A Pharmacist-Managed Hydroxyurea Prescribing Protocol Improves Uptake and Optimization Among Patients with Sickle Cell Disease within the Southern Alberta Rare Blood and Bleeding Disorders (SARBBD) Comprehensive Care Program

Introduction: Sickle cell disease (SCD) is associated with major morbidity and mortality and yet many of our patients are not using the available disease modifying medication, hydroxyurea (HU). Furthermore, dose-titration of HU is required in order to achieve the maximum therapeutic benefit. Certain challenges can limit HU acceptance, such as misconceptions about safety, frequency of monitoring, and ease of access (i.e. insurance). Incorporating a pharmacist-managed HU hydroxyurea prescribing protocol into the SARBBD Comprehensive Care Program will help to address many of the barriers responsible for poor HU uptake among SCD patients and improve HU utilization.

Objectives: To improve the uptake and optimization of HU among patients with Sickle Cell Disease within the SARBBD Comprehensive Care Program.

Methods: Commencing in January 2020, clinic pharmacist support of 0.2 full-time equivalents (FTEs) was made available to the SARBBD program, and a pharmacist-led comprehensive HU prescribing protocol was adapted from the current CanHaem and National Heart, Lung, and Blood Institute guidelines. The clinical pharmacist was available for all Sickle Cell Disease clinic appointments, and was responsible for all aspects of HU management, including educating, counselling, and prescribing (titrating and monitoring as outlined in the prescribing protocol). It is worth noting that independent pharmacist prescribing is permitted in Alberta (Alberta College of Pharmacists, 2021).

Patients were initiated on HU at a low dose of 500 mg daily to limit gastrointestinal sensitivities, and then increased to 1000 mg daily after one week. Thereafter the dose was titrated every 2-4 weeks as permitted by the patient's tolerance and laboratory parameters (i.e., CBC, liver and renal function, reticulocyte count) up to their maximum tolerated dose (MTD), defined as the maximum dose that maintains neutrophils ≥ 1.5 x 10 ⁹/L, platelets > 80 x 10 ⁹/L, and hemoglobin > 50 x 10 ⁹/L. Following HU initiation and after every laboratory visit, the clinical pharmacist followed-up with patients via telephone to discuss HU tolerance, adherence, and dosing. Perceived benefits (i.e., pain episodes), medication supply, drug access (insurance), and planning for future follow-ups were also addressed as necessary.

Results: As of January 2020, the SARBBD program provided care to 119 patients with SCD. Of those patients, 7 patients were managed with a transfusion exchange protocol, and therefore were not considered HU candidates. Of the 112 eligible SCD patients, 39 (34.8%) were already on HU therapy, 15 of whom were at MTD (38.4% of HU patients, 13.4% of 112 eligible SCD population). By June 2021 (18 months of pharmacist managed HU), there were 123 eligible SCD patients, of whom 71 were on HU (57.7%), with 37 at MTD (52.1% of HU patients, 30.1% of total eligible SCD population). Every month on average the pharmacist; has 27 interactions (phone, email) with SCD patients, reviews 18 lab reports, initiates HU for 2 patients, and will make over 4 dose adjustments.

A majority of patient interactions involved educating patients on HU, and addressing common misconceptions about HU adverse effects and risks. Further, a significant proportion of HU initiations required pharmacist assistance with insurance authorization. Overall, patient acceptance of the pharmacist-managed HU prescribing was positive. One patient commented, "Working with [the pharmacist] has been great as he diligently has been able to keep a close eye on my blood results while making adjustments to my dosage of HU, without requiring a visit to the doctor. This was great as it didn't tie the doctors up, but also I was able to communicate with [the pharmacist] and get the same information at a convenient time. [The pharmacist] has also been extremely supportive, open and positive while answering questions".

Conclusion: Incorporating a pharmacist into the SARBBD program, as well as implementing a pharmacist-managed HU prescribing protocol has led to improved HU uptake and optimization. In addition, a greater proportion of patients have been able to reach MTD. The most common barriers to HU utilization, such as miseducation, frequency of laboratory monitoring, and medication access, can be overcome with dedicated pharmacist involvement.

Funding: Sickle Cell Disease Association of Canada (SCDAC) grant and Novo Nordisk Investigator Initiated Grant