Matthew Lacroix Pharm D BCPS Assistant Professor University

Matthew Lacroix Pharm. D BCPS Assistant Professor University of New England College of Pharmacy April 26, 2014 NEW DRUG UPDATE 2014

Objectives Pharmacists objectives 1. Discuss the basic pharmacology of the new drugs presented and how the pharmacologic actions relate to both therapeutic and adverse effects. 2. Discuss clinically significant adverse effects and drug interactions, and the appropriate dosing and monitoring of the new drugs presented. 3. Discuss therapeutic role of the new drugs presented as compared to agents already marketed. Technician objectives 1. List the new drugs presented. 2. Describe clinically significant adverse effects and drug interactions, and the appropriate dosing and monitoring of the new drugs presented.

Conflicts of Interest Dr. Lacroix has no conflicts to report

Best resource for new drug release Pharmacist Letter http: //pharmacistsletter. therapeuticresearch. com /pl/New. Drugs. aspx? cs=&s=PL&pt=20&yr=2013 Tend to highlight most important new agents, new formulations, and new biologics

How this presentation was developed There have been about 50 new agents since May 2013 Using the most scientific polling source I could find (Facebook) I asked about what new medications people most wanted to spend some time on That list was cross referenced with New Entities list from Pharmacist Letter© Drugs are introduced in two ways Quick hits � 1 slide on the medication as it may be rarer to see in practice Topic reviews � 4 -5 slides on the medication, focusing on what is unique about the drug, key elements in patient counseling and monitoring, and the product that is currently the most similar to it on the market

Q 1) Lurasidone has FDA indications for which of the following 1) bipolar I; Schizophrenia 2)bipolar II; Schizophrenia 3) Bipolar I; Depression 4) Bipolar II; Depression

Lurasidone (Latuda©) Class: Atypical Antipsychotic Uses Depressive phase of bipolar Schizophrenia MOA high affinity for D 2, 5 -HT 2 A, and 5 -HT 7 receptors; moderate affinity for alpha 2 C-adrenergic receptors; and is a partial agonist for 5 -HT 1 A receptors No affinity for muscarinic M 1 and histamine H 1 receptors

Lurasidone (Latuda©) Adverse effects >10% Central nervous system: �Drowsiness �extrapyramidal reaction �Akathisia �parkinsonian-like syndrome Endocrine & metabolic: �Increased serum triglycerides �increased serum glucose �increased serum cholesterol Gastrointestinal: �Nausea

Lurasidone (Latuda©) Renal Dosing At Cr. Cl of 50 ml/min reduce dose by 50% Drug-Drug interactions CYP 450 3 A 4 substrate �Watch out for strong inhibitors and inducers �Moderate inhibitors (verapamil) PI indicates 50% dose Pregnancy rating-B Still risk, particularly in 3 rd trimester

Lurasidone (Latuda©) Key counseling points Patients do experience orthostatic hypertension Food should be taken with med to reduce symptoms Clear fluids; preferable non-caffeinated Available as 20, 40, 60, 80, 100, 120 mg tablets �Average cost about $800 for 30 days

Q 2) Estrogens (conjugated/equine) and Bazedoxifene is a combination of what two classes of medications? 1) estrogen derivatives and SERM 2) estrogen and progestogen 3) estrogen and SSRI 4) estrogen and SNRI

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©) Class: Estrogen Derivative; Selective Estrogen Receptor Modulator (SERM) Primary uses Postmenopausal osteoporosis prophylaxis Vasomotor symptoms MOA Conjugated estrogens act as an estrogen agonist and bazedoxifene acts as an estrogen agonist/antagonist depending on the specific tissue.

