Chronic osteoarthritis.(DRUG UPDATE)

The much publicized removal of all but one of the three cyclooxygenase-2 inhibitors from the U.S. market because of concerns over their cardiovascular risks has forced clinicians to reconsider pain control strategies for many of their patients with osteoarthritis. The COX-2 inhibitors were developed for patients at increased risk for GI side effects associated with chronic treatment with traditional NSAIDs. But once approved, they were enthusiastically adopted for broader use in arthritic conditions, even among patients at less risk. And many clinicians and patients perceived COX-2s to be more effective pain relievers than traditional NSAIDs, although this was never shown in clinical trials.

Following the February 2005 meeting of the Food and Drug Administration's advisory panel on the cardiovascular safety of the COX-2 selective and nonselective NSAIDs, the agency announced it would require changes to the labeling of all prescription and nonprescription NSAIDs, including celecoxib. The changes include a boxed warning about the serious cardiovascular risks and potentially life-threatening GI bleeding associated with this class of drugs and a contraindication for patients who have recently undergone coronary bypass surgery.

Until more comprehensive data on the long-term safety of NSAIDs become available, experts emphasize that decisions on pharmacologic management of osteoarthritis must include a risk-benefit assessment balancing potential GI hazards with cardiovascular risk, based on a patient's history and clinical condition.

Many patients do well with standard doses of over-the-counter drugs, such as ibuprofen, naproxen, and acetaminophen. The potential for NSAID toxicity is lower since OTC formulations contain lower doses, and GI side effects are dose related. But for patients with more severe symptoms and for those such as the elderly who have risk factors for complications, many prescription NSAIDs are still available. Those with greater COX-2 selectivity are safer from a GI standpoint, and for patients with GI risks, a proton pump inhibitor (PPI) can be given as cotherapy. The use of concurrent low-dose aspirin therapy must be considered in patients taking NSAIDs for osteoarthritis. If these patients are at risk for GI complications, they need to take gastroprotective cotherapy, either a PPI or misoprostol. However, diarrhea associated with misoprostol can limit its use.

Low-dose opiates and combinations such as hydrocodone plus acetaminophen (Vicodin, Norco, and others) and propoxyphene (Darvon) are another option. It is important to monitor elderly patients on these drugs for sedation and constipation.

Nonpharmacologic strategies to manage osteoarthritis pain have assumed greater importance as awareness has grown regarding potential long-term hazards associated with drug treatment. Modalities such as water aerobics, exercise, and massage can be helpful. Many patients report relief from Bengay and Aspercreme use, but only capsaicin cream has been demonstrated to be effective in providing local pain relief in placebo-controlled studies. Support groups and self-help programs can help patients cope with their condition and help them remain active and functional.

 
Drug           Cost/Day *               Dosage       What the Experts 
                                                     Say ** 
 
 NONPRESCRIPTION DRUGS 
 
acetaminophen  $0.12 (325 mg q.i.d.)    325-1,000    At some centers, 
                                        mg every     now used more 
                                        4-6 hours    widely as 
                                                     first-line 
                                                     treatment for 
                                                     osteoarthritis 
                                                     (OA) because of 
                                                     its overall 
                                                     safety, 
                                                     including lack 
                                                     of 
                                                     cardiotoxicity. 
                                                     Also recommended 
                                                     for use in 
                                                     patients with a 
                                                     history of GI 
                                                     bleed. Its 
                                                     effects are 
                                                     primarily 
                                                     analgesic, 
                                                     rather than 
                                                     anti- 
                                                     inflammatory, 
                                                     although this 
                                                     has not been 
                                                     proved, so it is 
                                                     more likely to 
                                                     be beneficial in 
                                                     patients whose 
                                                     primary symptom 
                                                     is pain and who 
                                                     have little 
                                                     joint 
                                                     inflammation. 
                                                     Also available 
                                                     in combination 
                                                     with codeine and 
                                                     other analgesic 
                                                     medications. 
 
ibuprofen       $0.20 (200 mg q.i.d.)   200-400 mg   Ibuprofen has a 
 [Motrin]      [$0.32 (200 mg q.i.d.)]  every 4-6    long history of 
 [Advil]       [$0.38 (200 mg q.i.d.)]  hours        successful 
                                                     treatment of OA, 
                                                     and is not 
                                                     associated with 
                                                     a high risk of 
                                                     GI bleeding at 
                                                     OTC doses. 
                                                     Available in 
                                                     multiple OTC and 
                                                     prescription- 
                                                     strength 
                                                     formulations. 
 
naproxen        $0.14 (220 mg b.i.d.)   220 mg       Data presented 
 [Aleve]       [$0.18 (220 mg b.i.d)]   every 8-12   in February 2005 
                                        hours        to the FDA 
                                                     advisory panel 
                                                     suggested that 
                                                     naproxen may be 
                                                     associated with 
                                                     a lower 
                                                     cardiovascular 
                                                     risk than the 
                                                     other 
                                                     nonselective 
                                                     NSAIDs. But it 
                                                     is more 
                                                     ulcerogenic than 
                                                     ibuprofen, so 
                                                     patients at risk 
                                                     for GI adverse 
                                                     effects should 
                                                     take a PPI. 
                                                     Also available 
                                                     as prescription 
                                                     generic and 
                                                     trade 
                                                     formulations 
                                                     (Naprosyn, 
                                                     Anaprox, 
                                                     Naprelan), at 
                                                     250-500 mg 
                                                     b.i.d. 
 
 PRESCRIPTION DRUGS 
 
diclofenac      $1.73 (100 mg/day)      100-150      Nonselective 
 [Cataflam]    [$5.59 (100 mg/day)]     mg/day in    NSAIDs. The FDA 
 [Voltaren]    [$4.04 (100 mg/day)]     divided      has stated that 
                                        doses        available data 
                                                     suggest that use 
etodolac       $1.44 (200 mg every 6    200-400 mg   of any 
               hours or t.i.d.)         every 6-8    prescription- 
 [Lodine]      [$4.47 (200 mg every 6   hours        strength NSAID 
               hours or t.i.d)]                      may increase 
                                                     cardiovascular 
meloxicam      no generic available     7.5-15       risk, but 
 [Mobic]       [$3.13 (7.5 mg)]         mg/day       because 
                                                     long-term 
nabumetone     $3.10 (1,500 mg/day)     1,500-2,000  controlled 
 [Relafen]     [$4.23 (1,500 mg/day)]   mg/day       trials have not 
                                                     been conducted 
                                                     for most of 
                                                     these drugs, it 
                                                     is difficult to 
                                                     draw conclusions 
                                                     about 
                                                     differences 
                                                     in 
                                                     cardiovascular 
                                                     risk (other than 
                                                     for naproxen). 
                 ...