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Disclosure  Melinda C. Joyce declares that she has nothing to disclose for this presentation.

KANPNM Conference April 23, 2021

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Objectives Annual New Drug Approvals: 2010-2020

1. Discuss new medications that have been recently approved by the FDA, focusing on indications for use, potential adverse reactions, and contraindications

2. Evaluate the place in therapy of new medications compared to existing therapies

3. Review safety concerns for the new medications and how these concerns may impact their use

www.fda/gov/drugs Center for Drug Evaluation and Research 3 4

Novel Drugs: 2020 First-In-Class

Cardiology Women's Health GI  39.6% of those approved in 2020 were identified as First-In-Class Dermatology  A new and unique mechanism of action for treating a medical condition  Mechanism of action is often different than what is currently available Infectious Disease Oncology  Noteworthy First-In-Class are those agents that are likely to quickly make a positive impact on care  Fostemsavir (Rukobia) – A new type of oral antiretroviral medication for adults living with HIV-1 whose HIV-1 cannot be successfully treated with currently available agents Neurology  Remdesivir (Veklury) – the first medication in the United States specifically indicated for treatment of the SAR-CoV-2 virus

Rare Diseases 5 6

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Drugs for Cancer Drugs for Rare Diseases

 39.6% of the new drugs are for the treatment of cancer  58.5% were approved to treat rare or “orphan” diseases that affect 200,000 or  Two new treatments were approved for small cell lung cancer and nine to fewer Americans treat various forms of non-small cell lung cancer  There were new advances in the treatment of metastatic breast cancer,  Berotralstat (Orladeyo) – oral agent to prevent attacks of hereditary metastatic colorectal cancer, and metastatic prostate cancer angioedema  Drug therapy for other types of cancer:  Nifurtimox (Lampit) – first therapy to treat pediatric patients with Chagas  Thyroid cancer Disease, a rare parasitic disease  Prostate cancer  Bladder cancer  If untreated, could progress to heart failure  Multiple myeloma  Risdiplam (Evrysdi) – oral solution to treat patients two months of age and older  Neurofibromatosis type 1 with spinal muscular atrophy  New advances in detections of certain cancers were also approved  Rare and often fatal genetic disease affecting muscle strength and movement

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Generic Name Trade Name Brief Indication Dosage Form Clascoterone Winlevi Acne Cream Abametapir Xeglyze Headlice Lotion Copper Cu 64** Detectnet Detect certain types of neuroendocrine tumors Injection Decitabine and Inqovi Adult patients with myelodysplastic syndromes Tablet Amisulpride Barhemsys Prevention of post-surgical nausea and vomiting Injection Cedazuridine** Ansuvimab-zykl** Ebanga Ebola Injection Eptinezumab-jjmr Vyepti Prevention of migraines in adults Injection Artesunate** Artesunate Severemalaria Injection Flortaucipir F18 Tauvid Diagnostic agent for patients with Alzheimer’s Injection Disease Atoltivimab/ Inmazeb Ebola Injection Maftivimab/ Fluoroestradiol F18 Cerianna Diagnostic imaging agents for certain patients with Injection Odesivimab** breast cancer Avapritinib** Ayvakit Unresectable or metastatic gastrointestinal stromal Tablet Fostemsavir Rukobia HIV disease Tablet tumor (GIST) Gallium 68 PSMA-11 Gallium 68 Detection and localization of prostate cancer Injection Belantamab Blenrep Multiple myeloma Injection PSMA-11 mafodotin-blmf** Inebilizumab-cdon** Uplizna Neuromyelitisopticaspectrum disorder Injection Bempedoic acid Nexletol Dyslipidemia Tablet Isatuximab** Sarclisa Refractorymultiple myeloma Injection Berotralstat** Orladeyo Prevention of hereditary angioedema attacks Capsule Lactitol Pizensy Chronic idiopathicconstipation in adults Powderfor Capmatinib** Tabrecta Metastatic non-small cell lung cancer Tablet solution

** denotes orphan drug ** denotes orphan drug 9 10

Lonafarnib** Zokinvy To reduce death from rare conditions related to Capsule premature aging Pralsetinib** Gavreto Non-small cell lung cancer Capsule Lumasiran** Oxlumo Hyperoxaluriatype 1 Injection Relugolix Orgovyx Advancedprostate cancer Tablet Lurbinectedin** Zepzelca Metastatic small cell lung cancer Injection Remdesivir Veklury COVID-19 Injection

