PL CE LIVE May 2012 Forum

Transcription

1 CE Information CE Information Pharmacist's Letter / Therapeutic Research Center is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. PL CE LIVE editors disclose: No financial interests related to the content No commercial support and no advertising Supported entirely by subscriptions PL CE LIVE Drug Information Analysts disclose: Dr. O Mara reports that her spouse is employed by Celgene Today s topics from the May issue of Pharmacist s Letter May 2012 PL CE LIVE Rachel Maynard, Pharm.D. Assistant Editor Pharmacist s Letter/Pharmacy Technician s Letter Sherri Boehringer, Pharm.D., BCPS Associate Editor Pharmacist s Letter/Pharmacy Technician s Letter How Plavix (clopidogrel), Effient (prasugrel), and Brilinta (ticagrelor) stack up What works for heavy menstrual bleeding Whether there s benefit to using Alzheimer s drugs New recommendations for liver function tests in statin patients New drug Intermezzo (zolpidem) Antiplatelet Drugs for Acute Coronary Syndrome Acute Coronary Syndrome What is it? Unstable angina Heart attack How is it treated? Acutely GP IIB/IIIA receptor antagonists Dual antiplatelet therapy Aspirin plus clopidogrel (Plavix) Aspirin plus prasugrel (Effient) Aspirin plus ticagrelor (Brilinta) 1

2 How Do the Different Antiplatelets for Acute Coronary Syndrome Work? P2Y12 How Do the Different Antiplatelets for Acute Coronary Syndrome Work? P2Y12 Platelet Platelet GP IIB/IIIA Thromboxane GP IIB/IIIA Thromboxane Platelet Activation and Aggregation CLOT How Do the Different Antiplatelets for Acute Coronary Syndrome Work? P2Y12 How Do the Different Antiplatelets for Acute Coronary Syndrome Work? P2Y12 GP IIB/IIIA ReoPro Integrilin Aggrastat Platelet aspirin Thromboxane GP IIB/IIIA clopidogrel prasugrel ticagrelor Platelet Thromboxane Platelet Activation and Aggregation Platelet Activation and Aggregation CLOT CLOT How Do the Different Antiplatelets for Acute Coronary Syndrome Work? GP IIB/IIIA clopidogrel prasugrel ticagrelor P2Y12 Platelet Platelet Activation and Aggregation aspirin Thromboxane How Does Clopidogrel Compare to Effient or Brilinta? Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta) Efficacy Bleeding Shortness of Breath Dosing Frequency ++ Once daily Once daily TWICE daily Cost $189/month $203/month $261/month CLOT 2

3 How Does Clopidogrel Compare to Effient or Brilinta? How Does Clopidogrel Compare to Effient or Brilinta? Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta) Efficacy Clopidogrel (Plavix) Prasugrel (Effient) Ticagrelor (Brilinta) Efficacy Bleeding Shortness of Breath Dosing Frequency ++ Once daily Once daily TWICE daily Cost $189/month $203/month $261/month Bleeding Shortness of Breath Dosing Frequency ++ Once daily Once daily TWICE daily Cost $189/month $203/month $261/month What to Expect? Expect to gradually dispense more Brilinta Expect to still see clopidogrel used a lot More indications Generics Expect to see Effient used as an alternative to clopidogrel or Brilinta Recommendations - Clopidogrel Don t recommend switching patients already on clopidogrel Recommend clopidogrel for other indications such as stroke, peripheral artery disease, etc Recommend clopidogrel for patients who are also on an anticoagulant Recommendations Brilinta Use with just 81 mg of aspirin Effient Avoid prasugrel in most patients over age 75 and those with a previous TIA or stroke Regardless of the Antiplatelet Drug Added to Aspirin Dispense a MedGuide Suggest dual antiplatelet drugs for at least one year after acute coronary syndrome Suggest low dose aspirin indefinitely 3

