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Targretin
Classes
Antineoplastic Retinoids
Topical Antineoplastic Retinoids
Administration
Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.
Take bexarotene as a single dose with food.
For external application only.
Use sufficient gel to cover the lesion with a generous coating; allow the gel to dry before covering with clothing.
Do NOT use occlusive dressings with bexarotene gel.
Avoid application of the gel to normal skin around the lesions to prevent irritation.
Do NOT apply on or near mucosal areas of the body (e.g., eyes, nostrils, mouth, lips, vagina, tip of the penis, rectum, or anus).
Wait 20 minutes after showering or bathing before applying the gel. Avoid bathing, showering, or swimming for at least 3 hours after any application, if possible.
Do NOT use insect repellents containing N,N-diethyl-m-toluamide (DEET) or other products containing DEET during bexarotene therapy.
Adverse Reactions
hypertriglyceridemia / Delayed / 6.7-46.0
hyperlipidemia / Delayed / 26.0-41.0
exfoliative dermatitis / Delayed / 6.0-28.0
asthenia / Delayed / 1.0-21.0
neutropenia / Delayed / 10.3-16.0
leukopenia / Delayed / 4.0-13.0
headache / Early / 4.0-11.0
coagulopathy / Delayed / 0-10.0
heart failure / Delayed / 0-10.0
stroke / Early / 0-10.0
pleural effusion / Delayed / 0-10.0
pulmonary edema / Early / 0-10.0
keratitis / Delayed / 0-10.0
visual impairment / Early / 0-10.0
hypercholesterolemia / Delayed / 2.0-9.0
hyponatremia / Delayed / 1.0-9.0
infection / Delayed / 0-8.0
pancreatitis / Delayed / 0-6.0
anorexia / Delayed / 0-6.0
diarrhea / Early / 2.0-6.0
hyperglycemia / Delayed / 1.0-6.0
hyperbilirubinemia / Delayed / 0-4.0
elevated hepatic enzymes / Delayed / 0-4.0
hypothyroidism / Delayed / 0-4.0
vomiting / Early / 0-4.0
rash / Early / 0-3.0
peripheral edema / Delayed / 0-3.0
hyperkalemia / Delayed / 0-2.0
hypernatremia / Delayed / 0-1.0
hypocalcemia / Delayed / 0-1.0
hepatic failure / Delayed / 0.2-0.2
erythema / Early / 0-72.0
cataracts / Delayed / 0-19.0
contact dermatitis / Delayed / 0-14.0
hyperamylasemia / Delayed / 0-10.0
thrombocytopenia / Delayed / 0-10.0
lymphocytosis / Delayed / 0-10.0
eosinophilia / Delayed / 0-10.0
skin ulcer / Delayed / 0-10.0
bullous rash / Early / 0-10.0
constipation / Delayed / 0-10.0
colitis / Delayed / 0-10.0
melena / Delayed / 0-10.0
hypertension / Early / 0-10.0
sinus tachycardia / Rapid / 0-10.0
chest pain (unspecified) / Early / 0-10.0
edema / Delayed / 10.0-10.0
angina / Early / 0-10.0
myasthenia / Delayed / 0-10.0
bone pain / Delayed / 0-10.0
confusion / Early / 0-10.0
ataxia / Delayed / 0-10.0
peripheral neuropathy / Delayed / 0-10.0
hyperesthesia / Delayed / 0-10.0
depression / Delayed / 0-10.0
dyspnea / Early / 0-10.0
hypoxia / Early / 0-10.0
hemoptysis / Delayed / 0-10.0
candidiasis / Delayed / 0-10.0
blepharitis / Early / 0-10.0
conjunctivitis / Delayed / 0-10.0
bleeding / Early / 0-10.0
dysuria / Early / 0-10.0
hematuria / Delayed / 0-10.0
urinary incontinence / Early / 0-10.0
hypoalbuminemia / Delayed / 0-10.0
lymphadenopathy / Delayed / 6.0-6.0
subdural hematoma / Early / 0-1.0
cholestasis / Delayed / 0.4-0.4
skin irritation / Early / 0-72.0
pruritus / Rapid / 0-40.0
xerosis / Delayed / 9.0-17.0
fever / Early / 5.0-17.0
nausea / Early / 8.0-16.0
chills / Rapid / 10.0-13.0
alopecia / Delayed / 4.0-11.0
abdominal pain / Early / 4.0-11.0
back pain / Delayed / 2.0-11.0
insomnia / Early / 5.0-11.0
acne vulgaris / Delayed / 0-10.0
maculopapular rash / Early / 0-10.0
vesicular rash / Delayed / 0-10.0
xerostomia / Early / 0-10.0
cheilitis / Delayed / 0-10.0
dyspepsia / Early / 0-10.0
gingivitis / Delayed / 0-10.0
flatulence / Early / 0-10.0
syncope / Early / 0-10.0
arthralgia / Delayed / 0-10.0
myalgia / Early / 0-10.0
hypoesthesia / Delayed / 0-10.0
dizziness / Early / 0-10.0
agitation / Early / 0-10.0
pharyngitis / Delayed / 6.0-10.0
cough / Delayed / 6.0-10.0
rhinitis / Early / 0-10.0
influenza / Delayed / 0-10.0
xerophthalmia / Early / 0-10.0
urinary urgency / Early / 0-10.0
otalgia / Early / 0-10.0
weight gain / Delayed / 0-10.0
weight loss / Delayed / 0-10.0
hyperhidrosis / Delayed / 0-6.0
paresthesias / Delayed / 6.0-6.0
photosensitivity / Delayed / Incidence not known
Boxed Warning
The use of bexarotene (both gel and capsules) is contraindicated during pregnancy. Retinoid agents are associated with birth defects in humans; therefore, bexarotene may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy while taking bexarotene. Immediately discontinue bexarotene if a patient becomes pregnant during therapy and discuss the potential hazard to the fetus. Fetal abnormalities including incomplete ossification, cleft palate, depressed eye bulge/microphthalmia, and small ears were observed following oral bexarotene administration in pregnant rats during organogenesis (days 7 to 17 of gestation); fetal death occurred at doses greater than 10 mg/kg per day.
