1. New Drugs 2005-2006 Learning and Teaching about New Drugs from the Group on Pharmacotherapy 39 th STFM Annual Spring Conference San Francisco, CA

2.  Michelle L. Hilaire, PharmD, CDE  L. Brian Cross, PharmD, CDE  Oralia V. Bazaldua, PharmD, BCPS  John M. Tovar, PharmD  Steve North, MD  A special “thank you” to all the members of the Group on Pharmacotherapy for their insight and input into this project Today’s Presenters

3. To provide a focused didactic presentation on learning and teaching about new drugs in an interactive small-group format. Purpose of today’s lecture

4. At the end of this seminar, participants should be able to:  List the benefits and disadvantages of six new drugs relevant to family practice  Demonstrate a thought process for deciding whether or not to incorporate a new drug into their practice  Demonstrate several different approaches for providing information on new drugs to learners Objectives

5.  Brief Introduction  Teaching About New Drugs  Drug Monograph Review  STEPS approach  Comparative approach  Group Discussion  Wrap-up and Questions Session Outline

6.  As a “teacher of family medicine” how are you keeping up with the 30+ new drugs that are approved each year? … this is in addition to new indications, black box warnings, new formulations and new strengths for old drugs  And then, how do you figure out if these drugs have a place in your practice? Overview

7.  Pharmaceutical representatives  Medical and pharmaceutical journals  InfoPoems and InfoRetriever  Treatment guidelines  Prescriber’s and Medical Letter  Your trustworthy pharmacist  The internet … Sources of Drug Information

8.  Lecture style format  Updates/e-mail information  Newsletters  One-on-one attending time in clinics How Do You Teach …

9. Drug Monograph Approach

10. PHARMACOLOGY  selectively binds (agonist) to melatonin type 1 (MT 1 ) and type 2 (MT 2 ) receptors in the suprachiasmatic nucleus INDICATIONS  treatment of insomnia characterized by difficulty falling asleep Ramelteon

11. PHARMACOKINETICS  Absorption – affected by high-fat meal  Tmax = 0.5 – 1.5 hrs  t 1/2 = 1-2.6 hrs (active)  Metabolism – 1 st pass (1A2/3A4/2C9)  Excretion – 84% in urine (metabolites) Ramelteon

12. ADVERSE EFFECTS  NO abuse potential or behavioral impairment  somnolence/dizziness  nausea/headache  Fatigue/insomnia  prolactin levels COST  $80.10 / month DOSING  8mg 30 min prior HS  caution in hepatic impairment OTHER INFO  Pregnancy Category C  not a controlled substance Ramelteon

13. PHARMACOLOGY  selectively binds (agonist) to the BDZ component of the GABA-A receptor INDICATIONS  for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance Zolpidem

14. PHARMACOKINETICS  Absorption - biphasic absorption  Tmax = 1.5 hrs  t 1/2 = 2.8 hrs (active metabolites)  Metabolism – metabolized to inactive metabolites that are eliminated primarily through urinary excretion Zolpidem

15. ADVERSE EFFECTS  somnolence/dizziness  nausea  headache  fatigue  abuse potential COST  $100.20 / month DOSING  12.5 mg immediately before bedtime (6.25 mg elderly)  caution in hepatic impairment OTHER INFO  Pregnancy Category C Zolpidem

16. STEPS Approach

17.  Incretin-mimetic that activates GLP-1 receptor  Promotes insulin release and lowers glucagon concentration.  Indicated as adjunctive therapy in patients with Type 2 DM Exenatide

18. Safety  CI: Type 1 DM, DKA, CrCl<30 ml/min  Not recommended in patients w/severe GI disease  Increased risk of hypoglycemia with sulfonylureas Exenatide Tolerability  Common: N/V/D, dizziness, headache  Withdrawal due to AE ~7% (mainly nausea) vs 3% for placebo.

