In This Issue Benralizumab for Severe Eosinophilic Asthma Buprenorphine Extended-Release Depot for From the Department of Pharmacy Opioid Use Disorder July/August Issue 2018 Volume 6, Issue 4 Formulary Update FDA Medication Safety Alert: Risk of VTE with TestBenralizumab for Severe Eosinophilic Asthma osterone By: James Blackmer, Pharm.D., MPA Background: Eosinophilic asthma is subunit of the human interleukin-5 re- Marcia J. Wyman, Pharm.D., BCPS characterized by increased numbers of ceptor (IL-5Rα). 1,5 The IL-5Rα receptor Drug Information Pharmacist Editor circulating and airway eosinophils, ac- is expressed on the surface of eosino- companied by more frequent asthma phils. By binding to this receptor, Mandy C. Leonard, Pharm.D., BCPS exacerbations and declines in lung func- benralizumab reduces the number System Director, Drug Use Policy and tion. 1 This form of severe asthma typi- of eosinophils by causing apotosis Formulary Management Editor cally affects less than 5% of the total through a process called antibody- cases of adult-onset asthma. 2 Mepoli- dependent cell-mediated cytotoxicity Meghan K. Lehmann, Pharm.D., BCPS zumab (Nucala ®; GlaxoSmithKline) and (ADCC). Benralizumab differs from the Coordinator, Drug Information Services reslizumab (Cinqair ®; Teva) are mono- other medications in its class by its Drug Information Specialist clonal antibodies approved by the Food speciLicity to the IL-5 receptor. Howev- Editor and Drug Administration (FDA) as er, its exact mechanism of action in the Marigel Constantiner, MSc, BCPS, CGP, CPh add-on therapies for the treatment treatment of eosinophilic asthma has Drug Information Specialist of eosinophilic asthma. 3,4 Benralizumab not been clearly established. 5 Associate Editor (Fasenra TM ; AstraZeneca), a monoclonal Christopher Snyder, B.S., R.Ph. antibody preparation with a unique Key Clinical Trial: Benralizumab’s Drug Information Pharmacist mechanism of action, was FDA- FDA approval was based on a random- Associate Editor approved in November 2017 as add-on ized, double-blind, placebo-controlled maintenance therapy for patients aged trial. Patients (N=220) underwent ran- Brian Hoffmaster, Pharm.D., BCPS ≥ 12 years with severe asthma with an Student Education Pharmacist domization in a 1:1:1 ratio to receive 5 Associate Editor eosinphilic phenotype. either benralizumab 30 mg subcutane- ously every 4 weeks (n=72), benrali- Benjamin Witt, Pharm.D., MBA, BCPS Mechanism of Action: Benralizumab, zumab 30 mg subcutaneously every Drug Information Pharmacist a humanized afucosylated monoclonal Associate Editor (Continued on page 2) antibody, directly binds to the alpha Scott Knoer, MS, Pharm.D., FASHP Chief Pharmacy OfPicer Buprenorphine Extended-Release Depot for Opioid Use Disorder By: Hanjie Mo, Pharm.D. Background: Opioid use disorder and the possibility of misuse. Buprenor- (OUD), characterized by an addiction to phine extended-release depot injection opioids, is a chronic, relapsing disease (Sublocade TM ; Indivior Inc.), a Schedule which adversely affects neurological III Controlled Substance, was approved function. 1 The 2013 National Survey on by the Food and Drug Administration From the Department of Pharmacy Drug Use and Health (NSDUH) indicat- (FDA) in November 2017 for the treat- Drug Information Service ed that 4.5 million Americans abused ment of moderate-to-severe OUD in pa- prescription opioid medications with tients who have initiated treatment (216) 444-6456, option #1 1.9 million diagnosed with OUD. Bu- with a transmucosal buprenorphine- prenorphine and buprenorphine/ containing product followed by dose Comprehensive information about naloxone sublingual and buccal dosage adjustment for a minimum of 7 days. 2,3 medications, biologics, nutrients, forms are often used to treat OUD; po- It must be used as part of a complete and drug therapy tential disadvantages of these agents treatment program that includes coun- are the requirement for daily dosing (Continued on page 3) (Continued from page 1) 4 weeks for the Lirst three doses and then every healthcare professional. It is recommended that the 8 weeks (n=73), or placebo administered every patient be monitored for adverse events after admin- 4 weeks (n=75) for 28 weeks. 1 The primary endpoint istration. Prior to administration, benralizumab may was the percentage reduction in the oral glucocorticoid be warmed to room temperature in its original carton dose from baseline to the Linal dose at the end of the for about 30 minutes; afterwards, it must be given maintenance phase while asthma control was main- within 24 hours. tained. Select secondary endpoints included the annu- Availability and Cost: Benralizumab is available as al asthma exacerbation rate and the forced expiratory a 30 mg/mL single-dose preLilled syringe. 5 The prod- volume in 1 second (FEV 1) before bronchodilation. The uct has an average wholesale price (AWP) of approxi- median reduction from baseline in the Linal oral gluco- mately $5,702 per syringe. 