Startseite
Impressum
Datenschutz
 
arznei-telegramm 2011; 42: 110

 


CAUTION - FAULTY INR READINGS WHEN TAKING DABIGATRAN (PRADAXA)

A 61-year-old with intermittent atrial fibrillation was receiving the thrombin inhibitor dabigatran (PRADAXA; 150 mg twice a day; see a-t 2011; 42: 74-7) for anticoagulation at a university hospital. Owing to persistent nausea, the GP initiated a switch to phenprocoumon (MARCUMAR, generics). Two days after withdrawal of dabigatran, the INR* could not be measured in the practice, the point-of-care monitor (INRatio 2) repeatedly showing "error". The INR determined at the same time in the laboratory was 1.2 (NETZWERK Report 16.012).

From the literature there are known reports of false high INR values as high as over 8 in point-of-care readings during treatment with dabigatran, which are not confirmed in laboratory check measurements. However, the false alarm has in some cases led to potentially dangerous, false consequences such as withdrawal of the anticoagulation (1,2). In the literature we cannot find any evidence of error messages from monitors in connection with dabigatran, but they seem plausible if the measuring range is exceeded (0.7 to 7.5 INR in the case of the device used by the NETZWERK reporter). On enquiry, Boehringer Ingelheim confirmed the occurrence of false high INR readings on dabigatran in point-of-care measurements, which are several times higher than in laboratory checks according to an as yet unpublished study by the company itself (3).

However, the INR measured in the laboratory is also elevated by dabigatran. Nevertheless, according to the manufacturer's information, concentrations above the therapeutic range are required for the value to rise to 2 (4). Unlike the Summary of Product Characteristics (SPC) here, the USA product information indicates that INR measurements may be increased when taking dabigatran and apparently up to at least two days after discontinuation (5).

The INR is unsuitable for monitoring anticoagulation on dabigatran - at present no routine tests for this purpose are available (see page 103). Owing to the potentially dangerous, false consequences that may arise from false high INR readings, such measurements should therefore be stopped during administration. Patients previously treated with MARCUMAR, who have so far done self-measurements to monitor anticoagulation, also need to know this.

However, the influence of the thrombin inhibitor on INR values is relevant particularly in situations such as that reported in the NETZWERK Report, namely when switching from dabigatran to vitamin K antagonists: in this instance, the anticoagulants have to be taken with a two or three-day overlap depending on renal function (6). The regular INR monitoring that is usually introduced on the third day after the start of coumarin administration (7) may be entirely distorted in point-of-care measuring, but the laboratory measurement also does not necessarily reflect the coumarin effect reliably. There are no recommendations by the authorities here regarding the procedure for monitoring the switch-over. According to information from the European Medicines Agency (EMA) the false high INR readings on dabigatran and the question of whether an appropriate note should be included in the SPC are currently being investigated (8). In response to our enquiry about the validity of the laboratory INR at switch-over, the Federal Institute for Drugs and Medical Devices (BfArM) had not issued any statement by the time of copy deadline.

The INR is not suitable for monitoring anticoagulation with dabigatran (PRADAXA). Therefore it should not be measured during its administration.

Point-of-care INR measurements while taking dabigatran can deliver false high extreme values. Owing to potentially dangerous false consequences, patients and medical staff need to know this.

When switching from dabigatran to vitamin K antagonists, it is essential to bear in mind that dabigatran can also contribute to the increase in INR values measured in the laboratory and that these values are therefore not necessarily a reliable reflection of the coumarin effect until at least two days after withdrawal.

Three months after authorisation for atrial fibrillation, in Germany there is still no official recommendation on how anticoagulation should be monitored when switching from dabigatran to vitamin K antagonists, in view of the difficulties in interpreting INR readings.

 

1

BARUCH, L., SHERMAN, O.: Ann. Pharmacother. 2011; 45: e40

 

2

DeREMER, C. E. et al.: Am. J. Med. 2011; 124: e5-6

 

3

Boehringer Ingelheim: letter, dated 22 Nov. 2011

 

4

VAN RYN, J. et al.: Thromb. Haemost. 2010; 103: 1116-27

 

5

Boehringer Ingelheim: US product information PRADAXA, dated Sept. 2011
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf

 

6

Boehringer Ingelheim: SPC PRADAXA, dated Aug. 2011

 

7

Meda Pharma: SPC MARCUMAR, dated Dec. 2010

 

8

EMA: letter, dated 24 Nov. 2011



© arznei-telegramm 12/11