PL CE LIVE September 2012 Long Guide

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1 This handout accompanies the related articles published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 ~ Volume 28 ~ Number 9 following PL CE LIVE September 2012 Long Guide ASPIRIN You ll hear NEW debate about when it makes sense to take MORE than 81 mg/day of aspirin to prevent cardiovascular events. VERY rarely. Most prescribers are comfortable using 81 mg/day of aspirin for some indications. But 325 mg/day is still being used to prevent recurrent events in high-risk patients. But lower aspirin doses usually work as well as higher doses...even after an acute coronary syndrome, stent, or ischemic stroke. This is probably because aspirin s antiplatelet effects are irreversible. So even low doses achieve a full effect after several days. Plus higher doses can DOUBLE the risk of GI bleeding. Now guidelines are also endorsing lower aspirin doses. For example, guidelines used to recommend 162 to 325 mg/day of aspirin in the first few months after a stent. But now they suggest 81 mg/day...because there s no extra benefit with the higher dose. Feel comfortable suggesting 81 mg/day in most patients who need aspirin...even those at high cardiovascular risk. Caution patients on the new antiplatelet, Brilinta (ticagrelor), to stick with low-dose aspirin. Higher doses can decrease its efficacy. Be aware of some exceptions. Continue to recommend using 162 to 325 mg for the FIRST DOSE for an acute heart attack or ischemic stroke. Help dispel the myth that taking aspirin twice daily or at bedtime improves outcomes. There s no proof this is true. Tell patients to take low-dose aspirin just ONCE daily...when it s most convenient. Don t recommend increasing the dose if patients have a thrombotic event while on aspirin...there s no evidence this improves outcomes. Instead, these patients may need a different antiplatelet drug or anticoagulant...depending on the type of event. To hear our team discuss why low aspirin doses are appropriate in most cases, go to our PL Detail-Document and click on PL VOICES. Also see our new PL Chart, Aspirin Dose for Cardiovascular Indications, for guideline dosage ranges based on indication. Go to the Debate over Aspirin Dose to Prevent Cardiovascular Events Detail- Document. What dose of aspirin to recommend DISCUSSION POINTS LEARN MORE ABOUT THIS POINT... (Just click on the link for access!) Detail-Doc Aspirin Dose for Cardiovascular Indications August 2008 Article whether they should take TWO aspirin daily Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

2 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 Aspirin Dose for Cardiovascular Indications Aspirin s cardiovascular benefits stem from its permanent inactivation of platelet COX-1. 8 Inactivation of COX-1 inhibits the production of thromboxane A2, and therefore inhibits thromboxane A2-dependent platelet function and vasoconstriction. 8 Complete or nearly complete inhibition of COX-1 can be achieved with only 75 to 150 mg of aspirin. 8 Daily doses in the range of 50 to 160 mg have been shown to be effective for primary and secondary prevention of cardiovascular events, including prevention of stent restenosis and stroke. 8 In addition to efficacy at the lower doses, there is evidence that gastrointestinal side effects and major bleeding are directly related to aspirin dose. 8 Higher doses can double the risk of GI bleed. 19 These facts support the use of the lowest dose of aspirin that has been found effective in treating/preventing cardiovascular events. 8 This is reflected in the aspirin dosing recommendations in the chart below. The chart provides the aspirin dose for different cardiovascular indications per various guideline-promulgating organizations. (This chart does not include aspirin dosing for orthopedic indications. See our PL Detail-Document, Aspirin for VTE Prophylaxis After Hip or Knee Replacement.) Aspirin dosing recommendations in the guidelines may not reflect the aspirin dosage strengths available on the market. For practical purposes, 81 mg could be used if 75 to 100 mg is recommended, for example. Aspirin should be continued indefinitely for all indications unless otherwise noted. Abbreviations: ACC = American College of Cardiology; ACCF = American College of Cardiology Foundation; ACCP = American College of Chest Physicians; AHA = American Heart Association; ACS = acute coronary syndrome; BMS = bare metal stent; CABG = coronary artery bypass graft; CAD = coronary artery disease; CCS = Canadian Cardiovascular Society; CV = cardiovascular risk; DES = drug-eluting stent; LV = left ventricular; MI = myocardial infarction; NSTEMI = non-st-elevation MI; PCI = percutaneous coronary intervention; SCAI = Society for Cardiovascular Angiography and Interventions; STEMI = ST-elevation MI; UA = unstable angina; USPSTF = United States Preventive Services Task Force. (See footnotes for more details regarding appropriate use.) Indication Aspirin Dose (Adults) Primary prevention of cardiovascular events w USPSTF: 75 mg once daily 1,a ACCP: 75 to 100 mg once daily 5,d CCS: 75 to 162 mg once daily 14,m ADA/AHA/ACCF: 75 to 162 mg once daily 17,u Primary prevention of stroke in women AHA/American Stroke Association: 81 mg once daily or 100 mg every other day 2,b P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 2

