Which Anticoagulant?

The information below is based on European or United Kingdom Summaries of Product Characteristics – approved uses and recommendations for drugs vary by region/country

This table is intended as a quick reference guide only and is not an exhaustive list; refer to local prescribing information for full drug information and use clinical judgement before prescribing

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Direct Factor Xa inhibitor
Direct Factor Xa inhibitor
Direct Factor Xa inhibitor
Direct Factor IIa (thrombin) inhibitor
Vitamin K antagonist
UFH
LMWH
LMWH
LMWH
Indirect Factor Xa inhibitor

Prevention of VTE

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery

Indication

Indication

Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery

Indication

Primary prevention of VTE in adult patients who have undergone elective total hip replacement surgery or total knee replacement surgery

Indication

Prophylaxis of venous thrombosis and PE

Indication

Prophylaxis of DVT and PE

Indication

Prevention of VTE, in moderate-to-high-risk surgical patients (in particular those undergoing orthopaedic or general surgery including cancer surgery) and in medical patients with an acute illness (e.g heart failure) and reduced mobility at increased risk of VTE

Indication

Peri- and post-operative surgical thromboprophylaxis, and the prophylaxis of proximal DVT in patients bedridden due to a medical condition

Indication

Prevention of VTE in adults undergoing surgery, particularly general, orthopaedic or oncological surgery, and in non-surgical adult patients immobilized because of acute medical illness (.e.g heart failure or active cancer)

Indication

Prevention of VTE in adults undergoing major orthopaedic surgery of the lower limbs (e.g. hip/knee replacement) or abdominal surgery if judged at high risk of thromboembolic complications (e.g. cancer surgery), and adult medical patients at high risk for VTE who are immobilized due to acute illness
Dose

Dose

2.5 mg twice daily; initial dose 12–24 hours after surgery

Dose

Dose

10 mg once daily; initial dose 6–10 hours after surgery provided haemostasis has been established

Dose

220 mg once daily taken as 2 capsules of 110 mg; initial half dose 1–4 hours after surgery

Dose

Induction dose of 10 mg daily for 2 days (tailored to individual requirements), followed by 3–9 mg once daily, depending on prothrombin time or other appropriate coagulation tests

Dose

5000 IU s.c. 2 h preoperatively, followed by 5000 IU s.c. every 8–12 h

Dose

– Surgical patients at moderate risk of VTE: 20 mg (2000 IU) once daily s.c. started approximately 2 hours pre-operatively
– Surgical patients at high risk of VTE: 40 mg (400 IU) once daily s.c. started 12 hours before surgery
– Medical patients: 40 mg (4000 IU) once daily s.c.

Dose

– Surgical patients at high risk of thrombosis: 2500 IU s.c. administered 1–2 hours before surgery, 2500 IU s.c. 8–12 hours later and 5000 IU s.c. each morning on the following days OR 5000 IU s.c. administered the evening before surgery and 5000 IU s.c. the following evenings
– After hip replacement surgery: 5000 IU s.c. administered the evening before surgery and 5000 IU s.c. the following evenings
– Medical patients: 5000 IU once daily

Dose

– Surgical patients at moderate risk of VTE: 3500 IU s.c. 2 hours before surgery and once daily thereafter
– Surgical patients at high risk of VTE (e.g. orthopaedic or cancer surgery): 4500 IU s.c. 12 hours before surgery and once daily thereafter
– Non-surgical patients immobilized because of acute medical illness: 3500 IU s.c. once daily in patients at moderate risk of VTE; 4500 IU s.c. once daily in patients at high risk of VTE

Dose

– Major orthopaedic surgery or abdominal surgery: 2.5 mg s.c. once daily; initial dose 6 hours following surgical closure provided that haemostasis has been established
– Medical patients: 2.5 mg s.c. once daily

Dose adjustments

Dose adjustments

None

Dose adjustments

Dose adjustments

None

Dose adjustments

150 mg once daily taken as 2 capsules of 75 mg (initial half-dose 1–4 hours after surgery) in patients: with CrCl 30–50 ml/min; taking concomitant verapamil, amiodarone or quinidine; or aged 75 years; consider a 75 mg daily dose in patients with CrCl 30–50 ml/min concomitantly treated with verapamil

Dose adjustments

Additional monitoring and a change in dosage may be required for patients with hyper- or hypothyroidism, changes in body weight, acute illness, smoking cessation, diarrhoea or vomiting or specific genetic polymorphisms

Dose adjustments

Dose reduction and monitoring of aPTT may be advisable in elderly patients

Dose adjustments

20 mg (2000 IU) once daily s.c. in patients with CrCl 15–30 ml/min

Dose adjustments

Adjust dose based on FXa activity in patients with CrCl <30 ml/min

Dose adjustments

Consider 50 IU/kg body weight in patients with very low or very high body weight as an alternative to fixed dosing

Dose adjustments

1.5 mg once daily in patients with CrCl 20–50 ml/min
Duration

Duration

32–38 days (hip) or 10–14 days (knee)

Duration

Duration

5 weeks (hip) or 2 weeks (knee)

Duration

28–35 days (hip) or 10 days (knee)

