Targretin®
Bexarotene, a synthetic retinoid analog, is an antineoplastic agent that selectively binds with and activates retinoid X receptor (RXR) subtypes (RXRα, RXRβ, and RXRγ).1
Bexarotene is used orally for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy.1, 8, 9
Efficacy of oral bexarotene was evaluated in 2 multicenter, open-label, historically controlled studies in patients with early stage or advanced CTCL refractory to at least one prior systemic therapy.1, 4, 5 At an initial dosage of 300 mg/m2 daily, 1.6 or 30% of patients had a complete or partial tumor response, respectively, by a composite assessment of index lesion severity.1 Responses to therapy were observed as early as 4 weeks after initiation of bexarotene, and new responses continued to be observed at later visits.1, 2, 4 Approximately 30% of patients who responded to therapy later relapsed over a median of 21 weeks of observation.1
For information on the topical use of bexarotene, see Bexarotene 84:92.
Within CTCL are numerous distinct skin manifestations with differing treatment approaches, which include mycosis fungoides, Sézary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders.10 Some experts suggest management of early stage mycosis fungoides with skin directed therapies, which includes treatment with topical corticosteroids, phototherapy, and topical nitrogen mustard.10, 11 In cases uncontrolled with initial therapies, skin directed treatment is combined with systemic treatments, which includes oral retinoids (e.g., acitretin, bexarotene), pralatrexate or low-dose oral methotrexate, pegylated interferon alfa, mogamulizumab, brentuximab, or histone deacetylase inhibitors (e.g., vorinostat, romidepsin, resminostat).10, 11 As an alternative to oral retinoids, topical retinoid agents such as alitretinoin, bexarotene, and taxarotene can be used.11 In more advanced disease (thick plaques, tumor stage), mono-agent chemotherapy with gemcitabine or pegylated liposomal doxorubicin is used, with CHOP -based chemotherapy regimens reserved for patients for extracutaneous spread.11 Additional treatment options in advanced mycosis fungoides include brentuximab vedotin in patients with CD30+ tumors, total skin electron beam therapy, extracorporeal photophoresis in erythrodermic mycosis fungoides, and allogeneic hematopoietic stem cell transplantation.10, 11 In Sézary syndrome, treatment strategies are similar to advanced stage mycosis fungoides, and include extracorporeal photophoresis combined with systemic therapies such as oral bexarotene initially.10, 11 Alemtuzumab and chemotherapeutic agents such as gemcitabine and pegylated liposomal doxorubicin are used in second-line treatment, with mogamulizumab also reported as an effective agent.11
Administer bexarotene orally once daily with a meal.1, 2, 3
Store at 2-25°C away from light, heat, and humidity.1
The recommended initial adult dosage of bexarotene for the treatment of skin manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy is 300 mg/m2 orally daily.1, 2, 3 If no tumor response is observed after 8 weeks and the 300 mg/m2 daily dosage is well tolerated, the dosage may be increased to 400 mg/m2 daily with careful monitoring.1 Refer to Table 1 for the initial bexarotene dose of 300 mg/m2 daily according to body surface area (BSA).
