Rofecoxib renal function effects

CICLOSPORIN ANALGESICS-NSAIDs 1. t risk of renal failure with NSAIDs 2. Diclofenac levels t by ciclosporin 3. Rofecoxib 1 plasma concentrations of ciclosporin, with risk of transplant rejection 1. Additive effect both can cause renal insufficiency 2. Uncertain 3. Rofecoxib is a mild inducer of CYP3A4 and not a substrate of CYP3A4 1. Monitor renal function closely 2. Halve dose of diclofenac 3. Be aware. May not be clinically significant... 

The blood pressure of a 59-year-old man with hypertension and normal renal function rose when rofecoxib 25 mg/day was added to lisinopril 10 mg/day (from an average of 135/80-85 to 168/98 mmHg within 5 weeks). Four days after rofecoxib was withdrawn the blood pressure was 127/78 mmHg. Rechallenge with the same dose of rofecoxib produced the same effect and the blood pressure fell when the dosage of lisinopril was increased to 20 mg/day on continuous rofecoxib. The authors did not report on the course of renal function. 

The incidence of adverse effects related to renal function in CLASS and VIGOR was low and similar (0.9% with celecoxib and 1.2% with rofecoxib). The incidence of increased creatinine and urea nitrogen concentrations was slightly lower in patients taking celecoxib than in those taking ibuprofen or diclofenac. Similar results have been documented in two other clinical trials. The... 

Methotrexate is often prescribed for the management of rheumatoid arthritis, and some NSAIDs have been reported to interact with it, causing increased plasma methotrexate concentrations, associated with impaired renal function. The safety of concurrent rofecoxib and oral methotrexate has been studied for 3 weeks in 25 patients with rheumatoid arthritis (7). Rofecoxib 12.5-50 mg/day had no effect on the plasma concentrations or renal clearance of methotrexate, but supratherapeutic doses of rofecoxib (75 and 250 mg) caused a significant increase in the plasma methotrexate AUC and reduced its renal clearance. 

In the recent 8000-patient celecoxib long-term arthritis safety study [123], significantly more patients receiving traditional NSAlDs (ibuprofen or diclofenac) experienced clinically significant elevations in serum creatinine and/or serum urea nitrogen levels when compared to celecoxib. In an equally large gastrointestinal safety trial with rofecoxib, the incidence of adverse effects related to renal function for rofecoxib was similar to naproxen (1.2% versus 0.9%, respectively) [124]. When rofecoxib and celecoxib were directly evaluated in elderly hypertensive OA patients who manifested "normal" serum creatinine at the time of study recruitment, the overall incidence of clinically... 

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