Duration

Not stated in eMC SmPC

Duration

7–10 days or until the patient is fully ambulant

Duration

– Surgical patients at moderate risk of VTE: 7–10 days, or until the patient no longer has significantly reduced mobility
– Following major orthopaedic surgery: up to 5 weeks
– Patients at high risk of VTE who undergo abdominal or pelvic surgery for cancer: up to 4 weeks
– Medical patients: 6–14 days regardless of recovery status. Benefit not established for treatment >14 days

Duration

– General surgery: 5–7 days, or until the patient is mobilized
– Hip replacement surgery: 5 weeks
– Medical patients: Up to 14 days

Duration

For as long as the patient is considered to be at risk of VTE

Duration

– Orthopaedic or abdominal surgery: 5–9 days or up to 24 days after hip fracture surgery
– Medical patients: 6–14 days

DVT and PE treatment

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults

Indication

Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults

Indication

Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults

Indication

Treatment of DVT and PE, and prevention of recurrent DVT and PE in adults

Indication

Treatment and prophylaxis of venous thrombosis and PE

Indication

Treatment of DVT and PE

Indication

Treatment of DVT and PE, excluding PE likely to require thrombolytic therapy or surgery

Indication

Treatment of VTE presenting clinically as DVT, PE or both (as bridging to oral anticoagulation) and extended treatment and secondary prevention of symptomatic VTE in patients with solid tumours

Indication

Treatment of venous thrombosis and thromboembolic disease in adults (as bridging to oral anticoagulation) and extended treatment and secondary prevention of VTE in adult patients with active cancer

Indication

Treatment of adults with acute DVT or PE (as bridging to oral anticoagulation)
Dose

Dose

– Treatment of DVT and PE: 10 mg twice daily for the first 7 days followed by 5 mg twice daily
– Prevention of recurrent DVT and/or PE following 6 months treatment for DVT or PE: 2.5 mg twice daily

Dose

60 mg once daily following initial use of parenteral anticoagulant for at least 5 days

Dose

– Treatment and prevention of recurrent DVT and PE: 15 mg twice daily for the first 21 days followed by 20 mg once daily
– Prevention of recurrent DVT and PE following at least 6 months of therapy for DVT or PE: 10 mg once daily (recommended) or 20 mg once daily (in patients at high risk of recurrence)

Dose

150 mg twice daily following initial treatment with a parenteral anticoagulant for at least 5 days

Dose

Induction dose of 10 mg daily for 2 days (tailored to individual requirements), followed by 3–9 mg once daily, depending on prothrombin time or other appropriate coagulation tests; warfarin may initially be given with a heparin until the INR is in the correct range

Dose

5000 IU i.v. followed by either: 1000–2000 IU/h by i.v. infusion; 10–20,000 IU 12-hourly s.c.; or 5–10,000 IU 4-hourly by i.v. injection; adjust dose to maintain an aPTT value 1.5–2.5 × midpoint of normal range or control value

Dose

1.5 mg/kg (150 IU/kg) once daily as s.c. injection (in uncomplicated patients with low risk of VTE recurrence) OR 1 mg/kg (100 IU/kg) twice daily as s.c. injection (in all other patients, e.g. those with obesity, symptomatic PE, cancer, recurrent VTE or proximal [vena iliaca] thrombosis)

Dose

– If using 10,000 IU/ml ampoules for bridging therapy: 200 IU/kg bodyweight once daily as s.c. injection OR 100 IU/kg bodyweight twice daily as s.c. injection in patients at increased risk of bleeding. Maximum daily dose should not exceed 18,000 IU
– If using prefilled syringes for bridging therapy: administer a single daily dose of either 7500, 10,000, 12,500, 15,000 or 18,000 IU s.c. depending on bodyweight
– For extended treatment of VTE in patients with solid tumours: administer a single daily dose of either 7500, 10,000, 12,500, 15,000 or 18,000 IU s.c. depending on bodyweight

Dose

175 anti-Factor Xa IU/kg once daily

Dose

– DVT/PE treatment: 7.5 mg s.c. once daily
Dose adjustments

Dose adjustments

None

Dose adjustments

30 mg once daily in patients with one or more of the following: CrCl 15–50 ml/min; body weight ≤60 kg; concomitant use of the P-gp inhibitors cyclosporine, dronedarone, erythromycin or ketoconazole

Dose adjustments

After day 21, use of 15 mg once daily rather than 20 mg once daily should be considered in patients with CrCl 15–49 ml/min if the patient’s assessed risk for bleeding outweighs the risk for recurrent DVT and PE

Dose adjustments

110 mg twice daily in patients 80 years or receiving concomitant verapamil; consider also for patients aged 75–80 years, patients with CrCl 30–50 ml/min, patients with gastritis, oesophagitis or gastroesophageal reflux, or patients at increased bleeding risk

Dose adjustments

Additional monitoring and a change in dosage may be required for patients with hyper- or hypothyroidism, changes in body weight, acute illness, smoking cessation, diarrhoea or vomiting or specific genetic polymorphisms

Dose adjustments

– A loading dose of 10,000 IU may be required in severe PE
– Dosage reduction may be advisable in elderly patients
– Children and small adults should receive a loading dose of 50 U/kg i.v. followed by either: 15–25 IU/kg/h by i.v. infusion; 250 IU/kg 12-hourly s.c.; or 100 IU/kg 4-hourly i.v.

