Patient leaflet - Targretin 75 mg soft capsules

1. What Targretin is and what it is used for

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.

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 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.

Warnings and precautions

Talk to your doctor before taking 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 you have ever had any mental health problems including
depression, aggressive tendencies or mood changes. This is because taking Targretin may affect your mood. 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.

Mental health problems

You may not notice some changes in your mood and behaviour and so it is very important that you tell your friends and family that this medicine could affect your mood and behaviour. They may notice these changes and help you identify any problems that you need to talk to your doctor about.

Children and adolescents

Targretin capsules should not be used in 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 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),
dexamethasone (used for inflammatory conditions),
insulin, agents enhancing insulin secretion, or insulin-sensitisers
(used against diabetes mellitus).
This is important as using more than one medicine at the same time can strengthen or weaken the effect of the medicines. Targretin with food and drink
Targretin should be taken with food (see section 3). 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 or breast-feeding, think you may be pregnant or are planning to
have a baby, ask your doctor for advice before taking this medicine. 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.
Targretin contains sorbitol and butylated hydroxyanisole
Targretin contains a small amount of sorbitol (a type of sugar). If you have an intolerance to some sugars, speak to your doctor before taking this medicinal product.
Butylated hydroxyanisole may cause irritation to the mucous membranes, therefore the capsules must be swallowed intact and
not chewed.

3. How to take Targretin

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The doctor will prescribe a suitable dose for you.

The recommended dose 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

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 forgotten dose the previous day.

If you stop taking Targretin

Your doctor should determine how long you should take Targretin, and when treatment may be stopped. Do not stop taking your medication until your doctor advises you to do so.

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.

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 up to 1 in 10 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 up to 1 in 100 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.

Reporting of side effects

If you get 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 via the Yellow Card Scheme at: www. mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play and Apple App store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 refers to the last day of that month.

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

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

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