PHARM NOTES. Neil Medical Group: The Leading Pharmacy Provider in the Southeast. Neil Medical Group: The Leading. Warfarin: An Overview.

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1 PHARM NOTES Neil Medical Group: The Leading Pharmacy Provider in the Southeast Neil Medical Group: The Leading Volume 12, 17, Issue 21 January/February 2014 What is warfarin? Warfarin is an anticoagulant (blood thinner) that is used to prevent the formation of blood clots. Warfarin may commonly be called by its brand names: Coumadin or Jantoven. How does warfarin work? Warfarin is a vitamin K antagonist. This means that warfarin will block the regeneration of vitamin K (1) epoxide, which is a vital component in the process of clot formation, resulting in the prevention of coagulation or clot formation. Warfarin: An Overview How is warfarin dosed? Warfarin is dosed with the goal of keeping a patient s blood at the right level of anticoagulation. If a patient s blood gets too thin, they run the risk of bleeding; if it gets too thick, they risk the formation of clots. Therefore, the doctor will monitor how thin the patient s blood is by obtaining a PT/INR lab value from a blood sample. PT stands for prothrombin time and is measured in seconds. It is a measure of how long it takes a patient s blood to clot. However, different labs have a lot of variability in the PT results they report. This makes it difficult to monitor and adjust a patient s warfarin therapy based on PT results. In order to create a more standardized process, the INR (international normalized ratio) was developed. It is derived from a mathematical formula that incorporates the PT value and provides more consistent results. Therefore, warfarin therapy changes are based on the patients INR value. The INR correlates with how thin a patient s blood is; a higher INR indicates thinner blood and a lower INR indicates thicker blood (more likely to form a clot). Increasing the warfarin dose will increase the INR while lowering the dose will decrease the INR. Warfarin is dosed based on the patient s target INR range. The desired INR range will depend on what diagnosis the patient has that is requiring warfarin therapy. The following chart shows what the INR goal is for common diagnoses that utilize warfarin therapy. Continued on page 4 Inside This Issue: Warfarin: An Overview Page New Drug Update Page 4 5 Conclusion: Warfarin - An Overview Pages 6-7 Hypertension and the Geriatric Population Page 8 NMG Contact Information

2 New Drugs of 2013 Drug Generic Indication Dosage & Administration Combivent Respimat Ipratropium bromide/ albuterol COPD Eliquis Apixaban Prevent stroke and embolism in patients with non-valvular A-fib Fetzima Bleeding, increased bruising levomilnacipran Fycompa Perampanel Invokana Canagliflozin Khedezla Desvenlafaxine ER Linzess Different salt form than Pristiq so cannot be substituted automatically Linaclotide Depression Partial onset seizures in patients 12 and older Diabetes mellitus type 2 1 puff QID not to exceed 6 inhalations in 24 hrs; Requires assembly prior to use; utilizes a dial feature 5mg po BID Available as 2.5mg and 5mg tablets Reduce dose to 2.5mg BID if patient meets 2 of the following: age > 80, SCr > 1.5mg/dl, Weight < 60kg Initial dose: 20 mg orally once a day for 2 days then increase to 40 mg orally once a day. Dose may be increased in increments of 40 mg at intervals of 2 or more days based on tolerability and efficacy. Maintenance dose: 40 to 120 mg orally once a day. Available as 40, 80, 120mg extended release capsule Do not crush, chew or open the capsule Starting dose is 2mg QD at HS; increase dose by 2mg per day increments no more frequently than every week to a dose of 4-8mg once daily taken at HS; Available as 2,4,6,8,10, and 12mg tablets Dose for CrCl > 60ml/min mg daily; For CrCl of ml/min 100mg/day; Take before first meal of the day; Available as 100mg and 300mg tablets Side Effects Urinary retention, dizziness, increased eye pressure, tachycardia, agitation, insomnia, constipation Nausea, vomiting, constipation, blurred vision, increased sweating, tachycardia, decreased sex drive and orgasm Dizziness, drowsiness, fatigue, irritability, falls, URTIs, weight gain, vertigo, ataxia, anxiety, blurred vision, weakness, aggression, sedation Can have a diuretic effect leading to volume depletion and orthostatic or postural hypotension most common during the first 3 months of therapy; UTIs, vaginal yeast infection, hypoglycemia