Dose adjustments

– 1 mg/kg (100 IU/kg) once daily s.c. in patients with CrCl 15–30 ml/min

Dose adjustments

By weight; in children or in patients with renal or hepatic failure dose adjustments may be needed based on Factor Xa monitoring; and in patients with chemotherapy-induced thrombocytopaenia dose adjustments may be needed according to platelet count

Dose adjustments

By weight

Dose adjustments

– DVT/PE treatment: 5 mg s.c. once daily in patients <50 kg; 10 mg s.c. once daily in patients >100 kg (consider reducing to 7.5 mg in patients >100 kg with CrCl 30–50 ml/min)
Duration

Duration

At least 3 months, based on risk factors for recurrent VTE

Duration

At least 3 months, based on risk factors for recurrent VTE

Duration

At least 3 months, based on risk factors for recurrent VTE

Duration

At least 3 months, based on risk factors for recurrent VTE

Duration

Not stated

Duration

no information provided in SmPC

Duration

Average duration of 10 days; initiate oral anticoagulation when appropriate

Duration

– Standard VTE treatment: At least 5 days and until adequate oral anticoagulation is established
– Extended VTE treatment in patients with solid tumours: 6 months; evaluate continuing treatment beyond this period according to individual benefit–risk ratio

Duration

– Standard VTE treatment: At least 6 days and until adequate oral anticoagulation is established
– Extended treatment of VTE in active cancer: 6 months, after which the benefit of continued therapy should be evaluated

Duration

– DVT/PE treatment: At least 5 days and until adequate oral anticoagulation is established

Prevention of stroke in patients with NVAF

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors, such as prior stroke or TIA; age ≥75 years; hypertension; diabetes mellitus; symptomatic heart failure (NYHA Class ≥II)

Indication

Prevention of stroke and systemic embolism in adult patients NVAF with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA

Indication

Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA

Indication

Prevention of stroke and systemic embolism in adult patients with NVAF with one or more risk factors, such as prior stroke or TIA; age ≥75 years; heart failure (NYHA Class ≥II); diabetes mellitus; or hypertension

Indication

Prevention of systemic embolism in patients with rheumatic heart disease and AF

Indication

Indication

Indication

Indication

Indication

Dose

Dose

5 mg twice daily

Dose

60 mg once daily

Dose

20 mg once daily

Dose

150 mg twice daily

Dose

Induction dose of 10 mg daily for 2 days (tailored to individual requirements), followed by 3–9 mg once daily, depending on prothrombin time or other appropriate coagulation tests

Dose

Dose

Dose

Dose

Dose

Dose adjustments

Dose adjustments

2.5 mg twice daily in patients with NVAF and CrCl 15–29 ml/min or at least two of the following characteristics: age ≥80 years; body weight ≤60 kg; serum creatinine ≥1.5 mg/dl (133 µmol/l)

Dose adjustments

30 mg once daily in patients with one or more of the following: CrCl 15–50 ml/min; body weight ≤60 kg; concomitant use of the P-gp inhibitors cyclosporine, dronedarone, erythromycin or ketoconazole

Dose adjustments

15 mg once daily in patients with CrCl 15–49 ml/min

Dose adjustments

110 mg capsule twice daily in patients 80 years or receiving concomitant verapamil; consider also for patients aged 75–80 years, patients with CrCl 30–50 ml/min, patients with gastritis, oesophagitis or gastroesophageal reflux, or patients at increased bleeding risk

Dose adjustments

Additional monitoring and a change in dosage may be required for patients with hyper- or hypothyroidism, changes in body weight, acute illness, smoking cessation, diarrhoea or vomiting or specific genetic polymorphisms

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Duration

Duration

Long term

Duration

Long term

Duration

Long term (provided the benefit of prevention of stroke/SE outweighs the risk of bleeding)

Duration

Long term

Duration

Not stated

Duration

Duration

Duration

Duration

Duration

Prevention of stroke in patients with VAF

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Indication

Indication

Indication

Indication

Prevention of systemic embolization in patients with rheumatic heart disease and AF

Indication

Indication

Indication

Indication

Indication

Dose

Dose

Dose

Dose

Dose

Dose

Induction dose of 10 mg daily for 2 days (tailored to individual requirements), followed by 3–9 mg once daily, depending on prothrombin time or other appropriate coagulation tests

Dose

Dose

Dose

Dose

Dose

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Additional monitoring and a change in dosage may be required for patients with hyper- or hypothyroidism, changes in body weight, acute illness, smoking cessation, diarrhoea or vomiting or specific genetic polymorphisms

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Duration

Duration

Duration

Duration

Duration

Duration

Not stated

Duration

Duration

Duration

Duration

Duration

Prevention/treatment of ACS

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Indication

Indication

Prevention of atherothrombotic events in adult patients after an ACS with elevated cardiac biomarkers, in combination with ASA alone or with ASA plus clopidogrel/ticlopidine. Patients should have no history of stroke/TIA

Indication

Indication

Indication

Treatment of unstable angina

Indication

Treatment of unstable angina and NSTEMI, administered concurrently with ASA; treatment of acute STEMI including patients to be managed medically or with subsequent PCI

Indication

Unstable angina and non-Q wave MI (unstable CAD), administered concurrently with ASA

