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Bexarotene (Systemic)

Medically reviewed by Drugs.com. Last updated on April 16, 2020.

Pronunciation

(beks AIR oh teen)

Index Terms

  • 3-methyl TTNEB
  • LGD1069

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Targretin: 75 mg

Generic: 75 mg

Brand Names: U.S.

  • Targretin

Pharmacologic Category

  • Antineoplastic Agent, Retinoic Acid Derivative

Pharmacology

Bexarotene selectively binds to and activates retinoid X receptors (RXRs). Once activated, RXRs function as transcription factors to regulate the expression of genes which control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin and induces tumor regression in vivo in some animal models.

Absorption

AUC increased 35% and Cmax increased 48% by a fat-containing meal.

Metabolism

Hepatic via CYP3A4 isoenzyme to four metabolites; further metabolized by glucuronidation

Excretion

Feces (primarily); urine (minimal, <1%)

Time to Peak

~2 hours

Half-Life Elimination

~7 hours

Protein Binding

>99% to plasma proteins

Use: Labeled Indications

Cutaneous T-cell lymphoma, refractory: Treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy

Contraindications

Known serious hypersensitivity to bexarotene or any component of the formulation; pregnancy.

Documentation of allergenic cross-reactivity for retinoids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Cutaneous T-cell lymphoma, refractory: Oral: Initial: 300 mg/m2 once daily taken as a single daily dose; if well tolerated, but no tumor response after 8 weeks, may increase to 400 mg/m2 once daily (Duvic 2001); continue as long as clinical benefit is demonstrated (bexarotene was administered in studies for up to 97 weeks).

Consensus recommendations (off-label dosing): Initial: 150 mg/m2 once daily; if lab work remains stable for at least 4 weeks, increase to 300 mg/m2/day. In patients with unstable lipids or other bexarotene toxicities, may increase in 75 mg/day increments every 2 to 4 weeks up to 300 mg/m2/day. Reduce dose in 75 mg/day decrements for toxicity. Continue until disease progression or unacceptable toxicity. Response may take up to 6 months; loss of response may require dose escalation or adjuvant therapy (Scarisbrick 2013). Refer to consensus recommendations for further details.

Cutaneous anaplastic large cell lymphoma (off-label dosing): Target dose (in patients who are unable to tolerate or are refractory to methotrexate): 300 mg/m2/day for up to 48 weeks or until disease progression or unacceptable toxicity (Prince 2017).

Mycosis fungoides/Sezary syndrome, refractory/resistant (off-label dosing): Induction: 150 mg/day for 1 to 2 months or 225 or 300 mg/day for 1 month, followed by maintenance therapy of 150 to 300 mg/day for 11 months. Bexarotene is administered in combination with varying schedules of PUVA; refer to protocol for further bexarotene and PUVA dosing details (Rupoli 2016).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

If necessitated by toxicity, may decrease dose from 300 mg/m2/day to 200 mg/m2/day, then to 100 mg/m2/day, or temporarily hold. Upon recovery, may titrate dose upward with careful monitoring.

Hypertriglyceridemia: Consider dose reduction, treatment interruption, and or antilipemic therapy.

Leukopenia and neutropenia: Leukopenia and neutropenia resolved after dose reduction or discontinuation.

Dosing: Obesity

American Society of Clinical Oncology Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of BSA- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Extemporaneously Prepared

A 1 mg/mL oral suspension may be prepared with capsules. Cut one 75 mg capsule in half, rinse the interior contents of the capsule, and suspend in 75 mL of water. Administer immediately after preparation. To ensure administration of full dose, rinse empty glass with half a glass of water and administer residue.

Targretin data on file, Eisai Inc.Lam MS. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy. 2011;31(2):164-192. doi:10.1592/phco.31.2.16421275495

Administration

Oral: Administer with a meal.

Storage

Recommended storage temperatures vary by manufacturer; refer to individual product labeling for details.

Store at 2°C to 25°C (36°F to 77°F). Protect from light. Avoid humidity and high temperatures after opening bottle.

