Older adults are at high risk of opioid-related adverse effects even when they use these medications as prescribed. Approximately one in three older adults receives at least one opioid prescription each year and many receive high amounts, with average doses that exceed recommendations on the drug labels. Opioids are responsible for more than 35,000 emergency room visits, nearly 125,000 hospitalizations, and nearly 9,000 deaths among older adults each year. Polypharmacy among older adults who use opioids is especially high. As compared to patients who do not use opioids, those that use opioids are more likely to have many other comorbidities, including depression and cardiovascular disease. On average, patients who use opioids fill 52 prescriptions per year from about 10 drug classes. A number of medications that are commonly used by older adults may interact with opioids to increase risk of opioid-related adverse events. For example, oxycodone, one of the most commonly used medications for chronic pain and the drug most frequently involved in opioid overdoses, is metabolized by the liver enzymes cytochrome P450 3A4 (CYP3A4) and CYP2D6. The selective- serotonin reuptake inhibitors (SSRIs) fluoxetine and paroxetine, which are among the most widely used antidepressant medications, inhibit CYP3A4. Interactions between these drugs could increase oxycodone concentrations in the body and potentially increase risk of adverse events leading to opioid-related emergency room visits and hospitalizations. Fentanyl is also metabolized by 3A4, hydrocodone is metabolized by 2D6, and tramadol is metabolized by 3A4, 2D6, and 2B6. Despite the potentially important role that drug interactions may play in older adults, little is known about whether these putative interactions are likely increase opioid-related emergency room visits and hospitalizations and whether there may be safer treatment alternatives for patients requiring opioid treatment. The overarching goal of this project is to generate novel evidence that will help patients and healthcare providers identify and avoid important drug interactions with opioids that have the potential to increase risk of opioid-related emergency room visits and hospitalizations. This project will focus on three comorbid conditions (depression, hypertension, and acute coronary syndromes) that commonly affect older adults and for which certain drugs may interact with opioids but where potentially safer alternatives are available.
The specific aims of this project are to evaluate whether: (1) SSRIs that inhibit 2D6 (fluoxetine, paroxetine) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use oxycodone, hydrocodone, or tramadol; (2) calcium channel blockers (CCBs) that inhibit 3A4 (diltiazem, verapamil) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use oxycodone, fentanyl, or tramadol; and (3) antiplatelet agents that inhibit 2B6 (clopidogrel, ticlopidine) increase rates of opioid-related emergency room visits and hospitalizations among older adults who use tramadol.
Older adults who use opioid analgesics often have multiple comorbid conditions that lead to treatment with many concomitant medications, including some that may interact with the opioids. Little is known about the extent to which drug-drug interactions increase rates of opioid-related emergency room visit and hospitalization. This project aims to generate evidence that will help patients and healthcare providers make better and safer treatment decisions to reduce opioid-related emergency room visits and hospitalization in older adults.
