Targretin 75 mg soft capsules

The active substance in Targretin, bexarotene, belongs to a group of medicines known as retinoids, which are related to vitamin A. Targretin capsules are used by patients with advanced stage 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 lymph system called T-lymphocytes become cancerous and affect the skin.

Do not take Targretin

• if you know that you are allergic (hypersensitive) to bexarotene or to any of the other ingredients.
• if you are pregnant or breast feeding or if you can become pregnant and are not using effective birth control measures.
• if you have a history of pancreatitis, have uncontrolled lipid (blood fats) elevations (high blood cholesterol or high blood triglycerides), have a condition known as hypervitaminosis A, have uncontrolled thyroid disease, have insufficient liver function or have an ongoing systemic infection.

Take special care with Targretin

• if you have a known hypersensitivity to retinoids (related to vitamin A), suffer from liver disease, have high blood lipids or take medicines which may cause high blood lipids, have uncontrolled diabetes mellitus (sugar diabetes), have had gall bladder or biliary tract disease, or consume excessive amounts of alcohol. If any of these apply, you should inform your doctor.

Your fasting blood lipid determinations may have to be performed before therapy is initiated and at weekly intervals afterwards, and then monthly while taking this medicine.

Blood tests to evaluate the function of your liver and thyroid gland and to monitor your red blood cell and white blood cell counts will be obtained before therapy is started and will be monitored during therapy.

Periodic eye exams may be needed if you experience visual difficulties while taking this medicine.

Minimise exposure to sunlight as much as possible and avoid exposure to sun lamps.

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

Targretin capsules should not be used in children or adolescents.

Taking other medicines

Before starting treatment, make sure your doctor knows if you are taking medicines (including those not prescribed by your doctor), such as ketoconazole and itraconazole (used against fungal infections), erythromycin, clarithromycin and rifampicin (used against bacterial infections), phenytoin and phenobarbital (used against seizures), gemfibrozil (used to reduce high levels of fats in the blood such as triglycerides and cholesterol), vitamin A supplements, protease inhibitors (used against viral infections), tamoxifen (used against some forms of cancer) or dexamethasone (used for inflammatory conditions). This is important as using more than one medicine at the same time can strengthen or weaken the effect of the medicines.

Taking Targretin with food and drink

Targretin should be taken with food. If you regularly consume grapefruit or grapefruit juice, please consult your doctor as these have the potential to alter your body?s response to Targretin therapy.

Pregnancy and breast-feeding

Targretin may be harmful to a developing foetus. DO NOT use Targretin if you are pregnant or breast-feeding. If you are pregnant, thinking of becoming pregnant, or breast-feeding, ask your doctor for more information.

If you are capable of becoming pregnant, you must have a pregnancy test within one week before you start therapy, confirming you are not pregnant. You must use effective contraception (birth control) continuously starting one month before beginning therapy until one month after you stop taking Targretin. It is recommended that two reliable forms of contraception be used together. If you are taking a hormonal contraceptive (for example, birth control pills), you should discuss this with your doctor.

If you are male and your partner is pregnant or capable of becoming pregnant, you must use condoms during sexual intercourse while taking bexarotene and for at least one month after the last dose.

Driving and using machines

It is not known whether Targretin has an effect on your ability to drive a car or operate machinery. If you experience dizziness or problems with your vision during therapy, do not drive or operate machinery.

Important information about some of the ingredients of Targretin
Butylated hydroxyanisole, an ingredient in Targretin, may cause irritation to the mucous membranes, therefore the capsules must be swallowed intact and not chewed.

Always take Targretin exactly as your doctor has told you. The doctor will prescribe a suitable dose for you, which is generally 4 to 10 capsules to be taken once daily. Take your prescribed number of capsules at the same time each day with a meal. The capsules can be taken immediately before, during or immediately after the course of the meal, if preferred. The capsules should be swallowed whole and not chewed.

How long you should take Targretin

Do not stop taking your medication until your doctor advises you to do so. Although some patients have improvement within the first several weeks, most patients require several months or more of treatment to improve.

If you take more Targretin than you should

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

If you forget to take Targretin

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

Like all medicines, Targretin can cause side effects, although not everybody gets them. Tell your doctor as soon as possible if you feel any deterioration in your condition while you are taking Targretin. Sometimes it is necessary to adjust the dose or interrupt treatment. Your doctor will advise you on what to do.

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

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

Low white blood cell count.
Lowering of thyroid hormones level.
Elevation of blood fats (triglycerides and cholesterol).
Skin reactions (Itching, redness, irritation, peeling).
Headache, fatigue, pain.

