PHARM NOTES. Neil Medical Group: The Leading Pharmacy Provider in the Southeast. Neil Medical Group: The Leading. Rheumatoid Arthritis.

Transcription

1 PHARM NOTES Neil Medical Group: The Leading Pharmacy Provider in the Southeast Neil Medical Group: The Leading Volume 12, 17, Issue 24 July/August 2014 Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and other organs in the body. This is a chronic, symmetrical, systemic and progressive disease. It occurs in about 1% of the adult population, and affects women six times more commonly than men. RA costs the U.S. $127.8 billion annually. The etiology of RA is unknown, but likely involves genetic and environmental components. Rheumatoid factor and antibodies may be present in patients with RA and tend to predict more severe and aggressive disease. Tumor necrosis factor (TNF) and interleukin (IL)-1 and IL-6 are a few key pro -inflammatory substances that contribute to joint destruction and disease progression. These substances also contribute to the swelling, redness and pain. Rheumatoid Arthritis RA presents first in the hands and feet. The inflammation leads to cartilage and bone destruction. Typical symptoms include morning stiffness, swelling, redness, edema, pain, decreased range of motion, muscle atrophy, weakness, and deformity. RA may also present additional symptoms such as morning fatigue, fever, weakness, loss of appetite, and joint and muscle pain. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) is critical to the control of RA and slows down disease progression. The diagnosis is usually based on symptoms since there is no one lab test available for the diagnosis of RA. DIAGNOSTIC CRITERIA 1-4 must be present for 6 weeks and 4 or more criteria must be present. 1. Morning stiffness around joints lasting > 1 hour 2. Soft tissue swelling in 3 or more joints 3. Swelling of hand, foot or wrist joints 4. Symmetric involvement 5. Subcutaneous nodules 6. Positive serum rheumatoid factor 7. Radiographic erosions in hand or wrist joints The severity of RA is classified into three categories: mild, moderate and severe. MILD RA: Less then 6 effected joints ; no systemic signs or joint erosions. MODERATE RA: 6 to 20 inflamed joints; may have elevated ESR or CRP; positive rheumatoid factor; bone loss in joints; small erosions. continued on page 4 Inside This Issue: Rheumatoid Arthritis Page 2 3 Managing clostridium difficile Infections Page 4 5 Rheumatoid Arthritis conclusion Page 6-7 Pharm Notes Short Subjects Page 8 NMG Contact Information

2 Managing Clostridium difficile Infections Clostridium difficile (C. diff.) is a gram-positive bacterium that spreads from person-to-person by the fecal -oral route and causes significant diarrhea. In severe cases, this infection may lead to death. Infections caused by C. diff. are a leading cause of health careassociated gastrointestinal illness. It is estimated that C. diff infections cost the US health system 3.2 billion dollars annually. Rates of C. diff. infection continue to rise, particularly among the elderly with a recent hospital stay or those who live in the long-term-care setting. Risk factors for developing an infection caused by C. diff. include antibiotic exposure, exposure to the organism and advanced age. Other factors that may increase the risk of developing the infection include gastrointestinal tract surgery, the use of medications that reduce gastric acid production (such as proton pump inhibitors), immunosuppression, admission to the intensive care unit, the number and severity of comorbid conditions, sharing a hospital room with a patient infected with C. diff., receiving nutrition via tube feeding, hospitalization in an area where there are a large number of patients infected with C. diff., the use of enemas, and receiving chemotherapy. With respect to antibiotic exposure, while all antibiotics may cause C. diff. infection, certain ones may be more problematic. These include: clindamycin, broad-spectrum penicillin agents (particularly amoxicillin-clavulanic acid), second- and third-generation cephalosporins (such as ceftriaxone and cefuroxime), and fluoroquinolones (such as levofloxacin). The longer the course of the antibiotic and the greater number of antibiotics received, the higher the risk for developing an infection caused by C. diff. The use of proton pump inhibitors (PPIs) is considered a risk factor for developing C. diff. infection based on data from observational studies. There are also studies that suggest an association between the use of PPIs and the development of recurrent C. diff. While these type of studies are helpful to determine if a subject warrants more rigorous research, a definite conclusion as to whether PPIs are a risk factor for developing C. diff. cannot be drawn. A more recent retrospective analysis of the electronic medical records of 894 patients who tested positive for C. diff. was conducted to assess PPI use. This analysis did not find an association between the use of PPIs and developing C. diff. Routine testing for C. diff. infection is not recommended. Practice guidelines indicate that only patients with diarrhea should be tested and asymptomatic carriers should not be treated. Repeat testing is discouraged in the most recent practice guidelines, and testing for cure is not recommended. Two keys to preventing this infection are managing antibiotic use and the implementation of comprehensive infection control measures. Antibiotic stewardship programs that restrict the use of antibiotics with the greatest risk of causing C. diff. infections have been shown to be effective in preventing C. diff. Successful infection control measures include: the implementation of contact precautions, the use of soap and water for hand washing, thorough hand hy- Page 2 Neil Medical Group Pharmacy Services Division

