Medical Assistance Division Medicaid Drug Utilization Review Newsletter

Medical Assistance Division Medicaid Drug Utilization Review Newsletter Volume 5 Issue 3 2 nd Quarter 2011 Osteoporosis: Evolving Treatment Options Janelle Sheen, PharmD Prevalence Osteoporosis is a major public health concern for approximately 44 million Americans. Of the ten million Americans that are estimated to have osteoporosis, eight million are women and two million are men. An additional 34 million Americans are estimated to have low bone density, placing them at increased risk for osteoporosis and fractures.¹ DUR Board Members William J. Apfeldorf, MD Amy Bachyrycz, RPh, PharmD Greg D'Amour, RPh, PhC, CGP Jami D. Frost, MD Martin Jagers, RPh, PharmD Dennis Raisch, RPh, PhD, MS John Seibel, MD Linda Stogner, MD Gregory Toney, RPh, PharmD, BCPP Dale Whittleton, RPh Inside This Issue Osteoporosis: Evolving Treatment Options Update to Herpes Zoster Vaccine Prevention Osteoporosis is a disease that is characterized by low bone mass and structural weakening of bone tissue that can lead to an increased risk of fractures. In 2005, osteoporosis was responsible for an estimated two million fractures and $19 billion in costs. By 2025, experts predict that osteoporosis will be responsible for approximately three million fractures and $25.3 billion in costs each year. 1 Osteoporosis is often left undiagnosed due to the absence of symptoms, and it is typically not a disease that is addressed until vertebral collapse or a fracture has occurred.¹ It is important that health professionals are aware of the recommendations for the prevention, diagnosis, and treatment of osteoporosis. Health care providers should educate their patients on the most efficacious prevention techniques, and these include recognizing risk factors as seen in Table 1, identifying those at high risk for falls, and reiterating healthy lifestyle changes. 2 These lifestyle modifications include aerobic exercise such as walking or bike riding for 30-60 minutes everyday. Smoking cessation has also been shown to decrease fracture risk by increasing bone mineral density (BMD). Alcohol moderation is another important component of fracture prevention. It is recommended that both men and women consume alcohol in moderation, as >/= 3 drinks has been found to be detrimental to bone health. 3 The longer a patient complies with osteoporosis recommendations, the lower the risk of a fracture. 4 Calcium and Vitamin D While all groups agree calcium and vitamin D supplementation are important, the recommended daily amounts of each vary from one professional group to another. In general, all adults should consume at least 800mg-1000mg of elemental calcium a day in at least two divided doses. Postmenopausal women over the age of 50 years should receive 1000mg-1200mg of elemental calcium per day in divided doses. 3,5,6 Men over the age of 50 years should receive 800mg-1000mg of calcium per day. 3,5,6 It is important to note that all calcium supplements differ in their elemental calcium content; for example, a 500mg Tums Regular Strength 7 chewable tablet of calcium carbonate contains only 200mg of elemental calcium. For more calcium supplement information refer to the Quick Reference below. Calcium Quick Reference 7 Calcium Supplement Type % Elemental Calcium Carbonate 40 Tricalcium phosphate 38 Citrate 21 Lactate 13 Gluconate 9

In the last several years there has been much debate about the appropriate recommended daily intake (RDI) of vitamin D. Current guidelines recommend 400-1000 IU per day of vitamin D 3 (cholecalciferol) for individuals age 50 and older. 3,6 Adults < 50 need 400-800 IU of vitamin D 3 daily. Vitamin D 3 is the form of vitamin D that best supports bone health. These recommendations were revised due to a growing body of evidence that calcium and vitamin D deficiency is widespread. Table 1: Risk Factors for Osteoporosis 1,2,8 Caucasian or Asian race Skeletal disorders: osteogenesis imperfecta, Female gender rickets, hypophosphatasia, and spinal cord injury. Postmenopausal women* with family Endocrine and metabolic: hypogonadism, history hyperparathyroidism, thyrotoxicosis, Cushing Advanced age (especially with recurrent syndrome, metabolic acidosis, and Gaucher's falls ) disease. Poor health, frailty, below healthy Other disease states: cystic fibrosis, systemic weight lupus, rheumatoid arthritis, end stage renal Personal history of fracture as an adult disease, malabsorption, bone marrow diseases, Inadequate physical activity and hypercalciuria. Excessive alcohol intake Medications: glucocorticoids, phenytoin, Anorexia gonadotropin releasing hormone agonists, Current cigarette smoking methotrexate, excess thyroid hormone, heparin, Low calcium intake (lifelong) cyclosporine, and depot-medroxyprogesterone acetate. *Which can also include: menopause before age 45, having both ovaries removed, or the absence of menstrual periods for a year or more prior to menopause. Screening for Osteoporosis The diagnosis of osteoporosis is established by measurement of BMD. Dual-energy x-ray absorptiometry (DXA) measurement of the hip and spine is used to establish or confirm a diagnosis of osteoporosis, predict future fracture risk and monitor patients by performing serial assessments. 