3 (PL Detail-Document #280901: Page 2 of 8) Indication Aspirin Dose (Adults) Atrial fibrillation (to prevent stroke) ACCP: 75 to 325 mg once daily 4.c CCS: 75 to 325 mg once daily 18,v CAD ACCP: 75 to 100 mg once daily 5 AHA/ACCF: 75 to 162 mg once daily 10,L CCS: 75 to 162 mg once daily 14 Peripheral artery disease AHA/ACCF: 75 to 325 mg once daily 10,L CCS: 75 to 162 mg once daily 14 STEMI AHA/ACCF: chew 162 to 325 mg immediately for acute MI symptoms (unless patient already taking daily aspirin), then 75 to 162 mg once daily 11,e,k (see recommendations for PCI and CABG, as pertinent) ACCP: 75 to 100 mg once daily (maintenance) 5,e,k (see recommendations for PCI and CABG, as pertinent) CSS: 75 to 162 mg once daily (maintenance) 14,k,o (see recommendations for PCI and CABG, as pertinent) UA/NSTEMI AHA/ACCF: chew 162 to 325 mg immediately for ACS symptoms (unless patient already taking daily aspirin), then 75 to 162 mg once daily 7,e,k (see recommendations for PCI and CABG, as pertinent) ACCP: 75 to 100 mg once daily (maintenance) 5,e,k (see recommendations for PCI and CABG, as pertinent) CCS: 75 to 162 mg once daily (maintenance) 14,k,n (see recommendations for PCI and CABG, as pertinent) P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 3

4 (PL Detail-Document #280901: Page 3 of 8) Indication CABG Aspirin Dose (Adults) AHA/ACCF: 100 to 325 mg once daily for one year 10,L (see recommendations for CAD, UA/NSTEMI, and STEMI, as pertinent) CCS: 75 to 162 mg once daily (maintenance) 14,r Acute ischemic stroke/tia ACCP: 160 to 325 mg within 48 hours after onset 6 Secondary stroke/tia prevention ACCP: 75 to 100 mg once daily 6 AHA/American Stroke Association: 325 mg within 24 to 48 hours after onset 13 AHA/ACCF: 75 to 325 mg once daily 10,L CCS: 75 to 162 mg once daily 14 PCI, no stent ACCP: 75 to 325 mg once daily for the first month, then 75 to 100 mg once daily (elective, patient with CAD) 5,h,j,k ACCF/AHA/SCAI: continue aspirin indefinitely (see UA/NSTEMI, STEMI, CAD, as pertinent) 9,j,k CCS: 75 to 162 mg once daily 14,k,p (see UA/NSTEMI, STEMI, CAD, as pertinent) PCI, elective, with stent ACCP: 75 to 325 mg once daily for the first month (BMS) or for three to six months (DES), then 75 to 100 mg once daily 5,g,j,k CCS: 75 to 162 mg once daily 14,k,q PCI with stent, post ACS ACCP: 75 to 100 mg once daily 5,e,j,k AHA/ACCF (UA/NSTEMI): 81 mg once daily 9,12.,i,j,k CCS: 75 to 162 mg once daily 14,k,q P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 4

5 (PL Detail-Document #280901: Page 4 of 8) Indication Anterior MI with LV thrombus, or at high risk of LV thrombus Aspirin Dose (Adults) ACCP: 75 to 100 mg once daily 5,f,k Mechanical Heart Valve ACCP: 50 to 100 mg once daily 16,t CCS: 75 to 162 mg once daily 14,s a. For men age 45 to 79 years of age and women 55 to 79 years of age if benefit outweighs risk. 1 The CV risk level varies with age and gender and is as follows, and applies only to patients not taking an NSAID who are free of upper GI pain and have no history of ulcer: 3 Men ages 45 to 59 years Women age 55 to 59 Men and women ages 60 to 69 years Men and women ages 70 to 79 years 4% or higher 3% or higher 9% or higher (men) 8% or higher (women) 12% or higher (men) 11% or higher (women) Risk calculators: CHD risk estimation tool (for men): Stroke risk estimation tool (for women): Note: AHA/American Stroke Association guidelines also recommend aspirin (dose not specified) for people with a 10-year cardiovascular event risk of at least 6% to 10%. 2 b. For women whose stroke risk is high enough to justify risks. 2 c. Consider for patients with atrial fibrillation with low stroke risk (CHADS 2 score 0). 2,4 Also option for patients with moderate stroke risk (CHADS 2 score 1) as an alternative to anticoagulation if bleeding risk, patient preference, and patient access to high-quality anticoagulation monitoring makes anticoagulation unfeasible. 2,4 The CHADS 2 score is determined as follows: 1 point each for congestive heart failure, history of hypertension, age over 75 years, or diabetes, and two points for prior stroke or TIA. 2,4 d. Suggested for people 50 years of age and older without symptomatic heart disease. 5 e. Dual antiplatelet therapy is recommended for the first year post-acs. 5,12 f. Without stent placement: add warfarin for the first three months, then switch to dual antiplatelet therapy for up to 12 months. 5 With BMS placement: triple therapy (warfarin plus dual antiplatelet therapy) is suggested for the first month. Warfarin and single antiplatelet therapy is suggested for the second and third months. Thereafter, dual antiplatelet therapy is recommended for up to 12 months. 5 P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 5