Depression 50mg and 100mg tablets Nausea, dizziness, insomnia, excessive sweating, constipation, anxiety, decreased appetite and sexual dysfunction IBS with constipation; chronic constipation in adults 145mcg/day for constipation and 290mcg/day for IBS; Loose stools, flatulence, abdominal pain and distention Important Information Replaces Combivent MDI No need to shake inhaler; Discard 3 months after first use or if canister locks, whichever comes first No labs required; no antidote to date; Avoid if user has mechanical heart valve or valvular A-fib; Cost $275/month Serotonin and norepinephrine reuptake inhibitor; Use lower doses in renal impairment. Contains boxed warning as other antidepressants for suicide risk Warning for serious neuropsychiatric events. Elderly patients: dose increases during titration are recommended no more frequently than every 2 weeks; Use lower doses in renal impairment New drug class called sodiumglucose co-transporter 2 (SGLT2) inhibitors; can be used as mono therapy or combination therapy; Avoid use in type I diabetics, severe renal impairment, ESRD or those with increased ketones in their urine or blood Take at least 30 minutes prior to 1 st meal of the day; Store capsules in original bottle with the desiccant due to stability issues; Take capsules whole; Cost $210/month Page 2 Neil Medical Group Pharmacy Services Division

3 Drug Generic Indication Dosage & Administration Side Effects Important Information Myrbetriq Mirabegron Overactive bladder Nesina Alogliptin Diabetes mellitus type 2 Ravicti Glycerol phenyl butyrate Urea cycle disorders that cause high ammonia levels Extended release tablet taken once daily; noncrushable; Available as 25mg and 50mg tablets Available as 6.25mg, 12.5mg and 25mg tablets; take once daily; Recommended dose is 25mg/d Adjust dose for CrCl ml/min to 12.5mg/day and CrCl 15-30ml/min to 6.25mg/day Liquid form given TID with food; dose varies with each patient Max dose is 17.5ml/day HTN, UTI, common cold symptoms, UTI, constipation, fatigue, tachycardia, abdominal pain URTIs, nasopharyngitis, HA, HTN, UTIs, back pain Diarrhea, HA, flatulence Avoid in patients with severe uncontrolled HTN, severe liver impairment, and ESRD: Cost $230/month Can be used as monotherapy or combination therapy Cost $275/month Patients must adhere to a low-protein diet accompanied by dietary supplements; orphan drug Tudorza Pressair Aclidinium bromide Long-term maintenance of COPD Dry powder inhaler used twice daily; Unique delivery system with a counter that drops by units of 10 ( ) and the line changes color to reflect that the dose was successfully administered Uceris Budesonide Ulcerative colitis 9mg extended release tablet taken once daily in the morning for up to 8 weeks; can take again in 8 week increments Vascepa Icosapent ethyl High triglyceride levels 4g daily with food Available as 1g capsules HA, cough, inflammation of the nasal passage, and warnings for paradoxical bronchospasm, new or worsened eye pressure; urinary retention HA, nausea, gas, abdominal pain, constipation, joint pain Arthralgia, sore throat Should NOT be used for rescue therapy. Good for 45 days once removed from pouch; Cost is $240/month Avoid grapefruit juice consumption; Targets the entire colon unlike other drugs; cost is $1200/month Monitor LFTs if existing hepatic impairment Cost $210 for 1 month Vibativ Telavancin Bacterial pneumonia caused by Staph. Aureus IV infusion once daily over 60 min for 7-14 days Can worsen kidney function Xeljanz Tofacitinib Moderate-severe active rheumatoid arthritis for patients who have failed MTX 5mg tablet taken twice daily; Use lower doses for moderate-severe renal impairment and moderate hepatic impairment HA, URTIs, diarrhea, serious opportunistic infections, TB and malignancies Use lower doses if taking with potent CYP3A4 inhibitors or drugs that results in both moderate CYP3A4 and potent CYP2C19 inhibition; May be used as monotherapy or combination therapy with other meds; Patients should NOT receive live vaccines while on this drug; Cost $1200/month Compiled by Bobbie Hall, Pharm D Neil Medical Group Pharmacy Services Division Page 3

