Analysis of Pharmacist Interventions Used to Resolve Safety Target of Polypharmacy (STOP) Drug Interactions
Background: Statin drug interactions commonly increase the risk of muscle-related toxicities. The medical literature supports consultative pharmacist interventions to resolve drug interactions, but studies demonstrating autonomous pharmacist interventions are lacking.
Objective: To evaluate the complementary impact of using pharmacist-led protocols and pharmacists with prescriptive authority to resolve statin drug interactions.
Methods: Pharmacist-led protocols were developed to address gemfibrozil-statin and niacin-statin interactions. Pharmacists discontinued gemfibrozil and niacin by protocol or referred patients to the Patient Aligned Care Team (PACT) Pharmacy Clinic for individualized management. After all drug interactions were addressed, a retrospective quality improvement analysis was conducted. The primary outcome was to evaluate the impact of gemfibrozil and niacin discontinuation by protocol on patients’ triglyceride (TG) laboratory results. The coprimary endpoints were the change in TGs and the percentage of patients with TGs ≥ 500 mg/dL, following pharmacist discontinuation by protocol. Secondary outcomes included the time required to resolve the interactions and a description of the PACT Clinical Pharmacy Specialists' (CPS) pharmacologic interventions.
Results: The gemfibrozil and niacin protocols addressed 397 drug interactions. Seventy-six patients underwent gemfibrozil discontinuation by protocol and had TG laboratory results available. TG levels decreased or increased by < 100 mg/dL for 62 patients (82%), and 1 patient (1.3%) experienced TG elevation above the threshold of 500 mg/dL. Thirty-six patients had niacin discontinued by protocol and available laboratory results. The TG levels decreased or increased by < 100 mg/dL for 33 patients (91.7%), and no patients had TG levels increase above the threshold of 500 mg/dL. The mean time required to resolve both gemfibrozil and niacin drug interactions was 15.5 minutes per patient. A total of 129 patients were referred to the PACT Pharmacy Clinic to manage gemfibrozil and niacin drug interactions. TG laboratory results were available for 80 gemfibrozil patients (74.8%) and 16 niacin patients (72.7%). The PACT CPS made 171 pharmacologic interventions to address drug interactions and the median of 2 encounters per patient.
Conclusions: This single-site quality improvement analysis supports the complementary use of protocols and pharmacists with prescriptive authority to resolve statin drug interactions. These data support expanded roles for pharmacists, across settings, to mitigate select drug interactions.
Discussion
Following gemfibrozil or niacin discontinuation by protocol, most patients with available laboratory results experienced either a decrease or modest TG elevation. The proportion of patients experiencing a decrease in TGs was unexpected but potentially multifactorial. Individual causes for the decrease in TGs were beyond the scope of this analysis. The retrospective design limited the ability to identify variables that could have impacted TG levels when gemfibrozil or niacin were started and discontinued. Although the treatment of TG levels is not indicated until it is ≥ 500 mg/dL, due to an increased risk of pancreatitis, both protocols excluded patients with a history of TGs ≥ 400 mg/dL.19 The lower threshold was set to compensate for anticipated increase in TG levels, following gemfibrozil or niacin discontinuation, and to minimize the number of patients with TG levels ≥ 500 mg/dL. The actual impact on patients’ TG levels supports the use of this lower threshold in the protocol.
When TG levels increased by 200 to 249 mg/dL after gemfibrozil or niacin discontinuation, patients were evaluated for possible underlying causes, which occurred for 4 gemfibrozil and 1 niacin patient. One patient started a β-blocker after gemfibrozil was initiated, and 3 patients were taking gemfibrozil prior to establishing care at the VA. The TG levels of the patient taking niacin correlated with an increased hemoglobin A1c. The TG level for only 1 patient taking gemfibrozil increased above the 500 mg/dL threshold. The patient had several comorbidities known to increase TG levels, but the comorbidities were previously well controlled. No additional medication changes were made at that time, and the TG levels on the next fasting lipid panel decreased to goal. The patient did not experience any negative clinical sequelae from the elevated TG levels.
Thirty-five patients (36%) who were referred to the PACT Pharmacy Clinic required only either gemfibrozil or niacin discontinuation. These patients were evaluated to identify whether adjustments to the protocols would have allowed for pharmacist discontinuation without referral to the PACT Pharmacy Clinic. Twenty-four of these patients (69%) had repeated TG levels ≥ 400 mg/dL prior to referral to the PACT Pharmacy Clinic. Additionally, there was no correlation between the gemfibrozil or niacin doses and the change in TG levels following discontinuation. These data indicate the protocols appropriately identified patients who did not have an indication for gemfibrozil or niacin.
In addition to drug interactions identified on the STOP report, the PACT CPS resolved 12 additional interactions involving simvastatin and gemfibrozil. Additionally, unnecessary lipid medications were deprescribed. The PACT CPS identified 13 patients who experienced myalgias, an ADR attributed to the gemfibrozil- statin interaction. Of those, 9 patients’ ADRs resolved after discontinuing gemfibrozil alone. For the remaining 4 patients, additional interventions to convert the patient to another statin were required to resolve the ADR.
Using pharmacists to address the drug interactions shifted workload from the prescribers and other primary care team members. The mean time spent to resolve both gemfibrozil and niacin interactions by protocol was 15.5 minutes. One hundred fortytwo patients (35.8%) had drug interactions resolved by protocol, saving the PACT CPS’ expertise for patients requiring individualized interventions. Drug interactions were resolved within 4 PACT CPS encounters for 93.8% of the patients taking gemfibrozil and within 3 PACT CPS encounters for 93.8% of the patients taking niacin.
The protocols allowed 12 additional pharmacists who did not have an ambulatory care scope of practice to assist the PACT CPS in mitigating the STOP drug interactions. These pharmacists otherwise would have been limited to making consultative recommendations. Simultaneously, the design allowed for the PACT pharmacists’ expertise to be allocated for patients most likely to require interventions beyond the protocols. This type of intraprofessional referral process is not well described in the medical literature. To the authors’ knowledge, the only studies described referrals from hospital pharmacists to community pharmacists during transitions of care on hospital discharge.20,21