Counsel patients about the reproductive risk and contraception requirements during treatment with bexarotene gel or capsules. Pregnancy testing should be performed in females of reproductive potential within 1 week prior to starting therapy. Start bexarotene on the second or third day of the patient’s normal menstrual period and only administer a 1-month supply of the medicine for each refill. Perform pregnancy testing once monthly and provide counseling regarding pregnancy avoidance and the risk of birth defects with bexarotene. Females of reproductive potential should avoid pregnancy and use effective contraception starting 1 month prior to and for at least 1 month after treatment with bexarotene. It is recommended that these women use 2 reliable forms of non-hormonal contraception or practice abstinence during therapy. Bexarotene may induce metabolic enzymes and cause a reduction in the plasma concentrations of oral or other systemic hormonal contraceptives. Patients who become pregnant while receiving bexarotene should be apprised of the potential hazard to the fetus. Due to male-mediated teratogenicity, men with female partners of reproductive potential should avoid fathering a child and use effective contraception (i.e., condoms) during therapy and for at least 1 month following the final dose of bexarotene.
Common Brand Names
Targretin
Dea Class
Rx
Description
A synthetic retinoid that activates retinoid X receptors
Used for the treatment of cutaneous manifestations (e.g., lesions) of refractory cutaneous T-cell lymphoma
Do not use bexarotene during pregnancy; retinoid use is associated with birth defects
Dosage And Indications
NOTE: Bexarotene has been designated an orphan drug by the FDA for this indication.
For the treatment of cutaneous manifestations of CTCL in patients who are refractory to at least 1 prior systemic therapy. Oral dosage Adults
300 mg/m2 orally once daily with food until disease progression; if there is no tumor response after 8 weeks of treatment and the initial dose is well tolerated, increase the dose to bexarotene 400 mg/m2 once daily and monitor patients carefully. The calculated dose should be rounded to the nearest dose using 75-mg capsules. Reduce the daily bexarotene dose in 100-mg increments (from 300 mg/m2 to 200 mg/m2 and from 200 mg/m2 to 100 mg/m2) if clinical toxicity occurs. Therapy may be resumed after the toxicity resolves and the bexarotene dose may be increased as tolerated. Bexarotene was evaluated in patients with cutaneous T-cell lymphoma (CTCL) in 2 multinational, open-label, controlled studies (n = 152); 102 patients had disease refractory to at least 1 prior systemic therapy (early stage, n = 12; advanced stage, n = 90). In 62 evaluable patients who received an initial bexarotene dose of 300 mg/m2 per day, the overall clinical tumor response rate was about 32% (complete response, 1.8%; partial response, 30%). Some responses were observed by week 4 of therapy. At a median follow-up time of 21 weeks, the median duration of response had not been reached in the 20 patients who had a tumor response; 6 of these patients had disease relapse defined as a 25% increase in target lesions (using a Composite Assessment of Index Lesion Disease Severity (CA)) or worsening of other aspects of disease. Bexarotene 300 mg/m2 per day resulted in a higher objective response rate (ORR) compared with bexarotene 150 mg/m2 per day in patients with CTCL in a phase IV clinical trial (n = 59). The ORRs were higher in the 300 mg/m2 per day arm when response was evaluated using a CA (34.5% vs. 23.3%), the Physicians Global Assessment (PGA; 37.9% vs. 20%), and percent body surface area involvement (%BSA; 34.5% vs. 23.3%). The median duration of response times were 86.5 days, 72 days, and 60 days and the median times to tumor progression were 77.5 days, 115.5 days, and 88 days using the CA, PGA, and %BSA assessment tools, respectively.