3 giene practices, boarding infected patients together or in private rooms, the use of single-use/disposable equipment, and disinfection of equipment using an Environmental Protection Agency (EPA)-registered disinfectant with C. diff-sporicidal specified in the product labeling. While there is some evidence that 2 probiotics (L. rhamnosus GG and S. boulardii) may decrease the incidence of C. diff., evidence is lacking that show they prevent C. diff. C. diff. infections are classified as mild-to-moderate, severe disease, severe and complicated disease, and recurrent C. diff. infection. The recommended treatment regimens for each are listed below:* Severity Treatment Comment Mild-to-moderate disease Severe disease Severe and complicated disease Recurrent C. diff. infection (defined as infection within 8 weeks of completion of therapy) Metronidazole 500 mg PO TID for 10 days. If unable to take metronidazole, vancomycin 125 mg PO QID x 10 days. Vancomycin 125 mg PO QID x 10 days Vancomycin 500 mg PO QID plus metronidazole 500 mg IV q8h, and vancomycin 500 mg in 500 ml saline as an enema QID (for ileus or toxic colitis) Repeat metronidazole or vancomycin regimen. Pulse therapy (medication given every 3 days for 10 doses after completion of daily therapy) may be considered. If improvement not seen in 5-7 days on metronidazole, consider changing to oral vancomycin. Surgical consult recommended. Consider fecal microbiota transplant. *Fidaxomicin was not included as a recommendation for severe or complicated disease in the 2013 practice guidelines because data were not available on the efficacy. Studies show that it was not inferior to vancomycin for the initial treatment of C. diff. infections. Although the C. diff. organism has not shown resistance to the antibiotics used to treat the infection, the Centers for Disease Control and Prevention (CDC) considers the threat level for antibiotic resistance to be urgent because the organism spreads rapidly and is naturally resistant to the antibiotics used to treat other infections. Other treatment considerations for C. diff. infections include limiting or avoiding anti-peristaltic (anti-diarrheal) agents, maintaining adequate fluid intake and replacing electrolytes as warranted. Article by: Lori C. Dupree, B.Sc., PharmD, BCPS Consultant Pharmacist Neil Medical Group Pharmacy Services Division Page 3

4 Rheumatoid Arthritis...continued from page 1 SEVERE RA: More than 20 inflamed joints; Signs of systemic inflammation (elevated ESR or CRP) and at least one of the following: Anemia, Positive rheumatoid factor and/or anti -CCP antibodies, Bone erosion and loss of cartilage, Extended disease such as vasculitis, pericarditis, etc. Pharmacologic Treaments The goal is to have the patient on a disease-modifying antirheumatic drug (DMARD) within 3 months of diagnosis. DMARDs act on the immune system via various mechanisms to slow down the disease and help prevent further joint damage. In addition, patients may require short-term or long-term use of anti-inflammatory medications such as NSAIDS or steroids. Non-steroidal Anti-inflammatory Drugs (NSAIDS) NSAIDs are used often as a bridge for pain relief in patients who are just starting a new DMARD. Anti-inflammatory doses of NSAIDs include max 3200 mg/day Ibuprofen, mg/day celecoxib, 1000 mg/day of naproxen. Given the risk of GI bleeding, renal disease and heart failure associated with NSAIDs, patients should be carefully assessed before NSAIDs are started. Among NSAIDs, ibuprofen and celecoxib seem to have the lowest GI risk. However, celecoxib may have increased GI risk if patients use it for longer than six months or if they also use aspirin. It is recommended to add a PPI or an H2-blocker for patients at moderate GI risk due to one or two risk factors: age over 65, concomitant daily aspirin use, high-dose NSAIDs, a prior uncomplicated ulcer, concomitant warfarin or corticosteroid use. Corticosteroids Using prednisone at a dose of up to 7.5mg/day can calm active acute joint inflammation and can help slow disease progression, but adding methotrexate or a biologic DMARD usually allows the discontinuation of the steroid within six months. High-dose corticosteroids may be used for a short period of time during an acute flare. Monitor blood pressure and blood sugar in patients taking chronic corticosteroids. Patients are also at risk for bone loss. Be sure they are getting calcium and a vitamin D supplement. Nonbiologic