Margetuximab-cmkb Margenza HER2+ breast cancer Injection Remimazolam Byfavo Procedural sedation Injection

Naxitamab-gqgk** Danyelza High-risk refractory or relapsed neuroblastoma Injection Rimegepant Nurtec ODT Acutetreatment of migraine in adults Disintegrating tablet Nifurtimox** Lampit Chagasdiseasein pediatric patients Tablet Ripretinib** Qinlock Advanced gastrointestinal stromal tumors (GIST) Tablet Oliceridine Olinvyk Severeacutepain in adults Injection Risdiplam** Evrysdi Spinalmuscular atrophy Powder for Opicapone Ongentys Patients with Parkinson’s disease experiencing “off” Capsule solution episodes Sacituzumab Trodelvy Adult patients with metastatic triple-negative breast Injection Osilodrostat** Isturisa Patients with Cushing’s disease who either cannot Tablet govitecan-hziy cancer who have failed previous therapies undergo pituitary gland surgery or have had surgery Satralizumab- Enspryng Neuromyelitisopticaspectrum disorder Injection but still have the disease mwge** Ozanimod Zeposia Relapsingforms of multiple sclerosis Capsule Selpercatinib** Retevmo Metastatic non-small cell lung cancer and thyroid Capsule cancers Pemigatinib** Pemazyre Locally advanced or metastatic cholangiocarcinoma Tablet

** denotes orphan drug ** denotes orphan drug 11 12

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Selumetinib** Koselugo Neurofibromatosistype 1 Capsule

Setmelanotide** Imcivree Obesity and control of hunger associated with Injection proopiomelanocortin deficiency Notable Patent Expirations in 2020 Somapacitan-beco Sogroya Growthhormone deficiency Injection Tafasitamab-cxix** Monjuvi Relapsed or refractory diffuse large B-cell Injection  Chantix (Varencline) lymphoma Tazemetostat** Tazverik Metastatic or locally advanced epitheliod sarcoma Tablet  Dulera Inhaler (Mometasone/ Formoterol)

Teprotumumab- Tepezza Thyroid eye disease Injection  Enbrel (Etanercept) trbw**  Forteo (Teriparatide) Tirbanibulin Klisyri Actinic keratosis of the face or scalp Ointment Triheptanoin** Dojolvi Molecularly long-chainfatty acid disorders Liquid Tucatinib** Tukysa Advanced unresectable or metastatic HER2+ breast Tablet cancer Vibegron Gemtesa Overactive bldder Tablet Viltolarsen** Viltepso Duchennemuscular dystrophy Injection

** denotes orphan drug 13 14

Notable Withdrawals in 2020  Lorcaserin (Belviq; Belviq XR)  Medication for weight loss  Was removed by the manufacturer due to safety concerns regarding an increased chance of cancer, including pancreatic, colorectal, and lung  Ranitidine (Zantac)  Medication for GI disorders, such as ulcers and gastro-esophageal reflux disease  Withdrawal of all products – prescription and OTC, brand and generic  Safety concerns of the contaminant N-Nitrosodimethylamine (NDMA) found in the products  Included in a category of possible human carcinogens

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Heterozygous Familial Dyslipidemia Hypercholesterolemia (HeFH) • Dyslipidemias (one or more abnormalities of blood lipids) produce  Heterozygous familial hypercholesterolemia (HeFH) is a monogenic atherosclerosis, which in turn produces coronary heart disease (CHD) and coronary artery disease (CAD) disorder that affects about 1 in 500 people • Puts patients at risk for the development of AMI and stroke  HeFH is characterized by: • Successful management of dyslipidemias alters the natural course of  Cholesterol deposits affecting the corneas, eyelids, and extensor tendons atherosclerosis and can prevent CHD  Elevated plasma concentrations of LDL cholesterol • About 48.6% of adults over the age of 40 would be eligible for statin therapy  Accelerated vascular disease, especially CAD based on the latest ACC/AHA guidelines • Fewer than 1 out of every 3 adults with high LDL cholesterol has the condition under control

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Adenosine Triphosphate-Citrate Bempedoic Acid Lyase (ACL) Inhibitor  Indications:  First new agent for the treatment of dyslipemias in many years  An ACL-Inhibitor used in conjunction with diet and maximally tolerated statin  Adenosine triphosphate-citrate lyase (ACL) is an enzyme upstream of 3- therapy for the treatment of adults with heterozygous familial hypercholesterolemia hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in the or established atherosclerotic cardiovascular disease who require additional cholesterol biosynthesis pathway lowering of LDL-C  Inhibition of ACL results in decreased cholesterol synthesis in the liver and  Efficacy: lowers LDL-C in blood via regulation of low-density lipoprotein receptors  Lowers LDL by about 15-17%  Low-density lipoprotein receptors helps to move LDL-C out of the blood  With the addition of the ezetimibe and the maximally tolerated statin, can see LDL levels decreased by 36%  Mechanism of Action:  An ACL-Inhibitor