Indication

Indication

Treatment of unstable angina or NSTEMI in adults for whom urgent (<120 mins) invasive management is not indicated or treatment of STEMI in adults who are managed with thrombolytics or who initially are to receive no other form of reperfusion therapy
Dose

Dose

Dose

Dose

2.5 mg twice daily in addition to either ASA 75–100 mg daily or ASA 75–100 mg daily plus clopidogrel 75 mg daily or a standard daily dose of ticlopidine; initiation as soon as possible after stabilization of the ACS event (including revascularization procedures), at the earliest 24 hours after admission to hospital and at the time when parenteral anticoagulation therapy would normally be discontinued

Dose

Dose

Dose

5000 IU i.v. followed by either 1000–2000 IU/h by i.v. infusion or 5–10,000 IU 4-hourly by i.v. injection; adjust dose to maintain an aPTT value 1.5–2.5 × midpoint of normal range or control value

Dose

– Unstable angina and NSTEMI: 1 mg/kg (100 IU/kg) s.c. every 12 hours in combination with antiplatelet therapy
– Acute STEMI: Single i.v. bolus of 30 mg (3000 IU) plus 1 mg/kg (100 IU/kg) s.c., then 1 mg/kg (100 IU/kg) s.c. every 12 hours (max 100 mg [10,000 IU] for each of the first two doses), in combination with appropriate antiplatelet therapy unless contraindicated; administer enoxaparin between 15 minutes before and 30 minutes after the start of fibrinolytic therapy, if applicable

Dose

120 IU/kg s.c. every 12 hours (maximum 10,000 IU/12 hours)

Dose

Dose

2.5 mg s.c. once daily, initiated as soon as possible following diagnosis; for patients with STEMI, the first dose is administered i.v. and subsequent doses are s.c.
Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

None

Dose adjustments

Dose adjustments

Dose adjustments

– Dosage reduction may be advisable in elderly patients
– Children and small adults should receive a loading dose of 50 IU/kg i.v. followed by either 15–25 IU/kg/h by i.v. infusion or 100 IU/kg 4-hourly by i.v. injection

Dose adjustments

– For patients managed with PCI: If the last enoxaparin administration was given <8 hours before balloon inflation, no additional dosing is needed; if >8 hours before balloon inflation, administer a 0.3 mg/kg (30 IU/kg) i.v. bolus
– For patients aged ≥75 years of age treated for acute STEMI: Omit the initial i.v. bolus and initiate dosing with 0.75 mg/kg (75 IU/kg) s.c. every 12 hours (maximum 75 mg for each of the first two doses only)
– Further dose adjustments required in patients with CrCl 15–30 ml/min (see prescribing information)

Dose adjustments

Patients needing treatment beyond 8 days, while awaiting angiography/revascularization, should receive a fixed dose of either 5000 IU (women <80 kg and men <70 kg) or 7500 IU (women ≥80 kg and men ≥70 kg) 12 hourly; additional dose adjustments may be needed in children and patients with hepatic failure based on Factor Xa monitoring

Dose adjustments

Dose adjustments

None
Duration

Duration

Duration

Duration

As long as the risk for ischaemic events outweighs the bleeding risk. Treatment beyond 12 months should be considered on an individual patient basis, as data up to 24 months are limited

Duration

Duration

Duration

not stated in SmPC

Duration

– Unstable angina and NSTEMI: 2–8 days or until clinical stabilization
– Acute STEMI: 8 days or until hospital discharge, whichever comes first

Duration

Up to 8 days unless patient is to undergo revascularization, in which case treatment is recommended to be given until the day of the revascularization procedure (PTCA or CABG) but not for more than 45 days

Duration

Duration

8 days or until hospital discharge, whichever occurs earlier

Prevention of atherothrombotic events in CAD or PAD

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Approved to use in this indication in EU/UK
Indication

Indication

Indication

Indication

Prevention of atherothrombotic events in adult patients with CAD or symptomatic PAD at high risk of ischaemic events

Indication

Indication

Indication

Treatment of acute peripheral arterial occlusion

Indication

Indication

Indication

Indication

Dose

Dose

Dose

Dose

2.5 mg twice daily in addition to ASA 75–100 mg daily

Dose

Dose

Dose

5000 IU i.v. followed by either 1000–2000 U/h by i.v. infusion or 5–10,000 IU 4-hourly by i.v. injection; adjust dose to maintain an aPTT value 1.5–2.5 × midpoint of normal range or control value

Dose

Dose

Dose

Dose

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

None

Dose adjustments

Dose adjustments

Dose adjustments

– Dosage reduction may be advisable in elderly patients
– Children and small adults should receive a loading dose of 50 IU/kg i.v. followed by either 15–25 IU/kg/h by i.v. infusion or 100 IU/kg 4-hourly by i.v. injection

Dose adjustments

Dose adjustments

Dose adjustments

Dose adjustments

Duration

Duration

Duration

Duration

As long as the risk of thrombotic events outweighs the bleeding risks

Duration

Duration

Duration

not stated in SmPC

Duration

Duration

Duration

Duration

Practical management

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Routine coagulation monitoring needed?

