Evaluation of Calcitonin Utilization in a Tertiary Healthcare - PowerPoint PPT Presentation

Evaluation of Calcitonin Utilization in a Tertiary Healthcare Setting Nicolas LaPlante, PharmD Candidate Bret LaForge, PharmD Candidate Matthew Marston, PharmD, BCPS

Objectives  Review common etiologies and consequences of hypercalcemia  Describe available treatment options for hypercalcemia  Discuss a recent medication use evaluation for injectable calcitonin conducted at Eastern Maine Medical Center 2 Together We’re Stronger

Hypercalcemia presents with a range of clinical sequelae Gastrointestinal Neurological Renal Cardiovascular Skeletal Nausea/Vomiting Confusion/delirium Polyuria/ Shortened QT- Arthralgia Polydipsia Interval Constipation Psychosis Nocturia Bradycardia Osteoporosis Anorexia Muscle weakness Nephrolithiasis Hypertension Abdominal pain Headaches Renal failure Arrhythmia • 90% of cases are caused by either primary hyperparathyroidism or malignancy Marx SJ. N Engl J Med . 2000; 343:1863-75. 3 Together We’re Stronger

Hypercalcemia of Malignancy (HCM) • Affects 44.2% of cancer patients 1 • Majority of HCM is caused by the production of parathyroid hormone- related protein (PTHrP) • Osteolytic metastases (e.g. breast cancer, multiple myeloma) can also raise serum calcium by increasing its release from bone • Multiple myeloma patients can present with asymptomatic pseudohypercalcemia • Carries significant morbidity and mortality, with an inpatient mortality rate of 6.8% 2 1. Mirrakhimov AE. N Am J Med Sci . 2015; 7(11):483-493. 2. Wright JD, Tergaas AI, Ananth CV, et al. Cancer Invest . 2015;33:331-9. 4 Together We’re Stronger

Calcitonin • Endogenous hormone that regulates calcium homeostasis • Reduces bone remodeling and calcium reabsorption by the kidneys • Calcitonin for medical use is derived from salmon and is available as a nasal spray and as a solution for injection • Tachyphylaxis tends to occur within 48-72 hours of use Marx SJ. N Engl J Med . 2000; 343:1863-75. 5 Together We’re Stronger

Calcitonin: Price on the Rise $2,500.00 $2,321.14 $2,006.85 Cost per Vial (USD) $2,000.00 $1,500.00 $1,000.00 $500.00 $69.05 $62.74 $69.29 $0.00 2012 2013 2014 2015 2016 Year 6 Together We’re Stronger

Treatment Options: Comparative Prices Treatment Price per Dose Dosing Frequency (82 kg patient) Calcitonin $2740.19 Every 6-12 hours Zoledronic Acid $72.00 Once; may repeat in 7 days Pamidronate $67.64 Once; may repeat in 7 days Denosumab $2512.80 Once every 4 weeks 7 Together We’re Stronger

Medication Use Evaluation: Methods • Retrospective analysis of all injectible calcitonin orders between the dates of 01/01/2014 and 06/01/2016 Number of calcitonin orders: 68 Patients who received calcitonin: 32 (47%) 8 Together We’re Stronger

Medication Use Evaluation: Methods • Reviewed patient charts in EMMC’s electronic medical record to determine the indications and durations of calcitonin use Dose Received by Indication Hypercalcemia OVCF* Osteoporosis *OVCF = osteoporosis vertebral compression fracture 9 Together We’re Stronger

Results: Treatment Duration 30 25 20 Osteoporosis 15 OVCF 10 Hypercalcemia 5 0 48 hours or Greater than Greater than less 48 to 72 hours 72 hours *OVCF = osteoporosis vertebral compression fracture 10 Together We’re Stronger

Cost-Savings Analysis 48-hour restriction $39,480/year 72-hour restriction $32,760/year Indications: • Restrict the use of injectable calcitonin use to hypercalcemia 11 Together We’re Stronger

Treatment of Hypercalcemia Mild Hypercalcemia Saline Hydration Corrected Ca: 10-12 mg/dL IV Bisphosphonates Moderate Hypercalcemia Corrected Ca: 12-14 mg/dL Denosumab Calcitonin Severe Hypercalcemia Corrected Ca: > 14 mg/dL Dialysis *Any patients with moderate hypercalcemia who are symptomatic should be treated as severe cases 12 Together We’re Stronger

Ionized Calcium Levels • Our lab reports ionized calcium based on whole blood samples rather than spun-down plasma • This leads to discrepancies between our reference ranges and those found in literature Serum Corrected Calcium / Ical Correlation 2.5 2 y = 0.1055x + 0.3044 Ionized Calcium R² = 0.6775 1.5 P < 0.00001 1 Linear Correlation 0.5 0 8 9 10 11 12 13 14 15 16 Corrected Serum Calcium 13 Together We’re Stronger

Summary  Injectable Calcitonin has an important role in the treatment of hypercalcemia, but should be used with discretion due to rising prices  Calcitonin provides a rapid response while bisphosphonates begin to take effect, but tachyphylaxis begins to develop after 48-72 hours  Through an MUE conducted at Eastern Maine Medical Center, we discovered that a potential $32,760 per year could be saved by: 1. Restricting the duration of use for IV calcitonin to 72 hours 2. Limiting its use to severe hypercalcemia or symptomatic moderate hypercalcemia  $39,480 could be saved if use was restricted to 48 hours 14 Together We’re Stronger

Acknowledgements  Eastern Maine Medical Center  Matthew Marston, PharmD, BCPS  Northern New England Clinical Oncology Society 15 Together We’re Stronger

Evaluation of Calcitonin Utilization in a Tertiary Healthcare Setting Nicolas LaPlante, nlaplante@une.edu Bret LaForge, laforgeb@husson.edu Matthew Marston, mjmarston@emhs.org

References 1. Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med . 2000; 343:1863-75. 2. Mirrakhimov AE. Hypercalcemia of malignancy: An update on pathogenesis and management. N Am J Med Sci . 2015; 7(11):483-493. 3. Wright JD, Tergaas AI, Ananth CV, et al. Quality and Outcomes of Treatment of Hypercalcemia of Malignancy. Cancer Invest . 2015;33:331-9. 4. Laroche M, Cantogrel S, Jamard B. Comparison of the analgesic efficacy of pamidronate and synthetic human calcitonin in osteoporotic vertebral fractures: a double-blind controlled study. Clin Rheumatol. 2006;25:683-686. 5. U.S. Food and Drug Administration. Background document for meeting of Advisory Committee for reproductive health drugs and drug safety and risk management advisory committee. March 5, 2013. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealt hDrugsAdvisoryCommittee/UCM34177 9.pdf 6. Ralston SH. Medical management of hypercalcemia. Br J Clin Pharmacol. 1992;34:11-20 7. Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials. Osteoporos Int. 2005;16:1281–1290. 8. Wells G, Chernoff J, Gilligan JP, Krause DS. Does salmon calcitonin cause cancer? A review and meta- analysis. Osteoporos Int . 2016;27:13–19. 17 Together We’re Stronger