BEXAROTENE (Systemic)?

Some commonly used brand names are:

In the U.S.?

• Targretin

? Not commercially available in Canada.

Category

• Antineoplastic

Description

Bexarotene (beks-AIR-oh-teen)belongs to the group of medicines known as retinoids ((RET-i-noyds)). It is used to treat a certain type of cancercalled cutaneous T-cell lymphoma. It works by interfering with the growthof the cancerous cells.

This medicine is available only with your doctor's prescription, in thefollowing dosage form:

Oral
• Capsule (U.S.)

Before Using This Medicine

In deciding to use a medicine,the risks of taking the medicine must be weighed against the good it willdo. This is a decision you and your doctor will make. For bexarotene, thefollowing should be considered:

Allergies?Tell your doctor if you have ever had any unusualor allergic reaction to bexarotene or other retinoid (vitamin A) preparations.Also tell your health care professional if you are allergic to any other substances,such as foods, preservatives, or dyes.

Pregnancy?Bexarotene must not be takenduring pregnancy because of the possible risks to the infant. In addition,bexarotene must not be taken if there is a chance that you may become pregnant1 month before treatment, during treatment, and within 1 month after treatmentis ended.Women who are able to have children must have a pregnancytest done within 1 week before starting bexarotene, to make sure they arenot pregnant. The pregnancy test must be repeated once a month during treatment.For 1 month before treatment with bexarotene, during treatment, and for 1month after treatment is over, you must use two effective forms of birth controlat the same time. Bexarotene may interfere with the effectiveness of hormonalbirth control (such as the pills), so one form of birth control should benon-hormonal, such as condoms. Male patients with sexual partners who arepregnant, possibly pregnant, or who could become pregnant must use condomsduring sexual intercourse while taking bexarotene and for at least 1 monthafter taking the last dose. Be sure you have discussed this information withyour doctor.

Breast-feeding?It is not known whether this medicine passesinto breast milk. However, bexarotene is not recommended during breast-feeding,because it may cause unwanted effects in nursing babies.

Children?Studies of this medicine have been done only inadult patients, and there is no specific information comparing the use ofbexarotene in children with use in other age groups.

Older adults?This medicine has been tested in patients 60 yearsof age or older and has not been shown to cause different side effects orproblems in older people than it does in younger adults. However, elderly patients may be more sensitive to the effects of bexarotene.

Other medicines?Although certain medicines should not be usedtogether at all, in other cases two different medicines may be used togethereven if an interaction might occur. In these cases, your doctor may want tochange the dose or other precautions may be necessary. When you are takingbexarotene, it is especially important that your health care professionalknow if you are using any of the following:

• Acyclovir (e.g., Zovirax) or
• Anticonvulsants (seizure medicine) or
• Antidiabetics, oral (diabetes medicine taken by mouth) or
• Anti-infectives by mouth or by injection (medicine for infection)or
• Antipsychotics (medicine for mental illness) or
• Captopril (e.g., Capoten) or
• Enalapril (e.g., Vasotec) or
• Flecainide (e.g., Tambocor) or
• Gold salts (medicine for arthritis) or
• Imipenem or
• Inflammation or pain medicine, except narcotics or
• Lisinopril (e.g., Prinivil, Zestril) or
• Maprotiline (e.g., Ludiomil) or
• Penicillamine (e.g., Cuprimine) or
• Pimozide (e.g., Orap) or
• Procainamide (e.g., Pronestyl) or
• Promethazine (e.g., Phenergan) or
• Ramipril (e.g., Altace) or
• Sulfasalazine (e.g., Azulfidine) or
• Tiopronin (e.g., Thiola) or
• Tocainide (e.g., Tonocard) or
• Tricyclic antidepressants (medicine for depression) or
• Trimeprazine (e.g., Temaril)?Concurrent use of these agentswith bexarotene may cause blood disorders

