m animals indicate that rivaroxaban is secreted into milk. Therefore Xarelto is contraindicated during breast feeding (see section 4.3). A decision must be made whether to discontinue breast feeding or to discontinue/abstain from therapy.
Fertility
No specific studies with rivaroxaban in humans have been conducted to eva luate effects on fertility. In a study on male and female fertility in rats no effects were seen (see section 5.3).
4.7 Effects on ability to drive and use machines
Xarelto has minor influence on the ability to drive and use machines. Adverse reactions like syncope (frequency: uncommon) and dizziness (frequency: common) have been reported (see section 4.8). Patients experiencing these adverse reactions should not drive or use machines.
4.8 Undesirable effects
Summary of the safety profile
The safety of rivaroxaban has been eva luated in eleven phase III studies including 32,625 patients exposed to rivaroxaban (see Table 1).
Table 1: Number of patients studied, maximum daily dose and treatment duration in phase III studies
Indication
Number of patients*
Maximum daily dose
Maximum treatment duration
Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery
6,097
10 mg
39 days
Prevention of venous thromboembolism in medically ill patients
3,997
10 mg
39 days
Treatment of DVT, PE and prevention of recurrence
4,556
Day 1 - 21: 30 mg
Day 22 and onwards: 20 mg
21 months
Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
7,750
20 mg
41 months
Prevention of atherothrombotic events in patients after an ACS
10,225
5 mg or 10 mg respectively, co-administered with either ASA or ASA plus clopidogrel or ticlopidine
31 months
*Patients exposed to at least one dose of rivaroxaban
The most commonly reported adverse reactions in patients receiving rivaroxaban were bleedings (see section 4.4. and 'Description of selected adverse reactions' below). The most commonly reported bleedings (≥4 %) were epistaxis (5.9 %) and gastrointestinal tract haemorrhage (4.2 %).
In total about 67% of patients exposed to at least one dose of rivaroxaban were reported with treatment emergent adverse events. About 22% of the patients experienced adverse events considered related to treatment as assessed by investigators. In patients treated with 10 mg Xarelto undergoing hip or knee replacement surgery and in hospitalised medically ill patients, bleeding events occurred in approximately 6.8% and 12.6% of patients, respectively, and anaemia occurred in approximately 5.9% and 2.1% of patients, respectively. In patients treated with either 15 mg twice daily Xarelto followed by 20 mg once daily for treatment of DVT or PE, or with 20 mg once daily for prevention of recurrent DVT and PE, bleeding events occurred in approximately 27.8% of patients and anaemia occurred in approximately 2.2% of patients. In patients treated for prevention of stroke and systemic embolism, bleeding of any type or severity was reported with an event rate of 28 per 100 patient years, and anaemia with an event rate of 2.5 per 100 patient years. In patients treated for prevention of cardiovascular deat
