7/17/2017. Innovations in Medications Kati Shell, PharmD, CpH, BCPS #FSHP2017 #FSHP2017 #FSHP2017

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1 New Drugs FSHP Disclosure I do not have (nor does any immediate family member have) a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias my presentation Innovations in Medications Kati Shell, PharmD, CpH, BCPS Objectives Discuss and review drug discovery process Describe various naming considerations and conventions Review key points of selected new medications New Drug Approval Process It takes about 12 years to get a new drug to market at a cost of approximately $350M A drug is tested in the lab for an average of 3.5 years prior to approval for testing on humans About one in 1000 compounds actually makes it to human testing FDA- Center for Drug Evaluation and Research (CDER) guides the pharmaceutical company at each step of the way Preclinical Work Drug is developed by a company Next step is animal testing Multiple types of animals used Followed by investigational new drug (IND) application Specifies composition and manufacturing Explains plan for human testing FDA ensures humans will not be placed at risk for harm Informed consent Human Subject Protection 1

2 Clinical Trials Number of patients Focus Average Duration Phase I healthy volunteers Safety 1 year Excretion and metabolism Phase patient volunteers Efficacy 2 years Compare to placebo, adverse effects Phase closely monitored patients Safety and Efficacy 3 years Compares doss/populations combines with other meds Final Approval After completion of the clinical trials, the manufacturer submits a New Drug Application NDA to the FDA for approval If FDA approves, the FDA assigns a team to review studies of safety and efficacy Labeling and information for patient and healthcare professionals is reviewed Manufacturing site is inspected FDA approval, medication is available Phase 4- post marketing monitoring stage Includes monitoring of adverse events in Medwatch Medwatch Novel Drug Naming Three names exist Chemical Generic named by the USAN Council Brand name used by company that brought to market for 17 years while they have exclusivity of the product Involves 5 steps New Chemical Entity NCE submission and patent application generic naming- short, easy to pronounce brand naming- easy to remember, distinct from other names FDA review final approval Drug Naming Conventions olol for beta blockers, pril for ACE inhibitors, nib for Tyrosine Kinase Inhibitors Monoclonal Antibodies Prefix Infix representing target or disease -t- for tumors, -l- immunomodulator, -b- bacterial Infix indicating the source -zu- humanized, -u- fully humanized, -xi- chimeric Stem used as a suffix MAB- monoclonal antibody, antibody fragments, radiolabeled antibodies Example: Infliximab Distinct Prefix Infli----xi-Chimeric source--- mab-monoclonal antibody 2

3 New Drug Approvals FDA releases a list of new drugs by year On the site, there is a link to the press release and drug trials snapshot New Drug Approvals Selected items that may be used in your hospital Bridion Sugammadex Praxbind Idarucizumab Tresiba Insulin degludec injection Entresto Sacubitril/Valsartan Radicava Epclusa Sofosbuvir and Velpatasvir Cinqair Reslizumab Tagrisso Sugammadex First drug approved in new class of medications Rocuronium and vecuronium are neuromuscular blocking drugs that cause temporary paralysis by interfering with nerve impulses to the muscle and are used to paralyze the vocal cords when patients require an artificial airway, during general anesthesia, or to prevent breathing when a patient is on a ventilator Sugammadex, in the clinical trials, reversed paralysis in most cases within 5 minutes Sugammadex Picture: chyqcres&q=sugammadex+2015&simid= &selectedindex=1&ajaxhist=0 Sugammadex Bridion Approved 12/2015 Category: Antidote/selective relaxant binding agent Indication: reverse effects of rocuronium and vecuronium used during surgery Dosing: 2-4mg/kg depending on level of sedation Storage: Protect from light at 25C Preparation/administration- IV push over 10 seconds undiluted from vial Sugammadex Adverse effects: Bradycardia (5-13%) Nausea (up to 26%), pain at injection site (50%) Pricing: AWP 200mg/20ml vial $114 Sugammadex: Lexi-Comp Online, accessed 5/20/17 Sugammadex: Lexi-Comp Online, accessed 5/20/17 3