Apply to affected areas once every other day for the first week; increase the frequency of application in weekly intervals to once daily, twice daily, 3 times daily, and then 4 times daily as tolerated. Continue therapy as long as benefit is demonstrated; bexarotene gel was applied for up to 172 weeks in clinical trials. Most patients tolerate an application frequency of 2 to 4 times daily. Reduce the application frequency if application toxicity occurs. If severe irritation occurs, hold bexarotene for a few days; therapy may be resumed when the symptoms subside. The overall response rate (defined as the complete clinical response (CCR) plus partial response) on the basis of the primary end point classification (PEC) was 54% in patients with refractory or persistent stage IA, IB, or IIA CTCL after 2 or more prior therapies (median of 3 therapies; range, 2 to 7 therapies) who received topical bexarotene in a multinational, phase III trial (n = 50). The CCR rate was 10%. PEC response was determined using response criteria for either the Physicians Global Assessment (PGA) or Composite Assessment of Index Lesion Disease Severity (CA); the higher response was used from either the PGA or CA assessment. The projected median time to response (at least 50% improvement) was 142 days; the latest time to response was 504 days.
400 mg/m2 orally once daily has been studied. First-line therapy with bexarotene plus cisplatin and vinorelbine did not improve the median overall survival (OS) time (8.7 months vs. 9.9 months), 2-year OS rate (13.2% vs. 15.7%), progression-free survival (PFS) time (4.3 months vs. 5 months), or overall response rate (ORR) (16.7% vs. 24.4%) compared with cisplatin and vinorelbine alone in a phase III trial in 623 NSCLC patients. Additionally, bexarotene plus carboplatin and paclitaxel did not improve the median OS time (8.5 months vs. 9.2 months), 2-year OS rate (12.4% vs. 16.3%), PFS time (4.1 months vs. 4.9 months), or ORR (19.3% vs. 23.5%) compared with carboplatin and paclitaxel alone as first-line therapy in 612 NSCLC patients in another phase III trial.
Dosage not established; 300 mg/m2 or 600 mg/m2 orally once daily has been studied. In 52 patients with advanced or recurrent NSCLC who had stable or responsive disease following platinum-containing chemotherapy, maintenance therapy with bexarotene 300 mg/m2/day PO, bexarotene 600 mg/m2/day PO, or placebo resulted in a median time to progression (TTP) of 82 days, 128 days, and 56 days, respectively, and median overall survival (OS) times of 382 days, 587 days, and 537 days, respectively. The TTP and OS times were not significantly different between the 3 study arms.
650 mg/m2 orally once daily resulted in an overall response rate of 33% (complete response, n = 1) in a phase II study in 49 patients with AIDS-related Kaposi sarcoma. Response was defined as 50% or greater disease improvement using the AIDS Clinical Trials Group criteria.
200 mg/m2 or 500 mg/m2 orally once daily demonstrated minimal benefit in 146 patients with progressive metastatic breast cancer refractory to chemotherapy and/or hormone therapy in a clinical study. Treatment with bexarotene resulted in a partial response in 5 patients and stable disease lasting at least 6 months in 26 patients; additionally, the median time to progression was 8.3 to 9.6 weeks. Patients with tamoxifen-resistant disease received tamoxifen in addition to bexarotene. No responses occurred in patients who received the higher dose of 500 mg/m2/day.
0.5 to 3 mg/kg orally once daily for 12 to 24 weeks resulted in a 50% or greater improvement in scores on a modified psoriasis area and severity index in 22% of patients with severe psoriasis in a phase II trial (n = 50). No dose-response effects were noted. Further studies are needed to determine the optimal dose.
†Indicates off-label use
Dosing Considerations
The clearance of bexarotene may be decreased in patients with hepatic impairment. Although specific guidelines for initial dosage adjustments in hepatic impairment are not available; interrupt or discontinue therapy in patients who develop elevated transaminase (e.g., AST or ALT) or bilirubin levels greater than 3-times the upper limit of normal during oral bexarotene therapy.
Renal ImpairmentBexarotene is extensively protein bound and its pharmacokinetics may be altered in patients with renal impairment. However, specific guidelines for dosage adjustments in renal impairment are not available.
Drug Interactions
Abacavir; Dolutegravir; Lamivudine: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bexarotene; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bexarotene is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Abemaciclib: (Major) Avoid coadministration of bexarotene with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Consider alternative treatments. Abemaciclib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 53%, 41%, and 29% respectively.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with bexarotene can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If bexarotene is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Bexarotene is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of oxycodone as needed. If bexarotene is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Albuterol; Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Alteplase: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Aminolevulinic Acid: (Moderate) Systemic or topical bexarotene may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Atorvastatin: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Celecoxib: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Coadministration of bexarotene and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Aprepitant, Fosaprepitant: (Major) Use caution if bexarotene and aprepitant, fosaprepitant are used concurrently and monitor for a possible decrease in the efficacy of aprepitant. Bexarotene is a moderate CYP3A4 inducer and aprepitant is a CYP3A4 substrate. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for low-to-moderate inducers.
Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as bexarotene may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Artemether; Lumefantrine: (Major) Bexarotene is a moderate CYP3A4 inducer and both components of artemether; lumefantrine are substrates of the CYP3A4 isoenzyme; therefore, coadministration may lead to decreased artemether; lumefantrine concentrations. Concomitant use warrants caution due to a possible reduction in antimalarial activity.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of oxycodone as needed. If bexarotene is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir; Cobicistat: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4.
Atogepant: (Major) Avoid use of atogepant and bexarotene when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with bexarotene. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Avacopan: (Major) Avoid concomitant use of avacopan and bexarotene due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Avapritinib: (Major) Avoid coadministration of avapritinib with bexarotene due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with bexarotene if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and bexarotene is a moderate CYP3A4 inducer.
Bedaquiline: (Major) Avoid concurrent use of bexarotene with bedaquiline. Bexarotene is a CYP3A4 inducer, which may result in decreased bedaquiline systemic exposure (AUC) and possibly reduced therapeutic effect.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with bexarotene may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If concomitant use is necessary, consider increasing the benzhydrocodone dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Discontinuation of bexarotene may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. If bexarotene is discontinued, consider a benzhydrocodone dosage reduction and monitor patients for respiratory depression and sedation at frequent intervals. Benzhydrocodone is a prodrug of hydrocodone. Bexarotene is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of hydrocodone.
Brexpiprazole: (Moderate) Because brexpiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as bexarotene may result in decreased plasma concentrations of brexpiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. An increase in brexpiprazole dosage may be clinically warranted in some patients.
Brigatinib: (Major) Avoid coadministration of brigatinib with bexarotene due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with bexarotene, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of bexarotene, resume the brigatinib dose that was tolerated prior to initiation of bexarotene. Brigatinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and bexarotene are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; bexarotene is a moderate inducer of CYP3A4.
Budesonide: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Budesonide; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering bexarotene with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Capmatinib: (Major) Avoid coadministration of capmatinib and bexarotene due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as bexarotene, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with bexarotene can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If bexarotene is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Bexarotene is a moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Chlorpropamide: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cholestyramine: (Moderate) Cholestyramine can bind with and possibly decrease the oral absorption of bexarotene. To minimize drug interactions, administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine.
Clarithromycin: (Major) Coadministration of bexarotene and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Cobicistat: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with bexarotene due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and bexarotene is a moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Codeine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with bexarotene can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If bexarotene is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Bexarotene is a moderate CYP3A4 inducer.
Colestipol: (Moderate) Colestipol can bind with and possibly decrease the oral absorption of orally administered vitamin A, such as bexarotene. Administer other drugs at least 1 hour before or at least 4 to 6 hours after the administration of colestipol.
Conjugated Estrogens; Medroxyprogesterone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as bexarotene. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with bexarotene is necessary. Dapsone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Daridorexant: (Major) Avoid concomitant use of daridorexant and bexarotene. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darunavir; Cobicistat: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4.
Deflazacort: (Major) Avoid concomitant use of deflazacort and bexarotene. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; bexarotene is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Desogestrel; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Dienogest; Estradiol valerate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Dolutegravir: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bexarotene; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bexarotene is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Dolutegravir; Lamivudine: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bexarotene; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bexarotene is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering bexarotene with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with bexarotene; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Bexarotene is an inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Doravirine: (Moderate) Concurrent administration of doravirine and bexarotene may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and bexarotene may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with bexarotene due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with bexarotene due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with bexarotene is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; bexarotene is a moderate inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Major) The concomitant use of dronedarone and bexarotene should be avoided. Coadministration of CYP3A4 inducers, such as bexarotene, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy. Dronedarone is metabolized by CYP3A. Bexarotene induces CYP3A4.
Drospirenone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Drospirenone; Estetrol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Drospirenone; Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Drospirenone; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Duvelisib: (Major) Avoid concomitant use of duvelisib with bexarotene. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When bexarotene has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with bexarotene. Duvelisib is a CYP3A substrate; bexarotene is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elacestrant: (Major) Avoid concurrent use of elacestrant and bexarotene due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with bexarotene. Bexarotene is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir. (Major) If possible, avoid concurrent administration of grazoprevir with bexarotene. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response. Bexarotene is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and bexarotene concurrently; the clinical impact of this interaction has not yet been determined. Administration of ivacaftor with strong CYP3A inducers is not recommended because sub-therapeutic ivacaftor exposure could result. Ivacaftor is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Co-administration with a strong CYP3A inducer decreased the ivacaftor exposure by approximately 9-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. (Major) Coadministration of elvitegravir with bexarotene is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of cobicistat with bexarotene is not recommended as there is a potential for decreased cobicistat concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. (Major) Coadministration of elvitegravir with bexarotene is not recommended as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Bexarotene is a CYP3A4 inducer, while elvitegravir is a substrate of CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering bexarotene with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering bexarotene with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Encorafenib: (Major) Avoid coadministration of encorafenib and bexarotene due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A4 auto-induction.