DMARDs Patients with mild symptoms may be able to be managed by non-biologic DMARDs including methotrexate (Rheumatrex), leflunomide (Arava), hydroxychloroquine (Plaquenil), sulfasalazine (Azulfidine) and the newest agent, tofacitinib (Xeljanz). Monotherapy with one of these agents is recommended in early disease. Methotrexate: Methotrexate (Rheumatrex) is the most commonly used non-biologic DMARD. It is effective, slows disease progression, and is inexpensive. Methotrexate is usually started at mg once weekly; maintenance doses typically are mg once weekly. The maximum dose is 25 mg once weekly. Adverse effects include stomatitis, nausea, diarrhea and alopecia. Adding folic acid 5mg once weekly on the day following the methotrexate dose is recommended for decreasing side effects. Patients should avoid alcohol while taking methotrexate due to the risk of liver toxicity. Leflunomide: Leflunomide (Arava) is as effective as methotrexate at reducing disease activity and progression. It is used in patients who don t tolerate or respond to methotrexate and can t take biologic DMARDs. The usual maintenance dose is 10 mg or 20 mg daily after a loading dose of 100 mg daily for three days. Side effects include diarrhea, alopecia, rash, headache and hepatotoxicity. Peripheral neuropathy can also occur, usually about six months after beginning the drug. Patients should be counselled to report any tingling, burning, numbness or weakness in their hands or feet. Drug should be discontinued if these symptoms occur. Hydroxychloroquine: Hydroxychloroquine (Plaquenil) is also a treatment option for RA. It can be used for certain patients with mild to moderate RA that lack poor prognostic factors such as a positive rheumatoid factor. It also can be useful in women who may become pregnant due to its pregnancy category C. The usual maintenance dose is 200 mg twice daily. It typically has a longer onset of action and may show effect in 8-12 weeks. Adverse effects include nausea, diarrhea, rashes, pigmentation of skin and hair, vision changes. Sulfasalazine: Sulfasalazine (Azulfidine) is similar in efficacy to methotrexate or leflunomide monotherapy. It can be used as monotherapy in patients with early, moderate active RA, but methotrexate is a better choice especially in patients with poor prognostic factors. The usual maintenance dose of sulfasalazine is 1000 mg two or three times daily. Sulfasalazine side effects include nausea and abdominal discomfort. It can cause sun sensitivity so patients should avoid the sun or use protection. Tofacitinib: Tofacitinib (Xeljanz) became available in the U.S. in late It is a Janus Kinase (JAK) inhibitor and can suppress immune function. It is not a first-line agent. It is used for patients with moderate to severe RA who have had inadequate response or who cannot tolerate methotrexate. It can also be combined with methotrexate or other non-biologic DMARDs. The recommended dose is 5 mg twice daily. Dose should be reduced if patients take other potent CYP3A4 inhibitors (e.g. fluconazole, amiodarone, isoniazid etc.). Tofacitinib can increase cholesterol and liver enzymes and lower blood cell counts. Biologic DMARDs Biologic DMARDs target molecules on cells of the immune system, joints and the products that are secreted in the joints, all of which can cause inflammation and joint destruction. Biologic agents were designed to prevent or reduce the inflammation that damages joints. There are nine biologic Page 4 Neil Medical Group Pharmacy Services Division

5 DMARDs. Six of them are monoclonal antibodies including infliximab (Remicade), adalimumab (Humira), golimumab (Simponi), certolizumab pegol (Cimzia), tocilizumab (Actemra), rituximab (Rituxan). Three biologic agents are not monoclonal antibodies including Etanercept (Enbrel), Abatacept (Orencia), Anakinra (Kineret). According to the targets and mechanisms, biologic DMARDs are also classified as anti-tnf (tumor necrosis factor) agents and non-tnf agents. According to American College of Rheumatology guidelines, an anti-tnf agent can be used first line with or without methotrexate in patients with early disease of high activity with poor prognostic features. Some other guidelines recommend biologic DMARDs for patients who fail at least two nonbiologic DMARDs, alone or in combination. It is also recommended that an anti-tnf agent is the third step for patients with RA of low activity without poor prognosis who have failed three months of nonbiologic DMARD combination therapy. Anti-TNF Biologic DMARDs Etanercept: Etanercept (Enbrel) is not a monoclonal antibody. It is a TNF-soluble receptor protein and works by binding circulating TNF and preventing it from interacting with a cell receptor. It is a self-injectable. It is dosed either 25 mg twice weekly or 50 mg once weekly. Local injection site reactions are the most common side effect. Infliximab: Infliximab (Remicade) is a chimeric monoclonal antibody that binds to human TNF alpha. It is not a self-injectable, instead it requires an IV infusion. Infusion reactions are common. Pretreating with a corticosteroid and antihistamine is recommended to prevent infusion