Impact of prophylactic oseltamivir on INR in patients on stable warfarin therapy.

Influenza prophylaxis with oseltamivir is recommended for exposed high-risk patients. Patients with many comorbidities have an increased likelihood of co-administration of oseltamivir and warfarin. Evidence of a drug interaction is conflicting in the literature and is limited to a 5-day treatment course. This study evaluates the impact of prophylactic oseltamivir on international normalized ratio (INR) in patients taking warfarin. This retrospective cohort study conducted within the Veterans Health Administration included patients on warfarin who received oseltamivir for influenza prophylaxis. The primary endpoint was change in INR from baseline to day 10 of oseltamivir treatment. Secondary endpoints included change in INR based on renal function and duration of oseltamivir prophylaxis, trend in INR, and frequency of bleeding and thrombosis events. A total of 1041 patients were included and received oseltamivir for a mean of 12.9 days. The mean post-oseltamivir INR was significantly increased compared to the pre-oseltamivir INR (2.39 to 2.52; p < 0.001). Patients with a creatinine clearance of 31-60 mL/min had a significant increase in INR (2.40 to 2.59; p < 0.01). There was an increase in INR when oseltamivir was used for 7 or 8-10 days. Of included patients, 5.1% and 1.8% had a recorded thrombosis or bleeding event, respectively. There was a significant increase in INR in patients on chronic warfarin therapy and concomitant prophylactic oseltamivir, but this change may only be clinically significant for certain patient populations. The most impact on INR was within 7-10 days of oseltamivir initiation and in patients with impaired renal function.

Evaluating the Impact of Medication Safety Alerts on Prescribing of Potentially Inappropriate Medications for Older Veterans in an Ambulatory Care Setting.

Potentially inappropriate medications (PIMs) have been associated with poor outcomes in older adults. Electronic health record (EHR)-based interventions may be an effective way to reduce PIM prescribing. The main objective of this study was to evaluate changes in PIM prescribing to older adult veterans ≥65 years old in the ambulatory care setting preimplementation and postimplementation of medication alert messages at the point of computerized provider order entry (CPOE). Additional exploratory objectives included evaluating provider type and patient-provider relationship as a factor for change in PIM prescribing. A total of 1539 patients prealert and 1490 patients postalert were prescribed 1952 and 1897 PIMs, respectively. End points were reported as the proportion of new PIM orders of total new prescriptions. There was no significant difference in the rate of new PIMs prealert and postalert overall, 12.6% to 12.0% ( P = .13). However, there was a significant reduction in the rate of the top 10 most common newly prescribed PIMs, 9.0% to 8.3% ( P = .016), and resident providers prescribed fewer PIMs during both time periods. A simple, age-specific medication alert message during CPOE decreased the incidence of the most frequently prescribed PIMs in older adults receiving care in an ambulatory care setting.

Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans.

STUDY OBJECTIVE: To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. DESIGN: Case series. SETTING: Pharmacist-led anticoagulation clinic in a Veterans Affairs Health Care System. PATIENTS: Four patients aged 59-66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. MEASUREMENTS AND MAIN RESULTS: All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14-67% was required, with changes in warfarin doses starting 2-3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. CONCLUSION: To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.

The effect of angiotensin II receptor blockers on hyperuricemia.

The objective of this review was to explore the efficacy of angiotensin II receptor blockers (ARBs) for the treatment of hyperuricemia in individuals diagnosed with gout or hyperuricemia defined as ⩾7 mg/dl at baseline. A literature search of MEDLINE (1946 to June 2015) and EMBASE (1947 to June 2015) was conducted. The following search terms were used: 'uric acid', 'urate transporter', 'gout', 'angiotensin II receptor blockers', 'hyperuricemia' and the names for individual ARBs, as well as any combinations of these terms. Studies were excluded that did not explore fractional excretion or serum uric acid as an endpoint, if patients did not have a diagnosis of gout or hyperuricemia at baseline, or if they were non-English language. A total of eight studies met the inclusion criteria. Of the eight studies identified, six explored ARB monotherapy and two studies investigated ARBs as adjunct therapy. Losartan demonstrated statistically significant reductions in serum uric acid levels or increases in fractional excretion of uric acid in all studies, whereas no other ARB reached statistical benefit. The effect of ARBs on the occurrence of gout attacks or other clinical outcomes were not represented. Four studies evaluated safety effects of these agents indicating abnormalities such as minor changes in lab values. In conclusion, losartan is the only ARB that has consistently demonstrated a significant reduction in serum uric acid levels, although the significance of impacting clinical outcomes remains unknown. Losartan appears to be a safe and efficacious agent to lower serum uric acid levels in patients with hyperuricemia.

The emerging role of tacrolimus in myasthenia gravis.

OBJECTIVE: To describe and evaluate the available evidence assessing the role of tacrolimus in the management of patients with myasthenia gravis (MG). DATA SOURCES: A literature search of MEDLINE (1946 to September 2014) and EMBASE (1947 to September 2014) was performed using the terms 'tacrolimus' and 'myasthenia gravis'. Citations of retrieved articles were examined for relevance. STUDY SELECTION AND DATA EXTRACTION: The search was limited to prospective clinical trials focused on clinical outcomes in patients with generalized MG. Case reports, retrospective evaluations and non-English articles were excluded. DATA SYNTHESIS: A total of 12 studies met inclusion criteria, of which seven articles evaluated tacrolimus in steroid-dependent patients and two examined the utility of tacrolimus in patients failing corticosteroids and cyclosporine. Other studies evaluated early initiation of tacrolimus after thymectomy, effectiveness of tacrolimus in de novo MG and the effectiveness of tacrolimus post-thymectomy in thymoma patients versus nonthymoma. A total of eight trials showed statistically significant improvements in quantitative MG score (QMGS) and postintervention status criteria - Myasthenia Gravis Foundation of America (PSC-MGFA). Of the trials examining steroid reduction with tacrolimus, two reported high rates of complete withdrawal; however, the most robust trial was unable to detect a difference in mean steroid dose. Long-term effects of tacrolimus (up to 5 years) were assessed in eight trials, which consistently showed positive effects on QMGS or reduction in adjunct therapies. CONCLUSIONS: There is limited yet promising information to suggest a beneficial role for tacrolimus in reducing QMGS and corticosteroid burden in patients with refractory symptoms or new-onset MG. Long-term use appears to be safe in this population.

Inhaler misuse in an older adult population.

OBJECTIVE: To determine the prevalence of inhaler misuse in an older adult population. DESIGN: Prospective observational study. SETTING: Two primary care outpatient clinics in a Veterans Affairs Medical Center in North Carolina. PARTICIPANTS: Male veterans 65 years of age and older (N = 24) prescribed a pressurized metered dose inhaler (pMDI) or a dry powder inhaler (DPI). MEASUREMENTS: Inhaler technique was evaluated using placebo inhaler devices and a standardized technique assessment form that included critical steps. Potential risk factors for misuse were obtained from the medical record, and the time for technique evaluation was collected. MAIN RESULTS: Study participants yielded 44 unique device observations. Patients were male with an average age of 82 years. All patients made at least one error, with a mean error rate of 2.5 errors/patient/inhaler, while 20 of 24 (83%) patients made at least one critical error with a mean error rate of 1.2 critical errors/patient/inhaler. Assessment of inhaler technique required 2.3 minutes/inhaler. Critical errors were made during 15 of 19 (79%) pMDI observations and 22 of 25 (88%) DPI observations. Patients with multiple inhalers or a history of stroke committed errors more often, although no risk factors demonstrated meaningful differences in error rates. CONCLUSIONS: Inhaler misuse in older adults is common, including committing critical errors that have been shown to reduce drug delivery. The time necessary for technique evaluation is relatively small. The high rate of misuse observed should serve as motivation for increased vigilance, individualized technique education, and routine re-assessment in the highly heterogeneous older adult population.