6 (PL Detail-Document #280901: Page 5 of 8) With DES placement: triple therapy (warfarin plus dual antiplatelet therapy) is suggested for the first three to six months. Thereafter, dual antiplatelet therapy is recommended for up to 12 months. 5 g. AHA/ACCF: Dual antiplatelet therapy is recommended for at least the first month after placement of a BMS, and for three to six months after placement of a DES. Continuation of dual antiplatelet therapy for up to 12 months is suggested. 5 AHA/ACCF/SCAI: Use dual antiplatelet therapy for at least 12 months after DES placement if the patient is not at high risk of bleeding. 9 After BMS placement, use dual antiplatelet therapy for at least the first month, and ideally for up to 12 months. If the patient is at increased risk of bleeding risk, then dual antiplatelet therapy should be given for at least two weeks after BMS placement. 9 h. Dual antiplatelet therapy is suggested for the first month. 5 i. With BMS placement: Provide dual antiplatelet therapy for up to 12 months. 12 Other guidelines recommend dual antiplatelet therapy for at least 12 months. 9 Consider earlier discontinuation of second agent if risk of bleeding outweighs anticipated benefits. 12 With DES placement: Provide dual antiplatelet therapy for at least 12 months. 12 Consider earlier discontinuation of second agent if risk of bleeding outweighs anticipated benefits. 12 j. Patients undergoing PCI who have not been taking aspirin should take nonenteric-coated aspirin 325 mg before PCI. Patients already taking aspirin should take 81 to 325 mg before PCI. Patients getting a stent will also receive a loading dose of a P2Y12 inhibitor (e.g., clopidogrel, etc). 9 k. Preference is given to 81 mg daily after PCI as opposed to higher doses. 9,10,12 Use an aspirin maintenance dose of 81 mg with ticagrelor (Brilinta). 12 Canadian ticagrelor labeling recommends an aspirin dose of 75 to 150 mg daily with ticagrelor. 15 L. Use aspirin 75 to 81 mg if the patient is also taking warfarin (e.g., for atrial fibrillation). 10 m. Consider aspirin for patients with: high cardiovascular risk (e.g., multiple risk factors, vascular disease on imaging, elevated CRP) and low bleeding risk; diabetes, other cardiovascular risk factors, and age over 40, with low bleeding risk; or end-stage renal disease with low bleeding risk. 14 n. Use dual antiplatelet therapy for at least one month. Dual antiplatelet therapy can be continued for 12 months in patients without excessive bleeding risk. 14 o. Use dual antiplatelet therapy for at least 14 days, and up to 12 months or longer if bleeding risk is low. 14 p. Use dual antiplatelet therapy for 12 months. Dual therapy may be continued beyond 12 months if thrombosis risk is high and bleeding risk is low. 14 q. BMS: use dual antiplatelet therapy for at least one month (at least two weeks with recent bleed or high bleeding risk), and up to 12 months if bleeding risk is not excessive. Consider dual therapy past one year if high risk of stent thrombosis and low bleeding risk. 14 DES: Use dual antiplatelet therapy for 12 months. Consider dual therapy past one year if high risk of stent thrombosis and low bleeding risk. 14 r. For Non-STEMI managed with CABG, dual antiplatelet therapy is recommended for at least one month, and up to 12 months. For CABG after PCI, use dual antiplatelet therapy for nine to 12 months unless stented vessel adequately bypassed. 14 s. Consider adding aspirin to warfarin, especially in patients with mechanical mitral valve or older caged-ball, tilting disk, or bileaflet mechanical aortic valve. 14 t. Aspirin is suggested as an add-on to warfarin for patients who have a mechanical mitral or aortic valve and low bleeding risk. 16 P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 6

7 (PL Detail-Document #280901: Page 6 of 8) u. Aspirin is reasonable for patients with diabetes and a 10-year cardiovascular event risk over 10% (e.g., men over 50 years of age and women over 60 years of age with one additional major cardiovascular risk factor [e.g., smoking, hypertension, dyslipidemia, family history of early cardiovascular disease, or albuminuria]) who are not at increased risk of bleeding. 17 v. For patients with a CHADS 2 score (see footnote c) of 0 plus either female sex or vascular disease, or as an oral anticoagulant alternative in patients with a CHADS 2 score of 1, based on risk/benefit. 19 w. Not strongly recommended by most experts. Reserve for high risk patients after a careful benefit/risk assessment. Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication. P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 7

