed whole, without chewing.

The duration of Targretin therapy

Although some patients notice improvement after the first few weeks of treatment, most patients require 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 forget to take Targretin

If you forget 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 in one day to make up for the missed doses 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.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you notice any worsening of your condition while taking Targretin, tell your doctor. Sometimes it is necessary to modify the dose or stop treatment. Your doctor will advise you what to do.

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

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

Low white blood cell count.

Decreased thyroid hormone levels.

Elevated fats in the blood (triglycerides and cholesterol).

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

Headache, fatigue, pain.

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

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

Thyroid problems.

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

Insomnia, dizziness, decreased sensation in the skin.

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, abnormal liver function tests, vomiting.

Dry skin, skin conditions, hair loss, skin ulcers, acne, thickening of the skin, skin nodules, increased sweating.

Joint pain, bone pain, muscle pain.

Chills, abdominal pain, allergic reaction, infection.

Uncommon (which may affect up to 1 in 100 patients treated):

Blood disorders, blood coagulation disorders, eosinophilia, leukocytosis, lymphocytosis, purpura, increased or decreased platelet count.

Overactive thyroid.

Elevated bilirubin in the blood, affected kidney function, gout, low HDL cholesterol.

Agitation, difficulty maintaining balance, depression, increased skin sensation to touch, abnormal nerve sensations, vertigo.

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

Swelling, bleeding, high blood pressure, rapid heartbeat, visible swelling of the veins, dilation of blood vessels.

Gastrointestinal disorders, liver failure, pancreatitis.

Hair disorders, herpes simplex, nail disorders, pustular eruption, serous discharge, skin discoloration.

Muscle weakness.

Protein in urine, abnormal kidney function.

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side 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 which is stated on the label. The expiry date is the last day of the month stated.

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 no longer required. 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 macrogol, polysorbate, povidone, and butylhydroxyanisole.

The outer capsule shell 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 (SDA 35A alcohol (ethanol and ethyl acetate), propylene glycol (E1520), black iron oxide (E172), polyvinyl acetate phthalate, purified water, isopropyl alcohol, macrogol 400, ammonium hydroxide 28%).

Appearance of the product and pack contents

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

Marketing authorisation holder

H.A.C. Pharma

Péricentre 2

43 Avenue de la Côte de Nacre

14000 Caen

France

Manufacturer

Creapharm Industry

29 rue Leon Faucher

51100 Reims

France

You can obtain further information on this medicine by contacting the local representative of the marketing authorisation holder:

Date of last revision 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.