4 How to Manage Heavy Menstrual Bleeding Heavy Menstrual Bleeding Affects about one out of every five women More than 80 ml of blood loss during a menstrual period and/or a period lasting more than 7 days Could include reports like: Need to double up on pads to control menstrual flow Blood flow soaks through one or more pads or tampons every hour for several hours in a row Passing blood clots larger than a quarter Causes of Heavy Menstrual Bleeding Structural issues Abnormal growths like fibroids or polyps Certain medical conditions Cancer, bleeding disorders Hormone imbalance especially too little progesterone Estrogen builds up the lining of the uterus Progesterone stabilizes the lining; a drop in progesterone causes the lining to break down Treatments for Heavy Menstrual Bleeding Oral contraceptives NSAIDs Progestins Heavy Menstrual Bleeding Lysteda (tranexamic acid) Surgical procedures How to Choose Desire for contraception NOT desired: Lysteda, NSAIDs, cyclic progestins Desired: Oral contraceptives, progestin only contraceptives (Depo Provera, etc) Dosage form Adherence Cost Side effects Efficacy 4

5 NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) Exact mechanism of action unknown Women with heavy menstrual bleeding may have high prostaglandin levels NSAIDs inhibit prostaglandin synthesis Start day before period and continue x 5 days or until heavy blood loss has stopped Diclofenac, ibuprofen, naproxen, etc have been used...choose based on tolerance Lysteda (tranexamic acid) Anti fibrinolytic Fibrin forms the building blocks of a clot Heavy menstrual bleeding has been associated with high rate of clot breakdown Lysteda slows the breakdown of fibrin and prevents clot breakdown 1300 mg TID x 5 days during menstruation Do not use in women at risk of blood clots Progestins Blunt endometrial growth and development Cyclic oral progestins Norethindrone, medroxyprogesterone, etc Taken on days 5 to 26 of the menstrual cycle (21 days) y) Progestin only contraceptives Mirena (levonorgestrel releasing intrauterine system) Implanon (etonorgestrol) Depo Provera (depot medroxyprogesterone) Progestin-Only Contraceptives Consider in women who want contraception, but an OC with estrogen isn t appropriate Obese Smoke Older than 35 years Recommend Mirena for more severe cases and women interested in long term contraception Used for up to 5 years Combined Oral Contraceptives (OCs) Reduce build up of endometrium Lack of controlled clinical trials, but generally accepted as effective first line agents Natazia is the first OC approved for heavy menstrual bleeding 5

6 Natazia (estradiol valerate/dienogest) Estrogen estradiol valerate No proof that it is better tolerated or has less negative effects on lipids/clotting than ethinyl estradiol Progestin dienogest g Most closely resembles drospirenone without the potassium sparing activity Strong progestin activity Natazia (estradiol valerate/dienogest) Unique regimen Four phasic, stepped dosing regimen Estrogen dose steps down while progestin dose steps up Two day hormone free interval Missed doses If dose delayed more than 12 hours, consider it a missed dose Complicated missed dose directions Bottom Line Other OCs are also effective for heavy menstrual bleeding Consider downsides of Natazia: Missed doses Cost(~$100 for one pack) Weigh patient factors when choosing an agent for heavy menstrual bleeding How to Manage Alzheimer s Mechanism of Alzheimer s Drugs Drugs for Alzheimer s Drug Class Brand (generic) Aricept (donepezil) Neurotransmitters: Acetylcholine Glutamate Cholinesterase inhibitors NMDA receptor antagonist Exelon (rivastigmine) Razadyne (galantamine) Cognex (tacrine) Namenda (memantine) 6

7 How Do Cholinesterase Inhibitors Work? Acetylcholine is important for memory Alzheimer s = acetylcholine Cholinesterase inhibitors prevent the breakdown of acetylcholine = acetylcholine Manage symptoms related to memory, cognition, judgment, etc Acetylcholine How Does Namenda (memantine) Work? Glutamate activates NMDA receptors Alzheimer s = glutamate May lead to cell death Memantine partially blocks NMDA receptors May protect against toxic effects of glutamate Glutamate Drugs for Alzheimer s Drug Class Brand (generic) Approved for Stages Current Practice Cholinesterase inhibitors hb Aricept (donepezil) Exelon (rivastigmine) Razadyne (galantamine) Mild, moderate, severe Mild to moderate Mild to moderate Cholinesterase Inhibitor NMDA receptor antagonist Cognex (tacrine) Namenda (memantine) Mild to moderate Moderate to severe Cholinesterase Inhibitor + Memantine Therapy for Alzheimer s With meds Therapy for Alzheimer s Only one in 12 patients on a cholinesterase inhibitor show any improvement Onein 12 patients have significant side effects GI effects: nausea, vomiting, diarrhea Fainting Slowed heart rate 7