8 (PL Detail-Document #280901: Page 7 of 8) Project Leader in preparation of this PL Detail- Document: Melanie Cupp, Pharm.D., BCPS References 1. U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: recommendation statement. AHRQ Publication No EF-2. March /aspirincvd/aspcvdrs.htm#clinical. (Accessed August 3, 2012). 2. Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42: U.S. Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: clinical summary. AHRQ Publication No EF-3. March /aspirincvd/aspcvdsum.htm. (Accessed August 3, 12). 4. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(Suppl 2):e531S-75S. 5. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(Suppl 2):e637S-68S. 6. Lansberg MG, O Donnell MJ, Khatri P, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(Suppl 2):e601-36S. 7. Wright RS, Anderson JL, Adams CD, et al ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-st-elevation myocardial infarction. J Am Coll Cardiol 2011;57:e Eikelboom JW, Hirsh J, Spencer FA, et al. Antiplatelet drugs: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(Suppl 2):e89S-119S. 9. Levine GN, Bates ER, Blankenship JC, et al ACCF/AHA/SCAI guidelines for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. Circulation 2011;124: Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-segment myocardial infarction: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). Circulation 2004;110:e Jneid H, Anderson JL, Wright S, et al ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non- ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation 2012 July 16 [Epub ahead of print]. 13. Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association stroke council, clinical cardiology council, cardiovascular radiology and intervention council, and the atherosclerotic peripheral vascular disease and quality of care outcomes in research interdisciplinary working groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38: Bell AD, Roussin A, Cartier R, et al. The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society Guidelines. Can J Cardiol 2011;27(Suppl A):S Product monograph for Brilinta. AstraZeneca Canada Inc. Mississauga, ON L4Y 1M4. May Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(Suppl 2):e576S-e600S. 17. Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation 2010;121: Skanes AC, Healey JS, Cairns JA, et al. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012;28: P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 8

9 (PL Detail-Document #280901: Page 8 of 8) 19. Serebruany VL, Steinhubl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol 2005;95: Cite this document as follows: PL Detail-Document, Aspirin Dose for Cardiovascular Indications. Pharmacist s Letter/Prescriber s Letter. September Evidence and Recommendations You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA ~ TEL (209) ~ FAX (209) Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to or 9

10 Aspirin and Your Heart How does aspirin prevent a heart attack or a stroke? Aspirin can change the way your blood clots. When you cut yourself, clotting cells in your blood (platelets) clump together forming a plug to stop the bleeding. However, if platelets clump together in your blood vessels, you could have a heart attack or stroke. Aspirin works on platelets to make it less likely that they will form a clump (clot) in your blood vessels. Should you take an aspirin to prevent a heart attack or stroke? It is a good idea to talk with your healthcare provider before you start or stop taking aspirin. You can discuss if the benefits of aspirin (preventing a heart attack or stroke) are greater than the risks of aspirin (bleeding in the stomach or brain). Aspirin is used by most people who have already had a heart attack or stroke, to prevent another one from occurring. Aspirin can also be used if you ve never had a heart attack or stroke, but your chances of having one are high. For example, people who smoke, have high blood pressure, high cholesterol, or diabetes have a higher chance of having a heart attack or stroke than people who do not have these conditions. People who have family members who had heart attacks or strokes also are at higher risk. But just because you may have some of these conditions, it does not mean that taking an aspirin every day is best for you. How much aspirin should I take? Most patients who have never had a heart attack or stroke only need to take 81 mg (one baby aspirin) daily. Other patients with certain heart conditions may need up to 325 mg of aspirin every day. Taking more aspirin will not be any better, and higher doses can increase the chances of having side effects. Your healthcare provider will tell you how much aspirin you should take. What are the possible side effects of daily aspirin? Because aspirin helps to prevent clots, it can sometimes cause bleeding or bruising. You may notice that when you cut yourself, it takes a little longer to stop the bleeding. Also, aspirin can irritate your stomach. Less common, but more serious side effects of aspirin are bleeding in the stomach or brain. Bleeding in the brain can also cause a stroke. If aspirin bothers your stomach, try taking it with food or a glass of milk. If you notice black, tarry stools or see blood in your stool, or if you have nausea or vomiting or a sudden severe headache, call your healthcare provider right away. Continue to the next page for more information Prepared for the subscribers of Pharmacist s Letter / Prescriber s Letter to give to their patients. Copyright 2011 by Therapeutic Research Center 10

11 Should I take an enteric-coated aspirin? A buffered aspirin? Enteric-coated aspirin is meant to pass through your stomach and not dissolve until it reaches your intestines. Buffered aspirin contains aspirin and antacids. Both of these types of aspirin may be gentler on your stomach. But some people can still get bleeding in their stomach, even if they use enteric-coated aspirin or buffered aspirin. If you have questions about what type of aspirin to take, ask your pharmacist or other healthcare provider. I am taking an aspirin every day. Can I stop it? Stopping aspirin can increase your chances of getting a blood clot and having a heart attack or stroke. If you want to stop taking your aspirin, it is important to talk with your healthcare provider first. What if I take other medications? Can they interact with a daily aspirin? There are a number of drugs which can interact with aspirin. If you regularly take ibuprofen (Motrin, others) or naproxen (Aleve, others) for pain with your daily aspirin, it could block the anticlotting effects of aspirin. If you need to take ibuprofen or naproxen, you should take it about one hour after the aspirin. Also avoid using enteric-coated aspirin with naproxen or ibuprofen. It is not known if separating the doses will prevent the interaction. Other drugs like Plavix (clopidogrel), Pradaxa (dabigatran; Pradax in Canada), or Coumadin (warfarin) can increase your chances of bleeding with aspirin. But sometimes you may need to take these medicines together. Talk with your pharmacist or healthcare provider about what to watch for. Always let your pharmacist know you are taking aspirin so they can check for other drug interactions. [January 2011] Prepared for the subscribers of Pharmacist s Letter / Prescriber s Letter to give to their patients. Copyright 2011 by Therapeutic Research Center 11

