|Trade names||Targretin, others|
|Main uses||Cutaneous T cell lymphoma (CTCL)|
|Side effects||By mouth: High cholesterol, headaches, low thyroid, low white blood cells, rash, nausea, infection, dry skin, peripheral swelling|
Topical: Rash, itchiness
|By mouth, topical|
|Typical dose||300 mg/m2/day|
|Elimination half-life||7 hours|
|Excretion||Parent drug and metabolites are eliminated primarily through the hepatobiliary system. Less than 1% is excreted in the urine unchanged.|
|Chemical and physical data|
|Molar mass||348.486 g·mol−1|
|3D model (JSmol)|
Bexarotene, sold under the brand Targretin among others, is a medication use to treat cutaneous T cell lymphoma (CTCL). It is used by mouth for advanced disease and applied to the skin for early disease. It is used when other treatments have failed.
Common side effects by mouth include high cholesterol, headaches, low thyroid, low white blood cells, rash, nausea, infection, dry skin, and peripheral swelling. Common side effects when applied to the skin include rash and itchiness. Other side effects may include liver problems, pancreatitis, and sunburns. Use in pregnancy may harm the baby. It is a retinoid. How it works is unclear.
Bexarotene was approved in the United States in 1999 and Europe in 2001. It is available as a generic medication. In the United Kingdom 100 pills of 75 mg costs the NHS about £940 as of 2021. This amount in the United States is about 2,050 USD.
Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).
It is generally taken at a dose of 300 mg/m2/day.
Known contraindications include:
- Hypersensitivity to the active substance or to any of the excipients in the preparation(s).
- Pregnancy and lactation
- Women of child-bearing potential without effective birth-control measures
- History of pancreatitis
- Uncontrolled hypercholesterolaemia
- Uncontrolled hypertriglyceridaemia
- Hypervitaminosis A
- Uncontrolled thyroid disease
- Hepatic insufficiency
- Ongoing systemic infection
Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism.
Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole. It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced. Likewise consumption of grapefruit juice might increase bexarotene's plasma concentrations, hence potentially altering its therapeutic effects.
Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A). By so doing it induces cell differentiation and apoptosis and prevents the development of drug resistance. It also has anti-angiogenic effects and inhibits cancer metastasis. The retinoic acid receptors (RARs) regulate cell differentiation and proliferation whereas RXRs regulate apoptosis.
The developer of bexarotene (brand name Targretin) was Ligand Pharmaceuticals, a San Diego biotech company which received FDA approval for the drug in 1999. The FDA approved bexarotene on 29 December 1999.
It received EMA approval on 29 March 2001.
Early-stage preclinical studies suggested that bexarotene reduced amyloid plaques and improved mental functioning in a small sample of mice engineered to exhibit Alzheimer's-like symptoms although subsequent studies have yielded mixed results.
The results of CCMR-One, a clinical trial of the effects of bexarotene on patients with multiple sclerosis operated by the University of Cambridge, have shown that the drug can cause remyelination, but will not lead to the drug being used as a therapy, due to its risk profile.
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