• Alpha interferons (e.g., Intron A, Roferon-A) or
• Amphotericin B by injection (e.g., Fungizone) or
• Antineoplastics, other (cancer medicine) or
• Antithyroid agents (medicine for overactive thyroid) or
• Azathioprine (e.g., Imuran) or
• Chloramphenicol (e.g., Chloromycetin) or
• Colchicine or
• Cyclophosphamide (e.g., Cytoxan) or
• Flucytosine (e.g., Ancobon) or
• Ganciclovir (e.g., Cytovene) or
• Zidovudine (e.g., AZT, Retrovir)?Concurrent use of these agentswith bexarotene increases the risk of infection

• If you have ever been treated with radiation or cancer medicines?Bexarotenemay increase the effects that these medicines or radiation therapy may haveon the blood

• Phenobarbital or
• Phenytoin (e.g., Dilantin) or
• Rifampin (e.g., Rifadin, Rimactane) or
• Erythromycin (e.g., E-Mycin, Ery-Tab, Ilotycin) or
• Grapefruit juice or
• Itraconazole (e.g., Sporanox) or
• Ketoconazole (e.g., Nizoral)?These medicines may increase ordecrease the metabolism (breakdown) of bexarotene, leading to higher-than-usualor lower-than-usual amounts of bexarotene in the body

• Gemfibrozil (e.g., Lopid)?This medicine may lead to higher-than-usualamounts of bexarotene in the body

• Insulin (e.g., Humulin, Novolin) or
• Medications that make your body more sensitive to insulin, such as:
  • Pioglitazone (e.g., Actos) or
  • Rosiglitazone (e.g., Avandia)
• Medications that help your body to secrete more insulin, such as:
  • Acetohexamide (e.g., Dymelor) or
  • Chlorpropamide (e.g., Diabinese) or
  • Glimepiride (e.g., Amaryl) or
  • Glipizide (e.g., Glucotrol) or
  • Glyburide (e.g., DiaBeta) or
  • Tolazamide (e.g., Tolinase) or
  • Tolbutamide (e.g., Orinase)?Use of bexarotene may increasethe effects of these medicines, which may cause low blood sugar (hypoglycemia)

• Tamoxifen (e.g., Nolvadex)?Bexarotene may lead to lower-than-usualamounts of tamoxifen in the body

• Vitamin A supplements (e.g., Aquasol A)?May increase the chanceof side effects

Other medical problems?The presenceof other medical problems may affect the use of bexarotene. Make sure to tellyour doctor if you have any other medical problems, especially

• Bone marrow depression, existing or
• Infection?There may be an increased risk of infections or worseningof infections because of the body's reduced ability to fight them
• Cataracts?May cause new cataracts or worsen previous cataracts
• Chickenpox (including recent exposure) or
• Herpes zoster (shingles)?Risk of severe disease affecting otherparts of the body
• Diabetes mellitus?May be more likely to experience low bloodsugar (hypoglycemia).
• High cholesterol?Bexarotene can cause an increase in cholesterollevels.
• Kidney disease?May increase the chance of side effects

• Liver disease?Effects of bexarotene may be increased becauseof slower removal from the body.

• Pancreatitis or
• Risk factors for pancreatitis, such as:
  • Drinking large quantities of alcohol or
  • Problems with your gallbladder or biliary tract or
  • Type 2 diabetes mellitus that is not well-controlledor
  • High cholesterol that is not well-controlled or
  • Taking medicines that cause high levels of triglycerides (fat-likesubstances) or
  • Taking medicines that are toxic to the pancreas or
  • Prior pancreatitis?Bexarotene can cause an increase in triglyceridelevels which can cause inflammation of the pancreas.
• Photosensitivity?Bexarotene may cause increased sensitivityof the skin to sunlight

Proper Use of This Medicine

Use this medicine exactly as directed by your doctor.Do not use more or less of it, and do not use it more often than your doctorordered. The exact amount of medicine you need has been carefully worked out.Using too much will increase the risk of side effects, while using too littlemay not improve your condition.

Dosing?The dose of bexarotene will be differentfor different patients. Follow your doctor's orders orthe directions on the label. The following information includes onlythe average doses of bexarotene. If your dose is different,do not change it unless your doctor tells you to do so.

