Apixaban

Monopgraph

Therapeutic action

New oral anticoagulants such as apixaban, have recently been approved for the prevention of thromboembolic diseases. These new anticoagulants have difficulties in monitoring the anticoagulant effect. One of its advantages over warfarin or acenocoumarol is that it doesn’t require monitoring, periodic analysis, except for emergency situations and INR determinations are not useful in the case of these drugs. It is possible to evaluate apixaban by prothrombin time, but these tests do not provide sufficiently precise determinations. The most reliable quantitative techniques are not routinely available.

Pharmacokinetics

The new oral anticoagulants undergo a relatively reduced hepatic metabolism. Apixaban, the agent which is most dependant on hepatic metabolism, is 75% metabolized through CYP3A4. The remaining drug is cleared through renal excretion. This means that there are not genetic polymorphisms that affect the emtabolism in a significant way. However, its levels are affected by the P-glycoprotein, encoded by the genMDR1(ABCB1), located in the luminal membrane of the enterocyle and modifies the bioavailability of the anticoagulant drug.Even though theABCB1gene presents functional polymorphisms, the consequence of the presence of these polymorphisms on the drug transport varies greatly from one substract to another and therefore it is not possible to do predictions without specific information concerning the a particular drug. Currently there is no data about the new oral anticoagulants, but it is probable that more information will be published with the increasing experience of use.

Given that the clearance of these drugs takes place greatly by renal excretion, the dose should be adapted for patients with reduced renal function, and it is contraindicated for patients with advanced chronic kidney diseases.

Interacciones con otras sustancias

Despite the low influence of the genetic markers, the possibility of an interaction with other drugs must be kept in mind.APIXABAN:apixaban has a hepatic metabolism that is highly dependent on CYP3A4. Many drugs that can trigger an interaction with apixaban, as well as rivaroxaban, do it by a joint action on the absorption mediated by P-glycoprotein and the metabolism mediated by CYP3A4.

Conclusions

Los nuevos anticoagulantes orales constituyen una nueva alternativa terapéutica a los anticoagulantes cumarínicos que se han usado durante décadas. Tienen a su favor que no requieren un seguimiento analítico para guiar la dosificación ni el intervalo de administración debido a una farmacocinética más estable, un inicio más rápido del efecto anticoagulante y menos susceptibilidad a las interacciones.However, there still are important interactions that can put a patient at risk of hemorrhages.The difficulty to assess the levels and effects of the drug as well as the lack of an antidote to revert the anticoagulation in case of emergency requires information to know and manage the potential interactions.When they are considered isolatedly they are better that the classical anticoagulants because they do not require regular laboratory control, and less risk of hemorrhage or thrombosis than with classical anticoagulant drugs (warfarin, acenocoumarol), but their anticoagulant action can become unbalanced –either for excess or for defect –  by drug interactions, without rutine laboratory tests available to monitor it.Therefore it is important to enter the whole medication that the patient is taking in the simulation program of the gNOMIC application ir order to detect the possible interactions due to concomitant medication, because for this drugs it is the weak point of the treatment safety.

Bibliography

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MarcBertranCendrósDegree inBiologyMasterinGenetic Counseling

Last modified: Sep 6, 2017 @ 09:59 am