12 HERPES ZOSTER There s new debate about how to treat or prevent ACUTE shingles. The question is which therapies work best to promote healing...reduce pain...and lower the risk of postherpetic neuralgia. Oral antivirals (famciclovir, etc) help speed healing and therefore reduce acute pain. Recommend starting it as soon as possible...preferably within 72 hours of the rash s onset. Suggest giving the antiviral for 7 days...or longer if patients continue to form vesicles or have ocular or other complications. It makes sense that antivirals might help reduce nerve damage that leads to postherpetic neuralgia...but this hasn t been proven yet. Analgesics should be given around the clock...not as needed. Suggest an NSAID, acetaminophen alone or with hydrocodone, or tramadol for mild to moderate pain...or a stronger opioid for severe pain. Oral corticosteroids might have a modest benefit for acute pain...but there s no proof they reduce the risk of postherpetic neuralgia. Gabapentin, pregabalin, or tricyclics don t have enough evidence of a benefit for pain...or to decrease the risk of postherpetic neuralgia. Suggest using these meds for patients who develop postherpetic neuralgia...but don t rely on them to prevent it. Zostavax is the best bet for prevention. Recommend it for people 60 and up...even if they ve already had shingles. Also suggest it for people in their fifties...but keep in mind insurance might not cover it. Tell patients that shingles can reoccur...but the risk seems low for 12 to 18 months after acute zoster due to residual immunity. Explain that there s no hurry to vaccinate patients after a definite case of shingles. But if the patient wants it sooner, advise waiting at least until the acute rash heals. To listen to our team discuss how to manage shingles and when to give Zostavax, go to our PL Detail-Document and click on PL VOICES. Go to the Prevention and Treatment of Shingles Detail-Document. How to manage shingles DISCUSSION POINTS LEARN MORE ABOUT THIS POINT... (Just click on the link for access!) Detail-Doc Management of Common Skin Diseases Detail-Doc Antiviral Agents for the Treatment of Common Herpetic Infections in Immunocompetent Patients Common questions about Zostavax January 2012 Article who should get meningitis and shingles vaccines May 2011 Article YOUNGER patients are now eligible for Zostavax to prevent shingles Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

13 Detail-Document # This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER October 2007 ~ Volume 23 ~ Number Management of Common Skin Diseases Background Patients often seek advice from pharmacists on how to manage skin problems. Some can be managed with over-the-counter (OTC) preparations. Others require evaluation by a physician and prescription medications. The following table includes descriptions and some online pictures of the most common conditions, as well as an outline of treatment and special considerations for patient counseling. A glossary of dermatologic terms is included below, in addition to a list of conditions according to body location. Glossary 1,2,3 Bulla: A large vesicle, greater than 0.5 to 1 cm in diameter. Example: Second-degree burn. Comedone: Blackhead or whitehead; plugs of sebaceous material in follicle. Example: Acne. Crust: Mass of skin exudate, color varies. Example: Impetigo. Erosion: A shallow lesion caused by the loss of epithelium. Exanthem: A skin eruption that bursts forth or blooms. Example: Measles. Fissures: Sharply-defined linear break in the skin. Example: Athlete s Foot. Lichenification: Diffuse thickened and scaly area. Macule: Small flat lesion, up to 0.5 to 1 cm in diameter. Example: Freckles. Nodule: Dome-shaped, round lesion, greater than 0.5 to 1 cm in diameter. Papule: Elevated lesion, up to 0.5 cm in diameter. Example: Wart. Patch: Large macule, greater than 0.5 to 1 cm in diameter. Example: Vitiligo. Petechiae: A circumscribed deposit of blood less than 0.5 cm in diameter. Plaque: A group of papules that are clustered together, circumscribed, elevated; greater than 1 cm in diameter; flat top. Example: Psoriasis. Pruritus: Itching. Pustule: Fluid-filled papule containing pus, circumscribed, elevated. Example: Acne, Impetigo. Scale: Shedding, dead skin cells. Examples: Dandruff (greasy), Psoriasis (dry). Telangiectasis: Dilated superficial blood vessels. Example: Rosacea. Ulcer: Lesion that is deeper than an erosion, caused by breakdown of epidermis and dermis. Urticaria: Hives. Vesicle: Blister; fluid-filled papule, circumscribed, elevated, up to 0.5 to 1 cm in diameter. Example: Early Herpes Zoster, Contact Dermatitis. Wheal: Edematous and transitory papule. Example: Hive. Common skin disorders by location Scalp: Seborrheic dermatitis, contact dermatitis, psoriasis, pediculosis. Ears: Seborrheic dermatitis, psoriasis, atopic dermatitis, actinic keratoses. Face: Acne, rosacea, impetigo, contact dermatitis, seborrheic dermatitis, herpes simplex, actinic keratoses. Eyelids: Contact dermatitis due to fingernail polish or hairspray, seborrheic dermatitis, atopic dermatitis. Posterior neck: Seborrheic dermatitis, psoriasis, contact dermatitis. Mouth: Herpes simplex. Axillae: Contact dermatitis, seborrheic dermatitis, erythrasma. Chest and back: Rosacea, acne, seborrheic dermatitis, psoriasis. Groin: Tinea, candida, bacterial infection, scabies, pediculosis. Penis: Contact dermatitis, fixed drug eruption, herpes simplex, scabies. Hands: Contact dermatitis, atopic dermatitis, psoriasis. Cubital fossae and popliteal fossae: Atopic dermatitis, contact dermatitis. Elbows and knees: Psoriasis, atopic dermatitis. Feet: Fungal infection, primary or secondary bacterial infection, contact dermatitis from footwear or foot care, atopic dermatitis, psoriasis. Copyright 2007 by Therapeutic Research Center Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