• For oral dosage form (capsule):
  • For cutaneous T-cell lymphoma:
    • Adults?Dose is based on body size and must be determined byyour doctor. The usual dose is 300 milligrams (mg) for each square meter ofbody surface area taken once a day with a meal. Your dose may then be adjustedby your doctor.
    • Children?Use and dose must be determined by your doctor.

Missed dose?If you miss a dose of this medicine, take itas soon as possible. However, if it is almost time for your next dose, skipthe missed dose and go back to your regular dosing schedule. Do not doubledoses.

Storage?To store this medicine:

• Keep out of the reach of children.
• Do not store in the bathroom, near the kitchen sink, or in otherdamp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Ask yourhealth care professional how you should dispose of any medicine you do notuse. Be sure that any discarded medicine is out of the reach of children.

Precautions While Using This Medicine

It is very important that your doctor check your progress atregular visits to make sure that this medicine is working properlyand to check for unwanted effects.

While you are being treated with bexarotene, and after you stop treatmentwith it, do not have any immunizations (vaccinations)without your doctor's approval. Bexarotene may lower your body's resistance,and there is a chance you might get the infection that the immunization ismeant to prevent. In addition, other persons living in your household shouldnot take oral polio vaccine, since there is a chance they could pass the poliovirus on to you. Also, avoid persons who have taken oral polio vaccine withinthe last several months. Do not get close to them, and do not stay in theroom with them for very long. If you cannot take these precautions, you shouldconsider wearing a protective face mask that covers the nose and mouth.

Bexarotene can temporarily lower the number of white blood cells in yourblood, increasing the chance of getting an infection. It can also lower thenumber of platelets, which are necessary for proper blood clotting. If thisoccurs, there are certain precautions you can take, especially when your bloodcount is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Checkwith your doctor immediately if you think you are getting an infectionor if you get a fever or chills, cough or hoarseness, lower back or side pain,or painful or difficult urination.
• Check with your doctor immediately ifyou notice any unusual bleeding or bruising; black, tarry stools; blood inurine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick.Your medical doctor, dentist, or nurse may recommend other ways to clean yourteeth and gums. Check with your medical doctor before having any dental workdone.
• Do not touch your eyes or the inside of your nose unless you havejust washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects suchas a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injurycould occur.

Bexarotene may cause your skin to be more sensitive to sunlight than itis normally. Exposure to sunlight, even for brief periods of time, may causea skin rash, itching, redness or other discoloration of the skin, or a severesunburn. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00a.m. and 3:00 p.m., if possible.
• Wear protective clothing, including a hat. Also, wear sunglasses.
• Apply a sun block product that has a skin protection factor (SPF)of at least 15. Some patients may require a product with a higher SPF number,especially if they have a fair complexion. If you have any questions aboutthis, check with your health care professional.
• Apply a sun block lipstick that has an SPF of at least 15 to protectyour lips.
• Do not use a sunlamp or tanning bed or booth.

Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects.Although not all of these side effects may occur, if they do occur they mayneed medical attention.

Since this medication is given in varying doses, the actual frequency ofside effects may vary. In general, side effects are less common with lowerdoses than with higher doses.

Check with your doctor as soon as possible if any of the following sideeffects occur:

More common

Unusual tiredness or weakness; skinrash or other skin and mucous membrane lesions; fever; increase in lipid or cholesterol levels; coldness, dry, puffy skin or weight gain; chills, cough, hoarseness, lower back or side pain or painful or difficulturination; swelling of the arms, feet, hands, orlegs

Less Common

Other side effects mayoccur that usually do not need medical attention. These side effects may goaway during treatment as your body adjusts to the medicine. However, checkwith your doctor if any of the following side effects continue or are bothersome:

More common

Abdominal pain; hair loss; loss of appetite; loss of strength orenergy, tiredness or weakness; back pain; diarrhea; dry skin; general feeling of discomfort or illness; troublein sleeping; headache; nausea or vomiting

Otherside effects not listed above may also occur in some patients. If you noticeany other effects, check with your doctor.