Safe Prescribing of Direct Oral Anticoagulants (DOACs)
This is the first in a series of DOAC blogs
- DOACs are high risk medicines commonly associated with prescribing errors
- Prescribing errors can lead to significant adverse events such as major bleeding or increased thrombotic risk due to suboptimal treatment
- When prescribing a DOAC, the following patient/clinical parameters must be considered: indication, age, actual body weight, renal/hepatic function, past medical history and concomitant medicines
- Always refer to the Summary of Product Characteristics (SPC) or BNF for full prescribing information
- Patients/carers should be provided with information to ensure the safe use of the DOAC prescribed
- In NHSGGC, apixaban is the preferred DOAC for the treatment of venous thromboembolism (VTE) and the prevention of the recurrence of VTE and edoxaban is the preferred DOAC for use in the prevention of stroke in patients with non-valvular atrial fibrillation (AF) requiring anticoagulation. Refer to the Adult Medicines Formulary for further information.
How can I reduce the risk of prescribing errors?
Examples of prescribing risks with DOACs include:
Inadvertent prescribing of a DOAC in combination with another anticoagulant/antiplatelet:
DOACs and low molecular weight heparin (LMWH) should never be prescribed together.
DOACs and fondaparinux should never be prescribed together.
A DOAC prescribed in combination with warfarin is rarely seen in practice and is only indicated during a switch from a DOAC to warfarin for a short period of time until INR is therapeutic. This combination should always be double-checked before prescribing or administering.
A DOAC prescribed in combination with single (SAPT) or dual antiplatelet therapy (DAPT) should always be double-checked to ensure the patient should be prescribed this combination. Seek advice from cardiology as appropriate.
Confusion between dosing schedules of different DOACs:
Examples of errors include prescribing the wrong frequency for a particular DOAC and indication (e.g. edoxaban incorrectly prescribed twice daily instead of the correct dosing schedule of once daily).
Overlooking the requirement for dose adjustments:
Dose adjustments can be required for a number of parameters including renal function, weight, age, and drug interactions depending on the indication and DOAC prescribed. Take time to check before prescribing.
How do I know what dose and duration to prescribe?
Apixaban, dabigatran, edoxaban and rivaroxaban all have different dosing schedules for different indications. It is essential to always consult the SPC or BNF when prescribing for full information, including dose adjustments and drug interactions.
Duration of treatment also varies depending on the indication. Please ensure treatment durations are documented and communicated across different care settings.
Are there common interactions to be aware of when prescribing DOACs?
All four DOACs are substrates of the transport protein, P-glycoprotein (P-gp) and therefore may theoretically interact with inducers or inhibitors of P-gp. Apixaban, edoxaban and rivaroxaban are all metabolised to varying degrees by the cytochrome enzyme, CYP3A4 and therefore may theoretically interact with inducers or inhibitors of CYP3A4.
It is important to check for interactions with inducers or inhibitors of both CYP3A4 and P-gp. Always check for interactions with existing medicines when prescribing any new medicine. Interactions can be checked using the BNF or the SPC, or Liverpool University HIV/HEP/Cancer Drug Interactions if prescribing a DOAC in combination with systemic anticancer treatment, HIV, hepatitis or COVID-19 medicines. Medicines Information may also be contacted by healthcare professionals working in NHSGGC for further advice on the management of interactions.
How do I switch from another anticoagulant to a DOAC?
- When switching from warfarin:
- Stop warfarin and initiate apixaban or dabigatran when INR is <2, edoxaban when INR ≤2.5, or rivaroxaban when INR ≤3 if AF indication, or ≤2.5 if VTE indication.
- When switching from a LMWH:
- Stop LMWH and give the first dose of the DOAC at least 12-24 hours after the last LMWH administration (i.e at the time when the next LMWH dose would have been scheduled), taking into consideration thrombotic versus bleeding risk.
- For patients undergoing surgery or other invasive procedures, refer to the following GGC guidelines:
- Do not prescribe or administer LMWH and a DOAC together. LMWH should always be stopped before starting a DOAC.
What about patient education?
Patients/carers should be provided with information to ensure the safe use of the DOAC prescribed. As the most serious adverse effect of DOACs is bleeding, patients/carers should be alert to signs of bleeding and be advised on when to seek medical advice. Further information can be found in the NHSGGC DOAC Patient Information Booklet. Patients should be advised to always carry an anticoagulant alert card.
Do I need to stop my patient’s DOAC if they are undergoing surgery or going to the dentist?
This will depend on the DOAC prescribed and the type of invasive procedure being carried out. Refer to the following guidance of further information:
- Factor Xa Inhibitors (apixaban, edoxaban, rivaroxaban): Management of Haemorrhage, Surgery and other Invasive Procedures
- Dabigatran, Management of Haemorrhage, Surgery or Other Invasive Procedures, Acute
- Anticoagulants and antiplatelets | Scottish Dental Clinical (sdcep.org.uk)
Do the DOACs have reversal agents?
Andexanet alfa is a factor Xa inhibitor reversal agent licensed to reverse anticoagulation in situations of life-threatening or uncontrolled bleeding in patients taking apixaban or rivaroxaban following discussion with haematology. Due to lack of clinical trial data, andexanet alfa is not licensed for use in patients taking edoxaban. However, based on the similarity of edoxaban’s mechanism of action when compared to apixaban and rivaroxaban, the off label use of andexanet alfa in patients taking edoxaban who present with life-threatening or uncontrolled bleeding is accepted across NHSGGC. Refer to Factor Xa Inhibitors (apixaban, edoxaban, rivaroxaban): Management of Haemorrhage, Surgery and other Invasive Procedures for further information.
Idarucizumab is a specific reversal agent for dabigatran. It binds to dabigatran with very high affinity and instantly reverses its anticoagulant effect. It should be considered in cases of major haemorrhage or when surgery cannot be delayed, and only prescribed after discussion with haematology. Refer to Dabigatran, Management of Haemorrhage, Surgery or Other Invasive Procedures for further information.
Where can I find further information on DOACs?
- SPCs via electronic medicines compendium (emc)
- BNF via Medicines Complete (log in may be required)
- NHSGGC guidance: Clinical Guidelines Platform or Adult Therapeutics Handbook
- NHSGGC DOAC Patient Information Booklet
Refer to other blogs in the DOAC series:
Published: 22/08/2022. Updated 06/01/2023. Medicines Update blogs are correct at the time of publishing.