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©) Vasomotor symptoms Most common 12 -24 months after last Menses Most common reason treatment is sought May interrupt sleep and cause insomnia Occur in 75%– 85% of women, usually within 12– 24 months after the last menstrual period May cause increased skin temperature, nausea, dizziness, headache, palpitations, diaphoresis, and night sweats

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©) Adverse effects Dizziness Gastrointestinal �Diarrhea �Nausea �Dyspepsia �upper abdominal pain Neuromuscular �Muscle spasm �neck pain Respiratory: �Oropharyngeal pain

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©) Renal dosing Not studied- no official recommendation �May consider stopping at 30 ml/min Drug-Drug interactions Anticoagulants �Reduce efficacy- consider different therapy CYP 450 3 A 4 �Estrogen is a substrate so be aware! Pregnancy category X

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©) Key counseling points Swallow tablet whole Any abnormal bleeding should be report to PCP Any signs of chest pain, stroke like symptoms Take at same time every day Available as 0. 45 -20 mg tablet $133. 03 for 30 Most like Prempro �Replaces the progestin with the SERM

Ospemifene (Osphena) Class: SERM Indication: use for Dyspareunia 60 mg once daily Not indicated for use for vasomotor symptoms CYP 3 A 4, 2 C 9 drug interactions

Q 3)Fluticasone/vilanterol inhalers most resemble which current inhaler on the market? 1) 2) 3) 4) Advair HFA Advair DPI Serevent diskus Proair HFA

Fluticasone and Vilanterol (Breo Ellipta©) Class: Combo long acting B 2 agonist; inhaled corticosteroid Primary Use COPD exacerbation reduction MOA Fluticasone is a corticosteroid with anti-inflammatory activity, immunosuppressive properties, and antiproliferative actions. Vilanterol, a long-acting beta 2 -agonist, relaxes bronchial smooth muscle by selective action on beta 2 receptors with little effect on heart rate.

Fluticasone and Vilanterol (Breo Ellipta©) Adverse effects Cardiovascular: Hypertension peripheral edema Central nervous system: Headache Gastrointestinal: Oropharyngeal candidiasis Diarrhea Neuromuscular Arthralgia back pain bone fracture Respiratory Nasopharyngitis upper respiratory tract infection Pneumonia

Fluticasone and Vilanterol (Breo Ellipta©) Renal dosing Inhaled-no adjustment needed Drug-Drug interactions The same as all other combo inhalers Pregnancy class C

Fluticasone and Vilanterol (Breo Ellipta©) Counseling points Unique inhaler delivery system http: //youtu. be/Cq 8 u. Qi_ETls Other key points are similar to other combo products (Advair) Available as 100/25 mcg inhaler Cost of ~$121 for 30 day supply �(slightly cheaper)

Umeclidinium/vilanterol (Anoro Ellipta©) Long acting anticholinergic/Beta-agonist for COPD Avoid other anticholinergics Potassium needs to be monitored, supplemental potassium held until patient is stabilized on medication Dosing: once daily (14 doses per inhaler)

Q 4) dapagliflozin reduces A 1 C by what percent? 1) 2) 3) 4) 0. 5% 1% 1. 5% 2%

Dapagliflozin (Farxiga©) Class: Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitor Use Treatment of type 2 DM MOA inhibits sodium-glucose cotransporter 2 (SGLT 2) in the proximal renal tubules, reduces reabsorption of filtered glucose from the tubular lumen SGLT 2 is the main site of filtered glucose reabsorption reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

Dapagliflozin (Farxiga©) Adverse effects Endocrine �Mild hypoglycemia �Dyslipidemia Gastrointestinal �Nausea �Constipation Hematologic �Increased hematocrit (1%, hematocrit >55%) Infection �Influenza Neuromuscular �Back pain Respiratory �Nasopharyngitis Genitourinary: �Fungal vaginosis �urinary tract infection �increased urine output �genitourinary fungal infections � dysuria

Dapagliflozin (Farxiga©) Renal dosing e. GFR <60 m. L/minute/1. 73 m 2: �Initial: Use not recommended. �persistent decrease in e. GFR to <60 m. L/minute/1. 73 m 2, dapagliflozin should be discontinued. Drug-Drug Interactions No significant CYP 450 interactions Caution in concurrent steroid use Pregancy Category: C Advise discontinuation in 2 nd and 3 rd trimesters

Dapagliflozin (Farxiga©) Counseling points Make sure to report soreness in genitals to PCP �High risk of infection secondary to medication You may initially need to void more frequently You may feel dizziness with this medication, check BG. If normal consider checking BP, consult with PCP Available as 5 and 10 mg capsule �Cost ~$347 for 30 day supply

