Wednesday, March 30, 2011

CONSULT ROUNDS: Ranolazine and the Kidney?

The cardiology world has become used to a new kid on the block in the last 5-6 years called Ranolazine or Ranexa. Ranolazine is indicated for the treatment of chronic angina. It has been shown to decrease angina episodes in individuals with coronary artery disease and it has been shown to both decrease angina episodes and increase exercise tolerance in individuals taking concomitant other anti anginal medications. It doesn't affect the blood pressure or heart rate that much. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.  

Why does this agent matter to us?1. It causes an increase in creatinine? Is it real renal injury or a false elevation? Ranexa produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function. The elevation has a rapid onset, shows no signs of progression during long-term therapy, is reversible after discontinuation of Ranexa, and is not accompanied by changes in BUN. In healthy volunteers, Ranexa 1000 mg twice daily had no effect upon the glomerular filtration rate. The elevated creatinine levels are likely due to a blockage of creatinine's tubular secretion by ranolazine or one of its metabolites. 
2. Ranolazine is primarily metabolized by CYP3A and has strong interactions with our transplant drugs calcineurin inhibitors like cyclosporine and tacrolimus. The drug increases the levels of tacrolimus and cyclosporine and could cause renal damage indirectly. Sounds like this is a good agent to use in angina but with caution and possibly in reduction of the CNI doses.
Check out below references:


  1. What if a patient is already ESRD and on dialysis. Is it safe for them to take Renexa?

  2. Is it excreted by peritoneal dialysis ?


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