title: [Clinical pharmacological aspects of new oral anticoagulants].
abstract: New oral anticoagulants such as the factor Xa inhibitors rivaroxaban and apixaban or the thrombin inhibitor dabigatran lack some of the limitations of the well-known vitamin K-antagonists. Although routine monitoring is not required, large variations in overall exposure can be seen under certain circumstances. Dabigatran is primarily eliminated in unchanged form in the urine and dose has to be adapted according to renal function. The factor Xa inhibitors are CYP3A4-substrates and combination with potent CYP3A4-inhibitors is not allowed. In cases of bleeding or thromboembolic events under treatment, targeted monitoring of drug concentration or anti-FXa- or anti-FIIa-activity may be helpful to identify the underlying cause. In contrast to vitamin K antagonists or heparin, no antidotes are available for the new anticoagulants and the optimal procedure in cases of life-threatening bleeding has not yet been defined. For certain indications such as prophylaxis of venous thromboembolism in acutely ill medical patients study data are (not yet) available. Concerning localization of bleeding sites the new compounds may display a different profile compared to vitamin K-antagonists (less intracranial bleedings). Experience with long-term use (> 5 years) is limited. Therefore careful clinical monitoring of patients considering co-medication and co-morbidity is necessary to allow safe therapy with the new oral anticoagulants.
authors.affiliation: Klinische Pharmakologie und Toxikologie, Universitätsspital Basel. mhaschke@uhbs.ch
authors.forename: M
authors.initials: M
authors.lastname: Haschke
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012307:Risk Factors; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013923:Thromboembolism / Q000097:blood / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D065692:Cytochrome P-450 CYP3A Inhibitors; D065427:Factor Xa Inhibitors; D009025:Morpholines; D011720:Pyrazoles; D011728:Pyridones; D013876:Thiophenes; D015091:beta-Alanine; D014812:Vitamin K; C522181:apixaban; D000069552:Rivaroxaban; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000069604:Dabigatran