Bexarotene
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]
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Overview
Bexarotene is an antineoplastic agent that is FDA approved for the treatment of {{{indication}}}. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
- Dosing Information
- Dosage
Condition2
- Dosing Information
- Dosage
Condition3
- Dosing Information
- Dosage
Condition4
- Dosing Information
- Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
- Developed by:
- Class of Recommendation:
- Strength of Evidence:
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Bexarotene in adult patients.
Non–Guideline-Supported Use
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Bexarotene in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Bexarotene in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
- Developed by:
- Class of Recommendation:
- Strength of Evidence:
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Bexarotene in pediatric patients.
Non–Guideline-Supported Use
Condition1
- Dosing Information
- Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Bexarotene in pediatric patients.
Contraindications
- Condition1
Warnings
- Description
Precautions
- Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Bexarotene in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Bexarotene in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
- Drug
- Description
Use in Specific Populations
Pregnancy
- Pregnancy Category
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Bexarotene in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Bexarotene during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Bexarotene with respect to nursing mothers.
Pediatric Use
There is no FDA guidance on the use of Bexarotene with respect to pediatric patients.
Geriatic Use
There is no FDA guidance on the use of Bexarotene with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Bexarotene with respect to specific gender populations.
Race
There is no FDA guidance on the use of Bexarotene with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Bexarotene in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Bexarotene in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Bexarotene in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Bexarotene in patients who are immunocompromised.
Administration and Monitoring
Administration
- Oral
- Intravenous
Monitoring
There is limited information regarding Monitoring of Bexarotene in the drug label.
- Description
IV Compatibility
There is limited information regarding IV Compatibility of Bexarotene in the drug label.
Overdosage
Acute Overdose
Signs and Symptoms
- Description
Management
- Description
Chronic Overdose
There is limited information regarding Chronic Overdose of Bexarotene in the drug label.
Pharmacology
There is limited information regarding Bexarotene Pharmacology in the drug label.
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.
Structure
- Targretin® (bexarotene) gel 1% contains bexarotene and is intended for topical application only. Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs).
- The chemical name is 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl] benzoic acid, and the structural formula is as follows:
- Bexarotene is an off-white to white powder with a molecular weight of 348.48 and a molecular formula of C24H28O2. It is insoluble in water and slightly soluble in vegetable oils and ethanol, USP.
- Targretin® gel is a clear gelled solution containing 1.0% (w/w) bexarotene in a base of dehydrated alcohol, USP, polyethylene glycol 400, NF, hydroxypropyl cellulose, NF, and butylated hydroxytoluene, NF.
Pharmacodynamics
There is limited information regarding Pharmacodynamics of Bexarotene in the drug label.
Pharmacokinetics
General
- Plasma concentrations of bexarotene were determined during clinical studies in patients with CTCL or following repeated single or multiple-daily dose applications of Targretin® gel 1% for up to 132 weeks. Plasma bexarotene concentrations were generally less than 5 ng/mL and did not exceed 55 ng/mL. However, only two patients with very intense dosing regimens (> 40% BSA lesions and QID dosing) were sampled. Plasma bexarotene concentrations and the frequency of detecting quantifiable plasma bexarotene concentrations increased with increasing percent body surface area treated and increasing quantity of Targretin® gel applied. The sporadically observed and generally low plasma bexarotene concentrations indicated that, in patients receiving doses of low to moderate intensity, there is a low potential for significant plasma concentrations following repeated application of Targretin® gel. Bexarotene is highly bound (>99%) to plasma proteins. The plasma proteins to which bexarotene binds have not been elucidated, and the ability of bexarotene to displace drugs bound to plasma proteins and the ability of drugs to displace bexarotene binding have not been studied . The uptake of bexarotene by organs or tissues has not been evaluated.
