Bexarotene

What it is and how it works

Mechanism of Action Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRß, 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.

Indications

® (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. TARGRETIN (bexarotene) is a retinoid 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 (summary)

The recommended initial dose of TARGRETIN is 300 mg/m 2 /day (see Table 1). TARGRETIN 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 ]. Table 1: TARGRETIN Initial Dose Calculation According to Body Surface Area Initial Dose Level (300 mg/m 2 /day) Number of 75 mg TARGRETIN Capsules Body Surface Area (m 2 ) Total Daily Dose (mg/day) 0.88 – 1.12 300 4 1.13 – 1.37 375 5 1.38 – 1.62 450 6 1.63 – 1.87 525 7 1.88 – 2.12 600 8 2.13 – 2.37 675 9 2.38 – 2.62 750 10 Dose Modification Guidelines: The 300 mg/m 2 /day dose level of TARGRETIN may be adjusted to 200 mg/m 2 …

Contraindications

• Pregnancy (Boxed Warning, 4.1 ) • Known hypersensitivity to bexarotene Pregnancy TARGRETIN can cause fetal harm when administered to a pregnant female. TARGRETIN is a member of the retinoid class of drugs that is associated with birth defects in humans and is contraindicated in females who are pregnant. Bexarotene was also teratogenic and caused developmental mortality when administered orally to pregnant rats.

Warnings and precautions

• Hyperlipidemia: TARGRETIN causes elevations in blood lipids. Obtain baseline values, monitor, and manage elevations during therapy by dose reduction, interruption, discontinuation and/or lipid lowering therapy. ( 5.1 , 5.11 ) • Pancreatitis: Interrupt TARGRETIN and evaluate if suspected. • Hepatotoxicity, Cholestasis, and Hepatic Failure: Interrupt or discontinue TARGRETIN and evaluate if liver chemistry tests exceed three times the upper limit of normal values. • Hypothyroidism: TARGRETIN therapy can cause hypothyroidism. Monitor and replace thyroid hormone if needed.

Pregnancy

Pregnancy Risk Summary TARGRETIN, a retinoid, can cause fetal harm based on findings from animal studies when administered to a pregnant female and is contraindicated during pregnancy. Bexarotene was teratogenic and caused developmental mortality in rats following oral administration during organogenesis .

Storage and supply

® (bexarotene) Capsules are supplied as 75 mg off-white, oblong soft gelatin capsules, imprinted with “Targretin”, in high density polyethylene bottles with child-resistant closures. Bottles of 100 capsules: NDC 0187-5526-75 Store at 2° to 25°C (36° to 77°F). Avoid exposing to high temperatures and humidity after the bottle is opened.

Source: Bexarotene (Targretin) — US FDA prescribing information, 2020-04-30, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.