NAPLEX Question of the Week: Drug Interaction?

Drug interaction assessment is a normal part of pharmacy practice, no matter the setting. Are you up for the challenge?
NAPLEX Question of the Week: Drug Interaction?

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A 47 year old female weighing 65kg presents to the pharmacy with a prescription for azathioprine 150mg by mouth daily (2.5mg/kg) for treatment of her Crohn's disease. Her current medications on file that have been filled in the last 30 days include famotidine 20mg by mouth twice daily, febuxostat 80mg once daily, rosuvastatin 20mg at bedtime, ramipril 10mg daily, HCTZ 25mg daily, and loratadine 10mg once daily.  The patient has normal renal function and confirms they are currently taking all of these medications. The physician's office is currently closed. What is the appropriate response to the patient regarding this prescription?

A. Fill prescription as is, no changes necessary.

B. Fill prescription as is, drug interaction identified but not clinically significant.

C. Fill prescription as is, tell patient will call prescriber in morning to discuss interaction.

D. Do not fill prescription, tell patient you will call in morning to discuss with prescriber.

Answer and Rationale:

The correct answer is D. This patient has a major drug interaction that could result in harm. Febuxostat's mechanism of action, similar to allopurinol, includes inhibiting xanthine oxidase to help decrease risk of gout attacks long-term by lowering uric acid concentrations. Azathioprine is converted via hepatic metabolism to 6-Mercaptopurine which is inactivated by xanthine oxidase. There are a number of reports in the literature of patients who after receiving both medications experience significant toxicity including  nausea, vomiting, and most importantly hematologic toxicity (bone marrow suppression) and therefore the combination is contraindicated. Management of this interaction could entail a number of options including choosing a different agent for Crohn's managment, assessing need for uric acid lowering therapy altogether, or switching from febuxostat to allopurinol if appropriate. Many patients only switch from allopurinol to febuxostat if the allopurinol was not effective in preventing gout attacks.  If the febuxostat is changed to allopurinol, decreasing the azathioprine dosage to 1/3rd or 1/4 of its original dosage is recommended with continued monitoring for side effects. All of these options would require speaking with the prescriber before filling and make answers A, B, and C incorrect.


1. Logan JK et al. Drug Interaction Between Febuxostat and Thiopurine Antimetabolites: A Review of the FDA Adverse Event Reporting System and Medical Literature. Pharmacotherapy. 2020;40:125-32. 

See everyone next week!

Dr. B

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