Bexarotene should be continued as long as the patient is deriving benefit from therapy.1, 2 Although therapy was continued for up to 97 weeks in clinical studies in patients with CTCL, the optimum duration is not known.1, 2, 3
Body Surface Area (m2) | Total Daily Dose (mg/day) |
|---|---|
0.88-1.12 | 300 |
1.13-1.37 | 375 |
1.38-1.62 | 450 |
1.63-1.87 | 525 |
1.88-2.12 | 600 |
2.13-2.37 | 675 |
2.38-2.62 | 750 |
Dosage Modification for Toxicity
If intolerable adverse effects occur, the dosage may be decreased to 200 mg/m2 daily, then 100 mg/m2 daily, or the drug may be temporarily discontinued.1, 2 When toxicity is controlled, the dosage may be carefully readjusted upward.1, 2
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Fetal/Neonatal Morbidity and Mortality
A boxed warning about the risk of birth defects is included in the prescribing information for bexarotene.1 Bexarotene, part of the retinoid class of drugs, is associated with birth defects in humans.1 Bexarotene is contraindicated for use in pregnant women, and in women who intend to become pregnant.1
May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.1, 2 No adequate and well-controlled studies to date in humans.1, 2 Pregnancy should be avoided during therapy.1, 2 If used during pregnancy, apprise of potential fetal hazard.1, 2 Contraception (using 2 reliable forms, including at least one nonhormonal method) should be used for 1 month before, during, and for at least 1 month after bexarotene administration.1, 2 Pregnancy tests should be repeated monthly during therapy.1 To facilitate pregnancy test assessment and counseling, dispense no more than 1 month supply.1 Male patients receiving the drug should use condoms during sexual intercourse with women who are or may become pregnant.1, 2
Hyperlipidemia occurred in 79% of patients receiving oral bexarotene in phase II-III clinical studies.1, 2 Elevations in fasting triglycerides and cholesterol and decreases in HDL cholesterol were observed in more than half of patients receiving 300 mg/m2 or more.1 Lipid abnormalities usually developed within 2-4 weeks and were reversible with cessation of therapy.1 If fasting triglycerides are elevated or become elevated during treatment, antilipemic therapy should be instituted, and the dosage of bexarotene reduced or suspended.1 However, concomitant gemfibrozil is not recommended due to a potential drug-drug interaction.1
Acute pancreatitis has been reported in several patients treated with bexarotene and has been fatal in at least one patient.1, 2 The manufacturer states that patients with CTCL who have risk factors for pancreatitis (e.g., prior pancreatitis, uncontrolled hyperlipidemia, excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract disease, or drugs associated with pancreatic toxicity or known to increase triglyceride concentrations) generally should not be treated with bexarotene.1, 2 Interrupt bexarotene treatment and evaluate if pancreatitis is suspected.1
Hepatotoxicity, Cholestasis, and Hepatic Failure
Elevations in AST and ALT have been observed in some patients receiving oral bexarotene.1, 2 In clinical trials, elevations in liver function tests resolved within 1 month in 80% of patients following a decrease in dosage or discontinuance of therapy.1, 2 If liver function tests are elevated (i.e., transaminases or bilirubin increase to 3 times the upper limit of normal), discontinue or interrupt bexarotene therapy.1, 2 Use with caution in patients with hepatic impairment.1, 2 Obtain liver function tests at baseline and monitor after 1, 2, and 4 weeks of treatment initiation, and if stable, at least every 8 weeks thereafter.1
Clinical or laboratory evidence of hypothyroidism in about 50% of patients treated with oral bexarotene.1, 2 Reduction of thyroid-stimulating hormone and total thyroxine (T4) observed in 60% and 45% of patients, respectively, receiving an initial dosage of 300 mg/m2 per day.1 Consider thyroid supplementation in patients with laboratory evidence of hypothyroidism.1 Obtain baseline thyroid function tests and monitor during treatment.1
Leukopenia (generally neutropenia) occurred in 18 or 43% of patients with CTCL receiving an initial dosage of 300 mg/m2 or >300 mg/m2 daily, respectively.1, 2 The time to onset was 4-8 weeks, and resolution occurred within 30 days of dosage reduction or discontinuance of the drug in 93% of patients.1, 2 Leukopenia and neutropenia were rarely associated with serious adverse events.1 Obtain baseline CBC and monitor periodically throughout treatment.1
