Drug interactions with Paxlovid common in older adults with polypharmacy: JAMA

Canada: Among the elderly on polypharmacy, drug-drug interactions (DDIs) with nirmatrelvir-ritonavir (Paxlovid) were most commonly reported with antithrombotics and statins, states an article published in the JAMA Network Open.

Anticipatory deprescribing could increase the proportion of older adults who benefit from nirmatrelvir-ritonavir, the researchers note. The study suggests that deprescribing potentially inappropriate medications (PIMs), rather than simply represcribing after receiving nirmatrelvir-ritonavir could be beneficial for older adults with polypharmacy. 

FDA granted an emergency use authorization (EUA) for nirmatrelvir-ritonavir (marketed as Paxlovid), the first oral antiviral for the treatment of COVID-19. Comparatively, Paxlovid is one of the most effective treatments for COVID-19 outpatients, among several novels or repurposed medications already studied. It reduces the risk of severe complications in high-risk, symptomatic, unvaccinated adults with COVID-19 but also has a long list of DDIs, limiting its safe use, especially among older adults with polypharmacy. Due to its potent CYP3A4 inhibition, nirmatrelvir-ritonavir is associated with many drug-drug interactions (DDI). 

Ross SB, McGill University, Montreal, Canada, and colleagues used data from the MedSafer cluster randomized clinical trial to identify DDIs between nirmatrelvir-ritonavir and potentially inappropriate medications (PIMs) in older adults with polypharmacy and to craft deprescribing guidance.

Researchers included 5698 hospitalized adults, age 65 years and older, with polypharmacy (≥5 usual home medications), with an expected survival of 3 months or longer for the study. Data about medications and comorbidities were analyzed according to an expert rule set for identifying PIMs. Deprescribing reports were provided to the treating teams and compared with usual care to prevent postdischarge adverse drug events.

Key findings of the study,

• In total, 67.9% of patients received at least 1 interacting medication prescription.

• The most common DDIs were with antithrombotic medications [37.4%] or statins [33.4%].

• Among the patients with interacting medication prescriptions, 21.3% had at least 1 PIM, of whom 76.2% had a high-risk DDI with nirmatrelvir-ritonavir.

• Common deprescribing opportunities included dual anticoagulant therapy without a recent coronary event or intervention [41.0%], alfuzosin or tamsulosin for benign prostatic hypertrophy in a person with orthostatic hypotension or recurrent falls [22.3%], and antipsychotics for sleep or agitation [22.6%].

The authors conclude that in older adults with polypharmacy, DDIs with nirmatrelvir-ritonavir were common. Many DDIs involved PIMs, which were candidate drugs for deprescribing. Not all DDIs could be mitigated by simply holding or dose-reducing a medication. Proactively deprescribing could increase the proportion of older adults who benefit from nirmatrelvir-ritonavir.

Reference:

Ross SB, Bortolussi-Courval É, Hanula R, Lee TC, Goodwin Wilson M, McDonald EG. Drug Interactions With Nirmatrelvir-Ritonavir in Older Adults Using Multiple Medications. JAMA Netw Open. 2022;5(7):e2220184. doi:10.1001/jamanetworkopen.2022.20184