ASK DIS: Celebrex : Renal Dose Adjustment

Renal Effect

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.
Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE-inhibitors, angiotensin II receptor antagonists, and the elderly.
Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Clinical trials with Celebrex have shown renal effects similar to those observed with comparator NSAIDs.

Studies & Evidences

40 patients on a low-salt diet were randomized to receive celecoxib (200 mg twice daily or 400 mg twice daily), naproxen (500 mg twice daily), or placebo. A single 400-mg dose of celecoxib significantly decreased GFR and renal plasma flow, demonstrating that COX-2 inhibition with this agent can affect renal function under conditions of increased renal dependence on PGs. As in the other studies, both celecoxib and naproxen produced transient reductions in urinary sodium excretion over the first 3 days of treatment.
In another study, 71 patients with stable chronic renal insufficiency were randomized to receive celecoxib (200 mg twice daily, naproxen (500 mg twice daily), or placebo for 7 days.^[65] After 7 days of treatment, statistically significant decreases in GFR were observed in patients receiving celecoxib and those receiving naproxen. Sodium excretion was transiently reduced with both active treatments

Renal Dose Adjustment

Contraindicated in severe renal impairment (creatinine clearance <30 mL/min or 0.5 mL/sec) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored)
In elderly volunteers with age-related reductions in glomerular filtration rate (GFR) (mean GFR >65 mL/min/1.73 m2) and in patients with chronic stable renal insufficiency (GFR 35-60 mL/min/1.73 m2) celecoxib pharmacokinetics was comparable to those seen in patients with normal renal function.
No significant relationship was found between serum creatinine (or creatinine clearance) and celecoxib clearance.
Severe renal insufficiency would not be expected to alter clearance of celecoxib since the main route of elimination is via hepatic metabolism to inactive metabolites.
No information is available from controlled clinical studies regarding the use of Celebrex in patients with advanced renal disease. Therefore, treatment with Celebrex is not recommended in these patients
If Celebrex therapy must be initiated, close monitoring of the patient's renal function is advisable.
In a cross-study comparison, celecoxib AUC was approximately 40% lower in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects with normal renal function.

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