Entrectinib: (Major) Avoid coadministration of entrectinib with bexarotene due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Eravacycline: (Major) Avoid the concomitant use of bexarotene and eravacycline due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
Erdafitinib: (Major) If coadministration of erdafitinib and bexarotene is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If bexarotene must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If bexarotene is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Erlotinib: (Moderate) There may be a risk of reduced erlotinib efficacy when coadministered with bexarotene; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and bexarotene is a moderate CYP3A4 inducer.
Estradiol; Levonorgestrel: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Estradiol; Norethindrone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Estradiol; Norgestimate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Estradiol; Progesterone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Estrogens affected by CYP3A inducers: (Major) Women taking both estrogens and bexarotene should report breakthrough bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed bexarotene. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 1 month after discontinuation of bexarotene. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on bexarotene, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A4 substrates and bexarotene is a moderate CYP3A4 inducer. Concurrent administration may increase estrogen elimination.
Ethinyl Estradiol; Norelgestromin: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Ethinyl Estradiol; Norgestrel: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Etonogestrel: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Etonogestrel; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with bexarotene is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
Fedratinib: (Major) Avoid coadministration of fedratinib with bexarotene as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of bexarotene is necessary. If bexarotene is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like bexarotene with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Finerenone: (Major) Avoid concurrent use of finerenone and bexarotene due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as bexarotene, is not recommended.
Fosamprenavir: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with bexarotene. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and bexarotene due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Gemfibrozil: (Major) Concomitant administration of bexarotene capsules and gemfibrozil is not recommended; concurrent administration results in increased bexarotene plasma concentrations. Due to low systemic exposure, clinically significant drug interactions are unlikely with bexarotene topical gel.
Glasdegib: (Major) Avoid coadministration of glasdegib and bexarotene due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after bexarotene has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Glimepiride: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Glipizide: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Glipizide; Metformin: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Glyburide: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Glyburide; Metformin: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Guanfacine: (Major) Bexarotene may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if bexarotene is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If bexarotene is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and bexarotene is a moderate CYP3A4 inducer in vitro.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of h
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with bexarotene can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If bexarotene is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with bexarotene. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Ibrutinib: (Moderate) Use ibrutinib and bexarotene together with caution; decreased ibrutinib levels may occur resulting in reduced ibrutinib efficacy. Monitor patients for signs of decreased ibrutinib efficacy if these agents are used together. Ibrutinib is a CYP3A4 substrate; bexarotene is a moderate CYP3A inducer. Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of oxycodone as needed. If bexarotene is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with bexarotene is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A4; bexarotene is a moderate CYP3A4 inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Infigratinib: (Major) Avoid concurrent use of infigratinib and bexarotene. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Insulins: (Moderate) Systemic bexarotene may enhance the action of insulin, resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with insulin therapy; monitor for hypoglycemia and need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with bexarotene may result in decreased concentrations of isavuconazonium. Caution and close monitoring are advised if these drugs are used together. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate.
Ivacaftor: (Moderate) Use caution when administering ivacaftor and bexarotene concurrently; the clinical impact of this interaction has not yet been determined. Administration of ivacaftor with strong CYP3A inducers is not recommended because sub-therapeutic ivacaftor exposure could result. Ivacaftor is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Co-administration with a strong CYP3A inducer decreased the ivacaftor exposure by approximately 9-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Coadministration of bexarotene and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and bexarotene due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If bexarotene is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of bexarotene. Larotrectinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with bexarotene unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Lefamulin is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Lemborexant: (Major) Avoid coadministration of lemborexant and bexarotene as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and bexarotene due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Lenacapavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and bexarotene. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Leuprolide; Norethindrone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Levonorgestrel: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Levonorgestrel; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and bexarotene may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; bexarotene induces CYP3A4.
Live Vaccines: (Contraindicated) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and bexarotene is contraindicated; concurrent use may decrease lonafarnib exposure, which may reduce its efficacy. Lonafarnib is a sensitive CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Lopinavir; Ritonavir: (Moderate) Avoid the concomitant use of bexarotene and lopinavir as decreased plasma concentrations of lopinavir may occur resulting in reduced therapeutic effect. Consider alternative therapy. Bexarotene is a moderate CYP3A4 inducer and lopinavir is a CYP3A4 substrate. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with bexarotene. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Lorlatinib: (Major) Avoid concomitant use of lorlatinib and bexarotene due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and bexarotene concurrently; the clinical impact of this interaction has not yet been determined. Administration of ivacaftor with strong CYP3A inducers is not recommended because sub-therapeutic ivacaftor exposure could result. Ivacaftor is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Co-administration with a strong CYP3A inducer decreased the ivacaftor exposure by approximately 9-fold.
