4/26/2016. Practical Pharm Tips. Jonathan R White, PharmD, BCPS, BCACP

Transcription

1 Practical Pharm Tips Jonathan R White, PharmD, BCPS, BCACP A day in the life of an adult in

2 What to do when clinical trials hit! (the popular media) 2

3 Patient Case 1 In a clinical trial Jardiance lowered death from heart disease 55 year old male with type 2 DM Metformin 1000 mg twice daily Glipizide 5 mg twice daily A1C 8.2% PMH sig for: MI 3 years ago BMP is WNL Asks What do you know about this drug? Much ado about SGLT-2 Lumen SGLT-2 Blocker Blood Na+ Glucose Glut2 Glucose SGLT2 Glucose Na+ ATPase K+ Na+ Glucose 3

4 SGLT-2 Inhibitors Canagliflozin (Invokana ) mg daily, do not use if egfr < 45 ml/min/1.73m 2 Dapagliflozin (Farxiga ) 5-10 mg daily, do not use if egfr < 60 ml/min/1.73m 2 Empagliflozin (Jardiance ) mg daily, do not use if egfr < 45 ml/min/1.73 m 2 SGLT-2 Inhibitors: Potential benefits and pitfalls Benefits Oral and once daily Lower FPG and PPG Expected A1C reduction 0.5-1% Weight loss (1-4 kg) Blood pressure lowering (~4/2 mmhg) Low risk hypoglycemia Pitfalls UTIs and genital mycotic infections Renal impairment/hyperkalemia Increase LDL-C 3-8% Bone loss (canagliflozin) Bladder/breast cancer risk (dapagliflozin) Questionable durability 4

5 EMPA-REG Outcome Trial Empagliflozin v placebo in patients with DM and CVD n = 7020 mean age: 63 years (72% male) Median observation time: 3.1 years NNT 63 Composite endpoint: 10.5% v 12.1%; HR 0.86 ( ) CV death: 3.7% v 5.9%, HR 0.62 ( ) MI or stroke: No significant difference NNT 46 A1C change: to % on anti-htn(s) 80% on statin 89% on aspirin Zinman B et al. NEJM 2015 Zinman B et al. NEJM

6 Explaining the EMPA-sible Subclinical heart failure? Approx 50% of type 2 DM may have form of diastolic dysfunction Hospitalization for HF/CV death composite: HR 0.66 (95% CI: ; p< 0.001) NNT 35 over 3 years Subgroup analysis showed no difference in patients with HF vs without HF A different diuretic? Fitchett D et al. European Heart Journal 2016 Poirier P et al. Diabetes Care 2001 Gilbert RE, Connelly KA. Lancet 2015 SGLT-2s: Practical use May be appropriate to use in combination with metformin or as part of a 3-drug regimen Metformin + SU + SGLT-2 Metformin + DPP4 + SGLT-2 Metformin + TZD + SGLT-2 Metformin + basal insulin + SGLT-2 May be most ideal in patients looking to avoid injections and are concerned about weight gain Unconfirmed, but potential benefit in HF patients* *personal opinion Diabetes Care

7 Patient case 2 78 year old man PMH sig for: Stroke, HTN, CKD (stage 3), hyperlipidemia, mild cognitive impairment Takes a large quantity of herbal supplements Wants to know Are any of my supplements dangerous? Dietary Supplements Send Thousands To ERs Yearly Emergency Department Visits for Adverse Events Related to Dietary Supplements Andrew I. Geller, M.D., Nadine Shehab, Pharm.D., M.P.H., Nina J. Weidle, Pharm.D., Maribeth C. Lovegrove, M.P.H., Beverly J. Wolpert, Ph.D., Babgaleh B. Timbo, M.D., Dr.P.H., Robert P. Mozersky, D.O., and Daniel S. Budnitz, M.D., M.P.H. New England Journal of Medicine 2015;373:

8 Emergency Department Visits for Adverse Events Related to Dietary Supplements Surveillance data from 63 EDs in U.S. from Est. 23,005 visits/yr attributed to dietary supplements and 2,154 admissions Mean age: 32 years old 28% were year olds 12.4% 65 years old Twice the risk of hospitalization (16% v 8.4%) Emergency Department Visits for Adverse Events Related to Dietary Supplements year olds Cardiac symptoms associated with weight loss or energy-promoting supplements Primary take home point: 65 year olds Talk to patients of all ages Swallowing problems (i.e., pill-induced dysphagia and choking) caused nearly about supplements 40% of the supplement-related visits Majority with Ca 2+ products 8

