Bexarotene (Topical) (Monograph)

Brand name: Targretin
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
VA class: AN900
Chemical name: 4-[1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl]benzoic acid
Molecular formula: C₂₄H₂₈O₂
CAS number: 153559-49-0

Medically reviewed by Drugs.com on Jan 22, 2024. Written by ASHP.

Introduction

Antineoplastic agent; synthetic retinoid analog.^{1 2 3 4 5 6 7 8 9 10 11 12}

Uses for Bexarotene (Topical)

Cutaneous T-cell Lymphoma

Treatment of skin lesions in patients with early (stage IA and IB) cutaneous T-cell lymphoma (CTCL) who have refractory or persistent disease after other therapies or who are unable to tolerate other therapies (designated an orphan drug by US FDA for this use).^{1 2 5 12 13 14}

Not studied in combination with other CTCL therapies.¹

Bexarotene (Topical) Dosage and Administration

Administration

Topical Administration

Topically apply a sufficient amount for a generous coating and rub gently into affected areas of skin.¹

Wait at least 20 minutes after bathing before application.^{1 2 5} Avoid use of occlusive dressings or wrappings.^{1 2 5}

Avoid contact with healthy skin or mucous membranes (e.g., eyes, mouth, vagina).^{1 2 5}

Allow gel to dry 5–10 minutes before covering a treated area with clothing.^{1 2 5}

Dosage

Adults

CTCL

Topical

Initially, once daily, every other day, for the first week.^{1 2 5}

Increase application frequency at weekly intervals to once, then twice daily, then 3 times daily, and finally 4 times daily, according to individual lesion tolerance.^{1 2 5}

If application site toxicity occurs, reduce application frequency; temporarily discontinue if severe irritation occurs.¹

Most responses occurred when applied ≥2 times daily in clinical studies.^{1 5} Therapeutic response may be observed as early as 4 weeks, but usually occurred later.^{1 5}

Continue as long as benefit is derived.^{1 5} Although continued for up to 172 weeks in clinical studies, optimum duration is not known.^{1 5 6 7 8 13}

Related/similar drugs

bexarotene, methoxsalen, vorinostat, Targretin, romidepsin

Cautions for Bexarotene (Topical)

Contraindications

• Known or suspected pregnancy.^{1 2 5}

• Known hypersensitivity to bexarotene or any ingredient in the formulation.^{1 2 5}

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals receiving oral bexarotene.^{1 2 5}

Exclude pregnancy 1 week prior to initiation of therapy.¹ Initiate therapy on second or third day of normal menstrual period.¹ Repeat pregnancy tests monthly during therapy.¹ To facilitate pregnancy test assessment and counseling, dispense no more than 1 month supply.^{1 2}

Use contraception (2 reliable forms) for 1 month before, during, and for 1 month after discontinuance.^{1 2 5} Male patients should use condoms during sexual intercourse with women who are or may become pregnant during and for at least 1 month after discontinuance.^{1 2 5}

If pregnancy occurs, immediately discontinue and apprise of potential fetal hazard.^{1 5}

Sensitivity Reactions

Hypersensitivity

Use with caution in patients with known hypersensitivity to retinoids.^{1 2 5}

Photosensitivity

Minimize exposure to sunlight and artificial UV light.^{1 2 5} Sunburn and skin sensitivity to sunlight observed in patients receiving oral bexarotene.¹¹

Specific Populations

Pregnancy

Category X.^{1 5} (See Fetal/Neonatal Morbidity and Mortality and also Contraindications under Cautions.)

Lactation

Not known whether bexarotene is distributed into milk.^{1 5} Discontinue nursing or the drug.^{1 2 5}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 5 13}

Geriatric Use

No substantial differences in safety relative to younger adults, but increased sensitivity cannot be ruled out.^{1 5}

Common Adverse Effects

Rash, pruritus, skin disorders (e.g., inflammation, excoriation, sticky or tacky skin sensation), pain, contact dermatitis.^{1 2 3 5 6 7 8 9 12 13}

Drug Interactions

Orally administered bexarotene is metabolized by CYP3A4.^{1 5 11 12}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP3A4: pharmacokinetic interaction unlikely with topical bexarotene because of low systemic exposure.^{1 5}

Protein-bound Drugs

Pharmacokinetic interaction unlikely with topicalbexarotene.^{1 13}

Specific Drugs

Bexarotene (Topical) Pharmacokinetics

Absorption

Bioavailability

Plasma concentrations generally were low or undetectable following single or multiple daily topical application of low to moderate dosage intensity and increased as surface area treated or amount applied increased.^{1 5 12}

Distribution

Extent

Distribution of bexarotene into organs or tissues has not been evaluated.¹ Not known whether bexarotene is distributed into milk.^{1 5}

Plasma Protein Binding

>99%.¹

Special Populations

In patients with renal impairment, pharmacokinetics may be altered because of substantial protein binding changes.¹

Elimination

Special Populations

In patients with hepatic impairment, greatly decreased clearance would be expected.^{1 11}

In patients with renal impairment, pharmacokinetics may be altered because of substantial protein binding changes.¹

Stability

Storage

Topical

Gel

25°C (may be exposed to 15–30°C); protect from light.¹

Avoid exposure to high temperatures and humidity after tube is opened.¹

Actions

• Selectively binds with and activates retinoid X receptor (RXR) subtypes (RXR_α, RXR_β, and RXR_γ).^{1 2 3 4 5 6 7 8 9 10 11 12} Activated RXRs function as transcription factors that regulate the expression of genes controlling cellular differentiation, apoptosis, and proliferation.^{1 3 4 5 10 11 12}

• Exact mechanism(s) of action not determined.^{1 11}

Advice to Patients

• Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.^{1 2 5}

• Importance of women and men taking measures to avoid pregnancy during therapy because of risk to fetus.^{1 2 5}

• Importance of men using condoms during sexual intercourse while receiving the drug and for at least 1 month after discontinuance.^{1 5}

• Importance of monthly pregnancy tests.¹

• Risk of photosensitivity reactions.^{1 2 5}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal products as well as any concomitant illnesses.^{1 5}

• Provide copy of manufacturer’s patient instructions.²

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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