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Abiraterone Acetate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abiraterone Acetate. Monitor therapy

Acalabrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Acalabrutinib. Monitor therapy

Alfentanil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Alfentanil. Management: If concomitant use of alfentanil and moderate CYP3A4 inducers is necessary, consider dosage increase of alfentanil until stable drug effects are achieved. Monitor patients for signs of opioid withdrawal. Consider therapy modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Apremilast: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Apremilast. Monitor therapy

Aprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Aprepitant. Monitor therapy

ARIPiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole. Monitor therapy

ARIPiprazole Lauroxil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of ARIPiprazole Lauroxil. Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

AtorvaSTATin: Bexarotene (Systemic) may decrease the serum concentration of AtorvaSTATin. Monitor therapy

Avanafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avanafil. Avoid combination

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Benzhydrocodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Benzhydrocodone. Specifically, the serum concentrations of hydrocodone may be reduced. Monitor therapy

Bortezomib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bortezomib. Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brexpiprazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brexpiprazole. Monitor therapy

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

Cabozantinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cabozantinib. Monitor therapy

Capmatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Capmatinib. Avoid combination

CARBOplatin: May increase the serum concentration of Bexarotene (Systemic). Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clarithromycin: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Clarithromycin. Management: Consider alternative antimicrobial therapy for patients receiving a CYP3A inducer. Drugs that enhance the metabolism of clarithromycin into 14-hydroxyclarithromycin may alter the clinical activity of clarithromycin and impair its efficacy. Consider therapy modification

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

Codeine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine. Monitor therapy

Copanlisib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Copanlisib. Monitor therapy

Crizotinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Crizotinib. Monitor therapy

CycloSPORINE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Dapsone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dapsone (Systemic). Monitor therapy

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

DexAMETHasone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of DexAMETHasone (Systemic). Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Doravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Doravirine. Monitor therapy

Elbasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Monitor therapy

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Estrogen Derivatives (Contraceptive): Bexarotene (Systemic) may decrease the serum concentration of Estrogen Derivatives (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form) due to the risk of decreased systemic hormone concentrations and fetal harm. Consider therapy modification

Etoposide: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etoposide Phosphate. Monitor therapy

Etravirine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Etravirine. Monitor therapy

Everolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Everolimus. Monitor therapy

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

FentaNYL: CYP3A4 Inducers (Moderate) may decrease the serum concentration of FentaNYL. Monitor therapy

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Fosaprepitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fosaprepitant. Specifically, CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite aprepitant. Monitor therapy

Gemfibrozil: May increase the serum concentration of Bexarotene (Systemic). Avoid combination

Glasdegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glasdegib. Management: Avoid use of glasdegib and moderate CYP3A4 inducers whenever possible. If combined, increase glasdegib dose from 100 mg daily to 200 mg daily or from 50 mg daily to 100 mg daily. Resume previous glasdegib dose 7 days after discontinuation of the inducer. Consider therapy modification

Glecaprevir and Pibrentasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Grazoprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase extended-release guanfacine dose by up to double when initiating guanfacine in patients taking CYP3A4 inducers or if initiating a CYP3A4 inducer in a patient already taking extended-release guanfacine. Monitor for reduced guanfacine efficacy. Consider therapy modification

HYDROcodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of HYDROcodone. Monitor therapy

Hydrocortisone (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Hydrocortisone (Systemic). Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Monitor therapy

Lapatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Larotrectinib. Monitor therapy

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Avoid combination

Lercanidipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lercanidipine. Monitor therapy

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lumacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumacaftor and Ivacaftor. Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Avoid combination

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Lurbinectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurbinectedin. Avoid combination

Macitentan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Macitentan. Monitor therapy

Meperidine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Meperidine. Monitor therapy

MethylPREDNISolone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of MethylPREDNISolone. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Naloxegol: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naloxegol. Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Oliceridine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Oliceridine. Monitor therapy

PACLitaxel (Conventional): May increase the serum concentration of Bexarotene (Systemic). Bexarotene (Systemic) may decrease the serum concentration of PACLitaxel (Conventional). Monitor therapy

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Monitor therapy

PAZOPanib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PAZOPanib. Monitor therapy

Pemigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pemigatinib. Avoid combination

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Monitor perampanel response closely, particularly with changes to CYP3A4 inducer therapy. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pexidartinib. Monitor therapy

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Pralsetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pralsetinib. Monitor therapy

PrednisoLONE (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of PrednisoLONE (Systemic). Monitor therapy

PredniSONE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of PredniSONE. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Bexarotene (Systemic) may decrease the serum concentration of Progestins (Contraceptive). Management: Women of childbearing potential receiving bexarotene should use two reliable forms of contraception (including at least one nonhormonal form) due to the risk of decreased systemic hormone concentrations and fetal harm. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Rimegepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rimegepant. Avoid combination