Measure drug level/activity using

Measure drug level/activity using

Calibrated anti-Factor Xa assay (quantitative)

Measure drug level/activity using

Calibrated anti-Factor Xa assay (quantitative)

Measure drug level/activity using

Calibrated anti-Factor Xa assay (quantitative)

Measure drug level/activity using

  • Calibrated dTT (quantitative)
  • TT, ECT, aPTT (qualitative)

Measure drug level/activity using

PTT (INR)

Measure drug level/activity using

aPPT

Measure drug level/activity using

Not described in SmPC

Measure drug level/activity using

  • Anti-Factor Xa assay (quantitative)
  • aPTT (as test of overdosage only)

Measure drug level/activity using

Anti-Factor Xa assay

Measure drug level/activity using

Not described in SmPC
Onset of full therapeutic effect (h)

Onset of full therapeutic effect (h)

3–4

Onset of full therapeutic effect (h)

1–2

Onset of full therapeutic effect (h)

2–4

Onset of full therapeutic effect (h)

0.5–2 (up to 6 h if administered postoperatively)

Onset of full therapeutic effect (h)

24–96

Onset of full therapeutic effect (h)

Not stated in SmPC

Onset of full therapeutic effect (h)

3–5

Onset of full therapeutic effect (h)

Not stated in SmPC

Onset of full therapeutic effect (h)

4–6

Onset of full therapeutic effect (h)

2
Approx. half-life (h)

Approx. half-life (h)

12

Approx. half-life (h)

10–14

Approx. half-life (h)

5–13

Approx. half-life (h)

12–18

Approx. half-life (h)

20–60

Approx. half-life (h)

Depends on the dose administered, the route of administration and is subject to wide inter- and intra-individual variation

Approx. half-life (h)

5–7

Approx. half-life (h)

2–4

Approx. half-life (h)

1.5

Approx. half-life (h)

17–21
Approx. renal excretion (%)

Approx. renal excretion (%)

27

Approx. renal excretion (%)

35

Approx. renal excretion (%)

33

Approx. renal excretion (%)

85

Approx. renal excretion (%)

Negligible

Approx. renal excretion (%)

Heparin and its metabolites are excreted in the urine

Approx. renal excretion (%)

10% (active fragments)
40% (active and
non-active fragments)

Approx. renal excretion (%)

Not stated in SmPC

Approx. renal excretion (%)

Not stated in SmPC

Approx. renal excretion (%)

64–77%
Food and drink

Food and drink

Take with or without food

Food and drink

Take with or without food

Food and drink

  • Take 15/20 mg doses with food
  • Take 10/2.5 mg doses with or without food

Food and drink

Take with or without food. Swallow capsules whole with a glass of water to facilitate delivery to stomach

Food and drink

  • INR may be increased by cranberry products, grapefruits and ingestion of large quantities of alcohol
  • INR may be reduced by foods high in vitamin K (e.g. broccoli, green leafy vegetables and liver)

Food and drink

No effects

Food and drink

No effects

Food and drink

No effects

Food and drink

No effects

Food and drink

No effects
Missed dose

Missed dose

Take dose immediately and continue with twice-daily intake thereafter

Missed dose

Take dose immediately and continue with usual once-daily dosing the next day; the dose should not be doubled within the same day

Missed dose

  • VTE prevention (10 mg once daily): take dose immediately and continue with usual once-daily dosing the next day
  • Acute phase of VTE treatment (15 mg twice daily): take missed dose immediately to ensure intake of 30 mg per day (two 15 mg tablets may be taken at once); continue with the regular 15 mg twice-daily intake on the following day
  • Post-acute phase treatment of VTE (i.e. after 21 days)/prevention of stroke in NVAF: (15/20 mg once daily): take dose immediately and continue with usual once-daily dosing the next day; the dose should not be doubled within the same day
  • Stroke prevention (20 mg once daily): take dose immediately and continue with usual once-daily dosing the next day; the dose should not be doubled within the same day
  • Secondary prevention of ACS or prevention of atherothrombotic events in CAD/PAD (2.5 mg twice daily): continue with the regular dose at the next scheduled time

Missed dose

  • VTE prevention: continue with the usual daily doses the next day
  • VTE treatment, NVAF: A forgotten dose may still be taken up to 6 hours prior to the next scheduled dose; thereafter, the missed dose should be omitted
  • In all cases, the dose should not be doubled

Missed dose

No advice in prescribing information

Missed dose

No advice provided

Missed dose

No advice provided

Missed dose

No advice provided

Missed dose

No advice provided

Missed dose

No advice provided
Patients needing surgery

Patients needing surgery

  • If possible, prior to elective surgery or invasive procedures discontinue at least 24 hours before procedures with low bleeding risk and 48 hours before procedures with moderate or high bleeding risk
  • Restart as soon as possible once adequate haemostasis is restored
  • Bridging with heparin not required

Patients needing surgery

  • If possible, discontinue at least 24 hours before procedure
  • Restart as soon as possible once adequate haemostasis is restored
  • Bridging with heparin not required

Patients needing surgery

  • If possible, discontinue at least 24 hours before procedure (for patients receiving doses ≥10 mg once daily) or at least 12 hours before procedure (for patients receiving 2.5 mg twice daily)
  • Restart as soon as possible once adequate haemostasis is restored
  • Bridging with heparin not required

Patients needing surgery

  • If possible, discontinue at least 24 hours before procedure and up to 4 days before, depending on renal function and bleeding risk of surgery; restart as soon as possible once adequate haemostasis is restored
  • For emergency surgery or urgent procedures, discontinue dabigatran therapy and, if rapid reversal is required, administer idarucizumab; restart dabigatran 24 hours after administration of idarucizumab if adequate haemostasis has been achieved
  • Bridging with heparin not required