4 Warfarin: An Overview....continued from page 1 Indication If the INR comes back too high, the doctor may reduce the warfarin dose; they may also hold a dose of warfarin if the INR is determined to be dangerously elevated. In less common cases such as an INR value exceeding 10, or in the presence of bleeding, the doctor may order the administration of vitamin K to reverse the effects of warfarin. Adverse Effects of Warfarin The most common adverse effect of warfarin is bleeding. Bruising is also common and almost expected, especially in elderly patients. Common signs and symptoms of bleeding include: Blood in the urine or stool (it may either be dark/ black or red in color) Vomiting of blood Cuts/nosebleeds that do not stop bleeding Unusual or extremely painful bleeding Confusion Dizziness Severe headache much more painful than a typical headache Other Adverse Effects of Warfarin: Taste disturbances Hair loss Rash Anemia Osteoporosis (with long-term use) Vomiting/Diarrhea INR Goal Non-valvular Atrial Fibrillation 2-3 Ischemic Stroke due to Atrial Fibrillation 2-3 LV Systolic Dysfunction with LV thrombus 2-3 Mechanical Aortic Valve 2-3 Bio-prosthetic Mitral Valve 2-3 Mechanical Mitral Valve Rheumatic Mitral Valve Disease (mitral stenosis) 2-3 Venous Thromboembolism (VTE) or Pulmonary Embolism (PE) treatment 2-3 Antiphospholipid Syndrome 2-3 Total Hip/Knee Replacement or Hip Fracture Surgery 2-3 Drug and Food Interactions Warfarin is associated with a multitude of drug interactions. Medications that may increase the anticoagulant effect of warfarin include: Cordarone (amiodarone) Diflucan (fluconazole) Flagyl (metronidazole) Levaquin and Cipro (levofloxacin and ciprofloxacin) Bactrim (trimethoprim/sulfamethoxazole) Tagamet (cimetidine) Erythromycin Serotonin Reuptake Inhibitors Celexa (citalopram) Cymbalta (duloxetine) Prozac (fluoxetine) Paxil (paroxetine) Ritonavir (in Kaletra and Norvir) Gengraf and Sandimmune (cyclosporine) NSAIDs Ibuprofen Mobic (meloxicam) Aleve or Naprosyn (naproxen) Voltaren/Cataflam (diclofenac) Celebrex (celecoxib) Antiplatelets Aspirin Plavix (clopidogrel) Aggrenox (dipyridamole and aspirin) Effient (prasugrel) Other Anticoagulants Argatroban Eliquis (apixaban) Pradaxa (dabigatran) Xarelto (rivaroxaban) Lovenox (enoxaparin) Heparin Herbal Supplements/Others Garlic Ginkgo biloba Grapefruit juice Alcohol Green Tea Page 4 Neil Medical Group Pharmacy Services Division

5 Medications that may DECREASE the effect of warfarin: Tegretol (carbamazepine) Dilantin (phenytoin) Phenobarbital Rifampin PPIs (e.g. omeprazole) Cigarette smoking Foods that contain Vitamin K can also decrease the effect of warfarin. The most common ones are dark green leafy vegetables such as: turnip/mustard/collard greens, kale, and spinach. Broccoli, cabbage, green leaf lettuce, Brussels sprouts, cauliflower, and liver also contain vitamin K, although to a lesser degree. It is ok to eat these foods as long as they are consumed on a consistent basis (the same amount each week) and not eaten in excess in one setting. Bridge Therapy Warfarin increases the risk of bleeding, especially during invasive procedures. Therefore, it is often necessary to hold warfarin and implement bridge therapy before and after a procedure that may be associated with bleeding. Bridge therapy is the term used when another anticoagulant such as Lovenox is used to provide anticoagulation in place of warfarin. Typically, warfarin will be stopped 3-7 days prior to the procedure and the patient will use Lovenox leading up to the procedure (Lovenox is usually started about 36 hours after the last dose of warfarin). The process of starting and stopping therapy is usually physician and procedure specific. Then, the patient may restart both warfarin and the other anticoagulant once the procedure is complete (usually the next day) and will continue to do so until their INR is stable again (usually 1 or 2 consecutive INR readings over 2.0). Once it is stable, they may continue treatment with only warfarin. Other Information It is best to administer warfarin at the SAME TIME each day. Missed doses MUST be documented for optimal therapeutic monitoring. Avoid the use of warfarin in pregnant women. Any signs or symptoms of bleeding should be reported and monitored because other, more serious bleeds may be occurring as well (e.g. GI or intracranial bleed). Other anticoagulants, antiplatelets, and their indications: Eliquis (apixaban) Non-valvular atrial fibrillation stroke/embolism prevention Neil Medical Group Pharmacy Services Division Xarelto (rivaroxaban) Postoperative prophylaxis of thromboembolism following hip/knee replacement surgery Non-valvular atrial fibrillation stroke/embolism prevention Treatment/risk reduction of DVT or PE Pradaxa (dabigatran) Non-valvular atrial