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Drug Interactions between bexarotene and Xanax

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

ALPRAZolam bexarotene

Applies to: Xanax (alprazolam) and bexarotene

MONITOR: Coadministration with bexarotene may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. The proposed mechanism is increased clearance due to induction of CYP450 3A4 activity by bexarotene, particularly at dosages above 300 mg/m2/day. In a study of patients with non-small cell lung cancer receiving bexarotene (400 mg/m2 orally once a day) plus either paclitaxel/carboplatin or cisplatin/vinorelbine chemotherapy, treatment with atorvastatin (a CYP450 3A4 substrate) or fenofibrate was given to manage bexarotene-induced hyperlipidemia. Investigators reported that bexarotene decreased mean atorvastatin systemic exposure (dose-corrected AUC) by approximately 50%, whereas atorvastatin had no significant effect on bexarotene plasma concentrations. The AUC of paclitaxel (200 mg/m2 IV over 3 hours), a substrate of both CYP450 3A4 and 2C8, was also decreased by 19% when coadministered with bexarotene. According to the product labeling, bexarotene may decrease the plasma concentrations of another CYP450 3A4 substrate, tamoxifen, by 35%.

MANAGEMENT: Caution is advised if bexarotene is prescribed concomitantly with medications that are primarily metabolized by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever bexarotene is added to or withdrawn from therapy.

References

  1. (2001) "Product Information. Targretin (bexarotene)." Ligand Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Wakelee HA, Takimoto CH, Lopez-Anaya A, et al. (2012) "The effect of bexarotene on atorvastatin pharmacokinetics: results from a phase I trial of bexarotene plus chemotherapy in patients with advanced non-small cell lung cancer." Cancer Chemother Pharmacol, 69, p. 563-71

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Drug and food interactions

Moderate

ALPRAZolam food

Applies to: Xanax (alprazolam)

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 7 references

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Moderate

bexarotene food

Applies to: bexarotene

ADJUST DOSING INTERVAL: Food may enhance the oral bioavailability of bexarotene. In one clinical study, bexarotene peak plasma concentration (Cmax) and systemic exposure (AUC) resulting from a 75 to 300 mg dose were 35% and 48% higher, respectively, when administered after a fat-containing meal relative to a glucose solution. In all clinical trials, patients were instructed to take bexarotene with or immediately following a meal.

Coadministration with inhibitors of CYP450 3A4 such as grapefruit juice may theoretically increase the plasma concentrations of bexarotene. In vitro studies suggest that bexarotene is metabolized by CYP450 3A4. However, concomitant administration with multiple doses of ketoconazole, a potent CYP450 3A4 inhibitor, did not alter bexarotene plasma concentrations, which would imply that bexarotene elimination is not substantially dependent on CYP450 3A4 metabolism in vivo.

MANAGEMENT: Because safety and efficacy data are based upon administration with food, bexarotene should be administered once daily with a meal. Patients may want to avoid consuming large amounts of grapefruit or grapefruit juice.

References

  1. (2001) "Product Information. Targretin (bexarotene)." Ligand Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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