Community Oncologist

I have a patient with cardiac amyloid who is receiving Dara-CyBorD based on the ANDROMEDA study published last year in NEJM. She recently started amiodarone for SVT. Would you dose adjust any of the Dara-CyBorD medications based on potential interactions with amiodarone?

Oncology Pharmacist

The drug interactions with amiodarone are complex given it’s CYP3A4 and PGP inhibition coupled with its very long variable half-life. The simplest answer is to investigate if the patient could utilize a different non-interacting agent for SVT instead. I’d be happy to help recommend non-interacting alternatives if you could provide more information on the cardiac history and what the patient previously tried before amiodarone. Amiodarone will not interact with daratumumab but will interact with both cyclophosphamide and bortezomib. Since cyclophosphamide is a pro-drug that requires CYP3A4 to be activated, inhibition of CYP3A4 could decrease cyclophosphamide efficacy. The only way to overcome this would be to increase the cyclophosphamide dose but any dose increases would be arbitrary since it is hard to know the extent of the CYP3A4 inhibition and may not be tolerated with this regimen especially in a patient with amyloid. Bortezomib is metabolized through CYP3A4 so you would be looking at increased bortezomib toxicities. If the patient cannot switch from amiodarone, you could consider a reduction to 0.7 mg/m2 and increase the dose from there as tolerated. Again, my concern would be reducing the efficacy of bortezomib. I worry about reducing the efficacy of this regimen given the ANDROMEDA trial was the first in a long time to improve outcomes in amyloid so I typically do my best to avoid the drug interactions if I can. Amiodarone can also increase steroid exposure since dexamethasone goes through CYP3A4. Depending on patients age you could decrease to 20mg or keep at full dose of 40mg and reduce based on tolerability.