3,9 The BMD diagnosis of normal, low bone mass, osteoporosis and severe or established osteoporosis is based on the World Health Organization (WHO) diagnostic classification. A BMD that is within 1 SD of a young normal adult (T-score at -1.0 and above) is considered normal. Low bone mass (osteopenia) is a T-score between -1.0 and -2.5 and osteoporosis is a T-score at or below -2.5. The decision to perform bone density assessment should be based on an individual s fracture risk profile and skeletal health assessment. The following are indications for BMD testing: Women age 65 and older and men age 70 and older, regardless of clinical risk factors Younger postmenopausal women and men age 50 to 69 about whom there is concern based on clinical risk factor profile Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk such as low body weight, prior low-trauma fracture or high risk medication Adults who have a fracture after age 50 Adults with a condition (e.g., rheumatoid arthritis) or taking a medication (e.g., glucocorticoids in a daily dose 5 mg prednisone or equivalent for three months) associated with low bone mass or bone loss Anyone being considered for pharmacologic therapy for osteoporosis Anyone being treated for osteoporosis, to monitor treatment effect Anyone not receiving therapy in whom evidence of bone loss would lead to treatment Postmenopausal women discontinuing estrogen should be considered for bone density testing Treatment Osteoporosis treatment has been greatly advanced within the last century. Candidates for treatment include those with a hip or vertebral fracture, those with a BMD T-score less than or equal to -2.5, postmenopausal women and in men 50 years and older who have low bone mass or osteopenia with a T-score of -1 to -2.5, and lastly those at significant risk for osteoporosis. 3,10 Traditionally, hormone therapy (HT) had been used for the prevention and treatment of osteoporosis. However, since the Women s Health Initiative (WHI) trial, the U.S. Food and Drug Administration (FDA) has discouraged using HT primarily for osteoporosis. Currently the 2

manufacturer s labeling for all HT products states that HT should only be used in low doses and for physicians to prescribe other non-hormone containing products for the treatment of osteoporosis. 10,11 Table 1 compares the currently available osteoporosis treatments. Bisphosphonates: The most commonly prescribed medications for the treatment of osteoporosis are the bisphosphonates. Agents in this class indicated for osteoporosis include the oral medications risedronate (Actonel, Actonel with Calcium, Atelvia ), alendronate (Fosamax, Fosamax Plus D), and ibandronate (Boniva ). Bisphosphonates work by inhibiting osteoclast adherence to the bone surface; therefore decreasing bone resorption. With proper use of these agents, the risk of fracture is reduced by 45-55% at all skeletal sites including vertebral, nonvertebral, and hip. 11 The most common adverse effects are nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal ulceration and bleeding can occur if administration directions are not followed. These medications should be taken in the morning with at least four ounces of water, and at least 30 minutes before consuming any food or other medications. The patient should not recline or lie down for at least 30 minutes after taking a bisphosphonate to reduce the risk of gastrointestinal irritation. 7 Contraindications for bisphosphonates are hypersensitivity, hypocalcemia, inability to sit or stand upright for 30 minutes, and any abnormalities of the esophagus. Bisphosphonates are also cautioned to have increased gastrointestinal side effects with the use of non-steroidal anti-inflammatory medications, and decreased efficacy when coadministered with metallic cations such as antacids and iron supplements. 7 Use of bisphosphonates in patients with renal impairment is cautioned while osteonecrosis of the jaw is yet another precaution to use of this class of drugs. Raloxifene: Raloxifene (Evista ) is currently the only selective estrogen receptor modulator (SERM) FDA approved for use in the prevention or treatment of osteoporosis. Raloxifene is an estrogen agonist in bone tissue but acts as an estrogen antagonist in the breast and uterus. It has been found to increase BMD by 2-3%, but it has not been shown to prevent nonvertebral fractures. 10 Raloxifene is typically well tolerated but hot flashes occur frequently (10%-29%) and may lead to discontinuation of therapy. 7 Arthralgia, flu-like syndrome, and increased risk of infection are also reported adverse reactions. Some other disadvantages of this medication are the three fold increased risk of venous thromboembolism and the immediate decline of BMD to baseline after discontinuation. 10 Raloxifene is contraindicated in active thromboembolic disease and the product should be discontinued at least 72 hours prior to prolonged immobilization. 7,10 The use of this product is cautioned in patients with high risk for thromboembolism, cardiovascular disease, a history of cervical/uterine cancer, and women with a history of hypertriglyceridemia. Calcitonin: Calcitonin nasal spray (Fortical or Miacalcin ) is a thyroid hormone that is naturally released when serum calcium is high in order to decrease osteoclastic bone resorption. 7 Treatment with this medication can reduce the incidence of new fractures by 36%, but efficacy with nonvertebral fractures has not been consistent. The reduction in new fracture risk for calcitonin nasal spray (Fortical) is not significant enough compared to other osteoporosis medications to warrant it being used as a first line treatment. Therefore, calcitonin is reserved primarily for use in patients who have failed primary therapy, contraindications, or have had intolerable adverse events to other more efficacious treatments. 