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

Selpercatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selpercatinib. Avoid combination

Selumetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Selumetinib. Avoid combination

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Sirolimus: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sirolimus. Monitor therapy

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

SUNItinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of SUNItinib. Monitor therapy

Tacrolimus (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tamoxifen: Bexarotene (Systemic) may decrease the serum concentration of Tamoxifen. Monitor therapy

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Avoid combination

Tetracyclines: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Avoid combination

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Monitor therapy

Ticagrelor: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Monitor therapy

Tofacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tofacitinib. Monitor therapy

Tolvaptan: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tolvaptan. Monitor therapy

Toremifene: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Toremifene. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Toremifene. Monitor therapy

Trabectedin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Trabectedin. Monitor therapy

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Consider therapy modification

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Valbenazine: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Valbenazine. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Valbenazine. Monitor therapy

Vandetanib: CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Vandetanib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vandetanib. Monitor therapy

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Vemurafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vemurafenib. Monitor therapy

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Verapamil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Verapamil. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vilazodone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vilazodone. Monitor therapy

Vitamin A: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Vorapaxar: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vorapaxar. Avoid combination

Voriconazole: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voriconazole. Monitor therapy

Vortioxetine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Vortioxetine. Monitor therapy

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Voxilaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxilaprevir. Avoid combination

Zaleplon: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zaleplon. Monitor therapy

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zolpidem: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem. Monitor therapy

Zopiclone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zopiclone. Monitor therapy

Test Interactions

Treatment with bexarotene may interfere with CA125 assay values in patients with ovarian cancer (per manufacturer's labeling).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not always defined.

>10%:

Cardiovascular: Peripheral edema (11% to 13%)

Central nervous system: Headache (30% to 42%), chills (10% to 13%), insomnia (5% to 11%)

Dermatologic: Exfoliative dermatitis (10% to 28%), skin rash (17% to 23%), xeroderma (9% to 11%), alopecia (4% to 11%)

Endocrine & metabolic: Hyperlipidemia (79%), hypercholesterolemia (32% to 62%), hypothyroidism (29% to 53%), increased lactate dehydrogenase (7% to 13%)

Gastrointestinal: Diarrhea (7% to 42%), anorexia (2% to 23%), nausea (8% to 16%), vomiting (4% to 13%), abdominal pain (4% to 11%)

Hematologic & oncologic: Leukopenia (17% to 47%), anemia (6% to 25%), hypochromic anemia (4% to 13%)

Infection: Infection (13% to 23%; bacterial infection: 1% to 13%)

Neuromuscular & skeletal: Weakness (20% to 45%), back pain (2% to 11%)

Respiratory: Flu-like symptoms (4% to 13%)

Miscellaneous: Fever (5% to 17%)

1% to 10%:

Cardiovascular: Angina pectoris, cardiac failure (right), cerebrovascular accident, chest pain, hypertension, subdural hematoma, syncope, tachycardia

Central nervous system: Agitation, ataxia, confusion, depression, dizziness, hyperesthesia, myasthenia, neuropathy

Dermatologic: Acne vulgaris, allergic skin reaction, cellulitis, cheilitis, cutaneous nodule, maculopapular rash, skin photosensitivity, pustular rash, skin rash, sunburn, vesiculobullous dermatitis

Endocrine & metabolic: Albuminuria, hyperglycemia, weight gain, weight loss

Gastrointestinal: Colitis, constipation, dyspepsia, flatulence, gastroenteritis, gingivitis, increased serum amylase, melena, pancreatitis, xerostomia

Genitourinary: Dysuria, hematuria, mastalgia, urinary incontinence, urinary tract infection, urinary urgency

Hematologic & oncologic: Acquired blood coagulation disorder, eosinophilia, hemorrhage, hypoproteinemia, lymphocytosis, thrombocythemia, thrombocytopenia

Hepatic: Hepatic failure, increased serum ALT, increased serum AST, increased serum bilirubin

Infection: Candidiasis, sepsis

Neuromuscular & skeletal: Arthralgia, arthrosis, myalgia, ostealgia

Ophthalmic: Blepharitis, cataract (new and worsening), conjunctivitis, corneal lesion, keratitis, visual field defect, xerophthalmia

