2.8.2 Oral anticoagulants

Coumarins and phenindione

Warfarin
  • Tablets 500 micrograms, 1mg, 3mg, 5mg

Notes

  1. See Anticoagulation Guidance for information on
    1. Indications
    2. Target INR
    3. Induction regimens
    4. Monitoring
    5. Adverse effects
  2. The yellow NPSA Oral Anticoagulant Therapy information pack may be used to support patient education in patients prescribed warfarin.
  3. Warfarin should be used in accordance with the requirements of the NPSA alert. The key points are:
    1. Patients should receive appropriate verbal and written information at the start of therapy and when necessary throughout the course of treatment. Supply each patient with an anticoagulation book and ensure they fully understand the contents.
    2. Before issuing a repeat prescription, check that the patient's INR is being monitored regularly, and is at a safe level, and that the patient understands the dose.
    3. Warfarin has many clinically important drug interactions, see BNF for details. If a patient is co-prescribed a drug which may affect INR, make arrangements for additional INR blood tests.
    4. For warfarin regimens, ensure that:
      1. The least number of tablets each day are used
      2. Doses are expressed in milligrams and not number of tablets
      3. NPSA recommend constant daily dosing and not alternate day dosing
      4. Do not use tablets that need to be halved; use 0.5mg (white) tablets instead if necessary.
  4. Warfarin dose should be taken at 6pm to obtain correct INR value with blood tests taken in the morning.
  5. Potentially serious errors can occur if patients confuse the 500 microgram and 5mg tablets. Prescribers should ensure that prescriptions are written clearly and patients are thoroughly counselled if they are given the 500 microgram strength tablets.
  6. The following recommendations are based on those of the British Committee for Standards in Haematology (2011) and current edition of BNF, and apply to patients taking warfarin:
    1. Vitamin K is very well absorbed orally.
    2. When partial correction is required it may be necessary to give intravenous vitamin K or alternatively give the intravenous preparation orally (Konakion® MM Paediatric 10mg/ml 0.2ml amp).
    3. Vitamin K will usually lower the INR within 12 to 24 hours. Repeat doses may be needed after 24 hours if the INR is still too high.
  7. For monitoring and adverse events, refer to Anticoagulation guidance
Phenindione
  • Tablets 10mg, 25mg, 50mg (£103.68 = 100mg daily)

Dose

  • 200mg on day 1; 100mg on day 2, then adjusted according to response; maintenance dose usually 50–150mg daily

Non-vitamin K oral anticoagulants (NOACs)

MHRA Drug Safety Update (October 2013, September 2016) New oral anticoagulants apixaban, dabigatran and rivaroxaban: risk of serious haemorrhage. See Anticoagulation Guidance for further prescribing information.

Apixaban
  • Tablets 2.5mg, 5mg (£53.20 = 2.5mg twice daily)

Dose

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) : 5 mg twice daily. For patients with severe renal impairment, and other dose reductions, see notes
  • Treatment of acute DVT and PE: 10 mg twice a day for 7 days, then 5 mg twice a day for at least 3 months. Short duration of treatment (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation)
  • Prevention of recurrent DVT and PE: 2.5mg twice daily, following 6 months of 5mg twice daily. For patients with severe renal impairment, see notes

Notes

  1. Apixaban is not recommended for people with CrCl less than 15 mL/min
  2. In patients with severe renal impairment (CrCl 15 - 29 ml/min) the following recommendations apply:
    1. For the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE, use with caution
    2. For the prevention of stroke and systemic embolism in patients with NVAF, reduce dose to 2.5mg twice daily
    3. Patients with serum creatinine ≥ 1.5 mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg should also receive the lower dose of apixaban 2.5 mg twice daily
  3. NICE Chronic Kidney Disease guideline (CG182): Consider apixaban in preference to warfarin in people with a confirmed eGFR of 30–50 ml/min/1.73 m2 and NVAF who have 1 or more risk factors.
  4. NICE TA245 Apixaban is recommended as an option for the prevention of venous thromboembolism after total hip or knee replacement in adults (January 2012)
  5. NICE TA275 Apixaban is recommended as an option for preventing stroke and systemic embolism in people with NVAF (February 2013)
  6. NICE TA341 Apixaban is recommended as an option for the treatment and secondary prevention of DVT and/or PE (June 2015)
Dabigatran etexilate
  • Capsules 110mg, 150mg (£47.60 = 150mg twice daily)
  • Capsules 75mg

Dose

  • Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors: 150mg twice daily, for patients with renal impairment, refer to notes
  • Treatment of DVT and PE, and prevention of recurrent DVT, and PE in adults: 150 mg twice daily following treatment with a parenteral anticoagulant for at least 5 days. For patients with renal impairment, refer to notes
    • The duration of therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding. Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation); longer durations should be based on permanent risk factors or idiopathic DVT or PE.
  • For all indications, reduce dose to 110mg twice daily in people aged 80 years or above (due to the increased prevalence of renal impairment in this population), or taking verapamil. Consider reducing dose to 110mg twice daily in people aged 75-80 years, or those with gastritis, esophagitis or gastroesophageal reflux, or those at increased risk of bleeding.