10,11 Adverse reactions to calcitonin include rhinitis and back pain most frequently, but other side effects may occur. Nasal adverse events may be more common in patients over 65 years of age, and if nasal ulceration occurs, temporary withdrawal may be necessary. Hypersensitivity is the main contraindication for this medication because the nasal spray is currently derived from salmon. 7 Teriparatide: Teriparatide (Forteo ) is a version of human parathyroid hormone that causes decreased osteoblast apoptosis and results in increased bone formation. Teriparatide has been found to reduce the risk of new vertebral fractures by 65% and nonvertebral fracture by 53% with a 20 mcg/day dosage. 11 It is important to note that teriparatide is only indicated for a duration of under two years and because it is an injection, these factors limit its use to a second-line therapy. 7,10 It should not to be used concomitantly with bisphosphonates because they may decrease the efficacy of teriparatide. Adverse reactions include hypertension, syncope, angina, and dizziness. Nausea, dyspepsia, rash, transient hypercalcemia, rhinitis, pharyngitis, arthralgia, and weakness occur less commonly. 7 Initially teriparatide may cause orthostatic hypotension. Therefore, patients should be instructed to administer this medication in a sitting or lying position. There are several contraindications with teriparatide: patients with Paget s disease, unexplained elevated alkaline phosphatase, open epiphyses, and prior skeletal radiation exposure. There is currently a black box warning in the manufacturer s labeling concerning osteosarcoma. This warning states that there is an 3

increased risk of osteosarcoma associated with the duration and dose of teriparatide. Therefore, any patients at risk for osteosarcoma should avoid use of this medication. 10 Injectable Treatments: A growing number of injectable treatments are available for the treatment of osteoporosis. Ibandronate (Boniva ) is a bisphosphonate given four times a year while zoledronic acid (Reclast ) is given only once yearly. 12 Both of these are given by intravenous infusion. A new agent is now available for subcutaneous injection, called denosumab (Prolia ). Denosumab is administered every six months and works by inhibiting osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in cortical and trabecular bone. 13 These treatments offer more options for patients looking for alternative agents for osteoporosis. Table 1: Osteoporosis Treatments 7 Drug Name Dosage Route Cost 18,19 Alendronate (Fosamax, Fosamax Plus D) Calcitonin (Fortical, Miacalcin ) 5mg/day 10mg/day 35mg/week 70mg/week 200IU/day (nasal) 100IU every other day (inj.) Oral * Nasal spray / SQ or IM Injection Denosumab (Prolia ) 60mg every 6 months SQ Injection *** Ibandronate (Boniva ) 150mg/month (oral) Oral and ** 3mg every 3 months (inj.) IV Injection Raloxifene (Evista ) 60mg/day Oral ** Risedronate (Actonel, Actonel with Calcium, Atelvia ) 5mg/day 35mg/week 75mg for 2 days monthly 150mg monthly Oral ** Teriparatide (Forteo ) 20mcg/day SQ Injection *** Zoledronic acid (Reclast ) 5mg once yearly (treatment) 5mg every two years (prevention) Cost Legend: *=low cost or generic available, **=mid cost, *** = high cost Conclusion Osteoporosis can be a devastating disease. Fortunately, new medications have been developed that offer safer and more efficacious options for the prevention and treatment of osteoporosis. Prescribers should be aware of the novel treatments and their place in therapy. Fractures are associated with significant morbidity and mortality. Six months after a hip fracture, only 15% of patients can walk across a room without aid. One in 4 ** IV Infusion *** Recent Concerns With Osteoporosis Drugs: Recent data suggest a rare but possible risk of atypical femur fractures with long-term bisphosphonate use. 14,15 The proposed mechanism is that long-term use might inhibit bone turnover and delay healing of micro-cracks which occur with normal daily activity. However, causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with bisphosphonates. Experts recommend stopping bisphosphonates after five years in patients at low risk for osteoporotic fractures, and recommend checking bone density at least every two years. Therapy can be restarted if bone density falls more than 4% in the spine or 5% in the hip. Patients at high risk due to very low bone density, previous fracture, or corticosteroid use, should consider continuation of the bisphosphonate. Physicians should consider the risks and benefits for each individual patient. There has also been data suggesting a correlation between bisphosphonates and osteonecrosis of the jaw (ONJ). While rare, it has been linked to dental procedures including tooth extractions. 16,17 Symptoms of osteonecrosis are severe pain and swelling in the jaw and loose teeth. Proper oral hygiene, including teeth brushing and flossing, can prevent jaw osteonecrosis. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk for ONJ. Clinical judgment of the treating health care provider should guide the management plan of each patient based on individual benefit/risk assessment.

