Pharmacology Update
Meloxicam Tablets 7.5 Mobic—Boehringer Ingelheim
By William T. Elliott, MD, FACP and James Chan, PharmD, PhD
Given the popularity of the new cox-2 inhibitors, the introduction of a new nonsteroidal anti-inflammatory drug (NSAID) seems positively old fashioned, but that is exactly what Boehringer Ingelheim has done. Meloxicam is a new NSAID that was recently approved by the FDA for marketing. It is an oxicam nonsteroidal anti-inflammatory agent chemically similar to piroxicam (Feldene). In contrast to the recently introduced selective cyclooxygenase (COX)-2 inhibitors such as celecoxib (Celebrex) and rofecoxib (Vioxx) which are primarily inhibitors of COX-2, meloxicam has as preferential cyclooxygenase-2 selectivity.1 Meloxicam will be marketed in this country by Boehringer Ingelheim and Abbott Laboratories.
Indications
Meloxicam is indicated for the relief of signs and symptoms of osteoarthritis (OA).
Dosage
The recommended starting and maintenance dose of meloxicam is 7.5 mg with a maximum dose of 15 mg/d.2 It may be taken without regard to meals or antacids. The drug is supplied as 7.5-mg tablets.
Potential Advantages
Meloxicam has a long elimination half-life (about 20 h) and is dosed once daily. No dosage adjustment is required in patients with mild to moderate renal or hepatic impairment. Meloxicam does not appear to affect the pharmacokinetics and the average anticoagulant effect of warfarin as determined by prothrombin time. However, monitoring is recommended, particularly in the first few days after initiating or changing meloxicam therapy in patients taking warfarin.2
Potential Disadvantages
Similar to other NSAIDs, gastrointestinal (GI) adverse events were the most frequently reported events in the clinical trials.2 GI side effects may be more frequent than originally expected as, after the product was launched in the United Kingdom, the product labeling had to be updated to include stronger warnings for GI side effects and skin reactions. Forty-one percent of suspected adverse reactions reported (1330 in the first 21 months) were GI-related, including 18% perforations, ulcerations, and bleeding. Fourteen percent were dermatological side effects.5,8 Meloxicam is only approved for use in OA.
Comments
Meloxicam is an oxicam NSAID with greater activity against the inducible isoform of COX-2 than the constitutive COX-1. Its efficacy is reported to be similar to other NSAIDs, such as piroxicam, diclofenac, or naproxen,1,2,6 but early clinical trials suggest that meloxicam had improved gastrointestinal tolerability compared to piroxicam, diclofenac, or naproxen.1,3,4,7 Meloxicam in doses of 7.5 mg-15 mg/d was compared to piroxicam 20 mg/d, diclofenac 100 mg/d, or naproxen 750 mg/d. A meta-analysis of meloxicam studies (10 randomized trials, n > 20,000, duration up to 24 weeks) suggests that it causes fewer GI adverse events than non-COX-2 selective NSAIDs, including less dypepsia, fewer PUBs, and less frequent withdrawal of NSAIDs because of adverse events.3 However, the postmarketing experience in the United Kingdom suggests that GI events may be higher than suggested by these trials. A possible explanation of this difference may be the dose. The two largest trials—the Meloxicam Large-scale International Study Safety Assessment (MELISSA, n = 9323) and Safety and Efficacy Large-scale Evaluation of COX-Inhibiting Therapies (SELECT, n = 8656), were conducted with the lower, 7.5-mg dose. Thus, the preponderance of the safety evidence is based on this dose. Some patients may need a higher dose as there was some evidence that meloxicam may be less efficacious than other NSAIDs. In the MELISSA trial, there were more patients who discontinued meloxicam (7.5 mg/d) because of lack of efficacy compared than to diclofenac (100 mg/d) (odds ratio 1.66; 95% CI: 1.16-2.38).4 Meloxicam in low doses may have less effect on platelet aggregation than non-COX-2 selective NSAIDs such as diclofenac or indomethacin.9,10
The product labeling for meloxicam, unlike the selective COX-2 inhibitors, did not mention reduced GI events with meloxicam and other NSAIDs.2 Meloxicam (7.5 mg) costs about $2 per day, which is lower than celecoxib and rofecoxib, which are about $2.50 per day.
Clinical Implications
It is not clear if meloxicam offers any clear advantage over non-COX-2 selective NSAIDs. There have been no published comparative trials between meloxicam and COX-2 preferential inhibitors, such as nabumetone or etodolac, or COX-2 selective agents, such as celcoxib and rofecoxib.
References
1. Noble S, Balfour JA. Drugs 1996;51(3):424-430.
2. Mobic Product Labeling. Boehringer Ingelheim. April 1999.
3. Schoefeld P. Am J Med 1999;107(6A):48S-54S.
4. Hawkey C, et al. Br J Rheumatol 1998;37(9):937-945.
5. FDC Report. The Pink Sheet 1998;60(51):5.
6. Lipscomb GR, et al. Br J Clin Pharmacol 1998;46:133-137.
7. Dequeker J, et al. Br J Rheum 1998;37:946-951.
8. FDC Report. The Pink Sheet 1998;60(37):13.
9. Tegeder I, et al. Clin Pharmacol Ther 1999;65(5):533-544.
10. de Meijer A, et al. Clin Pharmacol Ther 1999;66(4): 425-430.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content