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Bempedoic Acid Bempedoic Acid

 Warnings/ Limitations:  Drug Interactions:  Should be used cautiously with simvastatin or pravastatin as the bempedoic acid may  Avoid concomitant simvastatin > 20 mg or pravastatin > 40 mg increase the serum concentrations of these statins and increase the risk of myopathy  Increased risk for tendon rupture with corticosteroids or fluoroquinolone antibiotics  May cause fetal harm and should be discontinued  Breastfeeding not recommended  Availability:  Hyperuricemia, potentially leading to gout  180 mg tablets  Tendonitis  Dosage:  Adverse Effects:  180 mg once daily with maximally tolerated statin  Upper respiratory tract infections  Cost:  Back pain  Muscle spasms  $13.20/tablet  Extremity pain  Also available as a combination agent  Elevated hepatic enzymes  Bempedoic acid/ ezetimibe (180 mg/10 mg) once daily

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Migraine • 25% of women and 8% of men in the United States have had a migraine headache  Prevalence is highest between age 25 – 55 years • Headache lasting from 4 to 72 hours • At least two of the following: • Unilateral location • Pulsating quality • Moderate or severe intensity • Aggravation by routine physical activity • At least one of the following: • Nausea and/or vomiting • Photophobia and phonophobia • At least five attacks fulfilling these criteria with no evidence of organic disease

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Calcitonin Gene-Related Peptide Etiology of Migraine Headache (CGRP) Receptor Antagonists  May be due to both vascular changes and neuronal etiology  Vascular component - constriction of blood vessels followed by reflex dilation –  Calcitonin gene-related peptide (CGRP) is a potent endogenous vasodilator the dilation is what leads to the headache and pain signal-enhancing neuromodulator  Neuronal component – depressed neuronal activity spreads across the brain  CGRP receptor is believed to be released during a migraine and transmits and the headache occurs due to an inflammatory response due to signals that can cause incapacitating pain compensatory over-activity in certain nerves leading to release of substance P  By blocking the CGRP receptor, the drugs are thought to inhibit the effect of and other vasoactive substances the neuropeptide responsible for pain and sensitization associated with  Genetic component – familial tendencies migraine  Triggers  Some of the agents in this class are for preventive treatment while there are  Food triggers – cheese; wine; alcohol; chocolate; caffeine two that are approved for acute treatment of migraine  Behavior triggers – stress; sleep deprivation or excess; skipped meals; hormonal  Rimegepant (Nurtec ODT) changes  Ubrogepant (Ubrelvy)  Environmental triggers – glare or flickering lights; noise; odors; weather changes

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Calcitonin Gene-Related Peptide Rimegepant (Nurtec ODT) (CGRP) Receptor Antagonists  Indications:  Should be considered for patients that have failed treatment with two  For the acute treatment of migraine with or without aura in adults different triptans or cannot tolerate a triptan  Efficacy:  Both agents begin to reduce migraine pain within 60 minutes and MBS- most  Statistically significant effects of rimegepant as compared to placebo bothersome symptoms (the absence of the self-identified MBS, such as  Pain relief, as defined as a reduction in migraine pain from moderate to severe intensity to photophobia, phonophobia, or nausea) mild or none at 2 hours  These agents should be used only for acute treatment as there is no data on  59.3% vs 43.3% their benefit for prophylaxis  Freedom of most bothersome symptoms, such as nausea, photophobia, or phonophobia  35.1% vs 26.8%  Sustained pain freedom at 2 to 48 hours

 13.5% vs 5.4%  Use of rescue medications within 24 hours

 14.2% vs 29.2%

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Rimegepant Rimegepant

 Mechanism of Action:  Drug Interactions:  Calcitonin gene-related peptide receptor antagonist  Avoid strong CYP3A4 Inhibitors, as the concentration of the rimegepant may  Warnings/ Limitations: be increased  Itraconazole  Medication is for an acute migraine and not indicated for preventive treatment  For moderate CYP3A4 Inhibitors and P-gp inhibitors, may need to decrease  No adequate data to evaluate risk in pregnancy or breastfeeding the dose of the rimegepant  Safety and efficacy in pediatric patients has not been established  Avoid strong CYP3A4 Inducers, as the concentration of the rimegepant may  Adverse Effects: be decreased  Nausea  Rifampin  Drowsiness  Hypersensitivity reactions, such as dyspnea and rash (rare)