Patients needing surgery

  • Surgery with no bleeding risk can be performed at INR <2.5
  • For surgery where there is a risk of severe bleeding, warfarin should be stopped 3 days prior to surgery
  • Where it is necessary to continue anticoagulation, the INR should be reduced to <2.5 and heparin therapy should be started
  • If surgery is required and warfarin cannot be stopped 3 days beforehand, anticoagulation should be reversed with low-dose vitamin K
  • Treatment can usually be re-started as soon as the patient has an oral intake
  • 5

Patients needing surgery

No advice provided

Patients needing surgery

No advice provided

Patients needing surgery

No advice provided

Patients needing surgery

No advice provided

Patients needing surgery

  • Stop 24 hours before surgery if possible
  • In patients with ACS undergoing, CABG, restart fondaparinux 48 h postoperatively

Key interactions and contraindications

Apixaban Eliquis®
Rivaroxaban Xarelto®
Dabigatran Pradaxa®
Warfarin Warfarin
Unfractionated heparin Heparin
Enoxaparin Clexane®
Dalteparin Fragmin®
Tinzaparin Innohep®
Fondaparinux Arixtra®
Principal contraindications/recommendations against use

Principal contraindications/recommendations against use

  • Age <18 years
  • CrCl <15 ml/min or undergoing dialysis
  • Pregnancy/breastfeeding
  • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk/severe hepatic impairment
  • Active bleeding or clinically relevant bleeding risk
  • Prosthetic heart valve
  • After hip fracture surgery
  • Patients with PE who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy

Principal contraindications/recommendations against use

  • Age <18 years
  • CrCl <15 ml/min or undergoing dialysis
  • Pregnancy/breastfeeding
  • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk/severe hepatic impairment
  • Active bleeding or clinically relevant bleeding risk
  • Uncontrolled hypertension
  • Prosthetic heart valve/moderate to severe mitral stenosis
  • Patients with PE who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy

Principal contraindications/recommendations against use

  • Age <18 years
  • CrCl <15 ml/min
  • Pregnancy/breastfeeding
  • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child–Pugh B/C
  • Active clinically significant bleeding or clinically relevant bleeding risk
  • Prosthetic heart valve
  • Patients with PE who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy
  • Patients with a prior stroke or TIA (secondary prevention of ACS only)
  • Patients with a previous haemorrhagic or lacunar stroke, or any stroke within one month (prevention of atherothrombotic events in CAD/PAD only)

Principal contraindications/recommendations against use

  • Age <18 years
  • CrCl <30 ml/min
  • Pregnancy/breastfeeding
  • Hepatic impairment or liver disease expected to impact on survival
  • Patients with elevated liver enzymes >2 ULN
  • Active bleeding or clinically relevant bleeding risk
  • After hip fracture surgery
  • Prosthetic heart valves requiring anticoagulant treatment

Principal contraindications/recommendations against use

  • Haemorrhagic stroke
  • Clinically significant bleeding
  • Within 72 hours of major surgery with risk of severe bleeding
  • Pregnancy (first and third trimesters) or <48 hours postpartum

Principal contraindications/recommendations against use

  • Active or high risk of bleeding
  • Current or history of heparin-induced thrombocytopenia
  • Formulations containing the preservative benzyl alcohol should not be used in pregnancy

Principal contraindications/recommendations against use

  • Active/high risk of major bleeding including recent haemorrhagic stroke, gastrointestinal ulcer or malignant neoplasm at high risk of bleeding
  • History of immune-mediated HIT within the past 100 days or in the presence of circulating antibodies
  • Spinal or epidural anaesthesia or locoregional anaesthesia when enoxaparin sodium has been used for treatment in previous 24 h
  • End-stage renal disease (CrCl<15 ml/min)
  • Acute infective endocarditis

Principal contraindications/recommendations against use

  • History of HIT (type II)
  • Acute gastroduodenal ulcer
  • Cerebral haemorrhage
  • Known haemorrhagic diathesis or other active haemorrhage
  • Serious coagulation disorder
  • Acute or sub-acute septic endocarditis
  • Injuries to and operations on the central nervous system, eyes and ears
  • Intramuscular injection of dalteparin and intramuscular injection of other medicines when dalteparin dose >5000 IU/24 hours
  • Local and/or regional anaesthesia when dalteparin has been used for treatment of VTE/unstable CAD

Principal contraindications/recommendations against use

  • Current or history of HIT (type II)
  • Active or high risk of major bleeding
  • Septic endocarditis
  • Neuraxial/ locoregional anaesthesia in patients receiving treatment doses of tinzaparin
  • Prosthetic heart valve
  • Intramuscular injection of tinzaparin or other agents concurrently with tinzaparin
  • CrCl <30 ml/min
  • Formulations containing the preservative benzyl alcohol must not be given to premature babies or neonates

Principal contraindications/recommendations against use

  • Age <17 years
  • CrCl <20 ml/min (CrCl <30 ml/min in patients treated for acute VTE)
  • Active clinically significant bleeding
  • Acute bacterial endocarditis
  • Pregnancy and breastfeeding
  • Spinal or epidural anaesthesia (VTE treatment)
  • Must not be administered intramuscularly
Exercise caution