reactions. Adalimumab: Adalimumab (Humira) is a fully human monoclonal antibody that binds to TNF, blocking its interaction with TNF receptors. It is available as both a pre -filled syringe and an autoinjector. Humira is dosed every other week as a subcutaneous injection. Injection site reactions are the most common side effect. Golimumab: Golimumab (Simponi) is also a human monoclonal antibody that binds to TNF alpha. It is typically used in combination with methotrexate and is dosed once monthly. The autoinjector should be kept in the refrigerator and should sit at room temperature for 30 minutes before injecting. Certolizumab Pegol: Certolizumab Pegol (Cimzia) is a pegylated humanized antibody fragment of TNF monoclonal antibody. The drug binds to the TNF alphareceptor and blocks TNF alpha activity. It is given SC every 2 weeks for the first three doses, then every two to four weeks. The most common side effects are headache and upper respiratory tract infections. Non-TNF biologics Abatacept: Abatacept (Orencia) is a co-stimulation blocker and works by interfering with T lymphocyte activation. T cell activation leads to inflammation and disease progression in RA. Abatacept is reserved for patients who have not responded or not tolerated anti-tnf agents. It is started with an infusion as a loading dose, and then a subcutaneous dose is give within a day. After that, it is dosed subcutaneously once weekly. It also can be given as an infusion once monthly. Tocilizumab: Tocilizumab (Actemra) is a monoclonal antibody that binds to interleukin-6 (IL-6) receptors and blocks the action of IL-6, leading to a reduction of inflammatory response. It is used as a second line agent for patients who have not responded or not tolerated anti- TNF agents. It is given as a 1 hour IV every 4 weeks. Anakinra: Anakinra (Kineret) is a human recombinant protein that competitively blocks the IL-1 receptor and prevents inflammatory response. It is not used much anymore because it requires daily injections and it might be less efficacious than anti-tnf therapies. Rituximab: Rituximab (Rituxan) is a chimeric murine/ human monoclonal antibody that binds to CD20 antigen on B cells. Thus, it inhibits B cells and reduces inflammation. It is also used for patients with moderate-tosevere RA who are not having adequate response from nonbiologic or biologic DMARDs. It is given as two infusions two weeks apart, then every 24 weeks. Side effects include cough, rash, itching, and unstable blood pressure. Safety Issues and Precautions DMARDs can affect several organ systems, and biologic DMARDs increase risk of infection and malignancy. A complete blood count (CBC), serum creatinine, and liver function tests (LFTs) are recommended prior to initiating or resuming all DMARDs. These tests should be repeated every two to four weeks for three months after initiating and then should be repeated every 12 weeks. Acute hepatitis B or C is a contraindication to all DMARDs except hydroxychloroquine. Alcoholism and chronic liver disease, immunodeficiency, a creatinine clearance < 30 ml/min are contraindicated to methotrexate therapy. Tuberculosis should be screened and treated prior to starting biologics therapy. DMARDs should be held in the cases of serious infections. TNF-alpha blockers should not be used in patients with moderate to severe heart failure (class III or IV). There is no cure for rheumatoid arthritis, but the use of DMARDs can benefit patients by reducing pain, slowing joint destruction, improving functionality and improving quality of life. NSAIDs can be used to control pain and corticosteroids can be used to treat symptoms until a DMARD takes effect. Nonbiologic DMARDs are the first line therapy for most RA patients. The use of biologic DMARDs is increasing. Combination therapy is also very common. DMARDs can have serious adverse effects. Monitoring to manage and prevent adverse events is an important part of RA treatment. Article by Ming Li, Pharm D Candidate UNC School of Pharmacy Neil Medical Group Pharmacy Services Division Page 5

6 Pharm Notes: Short Subjects C-peptide and relation to insulin: A C-peptide test measures the level of C-peptide in the blood. C-peptide and insulin are linked when first made by the pancreas so they can be found in equal amounts in the blood. This allows it to be used as a marker of beta cell function and insulin production. A C-peptide test is done to: Help tell the difference between type 1 diabetes and type 2 diabetes. Type 1: low levels of insulin and C-peptide Type 2: normal or high levels of C-peptide Find the cause of low blood sugar or hypoglycemic events Check to see whether a tumor of the pancreas or insulinoma was completely removed. Pulmonary Vein Ablation : Pulmonary vein ablation is a therapeutic approach for controlling atrial fibrillation. Patients who receive pulmonary vein ablation are those who either continue to have AF symptoms despite medication use or those who cannot tolerate medication use. This procedure involves the use of a transcutaneous catheter technique that helps to control the mechanism of the arrhythmia. This procedure does have