five of those patients who were ambulatory prior to their fracture will now need long-term care. Lastly, an average of 24% of hip fracture patients age 50 years and over will die in the year following their fracture. 1 crucial to implement effective osteoporosis treatment and prevention strategies in eligible patients. It is References: 1. National Osteoporosis Foundation. Osteoporosis Fast Facts. January 25, 2011. Available at: http://www.nof.org/node/40. 2. American College of Rheumatology. Osteoporosis. January 25, 2011. Available at: www.rheumatology.org. 3. Clinician s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation. January 26, 2011. Available at: www.nof.org. 4. Gold DT. Understanding patient compliance and persistence with osteoporosis therapy. Drugs Aging 2001 Apr 1;28(4):249-55. 5. Spangler M, Phillips BB, Ross MB, et al. Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures. Am J Health Syst Pharm 2011 Feb 15;68(4):309-18. 6. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. November 2010. Available at: www.iom.edu/reports/2010. Accessed January 18, 2011. 7. Lexi-Comp Online. January 26, 2011. Available at: www.crlonline.com 8. Lewiecki EM. The role of risk communication in the care of osteoporosis. Curr Osteoporos Rep 2011 Apr 20 [Epub ahead of print]. 9. Cole RE. Clinical strategies to address patients concerns in osteoporosis management with bisphosphonates. Postgrad Med 2011 Mar;123(2):131-44. 10. Bushardt, R., Turner, J., Ragucci, K., Askins, D. Non-estrogen treatments for osteoporosis: An evidence-based review. Journal of the American Academy of Physicians Assistants 19.12 (2006): 25-30. 11. Watts NB, Bilezikian JP, Camacho PM, et al. American association of clinical endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis: executive summary of recommendations. Endocr Pract 2010 Nov-Dec;16(6):1016-9. 12. Recknor C. Zoledronic acid for prevention and treatment of osteoporosis. Expert Opin Pharmacother 2011 Apr;12(5):807-15. 13. Boonen S, Adachi JD, Man Z, et al. Treatment of denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 2011 Mar 16. 14. Schilcher J, Michaelsson K, Aspenberg P. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011 May 5;364(18):1728-37. 15. Kim SY, Schneeweiss S, Katz JN, et al. Oral bisphosphonate and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort. J Bone Miner Res 2011 May;26(5):993-1001. 16. Lewiecki EM. Safety of long-term bisphosphonate therapy for the management of osteoporosis. Drugs 2011 Apr 16;71(6):791-814. 17. Lo JC, Yang J, Hararah MK, et al. Oral health considerations in older women receiving oral bisphosphonate therapy. J Am Geriatr Soc 2011 May;59(5):916-22. 18. Claims Data. New Mexico Medicaid. Business Objects. April 18, 2011. 19. Source for pricing of injectables. FirstData Bank, Inc. San Bruno, CA. 2011. Update to Herpes Zoster Vaccine Zostavax is indicated for prevention of herpes zoster (shingles) in individuals 50 years of age and older and is not indicated for the treatment of zoster or postherpetic neuralgia or as a substitute for live varicella virus vaccine. It is not indicated for use in children or persons less than 50 years of age as there is insufficient data to recommend vaccination in these groups at this time. 1,2,3 Even though the safety and efficacy of Zostavax have not been studied in patients with a history of herpes zoster infection, these persons can still be vaccinated without any additional safety concerns. 2,4 References: 1. Kockler DR, McCarthy MW. Zoster vaccine live. Pharmacotherapy 2007;27(7):1013-19. 2. Harpaz R, Ortega-Sanchez IR, Seward JF. Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2008; 57:1-30. 5

3. Oxman MN, Levin MJ, Johnson GR et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005; 352:2271-84. 4. Adams EN, Parnapy S, Bautista P. Herpes zoster and vaccination: a clinical review. Am J Health-Syst Pharm. 2010; 67:724-7. To report medical fraud, contact the Medicaid Quality Assurance Bureau. NMMedicaidFraud@state.nm.us or (505) 827-3100 or (505) 827-3185. We appreciate your continued support of our efforts to encourage quality care for our Medicaid clients. Questions and/or comments about this newsletter may be directed to Diana Moya, R.Ph. at (505) 827-3174 or DianaJ.Moya@state.nm.us. DUR newsletters are posted on the New Mexico Human Services Department website: http://www.hsd.state.nm.us/mad/ppharmacy.html. 6