Here I will provide a few basic points about the labeling from her talk along with some additional information from external links.
The agents approved in the US are dabigatran (Pradaxa), rivaroxaban (Xarelto) and Apixaban (Eliquis). All three are approved for non valvular atrial fibrillation. Xarelto has the additional approved indications of VTE prevention and treatment. Elimination is 80% renal for Pradaxa, 30-60% renal for Xarelto and 25% renal for Eliquis.
Renal labeling for Eliquis is unusual and applies only if one of two other characteristics is present:
age greater than or equal to 80 years
body weight less than or equal to 60 kg
serum creatinine greater than or equal to 1.5 mg/dL
No data are available for patients with clearance below 15 or on HD.
Renal labeling for Xarelto is problematic because it is complex (varying significantly based on which indication) and is not contained in its entirety in some readily available references (eg Micromedex and Rxlist). The creatinine clearance cutoff below which use is contraindicated is 30 for for VTE treatment and prevention and 15 for a fib. For VTE treatment or prevention no renal adjustment is called for within the allowable range of renal function though for VTE prevention (only) at clearance of 30-50 the labeling says “use with caution.” (Does that mean we throw caution to the wind for other indications?). For a fib with clearance of 15-50 reduction to 15 mg daily is called for.
Adjustment of Pradaxa to half dose (75mg bid) is recommended for clearance of 15-30. More aggressive renal adjustment recommendations apply if certain interacting drugs are administered. See product labeling for those details. As with Eliquis, no information is available for patients with clearance below 15 or on HD.
Labeling for interacting drugs as well as other practical aspects of the use of TSOAC drugs covered in Dr. Minichiello's talk will be discussed in subsequent posts.
At first glance the TSOACs look like “cleaner” drugs with greater ease of use as compared to warfarin. What I learned from Dr. Minichiello's talk and break out session is that this is not necessarily true despite some advantages. You need to know a great deal about the pharmacokinetics of these agents in order to use them confidently and competently.