Exercise caution

  • CrCl 15–29 ml/min in patients receiving apixaban for the prevention of VTE after elective hip or knee replacement surgery or for the treatment of DVT/PE and prevention of recurrent DVT and PE; (for patients with NVAF, patients with CrCl 15–29 ml/min and patients with serum creatinine ≥1.5 mg/dl associated with age ≥80 years or body weight ≤60 kg should receive the lower dose of apixaban 2.5 mg twice daily)
  • Mild or moderate hepatic impairment (Child–Pugh A/B)
  • Elevated liver enzymes (ALT/AST >2× ULN or total bilirubin ≥1.5× ULN)
  • Neuraxial blockade (extreme caution is recommended with an interval of 20–30 h between the last dose of apixaban and catheter withdrawal; the next apixaban dose can be given at least 5 h after catheter removal)

Exercise caution

  • Mild or moderate hepatic impairment
  • Elevated liver enzymes (ALT/AST >2× ULN or total bilirubin ≥1.5× ULN)
  • Patients with NVAF and high CrCl (based on a trend towards decreasing efficacy with increasing CrCl)

Exercise caution

  • CrCl 15–29 ml/min
  • Patients with moderate renal impairment taking co-medications that result in increased rivaroxaban plasma concentrations
  • Neuraxial blockade (for doses ≥10 mg, recommended interval of ≥2 half-lives between last administration of rivaroxaban and catheter removal and of ≥6 h between removal and the next rivaroxaban dose)

Exercise caution

  • CrCl 30–50 ml/min
  • Age ≥75 years
  • Conditions or procedures with special haemorrhagic risks (e.g. congenital or acquired coagulation disorders, thrombocytopaenia, recent biopsy or major trauma, bacterial endocarditis, oesophagitis, gastritis or gastroesophageal reflux)

Exercise caution

  • Warfarin should be given with caution to patients at risk of serious haemorrhage, e.g.: – Recent ischaemic stroke – Bacterial endocarditis – Previous GI bleeding
  • Additional monitoring may be needed in patients at increased risk of over-coagulation, e.g. severe hypertension, liver or renal disease
  • Patients with active peptic ulcers should be treated with caution

Exercise caution

  • Patients with hypersensitivity to LMWH
  • Patients with increased risk of bleeding complications, hypertension, renal or hepatic insufficiency
  • Patients undergoing peridural or spinal anaesthesia; avoid administration of heparin until ≥4 h have elapsed after catheter removal
  • Take care when giving concomitant intramuscular injections, lumbar puncture and similar procedures

Exercise caution

  • Renal and hepatic impairment
  • Spinal anaesthesia
  • History of HIT >100 days (extreme caution)
  • Conditions with increased potential for bleeding, such as:
    – Impaired haemostasis
    – History of peptic ulcer
    – Severe arterial hypertension
    – Diabetic retinopathy
    – Recent neurologic or ophthalmologic surgery
    – Co-administration of other anticoagulants and agents affecting haemostasis
  • Patients with low body weight or obese patients receiving prophylactic doses (non-weight adjusted)

Exercise caution

  • Patients with increased bleeding risk (e.g. following surgery or trauma, haemorrhagic stroke, severe liver or renal failure, thrombocytopaenia, uncontrolled hypertension, hypertensive or diabetic retinopathy)
  • Rapidly developing thrombocytopenia and severe thrombocytopenia (<100,000/µl) associated with positive or unknown results of in vitro tests for antiplatelet antibody

Exercise caution

  • Neuraxial anaesthesia in patients receiving prophylactic doses of tinzaparin
  • Elderly patients

Exercise caution

  • Patients with increased bleeding risk (e.g. congenital or acquired bleeding disorders, active ulcerative gastrointestinal disease, recent ICH or shortly after brain, spinal or ophthalmic surgery)
  • Patients who have undergone recent surgery (<3 days; VTE treatment only)
  • Severe hepatic impairment (treatment or prevention of VTE and treatment of ACS)
  • Body weight <50 kg (treatment or prevention of VTE and treatment of ACS)
  • Elderly patients
  • Moderate renal impairment (VTE treatment and prevention)
  • History of HIT
Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • Systemic treatment with strong inhibitors of both CYP3A4 and P-gp e.g. azole antimycotics and HIV protease inhibitors
  • Strong inducers of both CYP3A4 and P-gp (e.g. St John’s wort) if used for acute VTE treatment
  • Other anticoagulants (except under specific circumstances)
  • Medicines associated with serious bleeding (e.g. clopidogrel, dipyridamole, dextran and sulfinpyrazone)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • Other anticoagulants (except under specific circumstances)
  • Chronic high-dose ASA (325 mg)
  • NSAIDs (chronic use)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • Systemic azole antimycotics
  • HIV protease inhibitors
  • Dronedarone
  • Strong CYP3A4 inducers (e.g. St John’s wort)
  • Other anticoagulants (except under specific circumstances)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • Other anticoagulants (except under specific circumstances)
  • Systemic ketoconazole, cyclosporine, itraconazole and dronedarone
  • Tacrolimus
  • Concomitant P-gp inducers (e.g. St John’s wort)
  • Protease inhibitors that affect P-gp (e.g. ritonavir)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • Fibrinolytic drugs (e.g. streptokinase and alteplase)
  • Glucosamine
  • St John’s wort
  • Other drugs used in the treatment of prophylaxis of thrombosis, or other drugs with adverse effects on haemostasis (except for heparins, when co-administered during the initial treatment of thrombosis)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

