Dosing, advantages, and disadvantages of anticoagulants used for VTE in patients with braincancer
| Drug . | Dosing . | Advantages . | Disadvantages . |
|---|---|---|---|
| Apixaban | 10 mg bid for 5 d, then 5 mg bid thereafter | Lowest overall bleeding risk in meta-analysis for all DOAC indications Low renal clearance (∼25%) | Very limited prospective evidence No licensed dose reduction for VTE Limited evidence of clinical benefit and limited availability of andexanet alfa |
| Dabigatran | LMWH for 5 d, then 150 mg bid thereafter. 110 mg bid for patients ≥80 y and those on verapamil 110 mg bid can be considered for patients aged 75-80 y, CrCl 30-50 ml/min and those at increased risk of bleeding | Lowest risk of ICH in meta-analysis (110 mg bid) of AF and VTE trials Licensed dose reduction (110 mg bid) Widespread availability of idarucizumab | Not well tolerated (large tablet) 80% renal clearance No prospective evidence in cancer-associated VTE and very little retrospective evidence Dose reduction to 110 mg bid based on pharmacokinetic data (was trialed in AF but not in VTE) Need to first give LMWH for 5 d |
| Edoxaban | LMWH for 5 d then 60 mg OD thereafter Reduce to 30 mg OD, if CrCl 15-50 ml/min, weight ≤60 kg, or on interacting medications (ciclosporin, dronedarone, erythromycin, ketoconazole) | Most prospective evidence of efficacy and safety OD dosing Licensed dose reduction (30 mg daily) Lactose free | No specific, licensed reversal agent Need to give 5 d LMWH first |
| Rivaroxaban | 15 mg bid for 21 d, then 20 mg thereafter If CrCl 15-49 ml/min, consider 15 mg OD after initial 21 d | OD dosing Extended higher dosing intensity period | Very limited prospective evidence Dose reduction to 15 mg OD not trialed Should be taken with 600 kcal of food Limited evidence of clinical benefit and limited availability of andexanet alfa |
| LMWH | Weight-adjusted dosing depending on formulation as OD or bid (split dosing) Reduce dose by 25% after 1 mo (dalteparin only) | Familiarity Similar outcomes to edoxaban in prospective trial Parenteral administration Few drug interactions | Retrospective data suggest not as safe as DOAC Parenteral administration Incomplete reversal with protamine |
| VKA | Dosed as per INR, with usual target of 2.5 Target of 3.5 if breakthrough thrombosis has occurred with VKA or other anticoagulants | Availability of clinically meaningful monitoring of therapeutic effect Suitable for patients with poor renal function NEW LINE Rapidly reversible with PCC | Need for regular blood tests Many drug interactions Increased intracranial bleeding compared with DOACs |
| Drug . | Dosing . | Advantages . | Disadvantages . |
|---|---|---|---|
| Apixaban | 10 mg bid for 5 d, then 5 mg bid thereafter | Lowest overall bleeding risk in meta-analysis for all DOAC indications Low renal clearance (∼25%) | Very limited prospective evidence No licensed dose reduction for VTE Limited evidence of clinical benefit and limited availability of andexanet alfa |
| Dabigatran | LMWH for 5 d, then 150 mg bid thereafter. 110 mg bid for patients ≥80 y and those on verapamil 110 mg bid can be considered for patients aged 75-80 y, CrCl 30-50 ml/min and those at increased risk of bleeding | Lowest risk of ICH in meta-analysis (110 mg bid) of AF and VTE trials Licensed dose reduction (110 mg bid) Widespread availability of idarucizumab | Not well tolerated (large tablet) 80% renal clearance No prospective evidence in cancer-associated VTE and very little retrospective evidence Dose reduction to 110 mg bid based on pharmacokinetic data (was trialed in AF but not in VTE) Need to first give LMWH for 5 d |
| Edoxaban | LMWH for 5 d then 60 mg OD thereafter Reduce to 30 mg OD, if CrCl 15-50 ml/min, weight ≤60 kg, or on interacting medications (ciclosporin, dronedarone, erythromycin, ketoconazole) | Most prospective evidence of efficacy and safety OD dosing Licensed dose reduction (30 mg daily) Lactose free | No specific, licensed reversal agent Need to give 5 d LMWH first |
| Rivaroxaban | 15 mg bid for 21 d, then 20 mg thereafter If CrCl 15-49 ml/min, consider 15 mg OD after initial 21 d | OD dosing Extended higher dosing intensity period | Very limited prospective evidence Dose reduction to 15 mg OD not trialed Should be taken with 600 kcal of food Limited evidence of clinical benefit and limited availability of andexanet alfa |
| LMWH | Weight-adjusted dosing depending on formulation as OD or bid (split dosing) Reduce dose by 25% after 1 mo (dalteparin only) | Familiarity Similar outcomes to edoxaban in prospective trial Parenteral administration Few drug interactions | Retrospective data suggest not as safe as DOAC Parenteral administration Incomplete reversal with protamine |
| VKA | Dosed as per INR, with usual target of 2.5 Target of 3.5 if breakthrough thrombosis has occurred with VKA or other anticoagulants | Availability of clinically meaningful monitoring of therapeutic effect Suitable for patients with poor renal function NEW LINE Rapidly reversible with PCC | Need for regular blood tests Many drug interactions Increased intracranial bleeding compared with DOACs |
AF, atrial fibrillation; bid, twice daily; CrCl, creatinine clearance; INR, international normalized ratio; OD, once daily; VKA, vitamin K antagonist; PCC, prothrombin complex concentrate