Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External:
Targretin: 1% (60 g) [contains alcohol, usp]
Pharmacology
Mechanism of Action
Binds to and activates retinoid X receptor subtypes. Once activated, these receptors function as transcription factors that regulate the expression of genes which control cellular differentiation and proliferation.
Pharmacokinetics/Pharmacodynamics
Absorption
Systemically absorbed following topical application (1% gel: generally less than 5 ng/mL and did not exceed 55 ng/mL)
Onset of Action
Response may be seen at 4 weeks, although longer application may be required for response (range: up to 56 weeks).
Protein Binding
>99% to plasma proteins
Use: Labeled Indications
Cutaneous T-cell lymphoma: Topical treatment of cutaneous lesions in patients with refractory or persistent cutaneous T-cell lymphoma (stage 1A and 1B) or who have not tolerated other therapies
Contraindications
Known hypersensitivity to bexarotene or any component of the formulation; pregnancy
Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Dosage and Administration
Dosing: Adult
Cutaneous T-cell lymphoma: Topical: Apply to lesions once every other day for first week, then increase on a weekly basis to once daily, 2 times daily, 3 times daily, and finally 4 times daily, according to individual lesion tolerance. Continue as long as deriving benefit. Response is usually observed with application at 2 to 4 times daily. May decrease frequency if local toxicity occurs; for severe irritation, temporarily withhold for a few days until symptoms subside.
Dosing: Geriatric
Refer to adult dosing.
Administration
Using a clean, dry finger, apply a sufficient amount to cover lesion with a generous coating. Allow gel to dry before covering with clothing. Avoid application to normal skin; do not apply near mucosal surfaces. Use of occlusive dressings is not recommended. If applying after bathing/showering, wait 20 minutes prior to application. Avoid bathing/showering/swimming for at least 3 hours following application (if possible). Following application, wipe excess gel from finger with a disposable tissue and wash hands with soap and water.
Storage
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Avoid exposure to high temperatures and humidity after the tube is opened. Protect from light. Keep away from open flame.
Drug Interactions
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Bexarotene (Topical). Management: Limit doses of vitamin A to 5,000 units per day if combined with topical bexarotene. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Bexarotene (Topical). Management: Limit doses of vitamin A to 5,000 units per day if combined with topical bexarotene. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Bexarotene (Topical). Management: Limit doses of vitamin A to 5,000 units per day if combined with topical bexarotene. Consider therapy modification
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin A: May enhance the adverse/toxic effect of Bexarotene (Topical). Management: Limit doses of vitamin A to 5,000 units per day if combined with topical bexarotene. Consider therapy modification
Adverse Reactions
>10%:
Central nervous system: Pain (30%), headache (14%)
Dermatologic: Skin rash (14% to 72%), pruritus (6% to 40%), contact dermatitis (14%)
Infection: Infection (18%)
1% to 10%:
Cardiovascular: Edema (10%)
Central nervous system: Paresthesia (6%)
Dermatologic: Diaphoresis (6%), exfoliative dermatitis (6%)
Endocrine & metabolic: Hyperlipidemia (10%)
Hematologic & oncologic: Leukopenia (6%), lymphadenopathy (6%)
Neuromuscular & skeletal: Weakness (6%)
Respiratory: Cough (6%), pharyngitis (6%)
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Use with caution in patients with known hypersensitivity to other retinoids.
- Photosensitivity: Retinoids may cause photosensitization; minimize sunlight and artificial UV light exposure during treatment.
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 supplements: Due to the potential for additive toxicities, patients should be advised to limit additional vitamin A intake to <15,000 units/day.
Special populations:
- Pregnancy: Bexarotene is a retinoid, a drug class associated with birth defects in humans; do not administer during pregnancy. Pregnancy test needed 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 1 month after last dose.
Other warnings/precautions:
- Insect repellents: Patients should avoid insect repellents containing N,N-diethyl-meta-toluamide (DEET) while using topical bexarotene (animal studies demonstrated increased DEET toxicity).
Monitoring Parameters
If female, pregnancy test 1 week before initiation then monthly while on bexarotene
Pregnancy
Pregnancy Considerations
Bexarotene use is contraindicated in pregnancy. Bexarotene is a member of the retinoid class of drugs that is associated with birth defects in humans. Bexarotene also caused birth defects when administered orally to pregnant rats. Bexarotene must not be administered to a pregnant woman. If a woman becomes pregnant while taking the drug, it must be stopped immediately and appropriate counseling be given.
Evaluate pregnancy status prior to use in females of reproductive potential. Effective contraception should be used for 1 month prior to initiating treatment, during therapy, and for at least 1 month after bexarotene is discontinued. Either abstinence or two forms of reliable contraception (one should be nonhormonal) are recommended. A negative pregnancy test (sensitivity of at least 50 mIU/mL) within 1 week prior to beginning therapy, and monthly, thereafter, is required for women of childbearing potential. A maximum 1-month supply is recommended so that pregnancy tests may be evaluated.
Male patients must use a condom during sexual intercourse with females who are pregnant, possibly pregnant, or who may become pregnant during therapy and for at least 1 month following discontinuation of bexarotene.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience burning, itching, redness, peeling, loss of strength and energy, sweating a lot, or headache. Have patient report immediately to prescriber signs of infection, burning or numbness feeling, edema, swollen glands, or severe skin irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