fibrillation stroke/embolism prevention Argatroban Prophylaxis/treatment of heparin-induced thrombocytopenia (HIT) Adjunct to percutaneous coronary intervention (PCI) in patients at risk for HIT-associated thrombosis Plavix (clopidogrel) Myocardial infarction (MI) Stroke Peripheral arterial disease Aspirin Mild-moderate pain, inflammation, and fever Prevention/treatment of acute coronary syndromes, acute ischemic stroke, and TIAs Rheumatoid arthritis, fever, and osteoarthritis Coronary artery bypass graft (CABG), stent implantation, or percutaneous transluminal coronary angioplasty (PTCA) Lovenox (enoxaparin) Acute coronary syndrome DVT prophylaxis/treatment Heparin Prophylaxis/treatment of thromboembolic disorders Arixtra (fondaparinux) DVT prophylaxis in hip/knee replacement or hip/ abdominal surgery DVT or PE treatment Refludan (lepirudin) HIT Angiomax (bivalirudin) (usually used with aspirin) Unstable angina undergoing PTCA or PCI with/ without risk of HIT Article by: Greg Browning, PharmD Candidate Page 5

6 Hypertension and the Geriatric Population Hypertension is one of the most common chronic disease states in the country, and it is not age specific, affecting pre-teenagers to elderly people. There are two kinds of hypertension, primary and secondary. Primary hypertension is normally caused by genetics or personality; whereas, secondary hypertension is caused by another source (such as caffeine, tobacco use, alcohol use, and renal disease, just to name a few). This disease state is called the silent killer because patients affected by it often do not feel their own blood pressure. Hence the thought occurs: if I cannot feel it, there must not be anything wrong. However, this is definitely not the case. Over time, hypertension damages multiple organ systems, including the cardiovascular, renal, and nervous systems. As the blood travels through the vessels, the increased pressure forces increased muscle mass to form around them. This increase in smooth muscle decreases the flexibility of the vessels, and increases the shearing strain on all the junctions. Also, the increase in blood pressure damages the kidneys. The increased pressure in the kidney causes damage to the nephrons, which will then not function as efficiently. Finally, the nervous system is affected by hypertension too. In a patient with uncontrolled hypertension, eyesight may be lost due to the rupturing of vessels within the eye. This blindness is irreversible. Currently, there are two sets of guidelines that are used to determine the diagnosis, goals, treatment options, and monitoring parameters for hypertension JNC-7 and ADA-AHA. There are small differences between the two, but they are generally the same. Unfortunately, neither guideline gives information about the geriatric population. They go so far to say that a healthy adult s blood pressure goal is <140/90, and give recommendations as to goals for people with diabetes, heart failure, heart remodeling, and other coronary risk factors. However, treating an elderly person for hypertension is more complex and difficult as compared to treating a younger person. A geriatric patient is at increased risk for falls, orthostatic hypotension, electrolyte disturbances, and other adverse effects in general. Therefore, the first line, go to agents may not be the best choice for an elderly person. Angiotensin converting enzyme inhibitors (ACE- I) and angiotensin receptor blockers (ARB) are the mainstay of hypertension treatment according to the JNC-7 and ADA- AHA guidelines, and they can cause increased potassium, serum creatinine (SCr), and blood urea nitrogen (BUN). As people age, their renal function declines, and the potential exists for Page 6 Neil Medical Group Pharmacy Services Division

7 these medications to cause acute kidney injury. Diuretics, the other first line agents, may cause electrolyte imbalances and kidney injury as well. However, diuretics also increase the frequency that people go to the bathroom. This may increase fall risk in the geriatric population. Di-hydropyridine calcium channel blockers (CCB) such as amlodipine, nifedipine, and felodipine, can cause fluid retention and orthostatic hypotension, both of which may be exacerbated in the geriatric population. Nondihydropyridine CCB s and beta-blockers slow the heart rate of patients, and may not be favorable for persons of advanced age. Vasodilators, like hydralazine, nitroglycerin, and isosorbide, have the chance to cause serious