4 Idarucizumab $6 Billion Market for oral anticoagulants In 2014, dabigatran prescriptions are over 2.2M With 3,592 Medwatch reports of serious side effects to the FDA, it averaged 14.1 for every 1,000 patient years. Approximately 75% of these reports involved internal bleeding events Idarucizumab Image: OIP.MiYMPJ3zEAGUpvKjObpYkwDIDq&q=praxbind&simid= &selectedIndex=3&ajaxhist=0 Idarucizumab Praxbind Approved 10/2015 Category: antidote, monoclonal antibody Indication: For use in patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse blood-thinning effects Dosing: IV: 5 g (administered as 2 separate 2.5 g doses no more than 15 minutes apart), potential for re-dose in specific situations Storage: Store intact vials at 36ºF to 46ºF. Do not freeze. Do not shake. Idarucizumab Preparation/administration: Undiluted as an IV bolus over 5-10 minutes via 60mL syringe or as an infusion by hanging the vial. Adverse effects: Delirium, hypokalemia, constipation (7%) Look alike-sound Alike: IDArubicin, infliximab, ipilimumab Pricing: AWP 2.5 gm/50 ml: $ Idarucizumab: Lexi-Comp Online, accessed 5/20/17 Idarucizumab: Lexi-Comp Online, accessed 5/20/17 Insulin Degludec Injection According to the Centers for Disease Control and Prevention, approximately 21 million people in the United States have been diagnosed with diabetes Long acting insulins are a mainstay of treatment due to daily dosing and less injections for patients Insulin Degludec Injection D01&thid=OIP.gu_u0CloW6EXa8Bk2vf50QEsDl&q=Insulin+Degludec 4

5 Insulin Degludec Injection Tresiba Approved 9/2015 Category: Long acting insulin Indication: Diabetes mellitus type 1 and 2 Adult Dosing: individualized dosing per patient depending on indication, administered daily Storage: Store unopened pens 36 F to 46 F until expiration date, or at room temperature below 86 F for up to 56 days. Preparation/administration: For subq administration into the thigh, upper arm, or abdomen; do not administer IM or IV, or in an insulin infusion pump Insulin Degludec: Lexi-Comp Online, accessed 5/20/17 Insulin Degludec Injection Adverse effects: Headache (9-12%) severe hypoglycemia (10-13%) nasopharyngitis (13-24%) Look Alike-Sound Alike: Tarceva High Alert Medication- double check process Pearls: U-200 FlexTouch pens do not allow odd numbered dosing of insulin units; patients requiring odd numbered doses should use the U-100 FlexTouch pen. Pricing: AWP 100 units/ml (3 ml): $ units/ml (3 ml): $ Insulin Degludec: Lexi-Comp Online, accessed 5/20/17 Sacubitril/Valsartan Heart failure is a common condition affecting about 5.1 million people in the United States. Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. It is a leading cause of death in the United States and a leading cause for readmissions in the hospital setting Sacubitril/Valsartan LexiComp online, sacubitril/valsartan, accessed 5/20/17 images YIregEyDL&q=entresto&simid= &selectedIndex=1&ajaxhist=0 Sacubitril/Valsartan Entresto Approved 7/2015 Category: Angiotensin II Receptor Blocker/Neprilysin Inhibitor Indication: Heart Failure Dosing: Patients not currently taking an ACE inhibitor or an ARB: Initial: Sacubitril 24 mg and valsartan 26 mg twice daily. Double the dose every 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg and valsartan 103 mg twice daily. Storage: store at 77F, protect from moisture administration: with or without food Sacubitril/valsartan: Lexi-Comp Online, accessed 5/20/17 Sacubitril/Valsartan Adverse effects: hypotension (18%) hyperkalemia (12%) Black Box Warning: fetal toxicity Pearls: Concomitant use of an ACE inhibitor is contraindicated; allow a 36 hour washout period when switching from or to an ACE inhibitor. Pricing: AWP mg (60): $ mg (60): $ mg (60): $ Sacubitril/Valsartan: Lexi-Comp Online, accessed 5/20/17 5

6 The Centers for Disease Control and Prevention estimates that approximately 12,000-15,000 Americans have amyotrophic lateral sclerosis (ALS.) ALS is a rare disease that attacks and kills the nerve cells that control voluntary muscles. The nerves lose the ability to activate certain muscles, which causes the muscles to become weak and leads to paralysis. ALS is a progressive disease and most patients die from respiratory failure, usually within three to five years from when the symptoms first appear. Radicava Approved 5/2017 Orphan Drug Designation Provides company various incentives Not subject to prescription drug user fee Category: free radical scavenger Indication: Treatment of amyotrophic lateral sclerosis (ALS) Dosing: An initial cycle with daily dosing for 14 days, followed by a 14-day drug-free period Subsequent cycles with daily dosing for 10 days out of 14- day periods, followed by 14-day drug-free periods. yfororphanproductdesignation/default.htm Storage: Store at up to 25 C,Protect from light. Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours. Preparation/administration: administer as prepared 30mg/100mL infusion x2, as total 60 minute infusion prescribing informration. Modana, Dan, Gets FDA Approval For ALS Treatment. May 6, 2017 Adverse effects: bruising, gait disturbance, headache Pearls- this is the first medication approved for ALS in 20 years Look alike, Sound Alike: Entacapone Pricing: $1086/treatment, annual cost would be $145,524 according to Mitsubishi Tanabe Pharma Sofosbuvir and velpatasvir According to the Centers for Disease Control, Approximately 3.5 million persons are currently infected with Hepatitis C Virus (HCV) Mortality among HCV-infected persons primarily adults aged years increased during In 2013, HCV associated deaths exceeded the combined number of deaths with 60 other infectious diseases as underlying causes First drug to treat all six major forms of HCV. 6