Alogliptin/metformin (Kazano©) Alogliptin/pioglitazone (Oseni©) Combo DPP-4 and biguanide Combo DPP-4 and Thiazolidinedione

Q 5) Qudexy XR an extended release formulation for what currently available anticonvulsant? 1) 2) 3) 4) Topiramate Phenytoin Carbamazipine Ethosuximide

Topiramate (Qudexy XR ©; Trokendi XR©) Class: Anticonvulsant Use: Extended release formulations for epilepsy as mono- or adjunctive therapy Both are new extended release formulations Qudexy XR is indicated for age 2 or greater Trokendi XR is indicated for age 6 or greater NOT BIOEQUVALANTS MOA Not fully described (AKA we don’t know but think something from below is involved) �Blocks neuronal voltage-dependent sodium channels �enhances GABA(A) activity �antagonizes AMPA/kainate glutamate receptors �weakly inhibits carbonic anhydrase

Topiramate (Qudexy XR ©; Trokendi XR©) Adverse Effects >10% Central nervous system: Paresthesia Drowsiness Dizziness Nervousness Fatigue Ataxia psychomotor retardation impaired speech memory impairment abnormal behavior confusion Endocrine Decreased serum bicarbonate Gastrointestinal Anorexia Nausea Ophthalmic Visual disturbance Renal Increased serum creatinine

Topiramate (Qudexy XR ©; Trokendi XR©) Renal dosing Cr. CL <70 ml/min reduce dose by 50% Drug-Drug interactions Oral contraceptives Anything that causes sleepiness; fatigue Pregnancy category: D

Topiramate (Qudexy XR ©; Trokendi XR©) Counseling points Same as topiramate noting side effects may last longer as the half life is about 5 times as long as IR topiramate Avoid beer, wine, or mixed drinks within 6 hours before or 6 hours after taking this drug. Available as 25, 50, 100, 200 mg (Tokendi XR) �Price range from ~$200 to ~$700 depending on strength for 30 tablets �Qudexy XR approved March 2014, expected shortly on shelves

Vortioxetine (Brintellix©) Class: SSRI Initial indication for Major depressive disorder Major substrate of CYP 2 D 6 Major side effect sexual disorder �Up to 30% of both men and women GI �Up to 30% dose dependent, tolerance can build

Q 6) Simeprevir and sofosbuvir are new medications introduced for the treatment of what disease at the end of 2013? 1) 2) 3) 4) COPD Menopause Hepatitis C bipolar disorder

Hepatitis C Simeprevir (Olysio) Oral: 150 mg once daily (in combination with peginterferon alfa and ribavirin). Treatment duration is indication and response-specific. Focus on HCV-RNA detection/undectable Cost: 150 mg (28): $26544. 00 Sofosbuvir (Sovaldi) Oral: 400 mg daily with concomitant ribavirin and with or without peginterferon alfa (maximum: 400 mg daily). Genotype specific for duration requirements Costs : 400 mg (28): $33600. 00

Hydrocodone (Zohydro ER) New stand alone product Highly controversial Starting dose is 10 mg in opioid naïve patients and titrated up q 3 -7 days Side effects are similar to hydrocodone/APAP with less liver side effects C-II

Hydrocodone (Zohydro ER) Conversion from transdermal fentanyl: Treatment with hydrocodone ER may be started 18 hours after the removal of the fentanyl transdermal patch. For every fentanyl 25 mcg per hour transdermal patch, initially substitute hydrocodone ER 10 mg every 12 hours. Monitor the patient closely. Previous Oral Opioid Oral Dosage Hydrocodone Oxycodone Methadone 3 Oxymorphone 10 mg 5 mg Approximate Oral Conversion Factor 2 1 1 1 2 Hydromorphone Morphine Codeine 3. 75 mg 100 mg 2. 67 0. 1 1 Approximate equivalent doses for conversion from current opioid therapy to hydrocodone ER. 2 Ratio for converting oral opioid dose to approximate hydrocodone ER equivalent dose. 3 Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.

Questions?