Bexarotene (Systemic)

• It is used to treat a type of lymphoma.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take bexarotene. This includes your doctors, nurses, pharmacists, and dentists.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• This medicine may cause high cholesterol and triglyceride levels. Talk with the doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Talk with your doctor before you take products that have vitamin A in them.
• Talk with your doctor before you drink alcohol.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• If the capsule is opened or broken, do not touch the contents. If you do touch the contents or get it in your eyes, wash the area right away and call your doctor.
• This medicine may make cataracts worse or may raise the chance of new cataracts. Talk with the doctor.
• If you are a man and have sex with a woman who is pregnant, may be pregnant, or can get pregnant, always use a condom during sex. Use a condom during treatment and for at least 1 month after treatment ends.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking bexarotene.
• Use of this medicine during pregnancy may cause birth defects or death of the unborn baby. You will need to have a pregnancy test to show that you are NOT pregnant before starting bexarotene. Talk with the doctor.
• A pregnancy test will be done every month during care.
• Use 2 kinds of birth control that you can trust 1 month before care begins, during care, and for at least 1 month after care ends.
• If you get pregnant while taking this medicine or within 1 month after your last dose, call your doctor right away.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of low thyroid levels like hard stools (constipation); not able to handle cold; memory problems; mood changes; or a burning, numbness, or tingling feeling that is not normal.
• Change in eyesight.
• Swelling in the arms or legs.
• Feeling very tired or weak.
• Very bad and sometimes deadly pancreas problems (pancreatitis) have happened with this medicine. Call your doctor right away if you have very bad stomach pain, very bad back pain, or very upset stomach or throwing up.
• Very bad and sometimes deadly liver problems have happened with bexarotene (systemic). Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

• 3-methyl TTNEB

• Targretin

Cutaneous T-cell lymphoma, refractory: Oral: Initial: 300 mg/m2 once daily taken as a single daily dose; if well tolerated, but no tumor response after 8 weeks, may increase to 400 mg/m2 once daily; continue as long as clinical benefit is demonstrated (bexarotene was administered in studies for up to 97 weeks).

Mycosis fungoides/Sezary syndrome, refractory/resistant (off-label dose): Oral: 75 to 150 mg daily in combination with PUVA; maximum dose: 300 mg daily (Rupoli, 2010; Singh, 2004)

A 1 mg/mL oral suspension may be prepared with capsules. Cut one 75 mg capsule in half, rinse the interior contents of the capsule, and suspend with 75 mL sterile water. Administer immediately after preparation. To ensure administration of full dose, rinse empty glass with half a glass of water and administer residue.

Store at 2°C to 25°C (36°F to 77°F). Protect from light. Avoid humidity and high temperatures after opening bottle.

Concerns related to adverse effects:

• Hepatotoxicity: Dose-related elevations in ALT, AST, and bilirubin have been reported; cases of cholestasis and liver failure (fatal) have occurred. Monitor for liver function test abnormalities and temporarily withhold or discontinue if ALT, AST, or bilirubin are >3 times the upper limit of normal (ULN). Liver function test elevations resolved within 1 month in most patients following dose reduction or discontinuation.

• Hypothyroidism: Bexarotene rapidly suppresses thyroid-stimulating hormone (TSH) levels by directly inhibiting TSH secretion, and also affects thyroid hormone metabolism (Hamnvik, 2011). Reductions in total thyroxine (T4) and thyroid-stimulating hormone (TSH) are reversible. Hypothyroidism commonly occurs. Monitor thyroid functions tests, including free T4 levels at baseline and during treatment. Thyroid supplementation is usually required; patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels (Hamnvik, 2011).

• Leukopenia: Grade 1 to 3 leukopenia has occurred (predominantly as neutropenia); the incidence is higher with doses >300 mg/m2/day. The onset of leukopenia was generally 4 to 8 weeks. Grade 3 and 4 neutropenia have occurred. Leukopenia and neutropenia typically resolved within 30 days after discontinuation or dose reduction. Monitor complete blood cell count (CBC) with differential at baseline and periodically during treatment. Leukopenia and neutropenia were rarely associated with severe conditions or serious adverse events.

• Lipid abnormalities: Bexarotene induces significant lipid abnormalities in a majority of patients (increased triglycerides and total cholesterol, and decreased high-density lipoprotein [HDL]) and usually occur within 2 to 4 weeks; effects are reversible on discontinuation or generally mitigated by dose reduction and/or antilipemic therapy. Monitor fasting lipid panel; may require dose reduction, treatment interruption, and/or concomitant antilipemic therapy. Fasting triglycerides should be normal (or normalized with appropriate therapy) prior to initiation; triglycerides should be maintained <400 mg/dL. In studies, HMG-CoA reductase inhibitors were used to manage lipids; gemfibrozil is not recommended due to potential for drug interactions.

• Pancreatitis: Pancreatitis associated with hypertriglyceridemia has been reported. Interrupt treatment and evaluate if pancreatitis is suspected. Cutaneous T-cell lymphoma patients with risk factors for pancreatitis (eg, prior pancreatitis, uncontrolled hyperlipidemia, excessive ethanol consumption, uncontrolled diabetes, biliary tract disease, concomitant medications causing hyperlipidemia or concomitant medications associated with pancreatic toxicity) may be at increased risk for bexarotene-associated pancreatitis.

• Photosensitivity: Retinoids are associated with photosensitivity; phototoxicity (sunburn, sunlight sensitivity) has occurred with bexarotene when patients were exposed to direct sunlight. Advise patients to minimize exposure to sunlight and artificial ultraviolet light during treatment.

• Visual disturbances: Any new visual abnormalities experienced by the patient should be evaluated by an ophthalmologist (cataracts may develop or worsen, especially in the geriatric population).

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; may enhance the actions of insulin, sulfonylureas, or thiazolidinediones, resulting in hypoglycemia in patients receiving these agents (hypoglycemia has not been observed with bexarotene monotherapy). Monitor blood glucose as necessary.

• Hepatic impairment: Use with extreme caution in patients with hepatic impairment; bexarotene undergoes extensive hepatic elimination.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Vitamin A: Due to the potential for additive toxicities, patients should be advised to limit additional vitamin A intake (in studies, additional vitamin A was limited to ≤15,000 units/day).

Special populations:

• Pregnancy: [U.S. Boxed Warning]: Bexarotene is a retinoid, a drug class associated with birth defects in humans; do not administer during pregnancy. Bexarotene caused birth defects when administered orally to pregnant rats. Pregnancy test needed within 1 week before initiation and every month thereafter. Effective contraception must be in place 1 month before initiation, during therapy, and for at least 1 month after discontinuation. Male patients with sexual partners who are pregnant, possibly pregnant, or who could become pregnant, must use condoms during sexual intercourse during treatment and for at least 1 month after last dose.