Endocrine therapy (ET) reduces recurrence and mortality rates in BC patients with estrogen-positive/progesterone-positive disease. Adherence to ET is essential to achieve maximal benefit. Numerous factors can play a role in contributing to medication nonadherence, among which can be the concern over drug-drug interactions; however, little is known as to whether this concern affects adherence to ET in BC patients.
Researchers conducted a cohort study using health record data from a private observational primary care database to determine whether potential drug-drug interactions (PDDIs) with tamoxifen or aromatase inhibitors (AIs) were associated with adherence in patients with early and advanced BC.
Data were analyzed between 1994 to 2021 of ET use among women aged 18 years or older who were enrolled in the French version of The Health Improvement Network, a private database that incorporated electronic health records from over 2,000 general practitioners (GPs). Eligible patients had to be on tamoxifen, letrozole, anastrozole, or exemestane; had to be enrolled in the database for at least 1 year; and had to have consulted the GP before and after initiation of therapy. The medication possession ratio (MPR), which is defined as the proportion of a time period where a medication supply is available, was used to assess compliance with a MPR of >0.8 indicating adherence. MRP and PDDI were assessed for a given 1-year period. Selected comedications with the potential for DDIs that were studied included lipid-lowering agents, antihypertensives, oral diabetic agents, insulin analogs, antidepressants, anxiolytics, antipsychotics, and opioids.
The Claude Bernard Drug Database was used to categorize the potential for a PDDI as minor (take note of), moderate (precaution advised), or major (not recommended) or contraindicated. Use categories for these medications included nonuse (no dispensing), infrequent use (one to two dispensed prescriptions during a given 1-year period) or frequent use (three or more dispensed prescriptions during a given 1-year period). Since adverse drug events (ADEs) were not collected in the database, the use of medications that are prescribed to manage usual ADEs to ET (e.g., nonsteroidal anti-inflammatory drug [NSAIDs], acetaminophen, duloxetine, venlafaxine, and oxybutynin) served as proxies.
A total of 10,863 patients were included in this analysis, of which almost one-third (32.3%) were aged 70 years or older.
In the tamoxifen group, PDDIs were identified in 13.5% at baseline but increased to 42.4% at Year 1 and decreased to 33.9% by Year 5. In the AI group, 8.0% had a PDDI at baseline, which increased to 31.8% at Year 1 and hit a peak at Year 4 at 32.8%. While major PDDIs decreased (37.3%-16.9%) over the 5-year study period, moderate PDDIs increased (60.4%-80.6%) during this time. Contraindicated prescriptions accounted for <1% of PDDIs. The most common PDDIs involved SSRIs (paroxetine, fluoxetine), duloxetine, and antacids.
Among AI users, PDDIs were identified in 8.0% at baseline but rose to 31.8% in Year 1 and peaked to 32.8% in Year 4. Almost all of the PDDIs were moderate (>95%), with <1.0% considered contraindicated. Antacids were the most common PDDI.
There was no evidence that PDDIs affected adherence for either tamoxifen or AIs groups; however, for the AI group, there was lower adherence among those with osteoarthritis (odds ratio 0.77; 95% CI, 0.66-0.90). There was an increase in the concomitant use of NSAIDs in the tamoxifen group shortly after starting the ET (by 5.9%), and this remained stable over time; however, the use of acetaminophen rose over the 5-year period (from 3.7% to 6.5%). The use of NSAIDs among AI users was more variable, peaking during the first year following the initiation of AI therapy at 40.6%, whereas acetaminophen use continued to increase during this period (3.7%-8.9%).
Although a retrospective observational study, this paper provides pharmacists with some reassurance of the relative safety of the use of ET with potentially interacting medications and for the lack of effect of these PDDIs on adherence.
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Published January 10, 2023