Otic: Otalgia, otitis externa

Renal: Increased serum creatinine, renal function abnormality

Respiratory: Bronchitis, cough, dyspnea, hemoptysis, hypoxia, pharyngitis, pleural effusion, pneumonia, pulmonary edema, rhinitis

Miscellaneous: Serous drainage

ALERT: U.S. Boxed Warning

Pregnancy:

Bexarotene (oral) is a member of the retinoid class of drugs that is associated with birth defects in humans. Bexarotene (oral) also caused birth defects when administered orally to pregnant rats. Bexarotene (oral) must not be administered to a pregnant woman.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: Dose-related elevations in ALT, AST, and bilirubin have been reported; cases of cholestasis and liver failure (fatal) have occurred. Monitor for liver function test abnormalities and temporarily withhold or discontinue if ALT, AST, or bilirubin are >3 times the ULN. Liver function test elevations resolved within 1 month in most patients following dose reduction or discontinuation.

• Hypothyroidism: Bexarotene is associated with a rapid and profound suppression of thyrotropin, which may commonly lead to hypothyroidism (Burch 2019). Bexarotene rapidly suppresses thyroid-stimulating hormone (TSH) levels by directly inhibiting TSH secretion, and also affects thyroid hormone metabolism (Hamnvik 2011). Reductions in total T4 and TSH are reversible. Hypothyroidism commonly occurs. Monitor thyroid functions tests, including free T4 levels at baseline and during treatment. Levothyroxine therapy should be initiated when oral bexarotene is initiated (use low-dose levothyroxine in patients with cardiovascular disease [CVD]); patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels (Hamnvik 2011; Scarisbrick 2013). Withhold levothyroxine if bexarotene is withheld; if bexarotene is permanently discontinued, stop levothyroxine (or revert back to doses used prior to bexarotene therapy) (Scarisbrick 2013). Recovery of thyroid function generally occurs within weeks of bexarotene discontinuation (Burch 2019).

• Leukopenia: Grade 1 to 3 leukopenia has occurred (predominantly as neutropenia); the incidence is higher with doses >300 mg/m2/day. The onset of leukopenia was generally 4 to 8 weeks. Grade 3 and 4 neutropenia have occurred. Leukopenia and neutropenia typically resolved within 30 days after discontinuation or dose reduction. Monitor CBC with differential at baseline and periodically during treatment. Leukopenia and neutropenia were rarely associated with severe conditions or serious adverse events.

• Lipid abnormalities: Bexarotene induces significant lipid abnormalities in a majority of patients (increased triglycerides and total cholesterol as well as decreased high-density lipoprotein cholesterol); the onset is usually within 2 to 4 weeks; effects are reversible on discontinuation or generally mitigated by dose reduction and/or antilipemic therapy. Initiate low-fat diet (<30% of calories from fat with saturated fats <10%) (Scarisbrick 2013). Monitor fasting lipid panel; may require dose reduction, treatment interruption, and/or concomitant antilipemic therapy. Fasting triglycerides should be normal (or normalized with appropriate therapy) prior to initiation; triglycerides should be maintained <400 mg/dL. Optimize lipids prior to bexarotene initiation in patients with preexisting CVD, type 2 diabetes, or a CVD risk >20%; otherwise, initiate lipid-lowering therapy with an appropriate agent that does not have potential drug interactions (Scarisbrick 2013). In studies, HMG-CoA reductase inhibitors were used to manage lipids; gemfibrozil is not recommended due to potential for drug interactions. If bexarotene therapy is withheld, lipid-lowering therapy may be continued; if bexarotene is permanently discontinued, discontinue lipid-lowering therapy or revert back to lipid-lowering therapy doses used prior to bexarotene therapy (Scarisbrick 2013).

• Pancreatitis: Pancreatitis (acute) associated with hypertriglyceridemia has been reported. Interrupt treatment and evaluate if pancreatitis is suspected. Cutaneous T-cell lymphoma patients with risk factors for pancreatitis (eg, prior pancreatitis, uncontrolled hyperlipidemia, excessive ethanol consumption, uncontrolled diabetes, biliary tract disease, concomitant medications causing hyperlipidemia or concomitant medications associated with pancreatic toxicity) may be at increased risk for bexarotene-associated pancreatitis.