9 Supplements and significant interactions CYP enzyme -black cohosh -ginkgo -garlic -echinacea Sedating -melatonin -valerian root -kava kava (intxn with seizure meds) Warfarin & antiplatelet -coenzyme Q10, saw palmetto, ginseng, feverfew, ginkgo, garlic, ginger + many others Cardiac -yohimbe, bitter orange, ma huang -various other weight loss or energy supplements 9

10 3 steps to safer supplements 1. The supplement may not have any Supplement Medication Supplement Disease + = Interactions The supplement must be safe for the patient 3 steps to safer supplements 2. The supplement must be affordable Patients should still be able to pay for 10

11 3 steps to safer supplements 3. The patient must perceive a benefit (this one promotes the most discussion) Additional benefits: Improves rapport with patient. Encourages engagement and reflection on management strategies Preventive: Generally more challenging. Symptom/Wellness: Promotes thoughtful and open discussion Patient Case 3 42 year old female PMH sig for: GERD, HTN, DM Meds: Omeprazole 20 mg twice daily x 6 years Metformin 500 mg daily Lisinopril 20 mg daily Wants to know Should I keep taking this medication? 11

12 PPIs and the Penal code Litigation may occur after the release of FDA alerts, of which there have 3 (so far) for PPIs PPIs increasing risk of c. difficile PPIs increasing risk of hypomagnesemia PPIs increasing risk of fracture/bone loss PPIs and the Penal Code (cont.) New safety alerts coming? Recent data showing increase in risk for heart disease, community acquired pneumonia, kidney disease, and dementia with PPI use Scales of Justice? Scale of benefit vs risk? 12

13 C. Difficile -Acute > outpatient -Older patients -Substantial data Hypomagnesemia -low risk with short-term -recommend labs with long-term use -caution with diuretics and digoxin Bone loss/fractures -hip, wrist and spine -associate with higher dose and longer duration Dementia -Study in pts 75 yo - ~40% relative risk -needs further evaluation -mechanism? Myocardial infarction % in PPI users vs 0.04% in PPI non-users -NNH [accessed April [accessed April 2016] -risks for PPI = general -No association with [accessed April 2016] Gomm W et al. JAMA Neurol Kuller risks H LH JAMA Neurol RA Lazarus B et al. JAMA Intern Med Wyatt CM Kidney International CKD -More association with twice daily dosing -Observational study, overall risk low Higher dose Longer duration Themes Particularly > 1 year Older patients (for some) Low overall risk for each 13

14 Assessing therapy regularly FDA 14 days up to 3 times per year Between 53% and 69% of PPI prescriptions are for inappropriate indications Indication Duration PPIs are effective at managing symptoms Duodenal ulcer 4-8 weeks Gastric ulcer AND days Erosive esophagitis 4-8 weeks are not associated with tachyphylaxis GERD Up to 4 weeks Forgacs I, Loganayagam A. Arch Intern Med Katz MH. Arch Intern Med. 2010;170(9): Haenisch B et al. Eur Arch Psychiatry Clin Neurosci Pasina L et. al. Eur J Intern Med 2011 Patient presenting with (or without) question Opportunity to discuss indication and benefits vs risks (consider themes) PPIs are associated with rebound hypersecretion that may last months Dramatic impact on ability to stop therapy Tapering may increase success 14

15 Tips for tapering Every other day is in play H 2 RA used intermittently or scheduled may assist Calcium carbonate where reasonaball No need for a fast break Take timeout to talk about expectations Summary SGLT-2 inhibitors Patients refusing injectibles and close to goal Cardiac effects likely independent of glucose lowering we still do not know why HF? Supplements assess in all patients > 20,000 ED visits due to supplements/yr Younger patients weight loss/energy Older patients difficulty swallowing (Ca 2+ ) PPIs Continuously reassess use Be sure to taper if discontinuing 15

16 Questions? 16