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Rimegepant Preventive Therapy for Migraines  Availability:  Will not “cure” migraines but can:  75 mg tablet  Reduce migraine frequency, severity, and disability  Dosage:  Improve response to acute therapy  It is an orally disintegrating tablet  Reduce reliance on poorly tolerated, ineffective or unwanted acute treatments  Patients should be instructed to use dry hands when opening the blister pack and the tablets should not be stored outside of the blister pack  Improve quality of life  75 mg as a single dose  Prevent headache  May give a second dose after 24 hours  Avoid escalation of headache medication use  If patient is taking a moderate CYP3A4 inhibitor a second dose should be avoided within 48 hours  Reduce headache-related distress and psychological symptoms  Should not be used in patients with severe hepatic impairment  Must have an adequate time to demonstrate benefit  Cost:  Beneficial result is noted by a 50% reduction in monthly migraine  $134/tablet (average wholesale price) occurrence

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Calcitonin Gene-Related Peptide Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists (CGRP) Receptor Antagonists  Data has shown that calcitonin gene-related peptide (CGRP) is released  Generally prevents one or two more episodic migraines per month than during acute migraine attacks that is associated with transmission of pain placebo and can decrease migraine days per month by at least 50% in impulses almost a quarter of patients  There are currently two CGRP antagonists that have been approved for  May be best for those patients with adherence issues, side effects, poor acute treatment and four CGRP antagonists that have been approved as response, or drug interaction concerns with oral preventive agents preventive agents for migraine  May be given in combination with other oral preventive agents  Eptinezumab (Vyepti)  Erenumab (Aimovig)  Fremanezumab (Ajovy)  Galcanezumab (Emgality)

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Eptinezumab (Vyepti) Eptinezumab  Warnings/ Limitations:  Indication:  Is an IV infusion  Preventive treatment of migraine in adults  Should not be used in patients with a history of angioedema  Efficacy:  Patients should be monitored for signs and symptoms of hypersensitivity  Clinical trials showed reduction in migraine days of at least 75% and sustained reactions with administration migraine improvement through 6 months as compared to placebo  Currently, not indicated in pregnancy  For 75% reduction, 22.2% vs 16.2%  Sustained 75% reduction for 3 months, 26.7% vs 15%  Adverse Effects:  Mechanism of Action:  Nasopharyngitis  Human immunoglobulin G2 monoclonal antibody that has high affinity binding to the  Nausea calcitonin gene-related peptide receptor (CGRP)  Fatigue  By blocking the CGRP receptor, the drug is thought to inhibit the effect of the  Hypersensitivity reactions (1-2%) neuropeptide responsible for pain and sensitization associated with migraine

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CGRP Antagonists for Prevention Eptinezumab Eptinezumab Erenumab Fremanezumab Galcanezumab

 Drug Interactions: Mechanism of Binds to the CGRP Selectively targets and Binds to the CGRP Binds to the CGRP Action ligand and blocks blocks the CGRP receptor ligand and blocks its ligand and blocks its  No known drug interactions its binding to the binding to the receptor binding to the receptor  Availability: receptor  100 mg vials Dosage/ 100 mg IV every 3 70 mg subcutaneously 225 mg subcutaneously Loading dose of 240 mg Administration months; May once monthly; may be once monthly or subcutaneously followed  Dosage: increase to 300 mg increased to 140 mg once 675 mg every 3 months by 120 mg once monthly  100 mg IV, infused over 30 minutes every 3 months every 3 months monthly

 Dose may be increased to 300 mg IV every 3 months if indicated Cost 100 mg dose: 70 mg auto-injector: 225 mg pre-filled pen: 120 mg pre-filled pen:  Cost: $1794.00 $600.00 $400.00 $600.00  $1794/ 100 mg vial Notes Should be infused The needle shield and cap The 675 mg dose is The loading dose is over 30 minutes of the pen contain natural given by three given by two rubber, which could be of consecutive injections of consecutive injections of concern for those that are 225 mg 120 mg sensitive to latex

