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2017 New Drug Update

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Financial Disclosures • Mark S. Johnson, Pharm.D., BCPS • Name of commercial interest(s) NEW DRUG UPDATE • Stockholder in Merck and various mutual funds Mark S. Johnson, Pharm.D., BCPS Professor of Pharmacy Practice Director of Postgraduate Education Bernard J. Dunn School of Pharmacy Shenandoah University Objectives FDA Approvals • Identify the new drugs approved by the FDA that are most • 2015 clinically relevant to general practice in 2017 • 45 New Molecular Entities / New Biologics • Discuss relevant indications, efficacy, pharmacokinetics, • 35 New Dosage Forms safety, and dosing of the new drugs • Discuss how the new drugs differ from existing drugs on • 2016 the market • 22 New Molecular Entities / New Biologics • 41 New Dosage Forms • Describe how to best incorporate the new drugs into clinical practice using a case-based format • 2017 to date • 20 New Molecular Entities / 14 New Biologics • 25 New Dosage Forms • 1 Withdrawal Withdrawals • Oxymorphone (Opana ER™)—Endo • Requested by FDA to be withdrawn due to concern of benefits no longer outweighing the risks • First time FDA has taken steps to remove a currently marketed opioid from sale due to the public health consequences of abuse • Post marketing data demonstrated increase in the route of abuse from nasal to injection following reformulation in 2012 (original approval in 2006), intended to make the drug resistant to physical and chemical manipulation for abuse by snorting or injecting • Injection abuse of reformulation associated with HIV, hepatitis C, thrombotic microangiopathy http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm534863.htm 1 Self Assessment Questions 1. Betrixaban (Bevyxxa™) is FDA-approved for which of the following indications? SIGNIFICANT NEW MOLECULAR A. Prophylaxis of venous thromboembolism (VTE) in adult patients ENTITIES/BIOLOGICS hospitalized for an acute medical illness B. Treatment of venous thromboembolism in adult patients hospitalized for acute DVT or PE C. Prophylaxis of stroke in patients with atrial fibrillation 2. The spectrum of antimicrobial activity of delafloxacin (Baxdela™) includes which of the following: A. Pseudomonas aeurginosa B. MRSA C. Enterococcus faecalis D. All of the above Self Assessment Questions Self Assessment Questions 3. Which of the following medications is FDA approved for 5. Sarilumab (Kevzara™) is a new medication for adjunctive treatment to levodopa/carbidopa in patients with rheumatoid arthritis approved as second line therapy. Parkinson’s disease experiencing “off” episodes? What is it’s route of administration? A. Safinamide (Xadago™) A. Oral B. Edaravone (Radicava™) B. Subcutaneous C. Valbenazine (Ingrezza™) C. Intravenous D. Intraarticular 4. Biosimilars are considered to be interchangeable with 6. The new drugs for plaque psoriasis (brodalumab and the reference product. guselkumab) are antagonist of which of the following: True or False A. IL-17 and IL-23 B. IL-4 and IL-6 C. Both inhibit TNF Betrixaban (Bevyxxa™) Cardiovascular Drugs Portola Pharm. • A factor Xa inhibitor indicated for the prophylaxis of venous thromboembolism (VTE) in adult patients hospitalized for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for VTE • First anticoagulant approved for in-hospital and extended-duration VTE prophylaxis in acutely ill medical patients www.drugs.com 2 Betrixaban (Bevyxxa™) Betrixaban (Bevyxxa™) Portola Pharm. Portola Pharm. • Efficacy: APEX • Efficacy and safety: APEX (from package insert) • N=7441 • Prevention of VTE in high-risk acutely ill medical patients • Betrixaban 35-42d vs. enoxaparin 6-14d followed by placebo • Eligible patients: >40y, hospitalized for an acute medical illness, at risk for VTE due to moderate or severe immobility, and had additional risk factors for VTE (≥ 75 years of age, 60-74y with D-dimer ≥ 2 ULN, or 40-59y with D-dimer ≥ 2 ULN and a history of either VTE or cancer; while the APEX Study was ongoing (after 35% enrollment), the study was amended to restrict further enrollment to patients ≥ 75y or with D- dimer values > 2 x ULN) • Expected duration of hospitalization was at least 3d and patients were expected to be moderately or severely immobilized for at least 24h • Causes for hospitalization: heart failure, respiratory failure, infectious disease, rheumatic disease, or ischemic stroke • Major bleeding: betrixaban (0.67%) vs. enoxaparin (0.57%) (p=0.554) • Clinically relevant nonmajor bleeding: betrixaban (2.45%) vs. enoxaparin (1.02%) (p<0.001) Betrixaban (Bevyxxa™) Betrixaban (Bevyxxa™) Portola Pharm. Portola Pharm. • Boxed warning • ADRs • Epidural or spinal hematomas may occur in patients receiving • Major bleeding (GI bleeding, intracranial