Table 1 Clinical profile of NOACs [7]
From: NOACs: an emerging class of oral anticoagulants-a review article
Anticoagulant | Dabigatran | Rivaroxaban | Apixaban | Edoxaban |
|---|---|---|---|---|
Mechanism of action | Direct thrombin inhibitor | Direct factor Xa inhibitor | Direct factor Xa inhibitor | Direct factor Xa inhibitor |
Prodrug | Yes | No | No | No |
Absorption | Rapid | Rapid | 3-4 h | Rapid |
Bioavailability | 6% | 66% w/o food Up to 100% with food | 50% | 62% |
Half-life | 12–17 h | 5-9 h(young) 11-13 h(elderly) | 12 h | 9-11 h |
Vd | 50–70 L | 50 L | 21 L | 107 L |
Time to reach max. plasma conc. | 0.5–2 h | 2-4 h | 1-4 h | 1-2 h |
Protein binding | 35% | 92-95% | 87% | 55% |
Liver metabolism | No | Yes | Yes | Minimal |
Renal excretion | 80% | 35% | 25% | 50% |
Gastro-intestinal tolerability | Dyspepsia | No Problem | No Problem | No Problem |
Absorption with food | No effect | 39% & above | No effect | 6-22% more |
Effect of diet | Delays absorption; time to reach peak level extends to 4 h | Peak levels attain at 3 h on fasting and 4 h with food. Factor Xa inhibition higher with food | No effect on exposure | No effect on exposure |
Effect of age | Bioavailability is 1.7–2 times high in elders | Bioavailability is greater in elderly with half-life 11-13 h with no difference in concentration | Exposure is 32% greater in patients above 65 years of age | Exposure is 32% greater in patients over 65 years of age |
Effect of body weight | None | Weight < 50 kg have 24% increased exposure & weight > 120 kg have 24% reduced exposure | Weight < 50 kg have 20-30% increased exposure & weight > 120 kg have 20-30% reduced exposure | Weight < 50 kg have 20-30% increased exposure & weight > 120 kg have 20-30% reduced exposure |
Effect of renal impairment | Severely impaired; 6 times higher exposure with half-life 28 h | Similar increase in exposure with moderate or severe renal impairment | No effect on peak concentration. Increase in exposure of 16, 29, and 44% for creatinine clearance of 51–80, 30–50, and 15–29% ml/min, respectively. | No effect on peak concentration. Increase in exposure of 16, 29, and 44% for creatinine clearance of 51–80, 30–50, and 15–29% ml/min, respectively. |
Effect of hepatic impairment | None with Child-Pugh classification B | Significantly increased on exposure with Child-Pugh classification B | No change in exposure with Child-Pugh classification A or B | No change in exposure with Child-Pugh classification A or B |
Doses | 75 mg, 110 mg, 150 mg | 2.5 mg, 10 mg, 15 mg, 20 mg | 2.5 mg, 5 mg | 15 mg, 30 mg, 60 mg |
Dosing | Two times a day | One time a day | Two times a day | One time a day |
Dosage form | Capsule | Tablet | Tablet | Tablet |
ADR | > 10% gastro-intestinal symptoms (like dyspepsia); 1–10% gastritis, esophagitis; < 1% allergic oedema, thrombocytopenia | >1 0% haematologic and oncologic haemorrhage; 1–10% pruritus, abdominal pain; < 1% angioedema, cholestasis | > 10% haematologic and oncologic haemorrhage; 1–10% haematuria, epistaxis; < 1% hyper-sensitivity reaction, haematoma | > 10% haematologic and oncologic haemorrhage; 1–10% skin rash, anaemia; < 1% intra cranial haemorrhage, interstitial pulmonary disease |
Contra indications | Serious hyper-sensitivity reactions | Serious hyper-sensitivity reactions | Serious hyper-sensitivity reactions | Serious hyper-sensitivity reactions |