6 Therefore, the cost of corticoid dose was 75% in patients who received ei- 12 months of therapy would be about $40,000. ther of the benralizumab regimens compared to a 25% reduction in the placebo group (P<0.001). In 33% of Formulary Status: The formulary status of benrali- patients who received benralizumab every 4 weeks zumab for the treatment of severe asthma is currently and 37% of patients who received benralizumab every under review by the Cleveland Clinic Health-System 8 weeks, there was a reduction of 90% or more from (CCHS) Pharmacy and Therapeutics Committee. baseline in their Linal oral glucocorticoid dose, com- pared to 12% in the placebo group. The annual asth- References: 1. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P et ma exacerbation rate for the benralizumab every al. Oral glucocorticoid-sparing effect of benralizumab in severe 4 week group and every 8 week group was 55% lower asthma. N Engl J Med. 2017;376:2448-58. (P=0.003) and 70% lower (P<0.001) respectively, 2. Wenzel SE. Eosinphils in asthma-closing the loop or opening the door? N Engl J Med. 2009;360(10):1026-28. compared to the placebo group. The FEV 1 before bron- 3. Nucala [package insert].Philadelphia, PA: GlaxoSmithKline; chodilation at week 20 was signiLicantly higher in both Dec 2017. treatment groups than in the placebo group. However, 4. Cinqair [package insert]. Frazer, PA: Teva Respiratory June by week 28, patients who received benralizumab in 2016. 5. Fasenra™ [package insert]. Wilmington, DE: AstraZeneca; Nov either group did not demonstrate a signiLicant im- 2017. provement in the FEV 1. From these results, the authors 6. Lexicomp Online, Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc; concluded that for patients with severe eosinophilic 2017;Accessed: December 30, 2017. asthma, benralizumab demonstrated a signiLicant re- duction in glucocorticoid use and asthma exacerbation rates, but without a sustained improvement in FEV 1. Safety: Hypersensitivity reactions (e.g., anaphylax- is, angioedema, uticaria, rash) may occur within hours of administration of benralizumab, but in some 5 cases, the reaction may take days to develop. While benralizumab has glucocorticoid-sparing effects, it is important to gradually taper steroids, if appropriate. Due to eosinophilic involvement in the immune re- sponse to parasitic (i.e., helminth) infections, patients should discontinue benralizumab if they become in- fected and do not respond to anti-helminth therapy. The most common adverse reactions were headache (8%), pharyngitis (5%), pyrexia (3%), and hypersensi- tivity reactions (3%). Dosing and Administration: The recommended dose of benralizumab is 30 mg administered subcuta- neously into the upper arm, thigh, or abdomen once every 4 weeks for the Lirst three doses and then once every 8 weeks thereafter. 5 The dose must be given by a 2 (Continued from page 1) seling and psychosocial support. This new long -acting dose increased to 300 mg monthly. There should also formulation, which allows for once-monthly admin- be a minimum of 26 days between doses. Occasional istration by a healthcare professional, may help im- delays in administration for up to 2 weeks is not ex- prove adherence and mitigate misuse. 4 pected to affect treatment efLicacy. No dosage adjust- ments are recommended with renal or mild hepatic Mechanism of Action: Buprenorphine provides an- impairment. However, it is not recommended in mod- algesia by binding with high afLinity mu-opioid recep- erate-to-severe hepatic impairment. tors in the central nervous system. 3,5 It exhibits partial mu-opioid agonist and weak kappa-opioid antagonist Risk Evaluation and Mitigation Strategy (REMS): effects. Buprenorphine’s high afLinity to mu-opioid re- Since serious harm or death may occur from inadvert- ceptors enables it to block other mu-opioid agonists ent intravenous administration, buprenorphine ex- which reduces opioid withdrawal. 6 tended-release depot injection is part of a detailed REMS program and is only available through REMS Key Clinical Trial: Buprenorphine extended-release certiLied pharmacies. 3,5 Key elements of this program depot injection received FDA approval based on a ran- are summarized in the Buprenorphine Extended- domized, double-blind, placebo-controlled, 24-week Release Injection (Sublocade TM ) document in the REMS trial that included 504 treatment-seeking adults with section of the CCHS Pharmacy SharePoint site. moderate-to-severe OUD. 3,7 Prior to the Lirst dose of buprenorphine extended-release depot injection, pa- Availability and Cost: Buprenorphine extended- tients were initiated on sublingual Lilm buprenor- release depot injections are available as a single-dose, phine/naloxone to control cravings and withdrawal preLilled syringe with safety needle in the following symptoms. Afterwards they were randomized to the doses: 100 mg/0.5 mL and 300 mg/1.5 mL. 3 following dosing regimens: 1) six once-monthly The average wholesale price (AWP) is $1896 per 300 mg doses of buprenorphine extended-release de- 100 mg syringe and $1264 per 300 mg syringe. pot injection (n=201), 2) two once-monthly 300 mg with an estimated yearly cost of about $22,000.