Bexarotene is a retinoid analogue that is used to treat the skin manifestations of cutaneous T cell lymphoma (CTCL). Bexarotene therapy is associated with a high rate of serum enzyme elevations and rare instances of clinically apparent acute liver injury.


Bexarotene (bex ar' oh teen) is a synthetic retinoid analogue and antineoplastic agent that acts through engagement of the retinoid receptors to regulate genes involved in cellular differentiation and growth. Bexarotene is considered a third generation retinoid because it has vitamin A-like activities, but is designed to optimize binding to retinoid X receptors (RXRs) which typically lead to malignant cell apoptosis as opposed to retinoic acid receptors (RARs) which affect cellular differentiation and cell growth. Bexarotene has potent activity on tumor cell lines and has been shown to induce partial or complete remissions in up to half of patients with cutaneous T cell lymphoma (CTCL) refractory to standard therapy. Bexarotene was approved for use in CTCL in 2000 and remains a second line therapy for the cutaneous manifestations of this form of lymphoma. Bexarotene is available as capsules of 75 mg under the brand name Targretin. The recommended dosage is 300 mg/m2 daily. Common side effects include hyperlipidemia, headache, weakness, leukopenia, anemia, infection, dry skin, rash and photosensitivity. Rare, but severe adverse events include cataracts, neutropenia, hypothyroidism, pancreatitis and hepatitis. Bexarotene, like other retinoids, is teratogenic and contraindicated during pregnancy and in women who are unable to practice adequate methods of birth control.


Serum aminotransferase elevations occur in 5% of patients treated with bexarotene, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. However, cases of clinically apparent liver injury with jaundice have been reported with bexarotene therapy, some of which were severe and even fatal. Hepatotoxicity appears to be more common with higher doses. The clinical features of the hepatic injury with bexarotene have not been described in any detail and case reports of hepatotoxicity have yet to be published. Nevertheless, the product label mentions hepatotoxicity and recommends prospective monitoring of routine liver tests.

Likelihood score: D (possible but uncommon cause of clinically apparent liver injury).

Mechanism of Injury

The cause of the liver injury from bexarotene and other retinoids is unknown, but may relate to their effects in inducing apoptosis. The clinically apparent liver injury from bexarotene is said to have features of hypersensitivity. Bexarotene is extensively metabolized by CYP 3A4 in the liver and is susceptible to multiple drug-drug interactions. Inhibitors of CYP 3A4 such as ketoconazole and clarithromycin can cause increases in bexarotene plasma levels with subsequent toxicity and, therefore, should be avoided.

Outcome and Management

The severity of the liver injury linked to bexarotene therapy has ranged from mild, transient and asymptomatic serum enzyme elevations to clinically apparent cholestasis to acute liver failure. Bexarotene has not been linked to cases of chronic hepatitis or vanishing bile duct syndrome. There is no information on cross sensitivity to hepatic injury between bexarotene and other retinoids, but some degree of cross sensitivity is likely.

Drug Class: Antineoplastic Agents, Retinoids



Bexarotene – Targretin®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 26 September 2017

Abbreviations: CTCL, cutaneous T cell lymphoma

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    (Expert review of hepatotoxicity of cancer chemotherapeutic agents published in 1999; discusses liver injury from retinoids, but not specifically bexarotene).
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    (Among 94 patients with advanced and refractory CTCL treated with bexarotene, clinical responses occurred in 45-55% and side effects were common but usually mild, but led to early termination of therapy in 10%; AST elevations occurred during the first month of treatment in 20% of patients).
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    (Among 58 patients with refractory or persistent CTCL treated with bexarotene at different doses, clinical responses occurred in 56% given 300 mg/m2 daily, while adverse side effects were common and ALT or AST elevations of 2.5 to 5 times ULN occurred in 10%).
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    (Among 16 patients with cutaneous T cell lymphomas treated with bexarotene for 24 weeks, ALT elevations were reported in 4 [25%] and led to early discontinuation in 1 [6%].