Pulmonary and Critical Care Medication Update 2020 Mark Malesker, Pharm.D., FCCP, FCCP, FCCM, FASHP, BCPS Professor of Pharmacy Practice and Medicine Creighton University 16th Annual Pulmonary, Critical Care, and Sleep Medicine Conference 2020 1 Faculty Disclosure 2 Mark A. Malesker, Pharm.D. Dr. Malesker has listed no financial interest/arrangement that would be considered a conflict of interest 2 1 Audience Question #1 3 How many new novel medications were FDA approved in 2019 ? A. 22 B. 39 C. 48 D. 59 3 Audience Question #2 4 What is the dose for budesonide/glycopyrrolate/formoterol (Breztri Aerosphere) ? A. One inhalation daily B. One inhalation twice daily C. Two inhalations daily D. Two inhalations twice daily 4 2 Audience Question #3 5 What is the indication for lefamulin (Xenleta) ? A. Community acquired pneumonia B. IBS with constipation C. Partial onset seizures D. Sickle cell disease 5 2019 Drug Approvals 6 The FDA approved 48 novel new drugs and biologics Average of 37 for 2010-2018 First in class (20/48) 42% Drugs with a new and unique mechanism for treating a medical condition Orphan drugs (21/48) 44% Drugs approved for small populations of patients with rare diseases (200,000 or fewer Americans) 6800 rare diseases identified affecting 30 million people Breakthrough (13/48) 27% Drugs for serious or life-threatening diseases for which there is unmet need and for which there is preliminary clinical evidence demonstrating that the drug may result in substantial improvement on a clinically significant endpoint www.fda.gov/drugs 6 3 2019 Drug Approvals 7 Fast track (17/48) 35% Drugs that have potential to address unmet medical needs Priority review (28/48) 58% A drug is given priority review if there is a potential to provide a significant advance in existing medical care, reviewed within eight months (standard 12 months) Accelerated approval (9/48) 19% Early approval based on markers that predict a reasonable benefit, with more testing to confirm clinical benefit after approval www.fda.gov/drugs 7 2019 Drug Approvals 8 First cycle (43/48) 90% Drugs that were approved without additional information that could delay approval and lead to another cycle of review First approved in U.S. (33/48) 69% Drugs that were approved in the United States before approved in another country www.fda.gov/drugs 8 4 Novel Drug Approvals 2010-2019 9 9 2019 Drug Approvals (1) 10 Brand Generic Description Accrufer Ferric maltol Iron deficiency anemia Adakveo Crizanlizumab- Reduce vaso-occlusive crisis tmca in sickle cell disease Aklief Trifarotene Acne vulgaris Balversa Erdafitinib Metastatic bladder cancer Beovu Brolucizumab- Macular degeneration dbll Brukinsa Zanubrutinib Mantle cell lymphoma Cablivi Caplacizumab- Thrombotic thrombocytopenic yhdp purpura www.fda.gov 10 5 2019 Drug Approvals (2) 11 Brand Generic Description Caplyta Lumateperone Schizophrenia Dayvigo Lemborexant Insomnia Egaten Triclabendazole Fascioliasis Enhertu Fam-trastuzumab Metastatic breast cancer deruxtec-an-nxki Evenity Romosozumab- Osteoporosis aqqg ExEm Foam Air polymer-type Dx agent for fallopian tube A assessment Fetroja Cefiderocol Complicated UTI www.fda.gov 11 2019 Drug Approvals (3) 12 Brand Generic Description Fluorodopa F18 Dx agent Parkinsonian syndrome Ga 68 DOTATOC Dx agent neuroendocrine tumors Givlaari Givosiran Acute hepatic porphyria Ibsrela Tenapanor IBS with constipation Inrebic Fedratinib Myelofibrosis Jeuveau Prabotulinumtoxin Lines between eye-brows A-xvfs Mayzent Siponimod Multiple sclerosis Nourianz Istradefylline Parkinson’s “off” episodes www.fda.gov 12 6 2019 Drug Approvals (4) 13 Brand Generic Description Nubeqa Darolutamide Prostate cancer Oxbryta Voxelotor Sickle cell disease Padcev Enfortumab- Refractory bladder cancer vedotin-ejfv Piqray Alpelisib Metastatic breast cancer Polivy Polatuzumab- Large B-cell lymphoma vedotin-piiq Pretomanid Resistant tuberculosis Reblozyl Luspatercept- Anemia associated with beta aamt thalessemia www.fda.gov 13 2019 Drug Approvals (5) 14 Brand Generic Description Recarbrio Imipenem, Complicated UTIs and cilastatin complicated intra-abdominal relebactam infections Reyvow Lasmiditan Migraine w/out aura Rinvoq Upadacitinib Rheumatoid arthritis Rozlytrek Entrectinib Non-small cell lung cancer Scenesse Afamelanotide Erythropoietic protoporphyria Skyrizi Risankizumab- Plaque psoriasis rzaa Spravato Esketamine Nasal spray for depression Sunosi Solriamfetol Narcolepsy or OSA www.fda.gov 14 7 2019 Drug Approvals (6) 15 Brand Generic Description