New treatments for the prevention of blood clotting

The authors provided information on several new oral anticoagulant drugs.

The clinical burden of thromboembolic diseases (diseases in which a clot forms in a blood vessel which may be carried by the blood stream to another vessel) and the limitations of current therapies have prompted the development of new oral anticoagulant agents (drugs that prevent blood clotting). In the past few years rivaroxaban (Xarelto), apixaban (Eliquis) and dabigatran etexilate (Pradaxa) have undergone extensive evaluation and gained approval for use in several diseases. This review describes the properties of these novel oral anticoagulants.

Rivaroxaban is a direct inhibitor of factor Xa (a protein that contributes to coagulation, or blood clotting). It is absorbed rapidly, with maximum blood concentration reached 2-4 hours after dosing. At a dose of 10 mg, rivaroxaban has an oral bioavaliabilty (the fraction of the drug that reaches circulation) of 80-100% under fasting conditions. Higher doses of 15-20 mg should be taken with food, which will result in incomplete absorption. It is eliminated via urine, kidneys and liver.

Apixaban is a direct inhibitor of factor Xa. The maximal blood concentration is achieved 1-3 hours after administration, with an oral bioavailability of approximately 66% at 10 mg. At this dose, apixaban can be taken with or without food. It is eliminated via kidneys, liver and intestines.

Edoxaban is a direct inhibitor of factor Xa. The maximal blood concentration is achieved 1-2 hours after oral administration, with an oral bioavailability of approximately 60%. At a dose of 60 mg edoxaban can be taken with or without food. It is eliminated via the liver and kidneys.

Dabigatran is an oral prodrug (a drug that is administered in an inactive form) that is absorbed rapidly and converted to the active form by proteins in the gut, blood and liver. The absolute bioavailability is 6-7%. Food does not affect this availability but without food maximal blood concentrations are reached 2 hours following administration, while with food this increases to 4 hours. It is predominantly eliminated via the kidneys. Age-related reductions in kidney function mean that exposure of the drug (the time between availability and elimination) can be twice as high in elderly patients, particularly female patients.

Rivaroxaban, apixaban and dabigatran have been approved for the prevention of deep vein thrombosis (the formation of a blood clot in a deep vein) and pulmonary embolism (blockage of one or more arteries in the lung). They have also been approved in several countries for the prevention of stroke and systemic embolism (blockage of one or more arteries throughout the body’s system) in patients with non-valvular atrial fibrillation (a heart rhythm disorder where the condition does not stem from dysfunction of the valves of the heart).

While these drugs have favorable properties, restrictions in use apply.

As with any drugs that are eliminated by the liver or kidneys, function of these organs is important to assess prior to administration of drugs, and no drugs should be taken without physician consultation.