OTC Case Studies: Arthritis

CASE 1: Topical Remedy

Q: WA is a 62-year-old woman who suffers from mild to moderate osteoarthritis in her knees. She visits the pharmacy on a Sunday while on vacation as she forgot to pack her prescription diclofenac gel and needs pain relief. The pharmacist contacts her insurer to initiate a vacation/lost medication override for the early refill but is not able to reach a representative. WA asks whether there is anything over the counter that could help her. She has gastroesophageal reflux disease, and her doctor has asked her to avoid medications such as ibuprofen. What advice should the pharmacist give WA?

A: Advise WA that the Voltaren (diclofenac) 1% topical gel, marketed as Voltaren Arthritis Pain, has been approved for OTC use to provide temporary relief of joint pain from arthritis. Remind WA to apply 4 grams of the gel to the affected knee(s) 4 times daily, with a maximum of 16 grams per joint per day.^1,2

CASE 2: Nonpharmacologic Therapy

Q: RC, a 67-year-old man, calls to seek advice after receiving a diagnosis of osteoarthritis of the knees. He says that he has chronic kidney disease, diabetes, and is obese. RC hopes to limit the number of medications he takes and asks if there are any exercises or other nonpharmacologic therapies that may aid in easing the pain and swelling associated with arthritis. What should the pharmacist recommend?

A: Data indicate that nonpharmacologic therapies such as exercise may improve function and offer pain relief. Study results suggest that a combination of aerobic and strengthening exercises would address osteoarthritis-related symptoms. However, RC should speak to his physician about setting up an individualized exercise plan. The results of a study show that patients who are obese or overweight find pain relief with at least 10% weight loss over 18 months.^3,4

Ice therapy is also recommended when patients with osteoarthritis are experiencing pain or swelling. Patients should apply ice to the injured area in 15- to 20-minute increments at least 3 or 4 times a day. The ice, which patients should not place directly on the skin without a damp cloth or a bag, should be applied for no longer than 15 to 20 minutes at a time, as direct application can result in blisters, burning, or vasoconstriction that reduces vascular removal of inflammatory mediators.^5,6

CASE 3: Supplements

Q: DR is a 53-year-old man who asks about supplements to aid in osteoarthritis treatment. His friend who has osteoarthritis takes nonsteroidal anti-inflammatory drugs (NSAIDs), but DR would like to try a natural product and avoid NSAIDs, if possible. DR has mild osteoarthritis of the knee and asks about evidence regarding the use of curcumin for pain and stiffness. What evidence should the pharmacist provide about curcumin?

A : Curcumin is the main curcuminoid present in the turmeric plant, Curcuma longa. Curcumin (turmeric) is a natural product with anti-inflammatory properties like NSAIDs that inhibits arachidonic acid, COX, and lipoxygenase, among other inflammatory mediators. When taken orally, curcumin is not adequately distributed into the bloodstream. However, a nanoparticle formulation with increased bioavailability has been formulated.⁷

In terms of clinical evidence, curcumin extract 30 mg 3 times per day has been compared with diclofenac 25 mg 3 times per day. Study results showed that curcumin decreased the COX-2 secretion into synovial fluid in a similar manner to diclofenac. Additionally, curcumin extract 1500 mg daily was compared with 1200 mg ibuprofen daily in a noninferiority trial for 4 weeks. The function, pain, and stiffness scores were all similar between the curcumin and ibuprofen groups. Patients in the curcumin group reported less abdominal pain and distention than those in the ibuprofen group.^8,9

Overall, curcumin is well tolerated up to 12,000 mg per day. The most common reported adverse effects include gastrointestinal (GI) discomfort and nausea. Additionally, curcumin inhibits platelet aggregation, so DR should discuss its use with his primary care provider and exercise caution if he is taking an antiplatelet or antithrombotic medication.^7,10

CASE 4: Acetaminophen Vs Ibuprofen

Q: EP is a 66-year-old woman who is picking up analgesic medications for osteoarthritis of the knee. She has been using a topical NSAID for a year and says it no longer provides pain relief. EP approaches the pharmacy counter with both acetaminophen 325-mg tablets and ibuprofen 200-mg tablets and asks which works better. She has no comorbidities and is not taking any other medications. What should the pharmacists advise?