8 Therapy for Alzheimer s Stress non drug therapies Low stress environment Avoid noise and glare Daytime engagement Security objects Therapy for Alzheimer s Mild to moderate disease Suggest a cholinesterase inhibitor if drug therapy is desired Watch for side effects Don t suggest Namenda (memantine) Balance risks and benefits of meds Side effects, cost, ease of use, questionable benefit Therapy for Alzheimer s Moderate to severe disease Think twice before adding memantine to a cholinesterase inhibitor Suggest switching to memantine if side effects are a problem with cholinesterase inhibitors Discourage against using Aricept 23 mg over 10 mg Watch for Namenda XR...FDA approved, but not yet launched When to Stop? No benefit by 3 to 6 months Side effects/cost outweigh benefits Dementia is severe (patient is bedridden, nonverbal, etc) When stopping, suggest tapering over 4 weeks Monitoring of Statins Case Sandra, a 46 year old female, comes to your pharmacy with a new prescription for atorvastatin 20 mg QHS. What does she need to know? 8

9 OLD Recommendations for Statin Monitoring Lab Test Frequency Rationale Liver function tests (e.g. ALT, AST, etc) Baseline, with dose increases, onceortwice or annually May cause dose dependent, asymptomatic increases in liver enzymes Why Was Routine Liver Monitoring Recommended? Up to 10% of patients starting a statin have a transient rise in liver enzymes Can occur with any statin at any dose, but risk seems to be dose dependent Previously recommended to stop statin if liver enzymes were more than 3x upper limit of normal Does a rise in liver enzymes = liver damage? Hepatotoxicity Elevated liver enzymes Do not necessarily indicate liver injury Liver injury clinically significant Symptoms May warrant therapy change Can develop into liver failure Liver failure Can result in need for liver transplant or death Hepatotoxicity from Statins Statins CAN increase liver enzymes, but it s usually transient Liver injury due to statins is idiosyncratic Not picked up with routine monitoring Liver failure is rare...if it happens at all One case of liver failure for every million patients per year on a statin...same rate as for those NOT on a statin New Recommendations Routine monitoring during statin therapy does not detect or prevent liver injury No need for routine periodic monitoring of liver enzymes in patients taking statins Check liver enzyme tests BEFORE starting a statin, and then only if the patient has symptoms NEW Recommendations for Statin Monitoring Lab Test Frequency Rationale Liver function Baseline, with dose May cause dosetests (e.g. ALT, AST, etc) increases, once or twice annually and when clinically indicated dependent, asymptomatic increases in liver enzymes 9

10 What to Tell Patients Tell patients to notify you if they have symptoms of liver injury Fatigue, yellow skin/eyes, abdominal pain, loss of appetite, nausea Continue to monitor and report other adverse effects...muscle pain/weakness, brown urine What About... Statins are okay in: Patients with elevated liver enzymes due to CHRONIC, stable liver disease Patients with a single test of increased liver enzymes Repeat test, determine cause Avoid statins in: Patients with ACUTE liver failure or decompensated cirrhosis Case Sandra, a 46 year old female, comes to your pharmacy with a new prescription for atorvastatin 20 mg QHS. What does she need to know? New Drug Intermezzo (zolpidem zolpidem) How is Intermezzo different? Duration of action 4 hours Dosing low dose, gender specific dosing 3.5 mg for men; 1.75 mg for women, seniors, liver dysfunction, with CNS depressants Formulation Sublingual tablet to be dissolved under tongue Cost ~$220 for 30 tabs Polls/Questions 10