7 Sofosbuvir and velpatasvir Sofosbuvir and velpatasvir Epclusa Approved 6/16 Category: Antihepaciviral NS5A Inhibitor Indication: Chronic Hepatitis C genotypes 1-6 Dosing: Without cirrhosis or with compensated cirrhosis (Child-Pugh class A): One tablet once daily for 12 weeks. With decompensated cirrhosis (Child-Pugh class B or C): One tablet once daily with concomitant ribavirin for 12 weeks. Sofosbuvir/Velpatasvir: Lexi-Comp Online, accessed 5/20/17 Sofosbuvir and velpatasvir Storage: Store below 30 C (86 F). Dispense in original container. Administration: Administer with or without food Adverse effects: Headache (22%), fatigue (15%) Boxed warning: Reactivation of Hepatitis B Pricing: AWP mg (28): $ Reslizumab According to the Centers for Disease Control and Prevention, as of 2013, more than 22 million people in the U.S. have asthma, Estimated more than 400,000 asthma-related hospitalizations each year Sofosbuvir/Velpatasvir: Lexi-Comp Online, accessed 5/20/17 Reslizumab Reslizumab Cinqair Approved 6/2016 Category: Interleukin Receptor-5 Antagonist, monoclonal antibody Indication: add-on maintenance therapy for asthma, eosinophilic phenotype Dosing: 3mg/kg IV infusion every 4 weeks Storage: Intact vials in refrigerator 36 F to 46 F. Protect from light. Preparation: Withdraw dose from vial and add slowly to 50 ml NS PVC or polyolefin infusion bag. Gently invert the bag; do not shake. Reslizumab: Lexi-Comp Online, accessed 5/20/17 7

8 Reslizumab Administration: Use an infusion set with an in-line, low protein-binding filter, infuse over 20 to 50 minutes Adverse effects: increased creatine phosphokinase (20%, transient) Black Box Warning: Anaphylaxis-0.3% of patients Look alike Sound Alike: Singulair montelukast Pricing: AWP 100 mg/10 ml : $ Lung cancer is the leading cause of cancer death in the United States Estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. The most common type of lung cancer, Non-Small Cell Lung Cancer (NSCLC) occurs when cancer cells form in the tissues of the lung EGFR is a protein involved in the growth and spread of cancer cells. Reslizumab: Lexi-Comp Online, accessed 5/20/17 Tagrisso Approved :11/2015 Category: Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor and Tyrosine Kinase Inhibitor Indication: Non-small cell lung cancer, metastatic (T790M EGFR mutation-positive) Dosing: Oral: 80 mg once daily until disease progression or unacceptable toxicity Storage: Store at 25 C Preparation: Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tab : Lexi-Comp Online, accessed 5/20/17 Preparation of Extemporaneous Suspension: NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. Administration: with or without food Adverse effects: Skin rash (41%), xeroderma (31%), nail disease (25%), pruritus (14%) Look alike Sound Alike: may be confused with olaparib, ospemifene. Tagrisso may be confused with Targretin, Tasigna High Alert- ISMP classified Hazardous- while not on NIOSH 2016 list, this meets criteria for hazardous handling Pricing: AWP: 40 mg (30): $ mg (30): $ : Lexi-Comp Online, accessed 5/20/17 : Lexi-Comp Online, accessed 5/20/17 8

9 References New Drug Approval Process, Drugs.com. accessed online 5/20/17 How Drugs are Developed and Approved, pproved/default.htm. Last updated 8/15, Monoclonal Antibodies. American Medical Association. LexiComp Online, accessed online 5/20/17 FDA approves new pill to treat certain patients with non-small cell lung cancer. released November 13, New Report Ranks Xarelto, Eliquis & Pradaxa By Safety Profile. 11/19/ accessed online 5/20/17. FDA approves Cinqair to treat severe asthma. 3/23/ References FDA approves Bridion to reverse effects of neuromuscular blocking drugs used during surgery. December 15, FDA approves two new drug treatments for diabetes mellitus. September 25, FDA approves new drug to treat heart failure. July 7, FDA approves Epclusa for treatment of chronic Hepatitis C virus infection June 28, FDA approves new drug for ALS. May 5, FSHP New Drugs Innovations in Medications Kati Shell, PharmD, CpH, BCPS 9