An NSAID such as diclofenac is indicated for this patient with knee osteoarthritis. In addition to the implementation of nonpharmacologic measures such as an exercise regimen and/or assistive devices, the initial pharmacologic management of osteoarthritis recommended in guidelines issued by various societies is acetaminophen in doses ≤3 g/d. If this offers inadequate relief, NSAIDs can be used. NSAIDs are more efficacious than acetaminophen in the relief of osteoarthritis pain. Treatment guidelines suggest using the lowest possible effective dose for the shortest time period because side effects are common and occasionally severe. However, many patients require years of NSAID use given the prolonged timeframe over which the disease is symptomatic and the small number of alternative pharmacologic treatments. NSAIDs are associated with important toxicities, particularly with prolonged exposure. The risk of peptic ulcer disease and gastrointestinal bleeding can be reduced with concomitant use of proton pump inhibitors. Cardiovascular risks can be mitigated by appropriate patient selection for chronic NSAID use.

Topical capsaicin can be used at any time to treat osteoarthritis as well; however, in the absence of an effect from acetaminophen, an NSAID is likely to give this patient more substantial relief of symptoms.

Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved to treat osteoarthritis pain but is slower acting than NSAIDs and requires ongoing, rather than intermittent and as-needed, administration.

Hyaluronic acid injections have shown only a minimal degree of benefit in the treatment of knee osteoarthritis; they also require an invasive procedure for administration and are expensive. Therefore, they would not be preferred to treatment with an NSAID.

Narcotics such as hydrocodone should be reserved for patients who have not responded to nonpharmacologic measures in addition to NSAIDs. An alternative to hydrocodone is tramadol, a centrally acting synthetic opioid analgesic that binds to μ-opioid receptors and inhibits reuptake of norepinephrine and serotonin. It can be used for analgesia when NSAIDs are not tolerated or are contraindicated. Side effects include headaches and dizziness. Tolerance can occur with long-term use; withdrawal symptoms can occur with discontinuation.