Rachel Kim, PharmD Candidate Cone Health Family Medicine News You Can Use… Rachel Kim, PharmD Candidate Pete Koval, PharmD Cone Health Family Medicine June, 2017

FDA Approval TymlosTM (abaloparatide) Class: Parathyroid Hormone Analog Second Agent in Class (Forteo® – teriparatide) Treatment of osteoporosis Dose: SubQ 80 mcg once daily Duration: 24 months total (Forteo combined) ADE: Increased uric acid, hypercalciuria, antibody development, erythema at injection site, tachycardia Patient should take calcium and vitamin D if dietary intake is inadequate. Inject into periumbilical region. Warnings: 1. Orthostatic hypotension- instruct patients to sit or lie down when administering 2. Hypercalcemia: Avoid use in pre-existing hypercalcemia, underlying hypercalcemic disorder such as primary hyperparathyroidism 3. Hypercalcemia and urolithiasis: monitor urine calcium if preexisting hypercalciuria or active urolithiasis are suspected https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208743lbl.pdf http://tymlos.com/

FDA Approval RadicavaTM (edaravone) Class: Free radical scavenger For the treatment of amyotrophic lateral sclerosis (ALS) Dose: 60 mg IV over 60 minutes daily Two weeks of treatment, followed by a 14 day drug free period ADE: contusion, gait disturbance, and headache Dosing: Initial treatment cycle: Daily dosing for 14 days followed by a 14 day drug-free period. Subsequent treatment cycles: daily dosing for 10 days out of the 14 day periods, followed by 14 –day drug free periods. 60 mg is 200 mL. Contains sodium bisulfite. Sulfite allergic reactions* https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209176lbl.pdf

NSAIDs and MI NSAIDS increase risk of acute myocardial infarction Meta-analysis of 446,763 individuals Increased risk of MI with consumption of NSAIDs for one week, one month, or more than a month Greater risk of MI during the first month of use and with higher doses After 1 week of NSAIDs, the probability of increased MI risk was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib.  BMJ 2017; 357:j1909

Invokana: Black Box Warning Invokana® (canagliflozin) causes an increased risk of leg and foot amputations Prior to starting, consider factors that may predispose to amputations: Prior amputation Peripheral vascular disease Neuropathy Diabetic foot ulcers Based on two large clinical trials: 1. The CANVAS 2. CANVAS-R These trials showed that leg and foot amputations occurred about twice as often in patients treated with Invokana compared to patients treated with placebo (inactive treatment). The CANVAS trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to: 5.9 out of every 1,000 patients treated with canagliflozin 2.8 out of every 1,000 patients treated with placebo The CANVAS-R trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to: 7.5 out of every 1,000 patients treated with canagliflozin 4.2 out of every 1,000 patients treated with placebo https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm

New FDA Indication Approval Actemra® (tocilizumab) On May 22nd, FDA has expanded the approved to include treatment of adults with giant cell arteritis (temporal ateritis) First FDA approval agent Dosing: 162 mg weekly +/- tapering steroid Tx Also approved for moderate to severe active rheumatoid arthritis No exact dose for GCA is released The decision follows consideration of data from a double-blind, placebo-controlled trial that included 251 patients with giant cell arteritis. A greater proportion of patients who received subcutaneous tocilizumab with standardized prednisone regimens achieved sustained remission from week 12 through week 52 — the primary efficacy endpoint — compared with those who received placebo with standardized prednisone regimens. The researchers defined sustained remission as the absence of giant cell arteritis symptoms, normalization of inflammatory laboratory tests, and tapering the use of prednisone. The cumulative prednisone dose was lower in patients who received tocilizumab than in those who received placebo. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm559791.htm?platform=hootsuite

FDA Approval KevzaraTM (sarilumab) Class: human interleukin-17 receptor A antagonist Indication: moderate to severe RA with inadequate response or intolerance to DMARDs Dose: SubQ 200 mg once every 2 weeks Warning: 1. Increased risk for developing serious infecitons that may lead to hospitalization or death. 2. Test for Tb before treatment with Kevzara. https://www.thepharmaletter.com/article/fda-approval-for-kevzara-in-rheumatoid-arthritis