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Acute Pain Oliceridine  Indications:  Each year, approximately 45 million hospital patients in the United States receive an IV opioid to treat acute pain  For the treatment of acute pain requiring IV administration when alternative agents are either not effective or not tolerated  The concern of opioid use disorder is significant as along with other  Medication is a CII considerations, such as elderly, obese, or renally-impaired patients  Efficacy:  There have been few new agents approved for the treatment of acute pain in  The drug was studied in hard and soft-tissue surgical cases and was found to be hospitalized patients more effective than placebo  Was also studied against morphine with similar results for pain management  1 mg oliceridine is roughly equivalent to morphine 5 mg  In animal studies, retained analgesic efficacy of morphine with lower rates of respiratory depression and GI adverse effects

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Oliceridine Oliceridine  Mechanism of Action:  Warnings/ Limitations:  Several boxed warnings  Acts as a complete opioid agonist that is relatively selective for the mu-opioid  Addiction, Abuse, and Misuse receptor. It is the first mu-opioid receptor G protein pathway selective modulator  It is an opioid and a patient’s potential risk for addiction should be assessed before prescribing  Patients should be monitored regularly for the development of potential behaviors associated with (μGPS). substance use disorder  G-protein activation is thought to be the principal mediator of opioid-induced analgesia  Life-Threatening Respiratory Depression  Monitor closely during administration  Neonatal Opioid Withdrawal Syndrome  Should not be used in pregnancy unless there are no alternatives  Monitor infant for signs and symptoms of neonatal opioid withdrawal syndrome  Concomitant Use with Benzodiazepines or Other CNS Depressants  May result in profound sedation, respiratory depression, coma, or death  If other agents are required, minimal doses should be employed  QT Interval Prolongation  May increase the risk for QT interval prolongation  Use cautiously with other agents that may also cause QT interval prolongation

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Oliceridine Oliceridine  Availability:  Adverse Effects:  1 mg/ml vial  CNS Effects: Dizziness (very common); Sedation; Drowsiness  2 mg/2 ml vial  GI: Constipation; Nausea; Vomiting  30 mg/30 ml vial  Hypotension  Dosage:  IV – intermittent doing  Respiratory depression  1.5 mg initial, followed by 0.75 mg every hour with a maximum cumulative daily dose of 27  Back pain mg  Pruritis  Administration beyond 48 hours has not been studied  PCA  Drug Interactions:  Initial dose by a healthcare provider: 1.5 mg  Similar to other opioid agents  Demand dose range: 0.35 to 0.5 mg  Other drugs that cause CNS depression  Lockout interval: 6 hours  A supplemental dose of 0.75 mg may be administered by a healthcare provider 1 hour after  Especially other opioids or benzodiazepines the initial dose  Other drugs that may prolong the QT interval  No dosage adjustment is need for renal impairment

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Oliceridine  Cost:  1 mg/ml vial - $21.00  2 mg/ 2 ml vial - $30.90  30 mg/30 ml vial - $132.00

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Diabetes Facts Diabetes Facts Data from the 2020 CDC Diabetes Statistics Report  Only 19.2% met all of the following criteria: 26.9 million children and adults in the US with diagnosed diabetes  A1C < 7.0%  The percentage did improve when the less stringent A1C < 8.0% was used  8.2% of the population  Blood Pressure < 140/90 mm Hg  26.8% of those individuals 65 and older have diagnosed diabetes  LDL Cholesterol < 130 mg/dL  1.4 million have type 1 diabetes  Non-Smoker Another 7.3 million with undiagnosed diabetes  89% were overweight, with 15.5% with a BMI > 40 10.9% of patients with diagnosed diabetes began using insulin within the year of their diagnosis  21.6% were active smokers More prevalent in minorities  50% had an A1C of 7.0% or higher  11.7% of African-Americans  22.3% had an A1C of 7.0 – 7.9%  12.5% of Hispanics  13.2% had an A1C of 8.0 -8.9%  9.2% of Asian-Americans  14.6% had an A1C higher than 9.0%

National Diabetes Statistics Report, 2020 National Diabetes Statistics Report, 2020 47 48

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Prevalence of Diabetes Aged 20 Semaglutide (Rybelsus) and Older  Indications:  Oral agent as an adjunct to diet and exercise to improve glycemic control in adults (18 years of age and older) with type 2 diabetes  Efficacy:  Overall, lowers A1c by about 1%  Statistically significant reduction in A1c as compare to placebo  Reduction of 1.2% with the 7 mg dose and 1.4% reduction with the 14 mg dose as compared to 0.3% reduction with placebo  Also studied against empagliflozin and sitagliptin in combination with metformin  Statistically significant reduction against empagliflozin (reduction of 1.3% vs 0.9%)  Statistically significant reduction against sitagliptin (reduction of 1.3% vs 0.8%)  May see about a 2.5 kg weight loss