14 This handout accompanies the related articles published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 ~ Volume 28 ~ Number 9 following Pharmacist's Letter; January 2012; Vol: 28 PL CE LIVE September 2012 Long Guide Vaccines New developments will raise questions about who should get meningitis and shingles vaccines. Meningitis. Texas will REQUIRE meningococcal vaccination for ALL entering college students. First state to do so. Many other states just RECOMMEND it...or require it only for dorm dwellers. Recommend giving meningococcal conjugate vaccine (Menactra, Menveo) to kids at age 11 or 12...then a booster at age 16 to protect them through their early adult years. Shingles. Zostavax is now APPROVED for people 50 and up...but CDC still recommends it for ages 60 and up. Lowering the age would add 40 million more patients and really stretch the vaccine supply. Offer Zostavax to these 50-somethings if you have enough...but keep in mind that not all insurers will cover it for this age group. If you're low on the vaccine, ration it to those at highest risk...people 60 and over, starting chronic immunosuppressive therapy, or not able to tolerate shingles due to chronic pain or other conditions. Avoid Zostavax in patients who are ALREADY immunosuppressed. Be prepared to settle disputes caused by a confusing difference between Zostavax labeling and CDC recommendations. The labeling suggests spacing shingles and pneumococcal vaccines 4 weeks apart. But CDC does NOT advocate waiting. Recent evidence shows that giving them together doesn't reduce efficacy. Feel comfortable giving Zostavax at the same time as pneumococcal and/or flu vaccine if needed. If your standing order calls for spacing them, get a new vaccine order. You CAN give Zostavax to patients who have already had shingles. It isn't proven to prevent a recurrence yet...but it's not harmful. Explain that you only have to wait until the ACUTE symptoms are gone. To get all of your required immunization CE, see our PL CE & Training Organizer. Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

15 PSORIASIS You ll have patients ask about topical options for psoriasis. Help them find a regimen they can stick with...poor adherence with topicals is common. Emollients (Vaseline, Aquaphor, etc) can be used along with soaking to help remove scales...or 20 minutes after a topical steroid to help the steroid work better. Topical corticosteroids are a good choice for most patients. Recommend starting with twice-daily applications with most agents...then decreasing the frequency as lesions improve. Suggest picking one based on lesions and their location...shampoos, foams, or solutions for the scalp...low-potency steroids (hydrocortisone 1%, etc) for the face...and higher potency ones (clobetasol, etc) for thick plaques. To lessen side effects, recommend limiting very high-potency steroids to 2 to 4 weeks...trying combo therapy to lower steroid doses...and using emollientonly drug holidays when possible. Use our PL Chart, Comparison of Topical Corticosteroids, to help choose the right steroid. Tacrolimus (Protopic) or pimecrolimus (Elidel) are appropriate for thinskinned areas to help avoid steroid side effects. Many think the FDA cancer warnings are overblown...but be cautious in patients on UV light therapy. The combo may be riskier. Calcipotriene (Dovonex, etc) can be used for maintenance. Suggest combining it with a steroid if monotherapy isn t enough. Suggest calcitriol (Vectical) if calcipotriene causes too much irritation. Tazarotene (Tazorac, etc) is an alternative to high-potency steroids...but warn about skin irritation and sun sensitivity. Avoid it during pregnancy...due to the risk of birth defects. Tar (Elta Tar, etc) is an old standby for psoriasis that still works and is available OTC. Consider it for patients having trouble affording Rx options...but caution about staining. Explain that systemic therapies (methotrexate, Enbrel, etc) are for more severe disease...or if topicals aren t enough. Go to the Comparison of Topical Psoriasis Treatments Detail-Document. Management of psoriasis DISCUSSION POINTS LEARN MORE ABOUT THIS POINT... (Just click on the link for access!) Detail-Doc Comparison of Topical Psoriasis Treatments Detail-Doc Management of Common Skin Diseases Sorting through the topical steroids December 2009 Article how to choose a topical corticosteroid for skin problems Detail-Doc Comparison of Topical Corticosteroids Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

