Bexarotene (2 brand names, 2 dosage forms, 2 routes)
Available dosage forms: CAPSULE, GEL.
Routes of administration: ORAL, TOPICAL.
Brand Names
- BEXAROTENE
- TARGRETIN
Boxed Warning
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. (8.1)
Indications and Usage
Bexarotene capsules are indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy.
Dosage and Administration
The recommended initial dose of bexarotene capsules is 300 mg/m 2/day (see Table 1). Bexarotene capsules should be taken as a single oral daily dose with a meal. For precautions to prevent pregnancy and birth defects in women of child-bearing potential [see Use in Specific Populations (8.1)] . Table 1: Bexarotene Capsules Initial Dose Calculation According to Body Surface Area Initial Dose Level (300 mg/m 2/day) Number of 75 mg Bexarotene Capsules Body Surface Area (m 2) Total Daily Dose (mg/day) 0.88 to 1.12 300 4 1.13 to 1.37 375 5 1.38 to 1.62 450 6 1.63 to 1.87 525 7 1.88 to 2.12 600 8 2.13 to 2.37 675 9 2.38 to 2.62 750 10 Dose Modification Guidelines: The 300 mg/m 2/day dose level of bexarotene capsules may be adjusted to 200 mg/m 2/day then to 100 mg/m 2/day, or temporarily suspended, if necessitated by toxicity. When toxicity is controlled, doses may be carefully readjusted upward. If there is no tumor response after eight weeks of treatment and if the initial dose of 300 mg/m 2/day is well tolerated, the dose may be escalated to 400 mg/m 2/day with careful monitoring. Duration of Therapy: In clinical trials in CTCL, bexarotene capsules was administered for up to 97 weeks. Bexarotene capsules should be continued as long as the patient is deriving benefit.
Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information: Hyperlipidemia [see Warnings and Precautions (5.1)] Pancreatitis [see Warnings and Precautions (5.2)] Hepatotoxicity, cholestasis, and hepatic failure [see Warnings and Precautions (5.3)] Hypothyroidism [see Warnings and Precautions (5.4)] Neutropenia [see Warnings and Precautions (5.5)] Cataracts [see Warnings and Precautions (5.6)] Vitamin A Supplementation Hazard [see Warnings and Precautions (5.7)] Hypoglycemia Risk in Patients with Diabetes Mellitus [see Warnings and Precautions (5.8)] Photosensitivity [see Warnings and Precautions (5.9)] Laboratory Tests [see Warnings and Precautions (5.10)] Drug/Laboratory Test Interactions [see Warnings and Precautions (5.11)]
Drug Interactions
Effect of Other Drugs on Bexarotene Gemfibrozil: Concomitant administration of bexarotene and gemfibrozil resulted in increases in plasma concentrations of bexarotene. Concomitant administration of gemfibrozil with bexarotene is not recommended. Effect of Bexarotene on Other Drugs Bexarotene may be an inducer for the CYP3A4 enzymes, and may reduce plasma concentrations of other substrates metabolized by CYP3A4. Drug products which may be affected include oral or other systemic hormonal contraceptives. Thus, if treatment with bexarotene is intended for a female with reproductive potential, it is strongly recommended that a non-hormonal contraception be considered [see Use in Specific Populations (8.3), Clinical Pharmacology (12.3)] . Laboratory Test Interference CA125 assay values in patients with ovarian cancer may be increased by bexarotene therapy.
Mechanism of Action
Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. The exact mechanism of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) is unknown.
Overdosage
Doses up to 1000 mg/m 2/day of bexarotene have been administered in short-term trials in patients with advanced cancer without acute toxic effects. Single doses of 1500 mg/kg and 720 mg/kg were tolerated without significant toxicity in rats and dogs, respectively. These doses are approximately 30 and 50 times, respectively, the recommended human dose on a mg/m 2 basis.