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Semaglutide Semaglutide  Mechanism of Action:  Limitations/ Warnings:  Acts as glucagon-like peptide 1 (GLP-1) receptor agonist that selectively binds to  Not recommended as first-line therapy and activated the GLP-1 receptor  Not for treating type 1 diabetes  Reduced blood glucose by stimulating insulin secretion and lowering glucagon in  Should only be used in pregnancy if benefit outweighs potential risk a glucose-dependent manner  Breastfeeding is not recommended  These agents are generally inactivated by stomach acid and have traditionally  Has not been studied in pediatric patients been available in only an injectable form  History of pancreatitis  Semaglutide (Rybelsus) is a specially formulated oral agent to prevent breakdown and improve oral absorption  History of diabetic retinopathy  Boxed warning for use with a history (personal or family) of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2

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Semaglutide Semaglutide  Adverse Effects:  Dosage:  Start with 3 mg orally once daily with no more than 4 oz (120 ml) of plain water, at least 30  GI effects: Nausea; Abdominal pain; Diarrhea; Vomiting; Decreased appetite minutes before first food, beverage, or other oral medications  Pancreatitis  Increase to 7 mg once daily after 30 days  Hypersensitivity reactions  May increase to 14 mg once daily if needed after 30 days  Drug Interactions:  Switch to Injection  Patient taking 14 mg orally once daily can switch to 0.5 mg SQ once weekly, beginning the  Increased risk of hypoglycemia with concomitant insulin secretagogues or insulin day following the last oral dose  May need to lower the dose of the insulin secretagogues or insulin  Switch from Injection  May affect absorption of other oral medications due to delayed gastric emptying  Patients using 0.5 mg SQ can switch to 7 mg or 14 mg orally, beginning 7 days following  Availability: the last SQ dose  3 mg, 7 mg, and 14 mg tablets  Cost:  $770 for a month’s supply for all three doses

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9 4/5/2021

Insulin Glargine (Semglee) Insulin Glargine

 Indications:  Limitations/ Warnings:  Long-acting (basal) insulin for the treatment of both type 1 and type 2 diabetes  Watch carefully for development of hypoglycemia  The product is considered to be a “follow-on”  Should not be given IV  Efficacy:  Adverse Effects:  Semglee has an identical amino acid sequency to Lantus and has been approved  Hypoglycemia for the same indications  Injection site reactions  Mechanism of Action:  Joint/ Back pain  Insulin acts via specific membrane-bound receptors in target tissues to regulate  Drug Interactions: metabolism of carbohydrate, protein, and fats  Potentiated by oral anti-diabetic agents; ACE-Inhibitors; angiotensin receptor  Target organs include liver, skeletal muscle, and adipose tissue blockers (ARBs); and sulfonamide antibiotics

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Insulin Glargine Insulin lispro-aabc (Lyumjev)  Availability:  Indications:  100 units/ ml vial  Ultra fast-acting insulin for the treatment of both type 1 and type 2diabetes in  100 units/ ml 3 ml pen adults  Dosage:  Formulated with treprostinil and citrate for faster absorption  Once daily at the same time each day  Efficacy:  Cost:  Has been found to be non-inferior to insulin lispro (Humalog)  $165 for a box of five 3 ml pens  Mechanism of Action:  Lowers glucose by stimulating peripheral glucose uptake by skeletal muscle and fat and by inhibiting hepatic glucose production  Insulin inhibits lipolysis and proteolysis and enhances protein synthesis

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Insulin lispro Insulin lispro  Limitations/ Warnings:  Availability:  Watch carefully for development of hypoglycemia  100 units/ ml vial  Adverse Effects:  100 units/ ml 3 ml pen  Hypoglycemia  200 units/ ml 3 ml pen  Injection site reactions  Dosage:  Joint/ Back pain  Dependent on the patient  Drug Interactions:  May be given one to three (or more) times daily  Potentiated by oral anti-diabetic agents; ACE-Inhibitors; angiotensin receptor  Should be injected with 20 minutes before a meal blockers (ARBs); and sulfonamide antibiotics  Cost:  Concomitant use of beta-blockers may blunt signs/ symptoms of hypoglycemia  $275/ vial  $530 for a box of five 3 ml pens

