DOAK

Products

Direct oral anticoagulants (abbreviation: DOAKs) are commercially available in the form of film-coated tablets and capsules. By definition, they are oral drugs. Some representatives of the corresponding drug groups are also available as infusion preparations. Rivaroxaban (Xarelto) and dabigatran (Pradaxa) were the first active ingredients to be approved in 2008. The DOAKs were developed as successors to the low-molecular-weight heparins and the vitamin K antagonists. As new drugs, the DOAKs and their antidotes are substantially more expensive than their predecessors.

Structure and properties

Factor Xa inhibitors are designed to bind in an L-shape to the active site of the drug target factor Xa. The modern and oral thrombin inhibitors have a nonpeptide structure.

Effects

The DOAKs (ATC B01AF, ATC B01AE) have anticoagulant and antithrombotic properties. Their effects are based on inhibition of blood clotting factors. Factor Xa inhibitors inhibit factor Xa and thrombin inhibitors inhibit thrombin (factor II). Both factors are central to blood clotting. The agents are referred to as direct because their effects are independent of antithrombin and they interact directly with clotting factors (rather than inhibiting their synthesis as do vitamin K antagonists).

Indications

For the prevention and treatment of thromboembolic disease, for example, deep vein thrombosis and pulmonary embolism.

Dosage

According to the SmPC. Unlike low-molecular-weight heparins, most DOAKs do not need to be injected but can be taken perorally, once or twice daily depending on the drug. Compared with vitamin K antagonists such as phenprocoumon, they have predictable and linear pharmacokinetics and a rapid onset of action. Dosing is simple (fixed) and no therapy monitoring is required. The relatively short duration of action compared with vitamin K antagonists may be a disadvantage if one or more doses are missed.

Agents

Factor Xa inhibitors:

  • Apixaban (Eliquis)
  • Betrixaban (Bevyxxa)
  • Edoxaban (Lixiana)
  • Rivaroxaban (Xarelto)

Thrombin inhibitors:

Interactions

Drug-drug interactions may occur with agents that affect blood clotting.

Adverse effects

The most common potential adverse effects include bleeding in various organs. Antidotes available include andexanet alfa and idarucizumab.