Top Tips for Safe NOAC Prescribing

I’m sure many of you remember, like me, when NOACs first came in and being really nervous about the bleeding risk (what? no blood monitoring?! Not sure about that…) yet now we are dishing them out left, right and centre.

There is a risk when we get to this stage of our prescribing of ‘less novel’ drugs that some of the messages about safety and appropriate prescribing can get lost or forgotten. So here are my top tips and useful snippets for safe NOAC prescribing that we’ve collated over the past few years:

1. Here’s the ‘science bit’ - A useful therapeutics review in the Lancet in 2020 highlighted the background, evidence and unresolved issues with NOACs at the time. NOACs bind to the active sites of either thrombin (factor IIb) or factor Xa. They are all at least partially renal cleared (hence the crucial need for dose adjustment with declining renal function - see below) and can all interact to a greater or lesser degree with drugs that induce or inhibit P-glycoprotein or cytochrome P450 (importance discussed below).
2. Review the other ‘bleeders’ - sounds obvious but easy to overlook other regular medications that can increase bleeding risk e.g. NSAIDS including aspirin (ask about OTC use), SSRIs etc - can they be reduced or stopped? 
3. Review BP - correcting hypertension can obviously reduce bleeding risk (particularly intracranial haemorrhage) and in the case of AF can also reduce overall CVD risk.
4. Be aware of the interactions with P-glycoprotein (P-gp) and cytochrome P450 (cyt-P450) inhibiting drugs. These enzymes are involved in NOAC clearance so if they are inhibited plasma NOAC levels can rise and bleeding risk increases. 
5. Don’t chuck out the rat poison just yet - there are some crucial times when we should NOT switch from warfarin to a NOAC - a) mechanical heart valves, b) moderate/severe mitral stenosis and c) people with anti phospholipid syndrome.
6. Be aware of extremes of weight - those over, or under weight are significantly under-represented in the trials so safe dosing in those <60kg and >120kg is uncertain. Some of the NOACs need dose adjusting if weight <60kg. The latest ISTH statement July 2021 recommends that dabigatran should not be used for treatment of VTE if either BMI >40 or weight >120kg due to lack of data.
7. Should I use a PPI to reduce GI bleeding risk? Well, possibly. A large observational study (Heart 2021) suggests that using PPIs in older adults >75 or those with high bleeding risk may reduce the risk of severe upper GI bleeds. It is only observational data so we need to be careful to be too certain on this finding, but it seems a relative safe option to add a PPI for those you identify at higher bleeding risk. 
8. Reversal agents - all NOACs in Australia have a reversal agent available for use in the case of severe or life threatening bleeding.
9. Monitor and adjust dose based on renal function - if there is one crucial take home point it is this one. As discussed above, as NOACs are all at least partially renal cleared, we need to be absolutely ‘on it’ to monitor and adjust the dose depending on renal function. Declining renal function and therefore overdosing is one significant bleeding risk we can effectively mitigate. Do NOT be tempted to use eGFR for dosing, as it is not accurate enough - use estimated creatinine clearance (easily worked out via most GP clinical systems or if not use the MDCalc online calculator), and make sure you are monitoring renal function at relevant time frames (good ‘rule of thumb’ recommended by the European Heart Rhythm Association is that once estimated creatinine clearance has fallen below 60, divide the CrCl by 10, to give the frequency of monitoring in months (e.g. CrCl = 50; divide 50/10 = 5, so do renal function every ~5 months).

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The blog was originally published on the NB Medical Education blog on 8th July 2022. It has been edited for an Australian audience.