What dose adjustments are needed for antirheumatic drugs in patients with renal insufficiency

What dose adjustments are needed for antirheumatic drugs in patients with renal insufficiency?

Serum creatinine may be an inaccurate measurement of renal function because as renal function declines, less creatinine is excreted by glomerular filtration and more is excreted by tubular secretion. The use of cimetidine (400 mg four times a day for 2 days) blocks the tubular secretion of creatinine and may improve accuracy of creatinine clearance measurements. Serum cystatin C may be a more accurate measure of estimated GFR since it is not affected by diet or muscle mass. After determining the correct GFR, the following guidelines can be used:

  • • Anakinra—GFR <30 mL/minute, decrease frequency from daily to 100 mg subcutaneously every other day.
  • • Antimalarials—40% to 50% excreted by kidneys. Reduce dose 50% or do not use at all in severe renal insufficiency GFR <30 mL/minute. Neuromyopathy, cardiomyopathy, and retinal toxicity increases with renal insufficiency. Cannot be hemodialyzed. Follow hydroxychloroquine serum levels.
  • • Allopurinol—GFR 30 mL/minute, use 100 mg; GFR 60 mL/minute, use 200 mg; GFR 90 mL/minute, use 300 mg daily. In patients on hemodialysis, give 100 mg daily after dialysis. Dialysis usually lowers uric acid without the need for allopurinol.
  • • Apremilast—GFR <30 mL/minute, max dose is 30 mg/day.
  • • Azathioprine—GFR 10 to 50 mL/minute, reduce dose by 25%; GFR <10 mL/minute, cut dose 50%. Give after hemodialysis.
  • • Baricitinib— GFR <60 mL/minute, max dose 2 mg/day or do not use; GFR <30 mL/minute, do not use.
  • • Biologics (monoclonal antibodies, decoy receptors, receptor antagonists)—most not tested but probably do not need dose adjustment. Chronic kidney disease is a risk factor for increased infections on biologic therapy.
  • • Bisphosphonates—avoid in ESRD. Use half oral dose or not at all in severe renal insufficiency (<30 mL/minute). Risedronate may be safer than alendronate. Intravenous (IV) bisphosphonates need to be administered more slowly with IV ibandronate safer than IV zoledronic acid in patients with moderate renal insufficiency (<50 mL/minute). Denosumab may be a better alternative but can cause hypocalcemia.
  • • Colchicine—avoid prolonged use in patients with GFR <50 mL/minute if possible. Use 0.6 mg daily for GFR <50 mL/minute and 0.3 mg daily for GFR <30 mL/minute. Do not use if GFR <10 mL/minute or on hemodialysis unless no other alternative. Watch for cytopenias and neuromyopathy. Cannot be hemodialyzed.
  • • Corticosteroids—no change in dose.
  • • Cyclophosphamide—GFR <25 mL/minute, reduce dose to 25% usual dose; GFR 25–50 mL/minute, reduce dose to 50%. If patient has ESRD, give the dose after hemodialysis.
  • • Cyclosporine—no dose adjustment for renal insufficiency. However, use of cyclosporine can worsen renal insufficiency. If creatinine rises, the cyclosporine dose needs to be lowered. Cannot be hemodialyzed.
  • • Dapsone—GFR <50 mL/minute, give every other day.
  • • Febuxostat—GFR <30 mL/minute, maximum dose is 40 mg/day.
  • • Leflunomide—insufficient data. The drug (40%–50%) is eliminated by the kidneys although the active metabolite is not increased in renal insufficiency as a result of increased enterohepatic excretion. Cannot be hemodialyzed.
  • • Methotrexate—reduce dose 50% with renal insufficiency. Should not be used or used with extreme caution owing to hematologic toxicity when GFR <50 mL/minute (max dose 5 mg weekly). Cannot be hemodialyzed.
  • • Mycophenolate mofetil—hepatic metabolism with 90% renally excreted. Enterohepatic circulation can be safety valve with renal insufficiency. Do not exceed 1 g twice daily for GFR <25 mL/minute or on peritoneal dialysis. Do not exceed 500 mg twice daily if on hemodialysis.
  • • Narcotics—GFR 10 to 50 mL/minute, use 75% usual dose; GFR <10 mL/minute, cut dose 50%. Avoid meperidine. Fentanyl is safest.
  • • NSAIDs—most are metabolized by liver except for diflunisal. All NSAIDs except salsalate can make renal insufficiency worse. No need for dose adjustment for NSAIDs in ESRD, except for diflunisal (decrease dose 50%). Avoid sulindac, owing to renal stone formation in patients with low urine output. Also avoid ketoprofen, because it will be metabolized back to active drug if it cannot be renally excreted.
  • • Probenecid—does not work if GFR <50 to 60 mL/minute. No dosage change for mild renal insufficiency.
  • • Romosozumab—no dose change in renal insufficiency.
  • • Sulfasalazine—no change in dose.
  • • Tacrolimus—same as cyclosporine.
  • • Teriparatide—no change in dose. Teriparatide effective for osteoporosis in patients with GFR as low as 30 mL/minute even if PTH mildly elevated (up to 150 pg/mL) as long as vitamin D is repleted.
  • • Tofacitinib—GFR <50 to 60 mL/minute, max dose is 5 mg/day. Use with caution if at all in patients on dialysis.
  • • Tramadol—give dose (50 to 100 mg) every 12 hours instead of every 6 hours if GFR <30 mL/minute or on hemodialysis. Give after dialysis.

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