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Emend (Fosaprepitant) and Xanax

Determining the interaction of Emend (Fosaprepitant) and Xanax and the possibility of their joint administration.

Check result:
Emend (Fosaprepitant) <> Xanax
Relevance: 15.11.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Fosaprepitant may increase the blood levels and effects of ALPRAZolam. This can increase the risk of side effects including excessive drowsiness and breathing difficulties. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR: Coadministration with aprepitant or its prodrug, fosaprepitant, may increase the plasma concentrations of benzodiazepines that are metabolized by CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by aprepitant. According to the manufacturer, coadministration of aprepitant (125 mg single dose on day 1 and 80 mg/day on days 2 through 5) and midazolam (2 mg orally on days 1 and 5) resulted in an increase in the area under the plasma concentration-time curve (AUC) of midazolam by 2.3-fold on day 1 and 3.3-fold on day 5. The same regimen of aprepitant given for 3 days with intravenous midazolam (2 mg prior to initiation of aprepitant and on days 4, 8 and 15) increased midazolam AUC by 25% on day 4 but decreased it by 19% on day 8. Midazolam AUC on day 15 was similar to that observed at baseline. Thus, the effect of aprepitant on the pharmacokinetics of CYP450 3A4 substrates is expected to be greater when the substrates are administered orally as opposed to intravenously and may be altered following prolonged administration. Benzodiazepines known to be metabolized by CYP450 3A4 include alprazolam, diazepam, midazolam, and triazolam.

MANAGEMENT: Caution is advised if aprepitant or fosaprepitant is administered with benzodiazepines that are metabolized by CYP450 3A4. The potential for increased pharmacologic effects of the benzodiazepine, including central nervous system and respiratory depression, should be considered. The interaction is not expected to occur with lorazepam, oxazepam or temazepam, which are primarily metabolized via glucuronidation. Chronic, continuous use of aprepitant for prevention of nausea and vomiting is not recommended because it has not been studied and because the drug interaction profile may change during long-term use.

References
  • Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  • "Product Information. Emend (aprepitant)." Merck & Company Inc, West Point, PA.
  • Majumdar AK, McCrea JB, Panebianco DL, et al. "Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe." Clin Pharmacol Ther 74 (2003): 150-6
  • Hardman JG, Limbird LE, Gilman AG, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 10th ed." New York, NY: McGraw-Hill (2001):
Emend (Fosaprepitant)

Generic Name: fosaprepitant

Brand name: Emend for Injection

Synonyms: Fosaprepitant

Xanax

Generic Name: alprazolam

Brand name: Niravam, Xanax, Xanax XR, Alprazolam Intensol

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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