A: Given that EP does not have comorbidities, such as chronic kidney disease or GI bleeding, advise her to initiate ibuprofen, as it has been proven to be superior to acetaminophen for osteoarthritis. It is appropriate to step up therapy from a topical to a systemic NSAID, as the topical one no longer provides her with relief. Both the American Academy of Orthopaedic Surgeons and the American College of Rheumatology strongly recommend oral NSAIDs for osteoarthritis pain relief. Because of the risk of unintentional overdose and the nonclinically meaningful benefits for pain relief, acetaminophen is no longer recommended over NSAIDs. If EP were to continue NSAIDs for chronic management of osteoarthritis pain, her primary care physician should consider starting her on a proton pump inhibitor to prevent the long-term adverse effects of NSAIDs. EP should take 200 mg of ibuprofen every 4 to 6 hours, although her dose may need to be increased with time to 400 to 800 mg 3 to 4 times per day, under physician supervision.^5,11-13

Ammie J. Patel, PharmD, BCPS, BCACP, is a clinical assistant professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway, and an ambulatory care specialist at RWJBarnabas Health Primary Care in Shrewsbury and Eatontown, New Jersey.Rupal Patel Mansukhani, PharmD, FAPhA, NCTTP, is a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey, and a transitions-of-care clinical pharmacist at Morristown Medical Center in New Jersey.

REFERENCES

• FDA approves three drugs for nonprescription use through Rx-to-OTC switch process. News release. FDA. Updated February 14, 2020. Accessed July 29, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-three-drugs-nonprescription-use-through-rx-otc-switch-process
• FDA approves GSK’s Voltaren Arthritis Pain for over-the-counter use in the United States. News release. GlaxoSmithKline; February 17, 2020. Accessed July 29, 2020. https://us.gsk.com/en-us/media/press-releases/fda-approves-gsk-s-voltaren-arthritis-pain-for-over-the-counter-use-in-the-united-states/
• Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476-499. doi:10.1016/j.joca.2010.01.013
• Bennell KL, Hinman RS. A review of the clinical evidence for exercise in osteoarthritis of the hip and knee. J Sci Med Sport. 2011;14(1):4-9. doi:10.1016/j.jsams.2010.08.002
• Hochberg MC, Altman RD, April KT, et al; American College of Rheumatology. American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res (Hoboken). 2012;64(4):465-474. doi:10.1002/acr.21596
• Osteoarthritis: care and management. National Institute for Health and Care Excellence. February 12, 2014. Accessed July 29, 2020. https://www.nice.org.uk/guidance/cg177/resources/osteoarthritis-care-and-management-pdf-35109757272517
• Agrawal S, Goel RK. Curcumin and its protective and therapeutic uses. Nat J Physiol Pharm Pharmacol. 2016;6(1):1-8. doi:10.5455/njppp.2016.6.3005201596
• Kertia N, Asdie AH, Rochmah W, Marsetyawan. Ability of curcuminoid compared to diclofenac sodium in reducing the secretion of cycloxygenase-2 enzyme by synovial fluid’s monocytes of patients with osteoarthritis. Acta Med Indones. 2012;44(2):105-113.
• Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, et al. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin Interv Aging. 2014;9:451-458. doi:10.2147/CIA.S58535
• Lopez HL. Nutritional interventions to prevent and treat osteoarthritis. Part II: focus on micronutrients and supportive nutraceuticals. PM R. 2012;4(suppl 5):S155-168. doi:10.1016/j.pmrj.2012.02.023
• Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225. doi:10.1136/bmj.h1225
• Roberts E, Delgado Nunes V, Buckner S, et al. Paracetamol: not as safe as we thought? A systematic literature review of observational studies. Ann Rheum Dis. 2016;75(3):552-559. doi:10.1136/annrheumdis-2014-206914
• Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition. American Academy of Orthopaedic Surgeons. May 18, 2013. Accessed July 29, 2020. https://aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-knee/osteoarthritis-of-the-knee-2nd-editiion-clinical-practice-guideline.pdf