Notes

  1. Dabigatran is contraindicated in patients with CrCL < 30 mL/min.
  2. For patients with CrCL 30-50 mL/min the recommended dose of dabigatran is 150 mg twice daily. However, for patients with high risk of bleeding, a dose reduction to 110 mg twice daily should be considered.
  3. Dabigatran is not suitable for use with a compliance aid (e.g. blister pack) as the capsules are moisture sensitive and should not be stored outside their packaging.
  4. NICE TA157 Dabigatran etexilate is recommended as a possible treatment for the prevention of venous thromboembolism after hip or knee replacement surgery in adults (Sept 2008)
  5. NICE TA249 Dabigatran etexilate is recommended as a possible treatment for the prevention of stroke and systemic embolism in AF (March 2012)
  6. NICE TA327 Dabigatran etexilate is recommended as a possible treatment for the treatment and secondary prevention of DVY and/or PE (November 2014)
  7. MHRA Drug Safety UpdatesMarch 2013: Dabigatran is now contraindicated in patients with prosthetic heart valve(s) requiring anticoagulant treatment related to their valve surgery, regardless of the length of time elapsed since valve replacement took place.
Edoxaban
  • Film-coated tablets 15mg, 30mg, 60mg (£51.80 = 60mg daily)

Dose

  • Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors: 60mg once daily, for patients with renal impairment, refer to notes
  • Treatment of DVT and PE; prevention of recurrent DVT and PE: 60mg once daily following at least 5 days of parenteral anticoagulant, for patients with renal impairment, refer to notes
    • Edoxaban and initial parenteral anticoagulant should not be administered simultaneously
    • Assess benefit vs bleeding risk to determine treatment duration. Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, or immobilisation). Longer duration should be based on permanent risk factors or idiopathic DVT or PE.

Notes

  1. Edoxaban is not recommended in patients with CrCl < 15 mL/min
    1. Dose should be reduced to 30mg once daily in patients with moderate to severe renal impairment (CrCl 15 – 50 mL/min), low body weight (up to 60kg), and patients also taking ciclosporin, dronedarone, erythromycin, or ketoconazole
  2. NICE TA354 Edoxaban for treating and for preventing deep vein thrombosis and pulmonary embolism (August 2015)
  3. NICE TA355 Edoxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation (September 2015)
Rivaroxaban
  • Tablets 15mg, 20mg (£50.40 = 20mg daily)
  • Tablets 2.5mg (£50.40 = 56 tablets) (only for use in patients who have had an ACS - see below)
  • Tablets 10mg

Dose

  • Prevention of stroke and systemic embolism: 20mg once daily, for patients with renal impairment, refer to notes
  • Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE: 15mg twice daily for the first three weeks followed by 20mg once daily for continued treatment and prevention of recurrence, for patients with renal impairment, refer to notes. Duration of therapy should be individualised after careful assessment of the treatment benefit and risk for bleeding. Short duration of therapy (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation) and longer durations should be based on permanent risk factors or idiopathic DVT or PE
  • Prevention of atherothrombotic events in people who have had an acute coronary syndrome (ACS) with elevated cardiac biomarkers: 2.5mg twice daily, co-administered with aspirin alone, or with aspirin plus clopidogrel or ticlopidine (see TA335)

Notes

  1. Rivaroxaban is not recommended in patients with creatinine clearance < 15ml/min.
  2. Patients with creatinine clearance 15 - 29ml/min, rivaroxaban should be used with caution. In patients with creatinine clearance 15 - 49ml/min the following dosage recommendations apply:
    1. For the prevention of stroke and systemic embolism in patients with NVAF, the recommended dose is 15mg once daily
    2. For the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE: A reduction of the maintenance dose to 15mg once daily should be considered if the patient's assessed risk for bleeding outweighs the risk for recurrent DVT and PE.
  3. NICE TA170 Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults (April 2009)
  4. NICE TA256 Rivaroxaban is recommended as a possible treatment for the prevention of stroke and systemic embolism in people with AF (May 2012)
  5. NICE TA261 Rivaroxaban is recommended as a possible treatment for the treatment of DVT and prevention of recurrent DVT and PE (July 2012)
  6. NICE TA287 Rivaroxaban is recommended as a possible treatment for treating PE and preventing recurrent venous thromboembolism (June 2013)
  7. NICE TA335 Rivaroxaban is recommended as a possible treatment for preventing adverse outcomes after acute management of acute coronary syndrome (March 2015)

Rapid reversal of dabigatran

Idarucizumab
  • Solution for injection/ infusion 2.5g in 50ml

 

Home > Formulary > Chapters > 2. Cardiovascular > 2.8 Anticoagulants and protamine > 2.8.2 Oral anticoagulants

 

  • First line
  • Second line
  • Specialist
  • Hospital