• Photosensitivity: Retinoids are associated with photosensitivity; phototoxicity (sunburn, sunlight sensitivity) has occurred with bexarotene when patients were exposed to direct sunlight. Advise patients to minimize exposure to sunlight and artificial ultraviolet light during treatment. The use of a high-factor sunscreen is recommended (Scarisbrick 2013).

• Visual disturbances: Any new visual abnormalities experienced by the patient should be evaluated by an ophthalmologist (cataracts may develop or worsen, especially in the geriatric population).

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; may enhance the actions of insulin, sulfonylureas, or thiazolidinediones, resulting in hypoglycemia in patients receiving these agents (hypoglycemia has not been observed with bexarotene monotherapy). Monitor blood glucose as necessary.

• Hepatic impairment: Use with extreme caution in patients with hepatic impairment; bexarotene undergoes extensive hepatic elimination.

Concurrent drug therapy issues:

• Vitamin A: Due to the potential for additive toxicities, patients should be advised to limit additional vitamin A intake (in studies, additional vitamin A was limited to ≤15,000 units/day). Consider avoiding vitamin A supplementation (Scarisbrick 2013).

Special populations:

• Pregnancy: [US Boxed Warning]: Bexarotene is a retinoid, a drug class associated with birth defects in humans; do not administer during pregnancy. Bexarotene caused birth defects when administered orally to pregnant rats.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.

Other warnings/precautions:

• Lifestyle modifications: Limit alcohol to <14 units/week (females) or <21 units/week (males) and consider exercise (Scarisbrick 2013).

Monitoring Parameters

If female, pregnancy test within 1 week before initiation then monthly while on bexarotene; fasting lipid panel (before initiation, then weekly until lipid response established [usually 2 to 4 weeks] and then at 8-week intervals thereafter); liver function tests (baseline, then at 1, 2, and 4 weeks after initiation, then at 8-week intervals thereafter if stable); monitor thyroid function tests (including free T4) at baseline and weekly for the first 5 to 7 weeks, then every 1 to 2 months (Hamnvik 2011); CBC with differential (baseline and periodic); blood glucose (in diabetic patients); ophthalmic exam (if visual abnormalities occur). Monitor adherence.

UK consensus monitoring recommendations: CBC with differential, urea, electrolytes, liver function tests, fasting lipid panel, free T4 and free T3 levels, blood glucose, and creatine kinase prior to treatment and every 1 to 2 weeks until stable for at least 1 month and for 2 consecutive tests, then every 2 weeks during dose escalations, then once a month after dose is optimized and blood work is stable for 2 consecutive tests. Thyroid-stimulating hormone at baseline (only). Refer to consensus recommendations for further details (Scarisbrick 2013).

Reproductive Considerations

Issues related to females:

Evaluate pregnancy status prior to use in females of reproductive potential. Effective contraception should be used for 1 month prior to initiating treatment, during therapy, and for at least 1 month after the last bexarotene dose. Either abstinence or two forms of reliable contraception (one should be nonhormonal) are recommended.

A negative pregnancy test (sensitivity of at least 50 mIU/mL) within 1 week prior to beginning therapy, and monthly, thereafter, is required for females of reproductive potential. Treatment should begin on the second or third day of a normal menstrual period. A maximum 1-month supply is recommended so that pregnancy tests may be evaluated.

Females who desire conception following bexarotene therapy should have a minimum washout period of 1 month (Scarisbrick 2013).

Issues related to males: Male patients must use a condom during sexual intercourse with females who are pregnant, possibly pregnant, or who may become pregnant during therapy and for at least 1 month after the last bexarotene dose.

Pregnancy Considerations

Bexarotene use is contraindicated in pregnancy. [US Boxed Warning]: Bexarotene is a member of the retinoid class of drugs that is associated with birth defects in humans. Bexarotene also caused birth defects when administered orally to pregnant rats. Bexarotene must not be administered to a pregnant woman. If a woman becomes pregnant while taking the drug, bexarotene must be stopped immediately and appropriate counseling be given.

Patient Education

What is this drug used for?

• It is used to treat a type of lymphoma that affects the skin.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Trouble sleeping

• Lack of appetite

• Abdominal pain

• Nausea

• Vomiting

• Diarrhea

• Hair loss

• Dry skin

• Flu-like symptoms

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Low thyroid level like constipation; trouble handling heat or cold; trouble with memory; mood changes; or burning, numbness, or tingling feeling

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Vision changes

• Swelling of arms or legs

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.