orthostatic hypotension to the point of passing out due to the quick onset of action. So, the question is what medication, or medication class, is the best choice for this population? Normally, studies are performed to determine that answer. But, almost no primary literature exists for the treatment of geriatric hypertension. The Systolic Hypertension in the Elderly Program (SHEP) was a landmark study, a doubleblind, randomized, placebo controlled trial, which looked at thiazide-like diuretic (chlorthalidone) treatment in people aged 60 and older. Over the follow up period (average 4.5 years), systolic pressure was reduced by 12 points and diastolic pressure by 4 points. Also, the rate of stroke and fatal and non-fatal myocardial infarction was significantly reduced. The Hypertension in the Very Elderly Trial (HYVET) is another geriatric high blood pressure study that included only those people over the age of 85 years. This study included the ACE-I perindopril and the thiazide-related diuretic indapamide. The goal pressure was set at <150/80, and the authors noted a possible increased morbidity and mortality as they continued to push lower, however this still needs more evidence. Results of the HYVET trial showed a 15 point systolic decrease and a 6 point diastolic decrease. According to the current guideline JNC-7, an ACE-I/ARB or diuretic are still considered first line therapies for the geriatric population, unless a compelling indication exists for another class of antihypertensive. But, JNC-7 is outdated, as it was originally written in Updated guidelines, JNC-8, are supposed to be published in the very near future. There are many rumors as to what JNC-8 will recommend. Here are the basics of what is expected. JNC-8 is going to be more of an evidencebased guideline, very similar to the National Institute for Health and Clinical Excellence (NICE) guidelines used by England. A calcium channel blocker is recommended first line in persons aged over 55 years, ACE-I/ARB second line, and diuretics third line. However, if the person has edema, heart failure, or cannot tolerate a CCB, then a thiazide-like diuretic is first line. In summary, current guidelines recommend ACE-I/ARB or thiazide-like diuretic first line, which is supported by the SHEP and HYVET trials. However, the JNC-8 guidelines (yet to be published) may recommend a CCB first line, unless a clinical contraindication exists. Still, hypertension in the geriatric population should be treated, to a goal of at least <140/90. Since this population is more at risk to experience adverse reactions, the old saying of start low and go slow should be followed, and the person must be monitored carefully and frequently. Article by : Christopher Skowronski, Pharm.D. Candidate, Wingate University School of Pharmacy Neil Medical Group Pharmacy Services Division Page 7

8 Kinston Pharmacy 2545 Jetport Road Kinston, NC Phone Fax Neil Medical Group Pharmacy Services Mooresville Pharmacy 947 N. Main Street Mooresville, NC Phone Fax a note from the Editor Greetings to all the PharmNotes Family, Another year is behind us and we continue to deal with the struggles of our ever evolving health care system. Some times as we look ahead, I know we are all somewhat frustrated with the continual changes, cutbacks and uncertainty. I hear the repeated refrain. How do they continue to expect us to do MORE with LESS? But then..the one constant that never seems to change, is our desire to remain dedicated and give quality care to the residents and patients that we are honored to serve. I know I speak on behalf of the entire Neil Medical Group in extending a big Thank You for allowing us to be part of your team.and to say we look forward to continuing to serve you in the coming New Year May all of you enjoy the blessings of this season! And speaking of blessings...mason sends his wish to all of you for the happiest of New Years! Till next time. Cathy Fuquay Pharm Notes Editor Pharm Notes is a bimonthly publication by Neil Medical Group Pharmacy Services Division. Articles from all health care disciplines pertinent to long-term care are welcome. References for articles in Pharm Notes are available upon request. Your comments and suggestions are appreciated. Contact: Cathy Fuquay (cathyf@neilmedical.com) ext Note: Periodically, we are asked to add a name to our distribution list. At this time, copies of Pharm Notes newsletters are distributed in bulk to Neil Medical Group customers only.