WINSTON-SALEM, NC.—Managing multiple medications poses a challenge for many older patients. Forty percent of people in the United States over the age of 65 regularly take five or more drugs, meeting the definition of polypharmacy. For patients with hematologic malignancies such as chronic lymphocytic leukemia (CLL), determining which medications are necessary and which interfere with cancer treatment is even more problematic.
Among veterans, the issue is even more acute. Nearly two-thirds of former servicemembers aged 49 to 64 prescribed five to nine drugs take at least one potentially inappropriate medication. For those aged 65 to 70 taking the same number of medications, nearly three in five are prescribed a potentially inappropriate medication.1
Even medications that are appropriately prescribed can cause undesirable interactions, a risk that increases with the number of drugs. Polypharmacy is associated with increased risk of falls , cognitive impairment, hospitalizations and death, particularly in elderly patients, according to the VA’s Center for Medication Safety in Aging.
Polypharmacy and CLL
Individuals combating cancer face further risk of adverse outcomes. In addition, the sheer burden of multiple pills and complex regimens increases the risk of medication errors, missed medications, drug-drug interactions, chemotherapy or other anticancer medication toxicity and poorer outcomes. Cancer treatment itself can also contribute to polypharmacy in attempts to manage adverse effects from chemotherapy and immunotherapies such as nausea and vomiting, fatigue and anemia.
Among elderly patients in the general population who were starting cancer treatment, 61.3% regularly took more than five drugs and 15% took more than 10, a team led by researchers at the University of Rochester Medical Center found.The most common medications included cardiovascular drugs at 47%, while nonprescription medications accounted for 26% of total medications and represented 40% of the potentially inappropriate medications.2.
One-quarter of the patients had a potential major drug-drug interaction (DDI) and 5.4% faced a potential major drug-cancer therapy interaction. “Each additional therapy increased the odds of a potential major DDI and DCI by 39% and 12%, respectively,” the researchers said.
CLL is the most common hematologic malignancy, representing about 40% of leukemias. It occurs more often among veterans than the general population as a result of exposure to Agent Orange and contaminated water at Camp LeJeune, qualifying it a presumptive condition. CLL primarily affects people in their later years, with an average age at diagnosis of 70, making its occurrence common among the older population primarily treated by the VA.
While the course of the CLL varies substantially from patient to patient, a watchful waiting approach is frequently recommended for those with a more indolent form of the disease. Delaying or avoiding treatment until clinically significant symptoms emerge enables patients to minimize the toxicities associated with the cancer therapies and has not been shown to impair overall survival.
Interaction with CLL therapies
In a recent review on the challenges of polypharmacy in older patients with cancer, Justin J. Cheng, MD, of Wake Forest University School of Medicine and colleagues at the University of California-Los Angeles David Geffen School of Medicine noted that recent advances in treatment for CLL make attention to the interaction of multiple medications more important.3
“The favored regimen for many older, and often frail, adults is Bruton’s tyrosine kinase (BTK) inhibitors, as daily oral targeted therapy with no primary fixed endpoint to the treatment course,” they wrote in an article in the November issue of Clinics in Geriatric Medicine. “There are important adverse events that can occur with these treatments, which factor into the risk for polypharmacy and the prescribing cascade.”
Ibrutinib, the first BTK inhibitor approved for CLL, increased risk of cardiac toxicities, hemorrhage, rash, diarrhea, and infections which lead between one-quarter and half of patients to discontinue the therapy. Acalabrutinib, a newer BTK, poses less cardiac risk compared to ibrutinib, but still requires require monitoring by a cardiologist, who may prescribe medications for arrhythmias or heart rate control.
Anticoagulants prescribed to reduce the risk of stroke may increase the likelihood of hemorrhage in patients on BTK inhibitors, requiring careful consideration of dosage and potentially discontinuation, the researchers noted. “The bleeding risk associated with BTK inhibitors is due to the off-target effect of BTK on platelet aggregation,” they added. “The risk of major bleeding while on a BTK inhibitor is increased when patients are concurrently on antiplatelet or anticoagulation therapy.” Some over-the-counter medications and supplements may also increase bleeding risk, including vitamin E, non-steroidal anti-inflammatories, and fish oil.
By affecting CYP3A4, BTK inhibitors interact with grapefruit, leading to increased levels of the drug in the blood stream and elevated frequency of adverse events. Proton-pump inhibitors decrease absorption of BTK inhibitors, which may also be impacted by H2-blockers and other antacids, Cheng and the study team said.
“An additional consideration for those with hematologic malignancies like CLL is the immunosuppressive effects of some cancer-directed therapies, which has implications for patients’ response to vaccines, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine,” they wrote. “Rituximab and obinutuzumab are commonly used anti-CD20 monoclonal antibody targeting B-cells in diseases like CLL. These antibodies trigger cell death of the cells of the immune system responsible for antibody production, which increases infection risk and decreases response to vaccines for older adults.” Consequently, patients who receive the monoclonal antibodies may have impaired response to vaccines for a year or more.
Management of CLL may involve prescription of “prophylactic antibacterial, antiviral, or antifungal medications, and depending on the assessed risk, patients may receive targeted prophylaxis against herpes simplex virus, varicella-zoster virus, cytomegalovirus, or Pneumocystis jirovecii,” noted Cheng and team. “It is imperative to note the prophylactic dosing of prescribed antimicrobial, antiviral, and antifungal medications may differ from treatment doses; therefore, careful attention should be paid to the dose and schedule of the medications in addition to monitoring for potential DDIs.”
Involving pharmacists in the care of patients with CLL and other cancers can reduce the risk of drug-drug interactions via medication reconciliation and assessments to identify polypharmacy, address use of potentially inappropriate medications and deprescribe medications as needed, while probing reasons for non-adherence, the authors concluded. “Interventions that reduce the impact of polypharmacy can ultimately improve cancer care in older adults, including quality of life and survival.”
- Guillot J, Rentsch CT, Gordon KS, Justice AC, Bezin J. Potentially inappropriate medication use by level of polypharmacy among US Veterans 49-64 and 65-70 years old. Pharmacoepidemiol Drug Saf. 2022 Oct;31(10):1056-1074.
- Ramsdale E, Mohamed M, Yu V, Otto E, Juba K, Awad H, Moorthi K, Plumb S, Patil A, Vogelzang N, Dib E, Mohile S. Polypharmacy, Potentially Inappropriate Medications, and Drug-Drug Interactions in Vulnerable Older Adults With Advanced Cancer Initiating Cancer Treatment. 2022 Jul 5;27(7):e580-e588.
- Cheng JJ, Azizoddin AM, Maranzano MJ, Sargsyan N, Shen J. Polypharmacy in Oncology. Clinics in Geriatric Medicine. 2022 Nov;38(4):p705-714.
