When non-drug methods do not provide adequate relief, medications are used to treat OA. Previous guidelines touted acetaminophen (Tylenol) as a first line agent, primarily due to its lack of negative side effects (when compared to non-steroidal anti-inflammatory medications), but more recent guidelines refute this recommendation.
Two extra strength acetaminophen tablets every eight hours is the maximum dose recommended. The maximum amount of acetaminophen is three grams a day. It can be taken on a routine basis or on an as needed basis. Prolonged use of acetaminophen in higher than recommended doses or when combined with alcohol or certain medicines such as statins (e.g., atorvastatin, simvastatin) can damage the liver.
Caution should be used in patients who take acetaminophen when they are on warfarin. The combination of acetaminophen and warfarin can increase the INR (but less than non-steroidal anti-inflammatory agents). Absolute contraindication to acetaminophen is liver failure while relative contraindications include chronic alcohol abuse or hepatic insufficiency.
The American Academy of Orthopaedic Surgeons23 does not recommend for or against the use of acetaminophen. Their position paper reports that acetaminophen has no benefit over placebo. Others recommend that acetaminophen is the least effective option when compared to NSAIDs or the combination of glucosamine and chondroitin.24 They do acknowledge that the side effect profile of acetaminophen is less toxic than non-steroidal anti-inflammatory agents (NSAIDs). NSAIDs are considered more effective than acetaminophen in providing relief from hip and knee pain in osteoarthritis.25 Like acetaminophen, they act synergistically with opioids.
NSAIDs, such as ibuprofen (Motrin, Advil), naproxen sodium (Aleve, Naprosyn), choline and magnesium salicylates (Trilisate), diclofenac sodium (Voltaren, Voltaren XR), celecoxib (Celebrex), meloxicam (Mobic), and nabumetone (Relafen), are recommended over acetaminophen.26
These medications have more side effects than acetaminophen. Side effects common to NSAIDs include hypertension, edema, gastrointestinal bleeding, dyspepsia, headaches, constipation, mental status changes and renal insufficiency/kidney failure.
Absolute contraindications to NSAIDs include chronic kidney disease, an active peptic ulcer, and heart failure. Relative contraindications include a Helicobacter pylori infection, history peptic ulcer disease, hypertension, or concomitant use of selective serotonin receptor inhibitors or corticosteroids. Common interactions with NSAIDs include aspirin, warfarin, antihypertensive medications, selective serotonin reuptake inhibitors and corticosteroids.
Risk factors for gastric ulceration include older age, current use of corticosteroids, bleeding problems, or a history of gastric ulceration. These individuals should likely not use NSAIDs. The use of a proton pump inhibitor or misoprostol reduces the risk of gastric ulceration with the use of NSAIDs.
Another option for those with risk for gastric ulceration is the use of celecoxib. Celecoxib is the only available selective inhibitor of cyclooxygenase (COX) -2. COX-2 inhibitors are less likely to lead to gastric irritation. In those at very high risk for gastrointestinal bleeding a COX-2 agent along with a proton pump inhibitor can be used. Monitoring for and eradication of Helicobacter pylori reduces the risk of NSAID induced gastrointestinal injury.
NSAIDs have the potential to cause nephrotoxicity because they inhibit prostaglandin synthesis which is associated with vasoconstriction of the afferent arteriole in the kidney and may lead to renal impairment. When compared to traditional NSAIDS, celecoxib has a lower risk of GI bleeding.27
NSAIDs are associated with cardiovascular complications. They interfere with the cardio protective effect of aspirin28, elevate blood pressure and may precipitate or aggravate heart failure. NSAIDs also may amplify the risk of clotting and need to be used cautiously in those with a history of venous thrombosis. They should also be avoided in those with thrombocytopenia.
Generally, NSAIDs are equally effective29, but if one agent is ineffective another NSAID may be effective as there is individual variation in response to different NSAIDs. One study showed that diclofenac 150 mg/day was the most effective NSAID in managing pain and improving function.30
Topical NSAIDs may be used especially if the disease is localized to one area. Topical agents are associated with a significantly less adverse event profile than systemic agents. In the United States, diclofenac sodium topical gel and diclofenac sodium topical solution are available for the management of osteoarthritis.
Other topical agents can provide significant relief for patients with OA. Capsaicin (Zostrix) decreases the neurotransmitter called substance P, which is involved in the transmission of pain. Capsaicin is applied three to four times a day. It takes Capsaicin a few weeks before it provides significant pain relief. Hands should be washed after contact with the substance.
Another topical agent sometimes used for the treatment of localized pain is the lidocaine patch. This is not approved by the Food and Drug Administration for use in OA but is often used. It is a small patch applied to the skin around the painful joint wore for no more than 12 hours a day.
Other agents used in the treatment of osteoarthritis include duloxetine and hydroxychloroquine. These agents are not approved by the Food and Drug Administration for OA. Duloxetine is sometimes tried in those who do not respond to or have contraindications to NSAIDs. Research has shown that these agents result in some improvement in function and a reduction in pain, but associated with significant side effects including fatigue, dry mouth, constipation, reduced appetite and nausea. Duloxetine has only been studied in OA in the short term (up to 13 weeks).12
Hydroxychloroquine is theorized to reduce synovitis and possibly help patients with hand arthritis. While it may be helpful in some individuals, research does not show it significantly improves symptoms in hand arthritis.12
Tramadol (e.g., Ultram®, Ultram® ER) is dosed 50-100 mg every 4-6 hours for the immediate release form and 100 mg daily for the extended release form. For individuals suffering from chronic arthritic pain, the immediate release is initiated at 25 mg in the morning and increased by 25-50 mg per day every three days. The maximum dose for the immediate release form is 400 mg per day. The extended-release form is started at 100 mg once a day and increased by 100 mg every five days with a maximum dose of 300 mg per day. Side effects include constipation, dizziness, nausea, vomiting, euphoria, headache, itching, agitation, somnolence, hallucinations, and anxiety.
Tramadol interacts with narcotic medications and many antidepressants. For those with moderate to severe renal insufficiency or severe liver insufficiency, it should be used carefully. Tramadol lowers the seizure threshold and should, therefore, be used cautiously in those with a history of seizures. Caution must be used with tramadol as it has abuse potential.
Narcotic medicines are used when pain cannot be controlled by other means. When used they should only be used on a time-limited basis in those with disabling symptoms and/or severe pain that have not responded to other treatment modalities. Prior to starting opioid therapy, it is important to determine the effect the pain is having on the patient’s life, including functional ability and psychological impact. Narcotics are more powerful pain medications but have side effects. Narcotics have the potential side effects of sedation, respiratory depression, dizziness, falls, constipation, addiction and dependence. Narcotics medications include codeine, hydrocodone, hydromorphone, oxycodone, fentanyl, and morphine.