TissueBlue Brilliant blue G Dye used in eye surgery Trikafta Elexacaftor, Cystic fibrosis tezacaftor, ivacaftor Turalio Pexidartinib Giant cell tumor Ubrelvy Ubrogepant Migraine Vumerity Diroximel Multiplesclerosis Vyleesi Bremelanotide Hypoactive sexual desire in premenopausal women Vyndaqel Tafamidis Amyloidosis meglumine www.fda.gov 15 2019 Drug Approvals (7) 16 Brand Generic Description Vyondys 53 Golodirsen Duchenne muscular dystrophy Wakix Pitolisant Narcolepsy Xcopri Cenobamate Partial-onset seizures Xenlata Lefamulin CABP Xpovio Selinexor Multiple myeloma Zulresso Brexanolone Postpartum depression www.fda.gov 16 8 2019 New Indications 17 Brand Generic Description Dupixent Dupilumab Moderate to severe asthma with an eosinophilic phenotype Ofev Nintedanib Interstitial lung disease associated with systemic sclerosis or scleroderma Symdeko Tezacaftor, Age 6 and older with cystic ivacaftor, fibrosis ivacaftor www.fda.gov 17 2019 New Formulations (1) 18 Brand Generic Description Avaclyr Acyclovir Ophthalmic ointment for acute herpetic keratitis Baqsimi Glucagon Nasal powder for severe hypoglycemia Biorphen Phenylephrine Anesthesia-induced hypotension Conjupri Levamlodipine Isomer of amlodipine Duaklir Aclidinium/ LAMA/LABA inhaler Pressair formoterol Myxredlin Short-acting human 100 units/100 mL insulin in 0.9% sodium chloride www.fda.gov 18 9 2019 New Formulations (2) 19 Brand Generic Description Nayzilam Midazolam Nasal spray Quzyttir Cetirizine Injection for urticaria Secuado Asenapine Transdermal patch Zykadia Ceritinib Tablet formulation www.fda.gov 19 2020 Drug Approvals (1) 20 Brand Generic Description Anjeso Meloxicam injection Moderate to severe pain Artesunate Artesunate IV formulation for initial treatment of malaria in adults and children Barhemsys Amisulpride Prevention of post-op N/V Breztri Budesonide/ ICS/LAMA/LABA for COPD Aerosphere glycopyrrolate/ Formoterol Brilinta Ticagrelor Risk reduction for CAD patients who have not had MI or stroke Byfavo Reimazolam Procedural sedation Elyxyb Celecoxib Oral solution for migraine Gimoti Metoclopramide Nasal spray for gastroparesis www.fda.gov 20 10 2020 Drug Approvals (2) 21 Brand Generic Description Ofev Nintedanib Chronic fibrosing ILDs with a progressive phenotype Olinvyk Oliceridine IV opioid for moderate to severe pain Recarbrio Imipenem/ New indication for hospital-acquired cilastatin/ bacterial pneumonia and ventilator- relebactam associated bacterial pneumonia Valtoco Diazepam Nasal spray formulation Xywav Oxybate mixed salts New mixed-salt oxybate for (calcium, magnesium, narcolepsy, 92% lower sodium potassium, sodium) content Trelegy Ellipta Fluticasone/ Label expanded to include asthma umeclidinium/ vilanterol www.fda.gov 21 Midazolam Nasal Spray (Nayzilam) 22 Indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy > 12 years Untreated seizure clusters can increase the risk of physical injury, neurological damage, prolonged seizures, and status epilepticus Tmax = 17.3 minutes Schedule IV controlled substance, packaged as single-use treatment that can be carried with a patient Two doses of 5 mg in clinical studies, 10 minutes apart Side effects include somnolence, headache, nasal discomfort, throat irritation, rhinorrhea https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-NAYZILAM-midazolam-nasal-spray 22 11 Diazepam (Valtoco) 23 Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy > 6 years Tmax = 1.5 hours Nasal spray dose is 0.2 mg/kg or 0.3 mg/kg depending upon patient’s age and weight https://www.valtoco.com/ 23 Diazepam (Valtoco) 24 Second Dose (if needed) A second dose, when required, may be administered after at least 4 hours after the initial dose. If the second dose is to be administered, use a new blister pack Maximum Dosage and Treatment Frequency Do not use more than 2 doses to treat a single episode It is recommended that VALTOCO be used to treat no more than one episode every five days and no more than five episodes per month Available in 5 mg, 7.5 mg, and 10 mg strengths, each nasal spray device contains 0.1 mL solution Most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort https://www.valtoco.com/ 24 12 Lemborexant (Dayvigo) 25 Orexin receptor antagonist indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance Inhibits neuropeptides orexin A and B, which promote wakefulness Dose is 5 mg immediately before going to bed, with at least 7 hours before the planned time of awakening In safety studies, 5 mg was not significantly different from placebo in next-day