Common (can occur in less than 1 in 10 but in more than 1 in 100 patients treated): Low red blood cell count, enlarged lymph nodes, worsening of lymphoma.
Thyroid disorder.
Elevation of liver enzymes, impaired kidney function, low protein in blood, weight gain. Insomnia, dizziness, reduced skin sensation.
Dry eyes, deafness, abnormal sensations of the eye including irritation and heaviness. Swelling of legs and arms.
Nausea, diarrhoea, dry mouth, dry lips, loss of appetite, constipation, excess gas, abnormal liver function tests, vomiting.
Dry skin, skin disorder, loss of hair, skin ulcer, acne, skin thickening, skin nodule, increased sweating. Joint aches, bone pain, muscle aches.
Chills, abdominal pain, allergic reaction, infection.

Uncommon (can occur in less than 1 in 100 but in more than 1 in 1000 patients treated): Blood disorders, eosinophilia, leukocytosis, lymphocytosis, purpura, elevated and decreased numbers of blood platelets.
Overactive thyroid.
Elevated bilirubin in the blood, impaired kidney function, gout, decreased HDL cholesterol. Agitation, difficulties with balance, depression, increased skin sensation on touching, abnormal nerve sensations, vertigo.
Abnormal vision, blurred vision, inflammation of the eye lids, cataract, inflammation of the white part of the eye, lesion of the cornea of the eye, ear disorder, defect in field of vision.
Swelling, bleeding, high blood pressure, fast heart rate, visible vein enlargement, dilation of blood vessels.
Gastrointestinal disorder, liver failure, inflammation of the pancreas.
Changes in hair, herpes simplex, nail disorder, pustular rash, serous drainage, skin discoloration.

Muscle weakness.
Proteins in urine, abnormal kidney function.
Back pain, skin infection, fever, parasitic infection, abnormal laboratory test, disorder of mucous membrane, tumour.

Rare fatal side effects are acute inflammation of the pancreas, bleeding in the head, and liver failure.

If any of the side effects gets serious, or if you notice any side effects not mentioned in this leaflet, tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use after the expiry date stated on the label.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Targretin contains

Each Targretin capsule contains 75 mg of the active substance bexarotene. The capsules also contain the other ingredients macrogol, polysorbate, povidone and butylated hydroxyanisole.

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

What Targretin looks like and contents of the pack

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

Marketing Authorisation Holder

Eisai Ltd.
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom

Manufacturer

Eisai Manufacturing Limited
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom

For any information about this medicine please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Cephalon BV De Waterlaat 3 NL 5571 MZ Bergeijk NEDERLANDPAYS-BASNIEDERLANDE TélTel 31 0497 551 050 LuxembourgLuxemburg Cephalon BV De Waterlaat 3 NL 5571 MZ Bergeijk PAYS-BASNIEDERLANDE TélTel 31 0497 551 050

Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka 68 PL - 02- 014 Warszawa Te. 48022 50 40 890 Magyarország Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka PL 02- 014 Warszawa LENGYELORSZÁG Tel 48022 50 40 890

eská republika Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka PL 02- 014 Warszawa POLSKA Tel 48022 50 40 890 Malta Eisai Ltd. Mosquito Way Hatfield Hertfordshire AL10 9SN RENJU UNIT Tel 44 020 8600 1400

Danmark Cephalon Pharma Aps Sluseholmen 2-4 DK - SV 2450 København Tlf 45 3694 4868 Nederland Cephalon BV De Waterlaat 3 NL 5571 MZ Bergeijk Tel 31 0 497 551 050

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Ferrer-Galenica A.E. A 2 GR- 104 37 30 210 52 81 700 Polska Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka PL 02- 014 Warszawa Tel 48022 50 40 890

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France Cephalon France 20 rue Charles Martigny F 94704 MAISONS-ALFORT Cedex Tél 33 01 49 81 81 00 România Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka 68 PL - 02- 014 Warszawa POLONIA Tel 48022 50 40 890

Ireland Cephalon Pharma Ireland Ltd Unit E, Glencormack Business Park Kilmacanogue IRL - County Wicklow Tel 353 01 201 4000 Slovenija Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka 68 PL - 02- 014 Warszawa POLJSKA Tel 48022 50 40 890

Ísland Cephalon Pharma Aps Sluseholmen 2-4 DK - SV 2450 Kaupmannahöfn DANMÖRK Sími 45 3694 4868 Slovenská republika Cephalon Sp. zo.o. Prima Court Ul. Nowogrodzka 68 PL - 02- 014 Warszawa POSKO Tel 48022 50 40 890

Italia SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. Viale Shakespeare, 47 I 00144 Roma Tel 39 06 91391 SuomiFinland Cephalon Pharma Aps Sluseholmen 2-4 DK - SV 2450 København TANSKA PuhTel 45 3694 4868

Sverige Cephalon Pharma Aps Sluseholmen 2-4 DK - SV 2450 Köpenhamn DANMARK Tel 45 3694 4868 Eisai Ltd. Mosquito Way Hatfield Hertfordshire AL10 9SN II 44 020 8600 1400

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Lietuva

Cephalon Sp. zo.o.Prima Court
Ul. Nowogrodzka 68
PL - 02- 014 Warszawa
LENKIJA
Tel: +48(0)22 50 40 890

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