With simultaneous use of dabigatran etexilate with digoxin, is a substrate of P-glycoprotein, pharmacokinetic interactions were observed. Neither testosterone blend dabigatran nor the prodrug dabigatran etexilate is not clinically relevant inhibitors of P-glycoprotein.
Concomitant use with inducers of P-glycoprotein:
Avoid co-administration of the drug PRADAKSA and inducers of P-glycoprotein, as the combined use reduces the exposure of dabigatran (See. “Special Instructions” section).
Rifampicin. Pretreatment with test inductor rifampicin 600 mg per day for 7 days resulted in mitigation of dabigatran. After the cancellation of the inductive effect of rifampicin decreased on day 7 the effect of dabigatran was close to the initial level. During the following seven days of further increasing the bioavailability of dabigatran was observed.
It is assumed that other inducers of P-glycoprotein, such as St. John’s wort or carbamazepine, may also reduce the concentration of dabigatran in blood and plasma must be applied with caution.
Concomitant use with antiplatelet
Acetylsalicylic acid (ASA). In the study of the simultaneous application of dabigatran etexilate 150 mg 2 times a day and acetylsalicylic acid (ASA) in patients with atrial fibrillation that the risk of bleeding can be increased from 12% to 18% (using ASA dose 81 mg) and 24% (using ASA 325 mg). It is shown that ASA or clopidogrel, applied simultaneously with dabigatran etexilate 110 mg dose or 150 mg 2 times daily, may increase the risk of major bleeding. Bleeding observed more frequently as well, while the use of warfarin or clopidogrel with ASA.
NSAIDs . The applied NSAIDs (non-steroidal testosterone blend anti-inflammatory drugs) for short-term analgesia after surgery did not increase the risk of bleeding when used simultaneously with dabigatran etexilate.Experience of long-term use of NSAIDs, T1 / 2 of less than 12 hours, with dabigatran etexilate is limited, there are no data on the additional increase in bleeding risk.
Clopidogrel. It was found that the concurrent use of dabigatran etexilate and clopidogrel does not lead to an additional increase of capillary bleeding times compared to clopidogrel monotherapy. Furthermore, it is shown that the values of AUC τ, ss and C max, ss dabigatran, and the parameters of blood coagulation, which were controlled to evaluate the effect of dabigatran (APTT, ekarinovoe clotting time and thrombin time (anti FIIa), and the degree of inhibition of platelet aggregation (main component clopidogrel effect) during combination therapy did not change compared with the corresponding figures in monotherapy. When using the “loading” dose of clopidogrel (300 or 600 mg), the values of AUC t, ss and C dabigatran were increased by 30-40 %.
Concomitant use with drugs that increase the pH of gastric contents
Pantoprazole. When the joint application of dabigatran etexilate and pantoprazole observed reduction in AUC of dabigatran is 30%. Pantoprazole and other proton pump inhibitors used in conjunction with dabigatran etexilate in clinical trials, the effect on the risk of bleeding or efficacy were observed.
Ranitidine. Ranitidine when applied in conjunction with dabigatran etexilate does not significantly affect the extent of absorption of dabigatran.
Identified during the analysis of population changes in pharmacokinetic parameters dabigatran under the influence of a proton pump inhibitor and antacid drugs were clinically insignificant, since the severity of these changes was small (reducing the bioavailability testosterone blend was not significant for antacids, and 14.6% was for proton pump inhibitors). It is found that the simultaneous administration of proton pump inhibitors is not accompanied by a reduction in the concentration of dabigatran average, only slightly reduces the concentration of drug in blood plasma (11%). Therefore, simultaneous administration of proton pump inhibitors, apparently does not lead to an increase in stroke or systemic thromboembolic events, especially in comparison with warfarin, and therefore decrease the bioavailability of dabigatran caused by simultaneous use of pantoprazole probably has no clinical significance.
Pregnancy and lactation:
Data on the use of dabigatran etexilate during pregnancy are not available. The potential risk in humans is unknown.
In experimental studies found no adverse effects on fertility or postnatal development of the newborns.
Women of childbearing age should use reliable methods of contraception in order to exclude the possibility of pregnancy in the treatment of drug PRADAKSA. In the event of pregnancy use of the drug is not recommended, except in cases where the expected benefits outweigh the potential risk.
If necessary, use during breastfeeding, due to a lack of clinical data, it is recommended to stop breast-feeding (as a precaution).