Novel Anticoagulants: Dosing Errors and Solutions

Mrs Thomas is an 81-year-old woman with dementia, hypertension, and atrial fibrillation and is taking the direct thrombin inhibitor dabigatran 150 mg twice daily. She has been having increasing issues with short-term memory loss and is becoming increasingly forgetful. She currently lives alone and arrangements are being made for her to be moved to a supervised living facility. 

Her daughter calls your office from her mother’s house, where she is visiting for lunch and has just noticed that her morning dabigatran capsule is still in the pill box. After talking to her mother, she is not sure whether her mother took her dabigatran directly from the bottle this morning or didn’t take it at all. Based on another answer her mother gave in some confusion, there is also a chance she may have confused her dabigatran with her blood pressure medicines and taken 2 of the anticoagulant capsules (her regular blood pressure dosing) instead of one.

Click here for answer and discussion.

Answer: A-More information should be ascertained about the dosing error in order to determine what the appropriate next step is.Discussion
Because of the relatively short half-life of these novel anticoagulant (NOA) agents compared with vitamin K antagonists, patient compliance and potential medication errors are important issues.

In this case, with twice-daily dabigatran, if a dose is accidentally forgotten, the forgotten dose may be taken up to the middle of the dosing interval, ie, up to 6 hours later. For Mrs Thomas, who is supposed to take her medications at 8 AM and 8 PM, a forgotten dose may be taken until 2 PM. If it is after 2 PM, the forgotten dose should be skipped altogether and the next dose should be taken on schedule at 8 PM. 

On the other hand, if a double dose of the twice-daily medication is accidentally taken, the next dose can be skipped altogether. So for Mrs Thomas, if it was determined that she had accidentally taken 2 capsules (300 mg) of dabigatran, she should skip her 8 PM dose and resume 150 mg the following morning at 8 AM. If there is any clinical evidence of major bleeding or a known overdose of NOAs, the patient may need to be admitted to a hospital for monitoring and transfusion of blood products, if needed. If the patient is clinically stable without any evidence of bleeding and if it was not a massive overdose, a hospital admission is not mandatory.

If the patient cannot remember whether a dose was taken or skipped and it is a twice-daily NOA (dabigatran, apixaban), then the patient should NOT take another dose and just resume the regular dosing schedule at the 12-hour interval. If a patient who is on once-daily rivaroxaban cannot remember whether the regular dose was taken, then another dose should be taken at the time of recognition of missed dose and regular dosing schedule should be resumed the following day. 

For Mrs Thomas, if the uncertainty could not be cleared up, pills should be counted to ensure that a double dose was not taken. Then, we are left with either a skipped dose or uncertainty about whether the dose was taken and you could tell her daughter to just resume her 8 PM dose as previously scheduled.

Reference:
Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Executive Summary. Eur Heart J. 2013;10.1093/eurheartj/eht134.