New cataracts or worsening of previously existing cataracts occurred in 15 of 79 patients monitored with serial slit lamp examinations.1 Due to the risk of cataract formation in older patient populations, the relationship of bexarotene to cataract formation cannot be determined.1 Patients with visual difficulties should receive an ophthalmologic examination.1
Vitamin A Supplementation Hazard
Due to the relationship between bexarotene and vitamin A, patients should limit vitamin A intake to <15,000 IU/day to limit toxic effects.1
Hypoglycemia Risk in Patients with Diabetes Mellitus
Patients using insulin, sulfonylureas, thiazolidinediones, or other oral agents while on bexarotene are at an increased risk for hypoglycemia, since bexarotene may enhance their effects.1 When used as monotherapy, bexarotene has not been associated with hypoglycemia.1
Use with caution in patients with known hypersensitivity to retinoids.1, 2 Photosensitivity reactions manifested as sunburn and skin sensitivity to sunlight were observed in patients exposed to direct sunlight while receiving bexarotene.1, 2 Minimize exposure to sunlight and artificial (UV) light.1, 2
Drug-Laboratory Test Interaction
In patients with ovarian cancer, CA125 assay values may be increased by bexarotene.1
Bexarotene, a retinoid agent, is contraindicated during pregnancy.1 Retinoid agents are associated with birth defects in humans.1 In animal studies, bexarotene administration resulted in fetal harm.1
Obtain a negative serum pregnancy test within 1 week prior to starting bexarotene therapy, and perform pregnancy testing at monthly intervals during therapy.1 Pregnancy should be avoided during therapy.1, 2 If used during pregnancy, apprise of potential fetal hazard.1, 2 Contraception (using 2 reliable forms, including at least one nonhormonal method) should be used for 1 month before, during, and for at least 1 month after bexarotene administration.1, 2 Male patients receiving the drug should use condoms during sexual intercourse with women who are or may become pregnant.1, 2
There are no data on the presence of bexarotene in human milk, the effects on the breastfed infant, or the effects on milk production.1 Discontinue nursing or the drug, taking into account the importance of the drug to the mother.1, 2
Females and Males of Reproductive Potential
Obtain a negative serum pregnancy test within 1 week prior to starting bexarotene therapy, and perform pregnancy testing at monthly intervals during bexarotene therapy.1 Contraception (using 2 reliable forms, including at least one nonhormonal method) should be used for 1 month before, during, and for at least 1 month after bexarotene administration.1, 2 At least one nonhormonal method is strongly recommended due to the risk of a drug-drug interaction with oral or other systemic hormonal contraceptives that may reduce their effectiveness.1 To ensure patients have a negative pregnancy test result and receive appropriate counseling on the risk of potential fetal hazard, no more than a 1 month supply should be dispensed to a patient at one time.1
Male patients receiving the drug should use condoms during sexual intercourse with women who are or may become pregnant, and for at least one month after discontinuing bexarotene.1, 2
Safety and efficacy not established in children <18 years of age.1, 2
No substantial differences in safety relative to younger adults, but increased sensitivity cannot be ruled out.1, 2
No specific studies have been conducted with bexarotene in patients with hepatic impairment.1 Hepatic impairment, however, is expected to decrease clearance. Monitor for signs and symptoms of toxicity in the presence of reduced hepatic function.1
No formal studies have been conducted with bexarotene in patients with renal impairment.1 Bexarotene elimination via the urine is a minor excretory pathway, but since renal impairment can result in changes in protein binding, the pharmacokinetics of bexarotene may be altered in renal impairment.1
The most common adverse reactions (occurring in >10% of patients in clinical trials and at least possibly related to treatment) include: lipid abnormalities (elevated triglycerides, elevated total and LDL cholesterol and decreased HDL cholesterol), hypothyroidism, headache, asthenia, rash, leukopenia, anemia, nausea, infection, peripheral edema, abdominal pain, and dry skin.1, 2