Lumateperone: (Major) Avoid coadministration of lumateperone and bexarotene as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may occur when the drug is co-administered with inducers of CYP3A4. Concurrent use of lurasidone and CYP3A4 inducers, such as bexarotene, may lead to a decrease in efficacy of lurasidone. If lurasidone is used with a moderate CYP3A4 inducer, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more).
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with bexarotene is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and bexarotene is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with bexarotene due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Medroxyprogesterone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Meglitinides: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., meglitinides or "glinides") resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Methotrexate: (Major) Concomitant use of systemic retinoids, such as bexarotene, and methotrexate could increase risk of liver-related side effects of methotrexate and such patients should be monitored closely during methotrexate therapy. Topical retinoid products do not appear to pose this increased risk for liver problems.
Methoxsalen: (Moderate) Use methoxsalen and retinoids together with caution; the risk of severe burns/phototoxicity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Methylprednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Mitapivat: (Major) Avoid coadministration of mitapivat with bexarotene, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and bexarotene. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with bexarotene is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with bexarotene. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Neratinib: (Major) Avoid concomitant use of bexarotene with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of bexarotene is necessary. Concomitant use of nirmatrelvir and bexarotene may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with bexarotene. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with bexarotene due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and bexarotene is a CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Norethindrone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Norethindrone; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Norgestimate; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Norgestrel: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Olaparib: (Major) Avoid coadministration of olaparib with bexarotene due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and bexarotene is a moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and bexarotene due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and bexarotene. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Orlistat: (Moderate) Due the effect of orlistat on fat absorption and the lower serum levels of fat-soluble vitamins noted during clinical trials, the bioavailability of orally administered retinoids, such as bexarotene may also be decreased.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of oxycodone as needed. If bexarotene is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pacritinib: (Major) Avoid concurrent use of pacritinib with bexarotene due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and other retinoids, such as bexarotene, due to the risk for hypervitaminosis A. Concomitant use may also decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and bexarotene due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime when using concurrently with bexarotene due to a potential reduction in perampanel plasma concentration. If introduction or withdrawal of bexarotene occurs during perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Bexarotene is a moderate CYP3A4 inducer, and perampanel is a CYP3A4 substrate.
Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Photosensitizing agents (topical): (Moderate) Systemic or topical bexarotene may increase the effects of photosensitizing agents used during photodynamic therapy; concurrent use of photosensitizing agents is often recommended against by the specific photodynamic therapy, or doses of the therapy may require adjustment.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as bexarotene. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pioglitazone; Glimepiride: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and bexarotene due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Platelet Inhibitors: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including bexarotene.
Porfimer: (Major) Avoid coadministration of porfimer with retinoids due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Pralsetinib: (Major) Avoid concurrent use of bexarotene and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with bexarotene, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Prednisolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Prednisone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Pretomanid: (Major) Avoid coadministration of pretomanid with bexarotene as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Progesterone: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Progestins: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Quizartinib: (Major) Avoid concomitant use of bexarotene with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Relugolix; Estradiol; Norethindrone acetate: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Reteplase, r-PA: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering bexarotene with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Bexarotene is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Rimegepant: (Major) Avoid coadministration of rimegepant with bexarotene; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Ripretinib: (Major) Avoid coadministration of ripretinib with bexarotene. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of bexarotene. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and bexarotene is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritonavir: (Moderate) Monitor for decreased efficacy of ritonavir if coadministered with bexarotene. Concurrent use may decrease the plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Ritonavir is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Roflumilast: (Major) Coadminister bexarotene and roflumilast cautiously as this may lead to reduced systemic exposure to roflumilast. Betaxortene induces CYP3A4 and roflumilast is a CYP3A4 substrate. In pharmacokinetic study, administration of a single dose of roflumilast in patients receiving another CYP3A4 inducer, rifampin, resulted in decreased roflumilast Cmax and AUC, as well as increased Cmax and decreased AUC of the active metabolite roflumilast N-oxide.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Coadministration of a CYP3A4 inducer, like bexarotene, may decrease systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as bexarotene, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition.
Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Major) Bexarotene capsules may theoretically increase the rate of metabolism and reduce plasma concentrations of substrates metabolized by CYP3A4, including oral contraceptives. It is recommended that two reliable forms of contraception be used simultaneously during oral bexarotene therapy. It is strongly recommended that one of the forms of contraception be non-hormonal. Additionally, because of possible CYP3A4 induction, bexarotene may also decrease the efficacy of hormones used for hormone replacement therapy.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and bexarotene due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and bexarotene due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Siponimod: (Moderate) Concomitant use of siponimod and bexarotene is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of bexarotene. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Sodium Thiosulfate; Salicylic Acid: (Moderate) Dryness of the skin and mucus membranes are common side effects of retinoid therapy. Simultaneous use of retinoids and topical drying agents, such as salicylic acid, can potentiate the drying effects of retinoids on the skin. Be alert for signs of skin irritation, the offending topical agents may need to be used less often or discontinued during retinoid therapy.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with bexarotene. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of CYP3A4; bexarotene is a moderate inducer of CYP3A.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with bexarotene. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a substrate of CYP3A4; bexarotene is a moderate inducer of CYP3A. (Major) Avoid coadministration of voxilaprevir (a CYP3A4 substrate) with moderate to strong inducers of CYP3A4, such as bexarotene. Taking these drugs together may significantly decrease voxilaprevir plasma concentrations, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and bexarotene; sonidegib levels may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A4 substrate and bexarotene is a CYP3A4 inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A4 inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
St. John's Wort, Hypericum perforatum: (Major) In theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's wort with other photosensitizing drugs such as retinoids.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if bexarotene must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with bexarotene is necessary; consider increasing the dose of sufentanil injection as needed. If bexarotene is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Sulfonylureas: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and bexarotene. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as bexarotene, may reduce the efficacy of tasimelteon.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with bexarotene as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Telmisartan; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as bexarotene, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Tenecteplase: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Tetracyclines: (Major) The concomitant use of systemic retinoid therapy, such as bexarotene, and systemic tetracyclines should be avoided due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retionoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and bexarotene concurrently; the clinical impact of this interaction has not yet been determined. Administration of ivacaftor with strong CYP3A inducers is not recommended because sub-therapeutic ivacaftor exposure could result. Ivacaftor is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Co-administration with a strong CYP3A inducer decreased the ivacaftor exposure by approximately 9-fold.
Thiazolidinediones: (Moderate) Systemic bexarotene may enhance the action of insulin sensitizers (e.g., thiazolidinediones) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Thrombolytic Agents: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Tolazamide: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Tolbutamide: (Moderate) Systemic bexarotene may enhance the action of agents that enhance insulin secretion (e.g., sulfonylureas) resulting in hypoglycemia. Patients should be closely monitored while receiving bexarotene capsules in combination with any of these agents; monitor for hypoglycemia and the need for diabetic therapy adjustments. Hypoglycemia has not been associated with bexarotene monotherapy.
Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Bexarotene is an inducer of CYP3A4. Coadministration may result in reduced plasma concentration and subsequent reduced effectiveness of tolvaptan therapy and should be avoided. If coadministration is unavoidable, an increase in the tolvaptan dose may be necessary and patients should be monitored for decreased effectiveness of tolvaptan.
Triamcinolone: (Minor) Because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents, such as bexarotene.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with bexarotene as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A4 substrate; bexarotene is a moderate CYP3A4 inducer.
Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and bexarotene is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and bexarotene; venetoclax levels may be decreased and its efficacy reduced. Venetoclax is a CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Consider alternative agents. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were decreased by 42% and 71%, respectively, following the co-administration of multiple doses of a strong CYP3A4 inducer. Use of venetoclax with a moderate CYP3A4 inducer has not been evaluated.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with retinoids is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like retinoids may increase the risk of a photosensitivity reaction.
Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including bexarotene. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including bexarotene. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Voclosporin: (Major) Avoid coadministration of voclosporin with bexarotene. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and bexarotene is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and bexarotene due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of vonoprazan and bexarotene due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer. (Major) Coadministration of bexarotene and clarithromycin may decrease clarithromycin serum concentrations due to CYP3A4 enzyme induction. While the 14-OH-clarithromycin active metabolite concentrations are increased, this metabolite has different antimicrobial activity compared to clarithromycin. The intended therapeutic effect of clarithromycin could be decreased. It is not clear if clarithromycin activity against other organisms would be reduced, but reduced efficacy is possible. Alternatives to clarithromycin should be considered in patients who are taking CYP3A4 inducers.
Voxelotor: (Major) Avoid coadministration of voxelotor and bexarotene as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; bexarotene is a moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with bexarotene is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Bexarotene is a moderate CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and bexarotene due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if bexarotene is discontinued. Zanubrutinib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Zolpidem: (Moderate) It is advisable to closely monitor for reductions in zolpidem efficacy during co-administration of moderate CYP3A4 inducers, such as bexarotene. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of significant decreases in systemic exposure and pharmacodynamic effects of zolpidem during co-administration of rifampin, a potent CYP3A4 inducer.
How Supplied
Bexarotene/Targretin Oral Cap: 75mg
Bexarotene/Targretin Topical Gel: 1%
Maximum Dosage
oral capsules, 400 mg/m2 per day; topical gel, 1 application 4 times daily.