16 PL Detail-Document # This PL Detail-Document gives subscribers additional insight related to the Recommendations published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 Comparison of Topical Psoriasis Treatments Adherence is an issue in the treatment of psoriasis. Help patients choose a treatment option they will use consistently and correctly, long-term. Choice of therapy should be individualized based on efficacy, safety, convenience, and cosmetic acceptability. 1 Topicals are first-line for mild to moderate psoriasis. 1,3 Topicals are also commonly used for scalp or nail psoriasis, especially if these are the only areas affected. Facial, flexural (e.g., armpit area, etc), and genital areas are sensitive to the effects of topical medications. For these areas, short-term use of low or moderate potency topical corticosteroids, tacrolimus ointment (Protopic), or pimecrolimus cream (Elidel) can be used. Topical agents are generally appropriate for children, with some special precautions. If treatment is required during pregnancy, topical corticosteroids, alone or with topical calcipotriene (calcipotriol), are preferred. Non-medicated emollients can be used in all patients and increase efficacy of topical medications. Phototherapy can be used in conjunction with topicals to improve efficacy while limiting ultraviolet radiation exposure. Calcipotriene (calcipotriol)/betamethasone can be used for moderate to severe disease. For moderate to severe disease, additional options include biologics (e.g., adalimumab [Humira], etanercept [Enbrel], etc), methotrexate, cyclosporine, and acitretin (Soriatane). Topical corticosteroids can also be used as an adjunct for moderate to severe disease. The following table provides role in therapy, select adverse effects, and other pertinent information for common topical psoriasis medications. 1 Medication Role in Therapy Selected Adverse Effects Comments Topical corticosteroids Mild to moderate disease (first-line); 1,3 moderate to severe disease (adjunct); nail psoriasis (first-line); 1 scalp psoriasis (first-line) 1 solution 1,3 Note: Salicylic acid is added to some Canadian products (Diprosalic, Nerisalic) to decrease scaling, soften plaques, and improve corticosteroid penetration. 1 Risk increases with duration of use and increasing potency. Skin changes (e.g., atrophy, striae, dermatitis, bruising, folliculitis), hair growth, HPA axis suppression. 1 Monitor growth in children with long-term use. 3 Few studies, but long history of use. Superior to placebo. Efficacy increases as potency increases. 1 Vehicles affect efficacy and utility. 3 For scalp, consider a foam, shampoo, or Use lower-potency agents on the face or thin-skinned areas. 3 For the face, consider a cream (e.g., hydrocortisone 1%). 3 Reserve potent agents (e.g., betamethasone ointment) for thick plaques. 3,5 Some experts start with twice daily dosing, then taper. Limit use of very high potency agents (e.g., clobetasol) to 2 to 4 weeks. 3 Can combine or alternate steroid with calcipotriene (calcipotriol), calcitriol, or emollient to improve efficacy and reduce adverse effects. 1,4,5 P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: ~ 16

17 Detail-Document # This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER December 2009 ~ Volume 25 ~ Number Comparison of Topical Corticosteroids Potency of topical steroids is based on vasoconstricting ability, and ranked on a scale of I-VII. Typically, drugs that rank I are classified as very high potency; II is considered high potency; III and IV are medium potency; and V-VII are low potency. Classification can vary however, especially in the medium and high range ,59 FDA package labeling notes that similar vasoconstricting ability does not imply therapeutic equivalence. Most steroids are labeled for more than once daily dosing. Experts say that once daily dosing is often effective. * Propylene glycol is added to optimize drug absorption in the augmented formulations. Drug Dose b Dosage Form and Sizes AWP ($) for Selected Products (Brand is listed if generic is unavailable) Very High Potency 54-56,59 Augmented* betamethasone dipropionate 1,2 (Diprolene) Generics available Clobetasol propionate (Clobevate, Clobex, Cormax, Embeline, Embeline E, Olux, Temovate) 3-7 Generics available QD to BID QD (Shampoo) BID 0.05% Lotion (30, 60 ml) 0.05% Oint (15, 45, 50 gm) 0.05% Cream (15, 30, 45, 60 gm) 0.05% Cream (emollient base) (15, 30, 60 gm) 0.05% Foam (50, 100 gm) 0.05% Gel (15, 30, 60 gm) 0.05% Lotion (60 ml, 120 ml) 0.05% Oint (15, 30, 45, 60 gm) 0.05% Scalp application (25, 50 ml) 0.05% Shampoo (120 ml) 0.05% Spray (60, 128 ml) 60 ml lotion gm oint gm oint gm cream (emollient) gm cream gm cream gm gel gm oint gm oint ml scalp application ml scalp application ml shampoo (Clobex) ml spray (Clobex) Copyright 2009 by Therapeutic Research Center Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: Comments a It is recommended that patients on very high potency steroids not be discontinued abruptly; but instead switch to a lower potency agent. 56 Treatment duration for most very high potency steroids should not exceed 2 weeks, per FDA-approved labeling. Total dose should not exceed 50 grams or 50 ml (60 gm for Vanos) per week because of the potential for adrenal suppression per FDAapproved labeling. Occlusive dressings should be avoided with very high potency corticosteroids per FDA-approved labeling. Clobestasol may cause HPA axis suppression at doses as 17