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10 4/5/2021

Chronic Idiopathic Constipation (CIC)

 Affects approximately 33 million Americans and an estimated 14% of the global population.  Functional GI disorder, defined by symptoms including  Fewer than three bowel movements per week  Hard to pass or incomplete bowel movements  There are several available treatments for CIC

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Lactitol (Pizensy) Lactitol  Indications:  Warnings/ Limitations:  Chronic idiopathic constipation  Should not be used in patients with known or suspected gastrointestinal  Efficacy: obstruction  As compared to placebo, lactitol was found to achieve a significantly greater  Has not been studied in the pediatric population efficacy response (26% vs 13%) with endpoints of at least 3 complete  May reduce the absorption of concomitantly administered oral medications spontaneous bowel movements (CSBMs) in a given week and an increase of at  Adverse Effects: least one CSBM) over baseline for at least 9 of 12 weeks  GI Effects: Flatulence (common); diarrhea; abdominal distention and/or pain  Mechanism of Action:  Increased blood pressure  Lactitol is a simple monosaccharide sugar that exerts an osmotic effect, causing  Urinary tract infections water influx into the small intestine leading to a laxative effect  Upper respiratory tract infections

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Lactitol Lactitol

 Drug Interactions:  For the 20 gram dose, fill the measuring cap twice to the top, marked by an arrow  Due to possible reduction in the absorption of other concomitantly administered  Pour the measured dose into an empty 8 ounce glass medications  Add 4 to 8 ounces of water, juice, or other common beverage (such as coffee,  Administer other medications at least 2 hours before or 2 hours after lactitol tea, or soda) and stir to dissolve  Availability:  Drink the entire contents of the glass  Multi-dose bottle: 280 grams or 560 grams of lactitol in powder form  Cost:  Unit-dose packets: Each packet contains 10 grams of lactitol in powder form  The product was approved by the FDA in 2020 but has not yet been marketed  Dosage:  20 grams placed in 4 to 8 ounces of liquid once daily  May decrease to 10 grams once daily for persistent loose stools

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Post-Op Nausea and Vomiting (PONV) Amisulpride (Barhemsys)  Post-operative nausea and vomiting (PONV) remains a major problem for  Indications: surgical patients  Prevention of PONV, either alone or in combination with an antiemetic from a  Occurs in approximately 30% of patients and up to 80% of high-risk patients different class  May also be used for treatment of PONV who received prophylaxis with an  High risk would include the use of anesthetic gases; opioids; and certain antiemetic from a different class or no prophylaxis types of surgeries  Efficacy:  Gynecological; Abdominal: Breast; Eye; Ear  A single dose of 10 mg of amisulpride was significantly more effective than  More common in cases that last for over an hour placebo in controlling PONV (42% vs 29%)  Few new treatments or therapeutic advances have been seen for the past 20  Mechanism of Action: years  Atypical antipsychotic agent with selective binding to the D2 and D3 receptors. Antagonism of these receptors in the chemoreceptor trigger zone relays  PONV is considered to be the most undesirable complication of surgery, even inhibitory stimuli to the vomiting center, decreasing emesis worse than pain

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Amisulpride Amisulpride  Warnings/ Limitations:  Drug Interactions:  May cause QT-interval prolongation  Other medications that may cause QT-interval prolongation  Should not be used in patients with eGFR < 30 ml/min  May diminish the effect of certain medications for the treatment of Parkinson’s disease,  Has not been studied in pediatric patients the dopamine agonists  Adverse Effects:  Availability:  Procedural hypotension  5 mg/2 ml vial  Hypokalemia  Dosage:  Increased serum prolactin  Prevention: 5 mg as a single dose, at the time of anesthesia induction  Lactating women may consider expressing and discarding breast milk for a period of 48  Treatment: 10 mg as a single dose, in patients who did not receive prophylaxis or hours after receiving amisulpride to minimize exposure to the breastfed infant received an agent of a different class  Abdominal distention  Slowly administer over 1 to 2 minutes  Infusion-site pain  Cost:  Chills  $25.50 per vial

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COVID-19

 A novel coronavirus was identified in Wuhan, China in 2019 and rapidly spread throughout the world, resulting in a global pandemic  The coronavirus responsible is SARS-CoV-2  The coronavirus spike protein mediates coronavirus entry into host cells  Patients can be asymptomatic, have mild cases, lasting about 2 weeks, or severe cases, that can lead to multiple organ failure and death

