Recommendations

Avoid CYP2D6 Inhibitors. I argue that we have reached a point where agnosticism on avoiding CYP2D6 inhibitors in patients on tamoxifen is not an ethically justifiable position. In patients on tamoxifen, avoid adding or continuing CYP2D6 inhibitors (Table 1) unless there is no alternative therapy and the risk of avoiding the CYP2D6 inhibitor is greater than the increased risk of breast cancer recurrence. There should be very few situations where that is the case. When starting an antidepressant in a patient on tamoxifen, avoid CYP2D6 inhibitors and use agents with little or no effect on CYP2D6 such as venlafaxine, desvenlafaxine, escitalopram, or citalopram. If a patient on tamoxifen is already taking an antidepressant that is a moderate to strong CYP2D6 inhibitor, carefully switch her/him to another antidepressant or other therapy if at all possible.

2. Avoid Enzyme/Transporter Inducers. In patients on tamoxifen, avoid adding or continuing enzyme/transporter inducers (Table 2) unless there is no alternative therapy and the risk of avoiding the inducer is greater than the increased risk of breast cancer recurrence. There should be very few situations where that is the case. The inducers that are well documented to be “broad-spectrum” inducers (those with an asterisk in Table 2) clearly should be avoided, because they are theoretically even more dangerous than CYP2D6 inhibitors in patients on tamoxifen. Whether the other drugs in Table 2 should be avoided is not as clear, and the issue should be debated before any firm recommendations are made.

3. Advise Patients to Avoid Interacting Drugs Including OTCs and Herbal Products. Given that people often have more than one prescriber, every patient on tamoxifen should be given a list of CYP2D6 inhibitors and enzyme/transporter inducers (such as Tables 1, 2) to take with them. They should be advised to show the list to any other health professional who is prescribing a drug for them. Patients on tamoxifen should be specifically advised to avoid St John’s wort due to its ability to induce enzymes and transporters (there are currently no OTC drugs in the USA that are known to induce enzymes/transporters). They should also be advised to avoid herbals and OTCs that inhibit CYP2D6 such as berberine (goldenseal), diphenhydramine, and chlorpheniramine. (Note that berberine has been studied as an agent to suppress breast cancer cell proliferation, but it is too early to tell if this will have any clinical utility in patients with breast cancer) [60]