18 LIMBREL You ll hear reports of acute liver injury linked to Limbrel. Limbrel (flavocoxid) is a mixture of plant-derived flavonoids that s marketed as a medical food for osteoarthritis. Medical foods are a little-known class of products that don t require specific FDA approval...but they must meet certain FDA requirements...and CAN be marketed for a specific disease. Now Limbrel is associated with rare cases of acute hepatitis...that can happen within 3 months of starting Limbrel and is reversible when it s stopped. The liver injury might be due to a hypersensitivity reaction...or possibly toxicity caused by one of the flavonoids. In fact, Limbrel is also associated with rare reports of hypersensitivity pneumonitis...an allergic reaction that causes chest tightness, trouble breathing, etc. Don t rely on Limbrel for osteoarthritis...there s no reliable evidence that it works. But if patients are already on it, tell them to immediately report signs of liver toxicity or allergic reaction. If you suspect an adverse reaction due to Limbrel or any other natural product, use our Natural MedWatch to report it. Go to the Liver Toxicity and Limbrel Detail-Document. Understanding medical foods DISCUSSION POINTS LEARN MORE ABOUT THIS POINT... (Just click on the link for access!) February 2010 Article Axona, Limbrel, CerefolinNAC, Foltx, etc are medical foods and NOT FDA-approved drugs October 2007 Article proliferation of new products in a little known category called medical foods Role of Limbrel in the management of osteoarthritis May 2005 Article Limbrel (flavocoxid) for osteoarthritis Continuing Education Course Natural Medicines in the Clinical Management of Osteoarthritis Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

19 This handout accompanies the related articles published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 ~ Volume 28 ~ Number 9 following Pharmacist's Letter; February 2010; Vol: 26 PL CE LIVE September 2012 Long Guide Medical Foods Most people don't realize that Axona, Limbrel, CerefolinNAC, Foltx, etc are medical foods and NOT FDAapproved drugs. Medical foods look just like traditional Rx meds...most say "Rx-only" on the label and have NDCs, package inserts, etc. But medical foods AREN'T reviewed and approved by FDA. Medical foods are completely legal under the law. They're supposed to meet unique nutritional needs for a specific disease that can't be met by ordinary foods. For example Phenyl-Free 1 formula for babies with phenylketonuria...cyclinex-1 for urea cycle disorder...and Ketonex-1 for maple syrup urine disease. But many medical foods push the envelope to the max. They often contain vitamins, minerals, or plant extracts just like dietary supplements. But medical foods CAN be promoted to manage a specific disease...supplements can't. Many manufacturers are using this to their advantage...to promote products that are not really different than supplements. Many products rely on some preliminary science...but there's often no real proof that they're beneficial. For example, Deplin is based on an association between low folate levels and depression. Folic acid MIGHT improve response to antidepressants...but there's no proof it helps depression by itself. Foltx has high-dose folic acid and other B vitamins for lowering homocysteine in patients at risk for cardiovascular disease. But these vitamins do NOT improve cardiovascular outcomes...and might even be harmful. DON'T recommend Foltx. And there's no reliable evidence that Limbrel helps arthritis. Tell patients not to expect miracles from many medical foods. Explain that there can even be risks. For example, folic acid 800 mcg/day or more might INCREASE cancer risk...and the prices can put a dent in the patient's pocketbook. Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

20 This handout accompanies the related articles published in PHARMACIST S LETTER / PRESCRIBER S LETTER September 2012 ~ Volume 28 ~ Number 9 following Pharmacist's Letter; May 2005; Vol: 21 PL CE LIVE September 2012 Long Guide Medical Foods People are asking about Limbrel (flavocoxid) for osteoarthritis. The name, flavocoxid, sounds like a COX-2 inhibitor. The product labeling looks like an Rx drug package insert... complete with chemical structure and NDC number. But Limbrel is NOT an Rx drug...not an OTC drug...and NOT a dietary supplement. The manufacturer is marketing it in the little-known category of "medical food." Medical foods are supposed to meet unique nutritional needs due to a specific disease that can't be met by ordinary foods. Some examples are Phenyl-Free-1 for babies with phenylketonuria... Pro-Phree for celiac disease...and Ketonex-1 for maple syrup disease. Ensure and many other enteral formulas aren't medical foods... because they're supplements to a normal diet, for the general population. "Medical foods" have a marketing advantage over "dietary supplements." Medical foods CAN claim to treat a medical condition such as arthritis. Supplements can only make structure and function claims such as "maintain healthy joints." Limbrel contains a combination of plant extracts called flavonoids. There's no proof it's effective for osteoarthritis...and it costs over $90 a month. Don't recommend it. Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax:

21 RESPIRATORY / ALLERGY You ll see Combivent Respimat (ipratropium/albuterol)...a new version of Combivent without chlorofluorocarbons (CFCs). The new device aerosolizes the drug without a propellant. Combivent Respimat will be available this September...and the old Combivent with CFCs will be phased out next year. The cost is similar...about $250 for 30 days of treatment. Help patients transition to the new device. Counsel patients to use just ONE spray QID of the new Combivent Respimat...instead of TWO sprays QID like Combivent. Combivent Respimat delivers less drug than Combivent...but more of it gets into the lungs so they are similarly effective for COPD. Point out that Combivent Respimat is NOT contraindicated in patients with soybean or peanut allergy...unlike the old Combivent. Pharmacist s Letter / Prescriber s Letter ~ P.O. Box 8190, Stockton, CA ~ Phone: ~ Fax: