Droxidopa management by an integrated health-system specialty pharmacy team.

BACKGROUND: Droxidopa, indicated for the treatment of symptomatic neurogenic orthostatic hypotension, can be challenging for patients to access owing to manufacturer and payer restrictions, and requires close monitoring to ensure safety and effectiveness. OBJECTIVE: This practice report describes the development and outcomes of an integrated neurology specialty pharmacy team for droxidopa management. PRACTICE DESCRIPTION: An integrated health-system specialty pharmacy (HSSP) connected to an academic institution with integrated specialty pharmacists working in collaboration with the providers in both the neurology and autonomic disfunction clinic. PRACTICE INNOVATION: In May 2017, the integrated HSSP developed droxidopa management services. Based on clinic-identified needs, the specialty pharmacy team completed droxidopa access requirements (insurance approval and affordability), provided comprehensive medication education at droxidopa initiation, and developed and executed droxidopa titration and monitoring plans in collaboration with providers. While patients were on droxidopa therapy, specialty pharmacist staff (pharmacists and technicians) monitored patients for safety and response to therapy and communicated with the health care team through the shared electronic health record. EVALUATION METHODS: We performed a retrospective cohort analysis of adult patients with at least 3 fills of droxidopa using the integrated specialty pharmacy services from May 2017 to April 2020. Outcomes included persistence (defined as lack of 60-day gap in treatment), adherence (calculated using pharmacy claims and proportion of days covered [PDC]), and number and type of pharmacist interventions after droxidopa initiation. RESULTS: Of the 83 patients reviewed, 60 patients (72%) were persistent on droxidopa therapy over the study period. The median PDC was 0.98 (interquartile range 0.90-1.00). Over 36 months, the specialty pharmacist performed 60 interventions after droxidopa initiation, most related to dose changes, drug-drug interaction management, and medication reconciliation. CONCLUSION: The development of integrated specialty pharmacy services for patients prescribed droxidopa resulted in high droxidopa persistence and adherence. Interventions from the specialty pharmacist ensured droxidopa remained safe and appropriate for patients.

Local Passive Heat for the Treatment of Hypertension in Autonomic Failure.

Background Supine hypertension affects a majority of patients with autonomic failure; it is associated with end-organ damage and can worsen daytime orthostatic hypotension by inducing pressure diuresis and volume loss during the night. Because sympathetic activation prevents blood pressure (BP) from falling in healthy subjects exposed to heat, we hypothesized that passive heat had a BP-lowering effect in patients with autonomic failure and could be used to treat their supine hypertension. Methods and Results In Protocol 1 (n=22), the acute effects of local heat (40-42°C applied with a heating pad placed over the abdomen for 2 hours) versus sham control were assessed in a randomized crossover fashion. Heat acutely decreased systolic BP by -19±4 mm Hg (versus 3±4 with sham, P<0.001) owing to decreases in stroke volume (-18±5% versus -4±4%, P=0.013 ) and cardiac output (-15±5% versus -2±4%, P=0.013). In Protocol 2 (proof-of-concept overnight study; n=12), we compared the effects of local heat (38°C applied with a water-perfused heating pad placed under the torso from 10 pm to 6 am) versus placebo pill. Heat decreased nighttime systolic BP (maximal change -28±6 versus -2±6 mm Hg, P<0.001). BP returned to baseline by 8 am. The nocturnal systolic BP decrease correlated with a decrease in urinary volume (r=0.57, P=0.072) and an improvement in the morning upright systolic BP (r=-0.76, P=0.007). Conclusions Local heat therapy effectively lowered overnight BP in patients with autonomic failure and supine hypertension and offers a novel approach to treat this condition. Future studies are needed to assess the long-term safety and efficacy in improving nighttime fluid loss and daytime orthostatic hypotension. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02417415 and NCT03042988.

Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure.

Postprandial hypotension is an important clinical condition that predisposes to syncope, falls, angina, and cerebrovascular events. The magnitude of the fall in blood pressure after meals depends on enteric glucose availability. We hypothesized that acarbose, an alpha-glucosidase inhibitor that decreases glucose absorption in the small intestine, would attenuate postprandial hypotension. Acarbose or placebo was given 20 minutes before a standardized meal in 13 patients with postprandial hypotension in the setting of autonomic failure (age: 65+/-2.64 years; body mass index: 25+/-1.08 kg/m(2); supine plasma norepinephrine: 110+/-26.6 pg/mL). Four patients were studied in a single-blind protocol and 9 patients in a double-blind, randomized, crossover fashion. Patients were studied supine, and blood pressure, heart rate, and neuroendocrine parameters were obtained at baseline and for 90 minutes after meal intake. After adjusting for potential confounders, acarbose significantly attenuated the postprandial fall in systolic and diastolic blood pressures by 17 mm Hg (95% CI: 7 to 28; P=0.003) and 9 mm Hg (95% CI: 5 to 14; P=0.001), respectively. Furthermore, acarbose effectively reduced plasma levels of insulin, a known vasodilator, by 11 microU/mL (95% CI: 5 to 18; P=0.001) compared with placebo. After adjusting for insulin levels, the attenuation of postprandial hypotension by acarbose remained significant, indicating that additional mechanisms contribute to this effect. In conclusion, 100 mg of acarbose successfully improved postprandial hypotension in patients with severe autonomic failure. This effect is not explained solely by a reduction in insulin levels.