Geriatricoral capsules, 400 mg/m2 per day; topical gel, 1 application 4 times daily.
AdolescentsSafety and efficacy have not been established.
ChildrenSafety and efficacy have not been established.
Mechanism Of Action
Bexarotene is a synthetic retinoid agent that activates retinoid X receptor (RXR) subtypes RXR-alpha, RXR-beta, and RXR-gamma. These retinoid receptors have biologic activity that is different from that of retinoic acid receptors (RARs). RXR binding forms heterodimers with other receptors such as RARs, vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). These receptors regulate the expression of genes that control cellular differentiation and proliferation. The exact mechanism of bexarotene in cutaneous T cell lymphoma is not known. In vitro, bexarotene inhibits the growth of some types of hematopoietic and squamous cell lines. Tumor regression has been observed in animal models.
Pharmacokinetics
Bexarotene is administered orally or topically. It is highly protein bound (> 99%). The terminal half-life is 7 hours. Bexarotene undergoes oxidative metabolism via CYP3A4; the oxidative metabolites are then glucuronidated. Four metabolites have been identified in plasma: 6- and 7-hydroxy-bexarotene and 6- and 7-oxo-bexarotene. The oxidative metabolites are active in vitro, but the relative contribution of the parent or bexarotene metabolites to the efficacy and safety of therapy is not known. Bexarotene and its metabolites are eliminated primarily through the hepatobiliary system. Less than 1% of the dose is excreted in the urine as bexarotene or its metabolites.
Affected cytochrome P450 isoenzymes: CYP2C8, CYP3A4
In vitro, bexarotene is a CYP3A4 substrate, a CYP3A4 inducer, and a CYP2C8 inhibitor. In a clinical study, the bexarotene plasma concentration was not altered following multiple doses of ketoconazole, a strong CYP3A4 inhibitor; therefore, bexarotene elimination may not be dependent on CYP3A4 metabolism. Bexarotene has been shown to decrease the plasma levels of some CYP3A4 substrates (e.g., atorvastatin, tamoxifen, paclitaxel). It does not significantly inhibit the following isoenzymes: CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. No formal studies to evaluate drug interactions with bexarotene gel have been conducted; concomitant use of other drugs that affect CYP3A4 levels or activity may affect bexarotene disposition.
Following oral administration, bexarotene reaches its Tmax in about 2 hours. In patients with advanced malignancy, bexarotene exhibited linearity within the therapeutic range following a single dose.
Effects of Food: Following a single dose of bexarotene (75 mg to 300 mg), the plasma AUC and Cmax values were 35% and 48% higher, respectively, following a fat-containing meal compared to a glucose solution.
There is a low potential for significant systemic bexarotene plasma concentrations following repeated topical administration in patients applying low to moderate doses. In clinical trials, plasma concentrations were typically less than 5 nanograms (ng)/mL and did not exceed 55 mg/mL following single or multiple daily application of bexarotene 1% gel for up to 132 weeks in patients with cutaneous T-cell lymphoma. More frequent application (e.g., 4 times daily) and larger treated body surface area (e.g., > 40% BSA lesions) were associated with increased systemic levels.
Pregnancy And Lactation
The use of bexarotene (both gel and capsules) is contraindicated during pregnancy. Retinoid agents are associated with birth defects in humans; therefore, bexarotene may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy while taking bexarotene. Immediately discontinue bexarotene if a patient becomes pregnant during therapy and discuss the potential hazard to the fetus. Fetal abnormalities including incomplete ossification, cleft palate, depressed eye bulge/microphthalmia, and small ears were observed following oral bexarotene administration in pregnant rats during organogenesis (days 7 to 17 of gestation); fetal death occurred at doses greater than 10 mg/kg per day.
Counsel patients about the reproductive risk and contraception requirements during treatment with bexarotene gel or capsules. Pregnancy testing should be performed in females of reproductive potential within 1 week prior to starting therapy. Start bexarotene on the second or third day of the patient’s normal menstrual period and only administer a 1-month supply of the medicine for each refill. Perform pregnancy testing once monthly and provide counseling regarding pregnancy avoidance and the risk of birth defects with bexarotene. Females of reproductive potential should avoid pregnancy and use effective contraception starting 1 month prior to and for at least 1 month after treatment with bexarotene. It is recommended that these women use 2 reliable forms of non-hormonal contraception or practice abstinence during therapy. Bexarotene may induce metabolic enzymes and cause a reduction in the plasma concentrations of oral or other systemic hormonal contraceptives. Patients who become pregnant while receiving bexarotene should be apprised of the potential hazard to the fetus. Due to male-mediated teratogenicity, men with female partners of reproductive potential should avoid fathering a child and use effective contraception (i.e., condoms) during therapy and for at least 1 month following the final dose of bexarotene.