complications such as the risk of CVA, cardiac tamponade, and loss of atrial rhythm and function. The pulmonary vein is the target for controlling atrial fibrillation because studies have shown that there are rapidly firing foci in and around the pulmonary vein and if these foci get ablated, then paroxysmal atrial fibrillation can disappear. When the vein gets ablated, the scars that form block the impulses that fire within the pulmonary veins from getting to the heart. It may take about 1-3 months for symptoms of AF to subside after the procedure because it takes that amount of time for the scars to form. Cystocele: Cystocele is when the bladder begins to droop into the vagina due to weakening of the wall that separates the bladder and the vagina. The wall can weaken during the time women go through menopause. The wall is kept strong through the hormone estrogen. As estrogen levels decline, the wall separating the bladder and vagina can start to weaken. This can cause urinary side effects such as being unable to completely empty the bladder and urine leakage. There are 3 stages that categorize cystocele, grades 1-3, with grade 1 being mild to grade 3 being the most advanced and bothersome. Causes: Muscle strain during child birth Heavy lifting Straining during bowel movements Diagnosis: symptoms/physical exam Voiding cystourethrogram x-ray done during urination Treatment: Ranges from no treatment to surgery Non-bothersome symptoms: avoid heavy lifting and straining. Moderate/bothersome: the doctor may insert a pessary device which helps to hold the bladder in place. These are removable. Surgery may be required for severe cases. Page 6 Neil Medical Group Pharmacy Services Division

7 Encephalopathy: Encephalopathy is a condition of brain dysfunction. There are many types of encephalopathy with hepatic encephalopathy being the most common. Hepatic encephalopathy is a worsening of brain function that occurs when the liver is no longer able to remove toxic substances in the blood. Symptoms include: Being confused Memory problems Mood changes Trouble speaking, drawing, and writing clearly Problems with sleep Moving more slowly than normal Flapping hands Ammonia: Ammonia is produced when proteins are broken down by the bacteria in the intestines. It is one of the harmful substances that is normally converted into urea by the liver. When the liver is damaged, ammonia will build up in the body. It can cause damage to the nervous system. Serum ammonia levels can be used for diagnosis of encephalopathy. Results are usually available within 12 hours. Normal ammonia value for adults is mcg/dl. Lactulose is a synthetic disaccharide that is a mainstay of therapy of hepatic encephalopathy. 70 to 80 percent of patients with hepatic encephalopathy can be improved on lactulose treatment. Lactulose works by preventing intestinal bacteria from creating ammonia and through leaching ammonia into the colon for excretion via bowl movements. The dose of Lactulose should be titrated to achieve two to three soft stools per day. Typically, lactulose is given as 30 to 45 ml [20 to 30 grams] two to four times per day. Treatment is usually well tolerated, and the major side effects include abdominal cramping, diarrhea, and flatulence. Schatzki ring: Schatzki Ring is a smooth, narrow ring of tissue in the lower end of the esophagus. It may be caused from long-term damage from stomach acid reflux. Management of these rings involves procedures that will stretch or fracture these rings to allow more free passage of solid food. This can be accomplished with endoscopes or tapered dilators inserted through the mouth. Calcium Supplementation: Calcium and Vitamin D supplementation recommendations vary by age. Recommended daily intake of calcium for postmenopausal women and men is 1000mg and for postmenopausal women is 1200mg. Recommended daily intake of vitamin D is 800 units for men >70 and postmenopausal women, whereas 600 units is recommended for premenopausal women or younger men with osteoporosis. This can be supplemented with a combination tablet of calcium 500 mg-vitamin D 400 units PO BID or TID. Chronic opioid induced Constipation: Patients who are using opioid analgesics on a frequent or chronic basis should be monitored and evaluated for constipation. The best prevention for opioid induced constipation is a bowel regimen including a stimulant laxative, such as docusate and senna. Contributions from Pharm D Candidates Ming Li and Logan Dawson 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 Pharm Notes Family, Just a few notable quotes to make you think.. Happiness is an attitude. We either make ourselves miserable, or happy and strong. The amount of work is the same. - Francesca Reigler Some days there won t be a song in you heart. Sing anyway. - Emory Austin About the only thing that comes without effort is old age. - Unknown Things turn out best for those who make the best of the way things turn out. - Jack Buck A positive attitude may not solve all your problems, but it will annoy enough people to make it worth the effort. - Herm Albright 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.