Gastric pH

Pantoprazole: When Pradaxa was co-administered with pantoprazole, a decrease in the dabigatran area under the plasma concentration-time curve of approximately 30 % was observed. Pantoprazole and other proton-pump inhibitors (PPI) were co-administered with Pradaxa in clinical trials, and concomitant PPI treatment did not appear to reduce the efficacy of Pradaxa.

Ranitidine: Ranitidine administration together with Pradaxa had no clinically relevant effect on the extent of absorption of dabigatran.

4.6 Pregnancy and lactation

 Pregnancy

There are no adequate data from the use of Pradaxa in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.

Women of child-bearing potential should avoid pregnancy during treatment with dabigatran etexilate. Pradaxa should not be used during pregnancy unless clearly necessary.

Breast-feeding

There are no clinical data of the effect of dabigatran on infants during breast feeding.

Breast-feeding should be discontinued during treatment with Pradaxa.
Fertility

No data human available.

In animal studies an effect on female fertility was observed in the form of a decrease in implantations and an increase in pre-implantation loss at 70 mg/kg (representing a 5-fold higher plasma exposure level compared to patients). No other effects on female fertility were observed. There was no influence on male fertility. At doses that were toxic to the mothers (representing a 5- to 10-fold higher plasma exposure level to patients), a decrease in foetal body weight and embryofoetal viability along with an increase in foetal variations were observed in rats and rabbits. In the pre- and post-natal study, an increase in foetal mortality was observed at doses that were toxic to the dams (a dose corresponding to a plasma exposure level 4-fold higher than observed in patients).

4.7 Effects on ability to drive and use machines

 No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable effects

 A total of 10.084 patients were treated in 4 actively controlled VTE prevention trials with at least one dose of the medicinal product. Of these 5419 were treated with 150 mg or 220 mg daily of Pradaxa, while 389 received doses less than 150 mg daily and 1168 received doses in excess of 220 mg daily.

The most commonly reported adverse reactions are bleedings occurring in total in approximately 14 % of patients; the frequency of major bleeds (including wound site bleedings) is less than 2 %.

Although rare in frequency in clinical trials, major or severe bleeding may occur and, regardless of location, may lead to disabling, life-threatening or even fatal outcomes.
Adverse reactions

Table 3 shows the adverse reactions ranked under headings of SOC and frequency using the following convention: very common ( 1/10); common ( 1/100, < 1/10); uncommon ( 1/1,000, < 1/100); rare ( 1/10,000, < 1/1,000); very rare (< 1/10,000); not known (can not be estimated from the available data).
SOC / Preferred Term.
 Dabigatran etexilate 150 mg
 Dabigatran etexilate 220 mg
 
Number of patients treated
 2737
 2682
Blood and lymphatic system disorders

Anaemia
 Commo