Dr Sharon Rees @reesprescribe
Day 1: As the gateway to the final common clotting pathway, factor Xa (FXa) was defined as a drug target. Mapping of this enzyme's pockets allowed computer aided testing of approximately 200 K small molecules for affinity and selectivity. #rivaroxaban showed high affinity and was licensed in 2008 in UK.
Dr Sharon Rees @reesprescribe
(cont) #rivaroxaban is one of the ‘direct’ oral anti-coagulants, named because it targets a single clotting factor; this reduces pharmacodynamic variability. These drugs (also apixaban and edoxaban) are now known as the ‘new’ oral anticoagulants; referred to as NOACs.
Dr Sharon Rees @reesprescribe
Day 2: VTE prophylaxis post hip/knee surgery 10 mg once daily (od) for 2 weeks (knee replacement) and 5 weeks (total hip repl); Treatment for DVT/PE 15 mg twice daily 21days then 20mg od. Prophylaxis of stroke/syst embolism 20 mg od; Prophylaxis thrombotic events in acute coronary syndrome and coronary/peripheral artery disease 2.5 mg twice daily (usually for 12 months ACS) (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 3: Kinetics #rivaroxaban has good oral bioavailability, increased by food. Protein binding ~95%. Major elimination is by CYP metabolism, producing inactive metabolites. Remaining is divided into renal and hepato-biliary excretion. #rivaroxaban is a substrate of P-gp, which enhances clearance; therefore, inhibition of P-gp leads to increased drug levels.
Dr Sharon Rees @reesprescribe
Day 4 Mechanism of action: FXa is pivotal to haemostasis, initiating the ‘thrombin burst’. #rivaroxaban inhibits free and clot bound FXa, exerting powerful control over clotting, as the reduced generation of thrombin impairs the final step of coagulation and inhibits fibrin clot formation.
Dr Sharon Rees @reesprescribe
Day 5: #rivaroxaban is still on black triangle/requires extra vigilance! Common known adverse drug events: dizziness, headache, anaemia, eye haemorrhage, nose bleed, GI haemorrhage, pruritis, rash and fever. Uncommon/serious; anaphylaxis, cerebral haemorrhage, renal failure, SJS and DRESS (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 5 (cont): No blood test is needed for routine monitoring of #rivaroxaban; this confers an advantage for all the NOACs over warfarin. Remains important to monitor/safety net to check for bleeding events and anaemia.
Dr Sharon Rees @reesprescribe
Day 6: #rivaroxaban drug-drug interactions (DDIs): All anti-coagulants, anti-platelets, SSRIs, NSAIDs increase the risk of bleeding. CYP3A4 and P-gp inhibitors eg macrolides and some azole anti-fungals increase exposure, especially if renal failure. Anti-epileptics eg phenytoin reduce exposure. All listed DDIs here are ‘severe’ (not exhaustive).
Dr Sharon Rees @reesprescribe
Day 7; Potentially fatal or uncontrolled bleeding while on #rivaroxaban can be reversed by stopping drug and andexanet alfa iv infusion. A recombinant form of FXa, it binds the drug while having no inherent activity, preventing further anti-coagulant effects. UK listed cost over £11K.
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate
Complete the additional reading suggested below and then answer the ten questions. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A, B, C, D option. If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Further reading on #rivaroxaban
- Rivaroxaban: https://bnf.nice.org.uk/drug/rivaroxaban.html
- Xarelto 10 mg film-coated tablets: https://www.medicines.org.uk/emc/product/6402/smpc#gref
Questions
1. Activated factor Xa is a protease enzyme
TRUE or FALSE?
2. Rivaroxaban targets several clotting factors
TRUE or FALSE?
3. Rivaroxaban is only used to prevent thrombotic events
TRUE or FALSE?
4. Which of the following is true?
- Targeting a single clotting factor means a weak anti-coagulant action
- Factor Xa is a good drug target because it begins the whole clotting process
- The NOACs are known as vitamin K inhibitors
- Factor Xa is the single and direct target of rivaroxaban
5. The majority of rivaroxaban is excreted whole
TRUE or FALSE?
6. Which best describes the mechanism of action of rivaroxaban?
- It is a direct thrombin inhibitor
- It is a selective factor Xa inhibitor
- It is a non-selective factor Xa inducer
- It is an anti-platelet drug
- P-gp is a cell transporter in the liver and gut which shifts rivaroxaban out of cells and back into the circulation or bile ducts.
7. Anything which inhibits this activity will increase the effect(s) of rivaroxaban
TRUE or FALSE?
8. Rash and fever are common adverse drug events when taking rivaroxaban
TRUE or FALSE?
9. Carbamazepine has a severe drug-drug interaction with rivaroxaban
TRUE or FALSE?
10. It is not possible to reverse the effects of rivaroxaban if there is a serious bleed
TRUE or FALSE?