Dr Sharon Rees @reesprescribe
Day 1: As the first new/non-vitamin K oral anti-coagulant (NOAC) in class and the first warfarin alternative for 50 years, #dabigatran was licensed in the USA/UK in 2010–11 for the treatment and prevention of DVT/PE, and prevention CVA/embolism in atrial fibrillation, if there is one or more risk factor
Dr Sharon Rees @reesprescribe
Day 2: #dabigatran is a direct thrombin inhibitor for adults, usually taken as 150 mg capsule twice daily, unless dose reduction is needed eg elderly >75 years, or in moderate renal impairment when dose 110–150 mg twice daily (not exhaustive)
Dr Sharon Rees @reesprescribe
Day 3: Kinetics; #dabigatran is a prodrug; post oral absorption, plasma + liver hydrolases convert it to the active form. Food delays time to peak plasma concentration. There is some conjugation converting to active metabolites, but most of the drug is excreted unchanged, t ½ 12–14 hrs. NOTE t½ is increased in renal impairment
Dr Sharon Rees @reesprescribe
Day 4: #dabigatran attaches to thrombin, as it looks like a peptide normally hydrolysed by thrombin as part of the coagulation cascade. Once bound, thrombin cannot perform its roles, such as converting fibrinogen to fibrin and catalysis of many other coagulation cascade reactions
Dr Sharon Rees @reesprescribe
Day 5: Adverse drug events; Common, abnormal hepatic function. Uncommon; bleeding eg nose bleeds (uncommon), anaemia, nausea/vomiting, abdominal pain (not exhaustive). Check renal function check before starting #dabigatran and and check dose adjustments. Minimum x1/year check for elderly. If overdose/haemorrhage, can reverse using Praxbind
Dr Sharon Rees @reesprescribe
Day 6: Drug-drug interactions; many ‘severe’ as increased bleeding eg anti-platelets, selective serotonin reuptake inhibitors, other anti-coagulants, non-steroidal anti-inflammatory drugs. #dabigatran is a P-gp transporter substrate; P-gp inhibitors eg itraconazole, lead to an increased drug concentration. There is reduced drug exposure re when given with P-gp inducers eg rifampicin, St John's Wort, phenytoin, carbamazepine (not exhaustive)
Dr Sharon Rees @reesprescribe
Day 7: When taking #dabigatran, a patient alert card should be carried. The NICE patient decision aid for atrial fibrillation can be used to support the clinician for this indication, as well as assist the patient-led selection of the best oral anti-coagulant for the individual
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
In addition to the tweets, read the BNF section on ‘Thromboembolism’ and the monograph on Dabigatran etexilate. Another useful source is the Summary of Product Characteristics for dabigatran etexilate. 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 #dabigatran
- Dabigatran etexilate : https://bnf.nice.org.uk/drug/dabigatran-etexilate.html
- Pradaxa 150 mg hard capsules : https://www.medicines.org.uk/EMC/medicine/24839/SPC/Pradaxa+150+mg+hard+capsules#gref
Dabigatran is licensed for both treatment and prevention of DVT and PE.
TRUE or FALSE?
Which is TRUE?
- Dabigatran is excreted whole, therefore renal impairment increases plasma levels of active drug
- Dabigatran is converted in the kidneys to its active form
- Formulations of dabigatran are all parenteral
- Metabolism is via the CYP450 system
The ‘N’ in the term NOAC is reported in the literature as meaning all of the following: new, novel or non-vitamin K antagonist ‘oral anti-coagulant.
TRUE or FALSE?
Dabigatran is an indirect prothrombin inhibitor.
TRUE or FALSE?
Thrombin is a proteolytic enzyme and when dabigatran attaches to it:
- It causes thrombin to auto-digest
- It prevents thrombin from catalysing other substances
- It sets off a chain reaction leading to the production of more clotting factors
- It directly breaks up fibrin strands
If dabigatran causes haemorrhage, the action of the drug cannot be reversed.
TRUE or FALSE?
Which of the following does NOT have an increased risk of bleeding when taken with dabigatran?
- Citalopram
- Clarithromycin
- Ibuprofen
- St John's Wort
Renal impairment is an issue with dabigatran use because most of the drug is excreted unchanged.
TRUE or FALSE?
Nausea and vomiting are common side-effects of dabigatran
TRUE or FALSE?