COX-2 Inhibitor Therapy: When Is Monitoring Required?

Q:Is periodic laboratory monitoring recommended for patients withosteoarthritis who are receiving long-term cyclooxygenase-2 (COX-2)inhibitor therapy and who have no GI or renal symptoms? Similarly,is laboratory monitoring recommended for women who take a selectiveCOX-2 inhibitor to alleviate menstrual cramps (eg, rofecoxib, 50 mg/d,3 to 5 days per month)?----Sarita Salzberg, MDColumbus, OhioA:The selective COX-2 inhibitors were designed to target the proinflammatoryprostaglandins produced by the COX-2 isoform while sparing thehomeostatic prostaglandins synthesized by the COX-1 isoform. Thus, it washoped that these new selective NSAIDs would relieve pain, inflammation, andfever without harming the GI system, platelets, kidneys, or other organs.ADVERSE EFFECTS OFSELECTIVE COX-2 INHIBITORSStudies have demonstrated that the COX-2 inhibitors are highly effectiveanalgesics and that they clearly reduce GI complications and appear to lowerperioperative bleeding risks compared with traditional nonselective NSAIDs.^1,2Bear in mind, however, that hypertension, edema, and renal dysfunction candevelop in certain patients who receive these agents.Although these cardiorenal adverse effects--which occur with celecoxib,rofecoxib, and valdecoxib--closely resemble the pattern of nephrotoxicityassociated with traditional nonselective NSAIDs, they typically develop only inpatients with underlying prostaglandin-dependent disease, such as hypertension,congestive heart failure, chronic renal insufficiency, volume depletion,nephrotic syndrome, or cirrhosis. Advanced age does not increase the risk ofadverse effects unless one of these conditions is present.WHO IS AT RISK?Patients who are otherwise healthy very rarely suffer from these druginducedcomplications. In fact, the overall renal safety of the selective COX-2inhibitors has been documented in large osteoarthritis trials that includedotherwise healthy subjects.^3,4Before you prescribe a selective COX-2 inhibitor, assess the patient forrisk factors that predispose to cardiorenal complications. This will helpyou determine appropriate monitoring strategies (Table). In patients whohave multiple risk factors for cardiorenal toxicity, use the lowest effectivedose of the NSAID--either selective or nonselective--or avoid these agentsaltogether.If adverse effects develop, either temporarily or permanently discontinuethe selective COX-2 inhibitor. Discontinuation of therapy permits reversal ofthe adverse effects and recovery to baseline blood pressure, body weight, andrenal function. Reinstitution of COX-2 therapy following correction of volumeissues or discontinuation of concomitant nephrotoxic medications is possiblebut only with the close clinical monitoring described in the Table.RECOMMENDATIONSFOR PATIENTS ATLOW RISKIn otherwise healthy patientswho are receiving long-term COX-2inhibitor therapy for osteoarthritis,regular laboratory monitoring is notrequired. However, consider screeningsuch patients intermittently forthe development of hypertension andedema, as well as occult GI blood loss (through stoolcards). Evaluation of renal function parameters (electrolyte,blood urea nitrogen, and serum creatinine levels) isalso reasonable if hypertension or edema develops after 6to 12 months of therapy. It is not known whether longtermuse of selective COX-2 inhibitors will induce analgesicnephropathy, but this is a potential complication withany type of NSAID.Similarly, healthy young women who use a selectiveCOX-2 inhibitor (eg, rofecoxib, 50 mg/d, for 3 to 5 daysper month) to relieve menstrual cramps do not need to bemonitored unless blood pressure increases or persistentedema develops. Adverse effects are highly unlikely becauseshort-term therapy does not persistently suppressprostaglandin synthesis in these healthy (non-prostaglandin-dependent) patients. In fact, because selectiveCOX-2 inhibitors do not impair platelet function or prolongbleeding time, their use during menses would likely resultin less menstrual blood loss than that associated with traditionalnonselective NSAIDs.

References:

REFERENCES:

1.

Scheiman JM. Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

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Katz WA. Cyclooxygenase-2-selective inhibitors in the management of acuteand perioperative pain.

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Whelton A, Maurath CJ, Verburg KM, Geis GS. Renal safety and tolerabilityof celecoxib, a novel cyclooxygenase-2 inhibitor.

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Cannon GW, Caldwell JR, Holt P, et al. Rofecoxib, a specific inhibitor of cyclooxygenase2, with clinical efficacy comparable with that of diclofenac sodium;results of a one-year, randomized, clinical trial in patients with osteoarthritis ofthe knee and hip. Rofecoxib Phase III Protocol 035 Study Group.

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