19. Effectiveness  Three 30-week trials – AMIGO studies  Mean baseline A1c = 8.2 - 8.7; decreased by 0.8-0.9  Body weight decreased 1.6 – 2.8 kg  A1c reduction not better when compared to insulin glargine. Exenatide

20. Simplicity  Twice daily injection  Available as a prefilled pen  Patient education is necessary  Must be stored in the refrigerator DRUGDOSECOST/MTH Exenatide10 mcg $220.19 Metformin850 mg $28.09 (generic) Glipizide10 mg $28.19 (generic) Insulin Glargine 1 vial $73.79 Price Exenatide

21.  Amylinomimetic  Supresses postprandial glucagon secretion  Modulates nutrient delivery from stomach to intestine  Indicated as adjunctive therapy in Type 1 or 2 diabetics. Pramlintide

22. Safety  CI: gastroparesis, inability to identify s/s hypoglycemia  No adjustment in renal impairment  Slows stomach emptying; can affect other drugs  Symlin & insulin should be given as separate injections Pramlintide Tolerability  Common: nausea, headache, anorexia, vomiting, abdominal pain  Does not cause hypoglycemia alone

23. Effectiveness VARIABLEPLACEBOSYMLIN Baseline A1C9.39.1 Change in A1C at 6 months- 0.17- 0.57 * Change in wt at 6 months+ 0.2 kg- 1.5 kg * % change in insulin doses at 6 months (short-acting) + 6.5- 3.0 * % change in insulin doses at 6 months (long-acting) + 5.2- 0.2 * * Statistically significant Pramlintide

24. Price DRUGDOSECOST/MTH Symlin60 mcg ? Metformin850 mg $28.09 (generic) Glipizide10 mg $28.19 (generic) Insulin Glargine 1 vial $73.79 Simplicity  SQ injection given before meals  Different doses in Type 1 and 2 DM  Patient education is essential before use  Must be stored in refrigerator Pramlintide

25. Comparative Approach

26. PARAMETERTYGECYCLINETETRACYCLINES MOABinds 30s ribosomal subunit ResistanceNoneEfflux and ribosomal modification Spectrum of Activity MRSA, MRSE, VRE, gram–, anaerobes, atypicals anaerobes, atypicals, easy-to-hit gram–, staph?, strep FormulationIVIV, PO Tigecycline

27. PARAMETERTYGECYCLINETETRACYCLINES Distribution into tissues ExcellentDoxycycline (good) Minocycline (poor) Half-life40 h (BID)15-24 h (BID) PrecautionsAvoid in children and pregnancy Side EffectsN/V/DN/V/D, photosensitivity Cost$$$$ Tigecycline

28. PARAMETERLINEZOLIDDAPTOMYCIN MOABinds to 50s ribosomal subunit Disrupts bacterial membrane function ResistanceVRE, MRSANone SpectrumMRSA, MRSE, VRE, DRSP, atypicals MRSA, MRSE, VRE, DRSP Available formsPO, IV (BID)IV (QD) PrecautionsMyelosuppression, SSRIs, pregnancy Renal dysfunction, myopathy (statins) Tigecycline

29.  Approved by the FDA on January 23 rd, 2006  Treatment of adult patients with type 1 and type 2 DM  Must be dispensed with a Medication Guide Inhaled Insulin

30. PARAMETER. EXUBERAHUMALOG Bioavailability<20%55-80% Peak action (h)0.8-1.00.5-2.5 Onset of action (h)0.25-0.5 Duration (h)4-63-5 Intraindividual variation 34%15-25% Inhaled Insulin

31. PARAMETEREXUBERAHUMALOG Antibody formationYes ContraindicationsSmoking lung disease None Ease-of-useInhalerInjection DoseMilligramsUnits StorageNoneRefrigerator Inhaled Insulin

32. PARAMETEREXUBERAHUMALOG Monitoring PFTs None Adverse eventsCoughNone Safety?Yes EfficacyYes Cost?7-8¢/unit Inhaled Insulin