THERAPEUTICS

Brands

• Pradaxa

Generic?

• No

Class

• Anticoagulant

Commonly Prescribed for

(FDA approved in bold)

• Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF)

• Primary prevention of venous thromboembolic (VTE) events in adult patients who have undergone elective total hip or knee arthroplasty

• Prevention of stroke and systemic embolism in patients with left ventricular thrombosis

How the Drug Works

• Dabigatran etexilate is a prodrug that is rapidly converted to its active compound, dabigatran, by non-specific esterase in the plasma and liver. Dabigatran is a reversible inhibitor for factor IIa (thrombin, free and clot-bound), thereby reducing the conversion of fibrinogen into fibrin and thrombus formation. Thrombin-induced platelet aggregation is also inhibited

How Long Until It Works

• Peak concentration in 1–2 hours

If It Works

• Monitor for signs of bleeding. Assess renal function periodically as clinically indicated

If It Doesn't Work

• Correct the underlying disorder. Use a higher dose or switch to different anticoagulant

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Based on RE-LY study, concomitant antiplatelet therapy has little effect on the relative advantages of dabigatran in comparison with warfarin on AF management

Tests

• A prolonged aPTT (> 1× control) is consistent with the presence of dabigatran, but the degree of prolongation does not correlate well with plasma concentrations. aPTT > 2 upper limit (after 12–24 hours) or thrombin time > 65 seconds may indicate greater bleeding risks. The Hemoclot thrombin clotting time is more accurate but not available in the US. aPTT < 1× control is at low risk of bleeding events

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• Reduced coagulation due to inhibited thrombin

Notable AEs

• Bleeding and GI events (e.g., diarrhea, dyspepsia, abdominal pain, hemorrhage)

• Compared with warfarin, dabigatran has lower rates of intracranial bleeding and life-threatening bleeding, but higher GI bleeding