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Remdesivir (Veklury)  Indication:  Treatment of COVID-19 in patients aged 12 and older weighing at least 40 kg requiring hospitalization  Current NIH guidelines recommend the use of remdesivir for hospitalized COVID patients who require supplemental oxygen  Patients receiving remdesivir that progress to high-flow oxygen, non-invasive ventilation, mechanical ventilation, or ECMO should continue the remdesivir therapy for a total of 10 days  Efficacy:  Several studies showed those patients with remdesivir as compared to placebo showed • The spike protein attaches via the ACE2 receptor, primarily found in the lungs clinically meaningful improvements across multiple outcome assessments • Normally, ACE2 plays a role in regulating blood pressure  Time to recovery (10 days vs 15 days) • When the coronavirus binds to the receptor, it sets off chemical changes that fuse  Incidence of new mechanical ventilation or ECMO ( 13% vs 23%) together the cell and the virus, allowing the virus’ RNA to enter the cell  Mortality (11.4% vs 15.2%) • The host cell, then translates that RNA into more copies if the virus, allowing healthy cells  Better results were noted in those patients requiring supplemental oxygen but who had not to become infected yet progressed to mechanical ventilation

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Remdesivir Remdesivir  Adverse Effects:  Mechanism of Action:  Transient elevations in liver enzymes (23%)  Antiviral agent that binds to the viral RNA polymerase inhibiting viral replication  Diarrhea (9%)  Broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, SARS, Marburg, MERS, and  Hypotension (8%) SARS-CoV-2  Rash  Warnings/ Limitations:  Acute kidney injury  Only indicated for hospitalized patients  Monitor:  Not evaluated for pregnant or breast-feeding patients  Infusion reactions  Not recommended for patients with eGFR < 30 ml/min  Renal and hepatic function  Should not administer if eGFR is < 30 ml/min or if patient is receiving dialysis  Must monitor hepatic tests  Should not administer if ALT or AST is > 10 times ULN  May consider discontinuation if ALT levels increase to greater than 10 times the upper limit of normal  Drug Interactions:  Must monitor for hypersensitivity reactions  Hydroxychloroquine might interfere with the antiviral activity of remdesivir

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Remdesivir  Availability:  100 mg/20 ml vials  Dosage:  200 mg IV over 30-120 minutes for 1 dose, followed by 100 mg IV daily beginning on day 2 for a total of 5 days or until hospital discharge  May continue for up to a total of 10 days if no clinical improvement at day 5 or if oxygen requirements escalate  Medication should be further diluted in 250 ml and preparation should not be shaken  Cost:  $624.00 per 20 ml vial

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Overactive Bladder (OAB) Vibegron (Gemtesa)  OAB is a clinical condition that occurs when the bladder contracts  Indications: involuntarily  Beta-3 agonist for the treatment of overactive bladder in adults  Symptoms include urinary urgency, urinary incontinence, frequent urination,  Efficacy: and nocturia  As compared to placebo, studies showed that vibegron resulted in statistically  More than 30 million Americans suffer from OAB significant reductions in daily urge urinary incontinence, micturitions, urgency  Non-pharmacologic measures, such as bladder training and scheduled voids, episodes, and an increase in volume voided limiting caffeine, avoiding late-evening fluid intake can work as well as  Mechanism of Action: medications, but patients must be diligent  Stimulate beta-3 receptors in the bladder causing the muscle to relax, increasing  Medications can be added to the behavioral therapies bladder capacity  Most agents have similar efficacy, reduction from three to one or two daily incontinence episodes

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Vibegron Vibegron  Warnings/ Limitations:  Drug Interactions:  Use cautiously in patients with bladder outlet obstruction and in patients using  May increase the serum concentration of digoxin concomitant muscarinic antagonists  Availability:  May lead to urinary retention  Not recommended with end-stage renal disease (CrCl < 15 mL/min) or severe  75 mg tablets hepatic impairment  Dosage:  Adverse Effects:  75 mg once daily  Headache  Cost:  Nasopharyngitis  $18.34/ each  GI: Diarrhea and Nausea (most common); Constipation  Xerostomia  Urinary retention

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Conclusions

 Medications, guidelines, and the world of pharmacy is continually changing  The number of new medications approved in 2020 is a bit higher than what we have seen in some previous years  New oncology drugs are the leading group  Necessary to stay as updated as possible  Medication regimens are more complicated than ever  Always consider potential drug-drug interactions and think drugs first when dealing with new symptoms

Melinda C. Joyce, Pharm.D., FAPhA, FACHE [email protected]

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