Drugs affecting platelet function or the coagulation system (e.g. platelet aggregation inhibitors, thrombolytic agents, salicylates, NSAIDs, VKAs, dextrans, activated protein C)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

  • High-dose ASA, systemic salicylates and NSAIDs
  • Thrombolytics (e.g. alteplase and streptokinase)
  • Other anticoagulants (except when initiating VKA therapy, when enoxaparin sodium should be co-administered with a VKA, until target therapeutic range is achieved)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

None specified

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

Concurrent anticoagulant/ antiplatelet agents/NSAIDs (if used, patients should be carefully monitored)

Key co-medications to avoid (concomitant treatment not recommended/ contraindicated)

If fondaparinux is used for VTE treatment or prevention, avoid agents that increase risk of haemorrhage (e.g. desirudin, fibrinolytic agents, GP IIb/IIIa receptor antagonists, heparins/heparinoids or LMWH)
Key co-medications that should be used with caution

Key co-medications that should be used with caution

  • Strong inducers of CYP3A4 and P-gp (e.g. St John’s wort) if used for VTE prevention, prevention of recurrent VTE or in patients with NVAF
  • Concomitant SSRIs/SNRIs or NSAIDs (including ASA)

Key co-medications that should be used with caution

  • Concomitant strong P-gp inducers (e.g. St John’s wort)
  • Concomitant ASA (>100 mg)/other antiplatelet agents
  • Concomitant SSRIs/SNRIs

Key co-medications that should be used with caution

Concomitant NSAIDs (including ASA) /antiplatelet agents/SSRIs/SNRIs

Key co-medications that should be used with caution

Concomitant mild-to-moderate P-gp inhibitors (e.g. amiodarone, verapamil, quinidine, clarithromycin, ticagrelor and posaconazole)

Key co-medications that should be used with caution

  • Drugs which potentiate the effect of warfarin warrant increased coagulation monitoring, e.g.: allopurinol, capecitabine, erlotinib, disulfiram, azole antifungals, omeprazole, paracetamol (prolonged regular use), propafenone, amiodarone, tamoxifen, methylphenidate, zafirlukast, fibrates some statins, erythromycin, sulfamethoxazole and metronidazole
  • Drugs which antagonize warfarin effect warrant increased coagulation monitoring, e.g.: barbiturates, primidone, carbamazepine, griseofulvin, oral contraceptives, rifampicin, azathioprine and phenytoin
  • Drugs which may have a variable effect on INR warrant increased monitoring on starting and stopping therapy, e.g.: corticosteroids, nevirapine and ritonavir
  • Concomitant medications that affect haemostasis by inhibition of platelet aggregation: clopidogrel, ASA, NSAIDs, SSRIs, SNRIs, dipyridamole, sulfinpyrazone and prostacyclin

Key co-medications that should be used with caution

Key co-medications that should be used with caution

  • Other agents affecting haemostasis such as:
    – Platelet aggregation inhibitors (including low-dose ASA, clopidogrel, ticlopidine and glycoprotein IIb/IIIa antagonists)
    – Dextran 40
    – Systemic glucocorticoids
  • Medications increasing serum potassium levels

Key co-medications that should be used with caution

  • Concurrent anticoagulant/antiplatelet agents/NSAIDs (with the exception of low-dose ASA in patients with unstable CAD)
  • Concomitant antihistamines, cardiac glycosides, tetracycline and ascorbic acid

Key co-medications that should be used with caution

Key co-medications that should be used with caution

  • If fondaparinux is used for the treatment of ACS, use with caution in patients concomitantly receiving agents that increase risk of haemorrhage
  • NSAIDs/antiplatelet agents/ASA

Approved for use in this indication in EU/UK

Approved for use in this indication in EU/UK
Not approved for use in this indication in EU/UK

aSome drugs may have other indications beyond those listed – refer to full local prescribing information; bapproved for VTE prevention after orthopaedic surgery in Japan; cnot an exhaustive list – refer to full prescribing information.

ALT, alanine transaminase; aPTT, activated partial thromboplastin time; AST, aspartate transaminase; CYP3A4, cytochrome P450 3A4; dTT, dilute thrombin time; ECT, ecarin clotting time; GI, gastrointestinal; GP IIb/IIIa, glycoprotein IIb/IIIa; HIV, human immunodeficiency virus; i.v., intravenous; NSAID, non-steroidal anti-inflammatory drug; NYHA, New York Heart Association; P-gp, P-glycoprotein; PT, prothrombin time; PTCA, percutaneous transluminal coronary angioplasty; s.c., subcutaneous; TT, thrombin time; ULN, upper limit of normal.

When to use a reduced NOAC dose

Patients receiving anticoagulation with a NOAC should receive a reduced dose in certain clinical situations
© Bayer AG, 2017 | Approval number: G.MKT.GM.XA.12.2017.2018

References

The information in this table is taken from the respective Summary of Product Characteristics for the therapies shown, available at the links provided in the table.

Approval Code: PP-XAR-ALL-0398-1