bleeding, ocular neuraxial anesthesia or undergoing spinal puncture hemorrhage, fatal bleeding): 0.67% • Risk of these events may be increased by use of in-dwelling • Clinically relevant non-major bleeding (mostly mild to moderate and epidural catheters or concomitant use of medical products affecting did not require medical intervention): 2.45% hemostasis • Epistaxis 2%, hematuria 2% • Hematomas may result in long-term or permanent paralysis • Other: nausea/diarrhea 2%, constipation 3%, urinary tract infection • Contraindications 3%, hypertension 2%, headache 2%, hypokalemia 3% • Active pathological bleeding • Severe hypersensitivity reaction to betrixaban Betrixaban (Bevyxxa™) Betrixaban (Bevyxxa™) Portola Pharm. Portola Pharm. • Drug Interactions • Dosing • P-glycoprotein (P-gp) inhibitors (amiodarone, azithromycin, • Initial single dose 160mg by mouth, followed by 80mg once daily by verapamil, ketoconazole, clarithromycin) increase levels of mouth, taken at the same time each day with food for 35 to 42 days betrixaban—need to reduce dose of betrixaban • Severe renal impairment (CrCl 15-29ml/min): 80mg single dose then 40mg daily • Hepatic impairment: use not recommended • Concomitant use of P-glycoprotein (P-gp) inhibitors: 80mg single dose then 40mg daily • Safety and efficacy not established with prosthetic heart valves as has not been studied • Availability/Cost • Capsules: 40 mg and 80 mg • Cost ? 3 Clinical Case Endocrine Drugs • A 76y M is admitted to the hospital for CHF. His past medical history is significant for CHF, HTN, type 2 diabetes, hypercholesterolemia. His home medications included enalapril, carvedilol, furosemide, metformin, aspirin, atorvastatin. NKDA BUN 16 SCr 1 • What would you recommend for VTE prophylaxis in this patient? • What would this patient be a candidate for betrixaban? Abaloparatide Injection (Tymlos™) Abaloparatide Injection (Tymlos™) Radius Health, Inc. Radius Health, Inc. • A synthetic peptide analog of hPTHrP (human parathyroid • Clinical Trials hormone-related protein) for the treatment of postmenopausal • The Phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral women with osteoporosis and high fracture risk (defined as a Endpoints)--randomized, double-blind, placebo-controlled, history of osteoporotic fracture, multiple risk factors for fracture, comparative, multicenter, 18 month international study in 2,463 or patients who have failed or are intolerant to other available postmenopausal women with osteoporosis designed to evaluate osteoporosis therapy) the efficacy and safety of abaloparatide-SC 80 mcg to reduce the risk of vertebral and nonvertebral fractures • Decreased the incidence of new vertebral (86%) and nonvertebral (43%) fractures (absolute risk reductions 3.6% and 2.0%) • Also increased bone mineral density (BMD) • ACTIVExtend, an extension of ACTIVE, enrolled patients who had completed 18 months of abaloparatide-SC or placebo in ACTIVE to receive up to 24 additional months of open-label alendronate • 1st 6 months recently published http://drugstorenews.com/sites/drugstorenews.com/files/field_main_image/2017-04/tymlos.jpg Abaloparatide Injection (Tymlos™) Abaloparatide Injection (Tymlos™) Radius Health, Inc. Radius Health, Inc. • Warning: Risk of Osteosarcoma • ADR’s • Abaloparatide caused a dose-dependent increase in the incidence • Most common adverse reactions (incidence ≥2%): hypercalciuria, of osteosarcoma, a malignant bone tumor, in male and female rats. dizziness, nausea, headache, palpitations, fatigue, upper Unknown if will cause osteosarcoma in humans abdominal pain, vertigo • Not recommended in patients at increased risk for osteosarcoma • Use for more than 2 years not recommended • Precautions • Orthostatic Hypotension: Instruct patients to sit or lie down if symptoms develop after dose administration • Hypercalcemia: Avoid use in patients with pre-existing hypercalcemia and those known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism • Hypercalciuria and Urolithiasis: Monitor urine calcium if preexisting hypercalciuria or active urolithiasis are suspected 4 Abaloparatide Injection (Tymlos™) Clinical Case Radius Health, Inc. • Dosing • A 70yo F with osteoporosis with high fracture risk has • Recommended dose is 80 mcg subcutaneously once daily into periumbilical region of abdomen been intolerant to bisphosphonates for osteoporosis. Her • Patients should receive supplemental calcium and vitamin D if dietary physician has prescribed abaloparatide injection intake is inadequate (Tymlos™) for this patient. NKDA • Administer initially where the patient can sit or lie down in case symptoms of orthostatic hypotension occur • The physician wants to know what contraindications and • Availability precautions
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