Metabolized by CYP3A4.1
In vitro, bexarotene inhibits cytochrome P-450 (CYP) isoenzyme 2C8 and induces CYP3A4.1
In vitro, bexarotene does not significantly inhibit CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4.1
Drugs Affected by Hepatic Microsomal Enzymes
May decrease exposure to CYP3A4 substrates.1 Atorvastatin exposure decreased by half when coadministered with bexarotene.1
Potential pharmacokinetic interaction (bexarotene displacement by, or bexarotene displacement of, other protein-bound drugs).1
Pharmacokinetic interaction (decreased plasma concentrations of paclitaxel by 19%).1 Additionally, when paclitaxel plus carboplatin was coadministered with bexarotene, plasma concentrations of bexarotene increased 2-fold.1
Pharmacokinetic interaction (increased plasma concentrations of bexarotene).1, 2, 3 Concomitant use not recommended.1, 2
Pharmacokinetic interaction (decreased plasma concentrations of tamoxifen by approximately 35%).1
Potential pharmacodynamic interaction (increased incidence of hypoglycemia) when bexarotene is used with these drugs (e.g., insulin, sulfonylureas or other oral antidiabetic agents).1, 2, 3
Potential pharmacokinetic interaction (decreased plasma concentrations of oral or other systemic hormonal contraceptives).1 Females of reproductive potential should use a non-hormonal method of contraception while on bexarotene.1
Bexarotene, a synthetic retinoid analog, is an antineoplastic agent that selectively binds with and activates retinoid X receptor (RXR) subtypes (RXRα, RXRβ, and RXRγ).1, 2, 3 Activated RXRs function as transcription factors that regulate the expression of genes controlling cellular differentiation and proliferation.1, 2, 3 Although the exact mechanism(s) of action of bexarotene in the treatment of cutaneous T-cell lymphoma (CTCL) has not been determined,1, 2, 3 the drug has activity in all clinical stages of CTCL.2
In vitro studies suggest that bexarotene is metabolized extensively in the liver principally via oxidation by the cytochrome P-450 (CYP) 3A4 isoenzyme.1 Biliary excretion apparently is the principal route of elimination of the drug and its metabolites.1, 2, 3 Following oral administration, peak plasma concentrations of bexarotene are attained within 2 hours.1 Plasma bexarotene concentrations after a 300-mg dose increased by approximately 48% after a meal containing fat compared with a glucose solution.1, 2, 3 The terminal half-life of bexarotene is approximately 7 hours.1 Bexarotene is highly bound (>99%) to plasma proteins.1 The renal elimination of bexarotene is minimal (<1% of administered dose in urine).1 No significant differences in pharmacokinetics based on age or gender.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 75 mg* | Targretin® | Ligand |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Bausch Health Companies. Targretin® (bexarotene) capsules prescribing information. Bridgewater, NJ; 2020 Apr
2. Ligand Pharmaceuticals. Targretin® capsules (bexarotene) product monograph. San Diego, CA; 2000 Feb.
3. Anon. Bexarotene (Targretin) for cutaneous T-cell lymphoma. Med Lett Drugs Ther . 2000; 42:31-2. [PubMed 10788961]
4. Duvic M, Martin AG, Kim Y et al. Phase 2 and 3 clinical trial of oral bexarotene (Targretin capsules) for the treatment of refractory or persistent early-stage cutaneous T-cell lymphoma. Arch Dermatol . 2001; 137:581-93. [PubMed 11346336]
5. Duvic M, Hymes K, Heald P et al. Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results. J Clin Oncol . 2001; 19:2456-71. [PubMed 11331325]
6. Ligand Pharmaceuticals. Targretin® (bexarotene) gel 1% prescribing information. San Diego, CA; 2001 Jan.
7. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2000 Aug 3. From FDA web site From FDA web site. [Web]
8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett . 2003; 1:41-52. [PubMed 15529105]
9. Mycosis fungoides (Including Sezary Syndrome) Treatment. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2022 February 28.
10. Sutton AM, Hurley MY. Clinical Practice Guidelines for Cutaneous Lymphomas. Mo Med. 2015;112(4):292-295.
11. Kempf W, Mitteldorf C. Cutaneous T-cell lymphomas-An update 2021. Hematol Oncol. 2021;39 Suppl 1:46-51. doi:10.1002/hon.2850