Metabolism
- Four bexarotene metabolites have been identified in plasma following oral administration of bexarotene: 6- and 7-hydroxy-bexarotene and 6- and 7-oxo-bexarotene. In vitro studies suggest that cytochrome P450 3A4 is the major cytochrome P450 responsible for formation of the oxidative metabolites and that the oxidative metabolites may be glucuronidated. The oxidative metabolites are active in in vitro assays of retinoid receptor activation, but the relative contribution of the parent and any metabolites to the efficacy and safety of Targretin® gel is unknown.
Elimination
- The renal elimination of bexarotene and its metabolites was examined in patients with Type 2 diabetes mellitus following oral administration of bexarotene. Neither bexarotene nor its metabolites were excreted in urine in appreciable amounts..
Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Bexarotene in the drug label.
Clinical Studies
- Targretin® gel was evaluated for the treatment of patients with early stage (Stage IA-IIA) CTCL in one multicenter, open-label, clinical trial as well as in a Phase I-II program (dose-seeking trials with different response criteria than the multicenter trial). These clinical studies enrolled a total of 117 patients.
- In the multicenter, open-label clinical trial, Targretin® gel was evaluated for the treatment of patients with early stage CTCL who were refractory to, intolerant to, or reached a response plateau for at least six months on at least two prior therapies. The study was conducted in the U.S., Canada, Europe, and Australia and enrolled a total of 50 patients; 46% of these patients were male, 80% were Caucasian, and the median age was 64 years (range 13 to 85).
- Targretin® gel was also evaluated for the treatment of patients with CTCL in a U.S. Phase I-II program involving patients with early stage CTCL. This program enrolled a total of 67 patients; 55% of these patients were male, 85% were Caucasian, and the median age was 61 years (range 30 to 87).
- In the multicenter, open-label clinical trial, considering prior systemic, irradiation, and topical treatments, patients had been exposed to a median of three prior therapies (range 2-7). All patients failed at least two treatments; the majority (68%) of patients were either refractory to two or more therapies or were refractory to one therapy and intolerant to at least one therapy.
- Patients were treated with Targretin® gel 1% for a planned 16-week period with an option to continue provided that no unacceptable toxicity was occurring.
- Tumor response was assessed in the multicenter study by observation of up to five baseline-defined index lesions using a Composite Assessment of Index Lesion Disease Severity (CA). This endpoint was based on a summation of the grades, for all index lesions, of erythema, scaling, plaque elevation, hypopigmentation or hyperpigmentation, and area of involvement. New cutaneous lesions or tumors and extracutaneous disease manifestations were not considered in response or disease progression assessments.
- All tumor responses required confirmation over at least two assessments separated by at least four weeks. A partial response was defined as an improvement of at least 50% in the index lesions. A complete clinical response required complete disappearance of the index lesions, but did not require confirmation by biopsy.
- Targretin® gel produced an overall response rate of 26% (13/50) with a corresponding exact 95% confidence interval from 14.6% to 40.3% by the Composite Assessment of Index Lesion Severity. For the Stage IA and IB patients, the response rate was 28% (13/47) with a corresponding exact 95% confidence interval from 15.6% to 42.6%. For the Stage II patients the response rate was 0% (0/3). Two percent of patients (1/50) had a clinical complete response. The median time to best response on the Composite Assessment of Index Lesion Severity (n=13) was 85 days (range: 36-154).
- The rate of relapse in responding patients by the Composite Assessment of Index Lesion Severity was 23% (3/13) over a median observation period of 149 days (range 56-342). *Fourteen patients developed new lesions in untreated areas (14/50; 28%). Four patients developed clinically abnormal lymph nodes (≥ 1 cm diam) (4/50; 8%). One patient developed a cutaneous tumor (1/50; 2%).
- The Phase I-II program (dose-seeking trials with different response criteria than the multicenter trial) was supportive of the multicenter study results.
How Supplied
Storage
There is limited information regarding Bexarotene Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Patient Counseling Information of Bexarotene in the drug label.
Precautions with Alcohol
- Alcohol-Bexarotene interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
- ®[1]
Look-Alike Drug Names
- A® — B®[2]
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
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