nly been performed in adults.
Concomitant administration of tigecycline and warfarin (25 mg single-dose) to healthy subjects resulted in a decrease in clearance of R-warfarin and S-warfarin by 40 % and 23 %, and an increase in AUC by 68 % and 29 %, respectively. The mechanism of this interaction is still not elucidated. Available data does not suggest that this interaction may result in significant INR changes. However, since tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT), the relevant coagulation tests should be closely monitored when tigecycline is co-administered with anticoagulants (see section 4.4). Warfarin did not affect the pharmacokinetic profile of tigecycline.
Tigecycline is not extensively metabolised. Therefore, clearance of tigecycline is not expected to be affected by active substances that inhibit or induce the activity of the CYP450 isoforms. In vitro, tigecycline is neither a competitive inhibitor nor an irreversible inhibitor of CYP450 enzymes (see section 5.2).
Tigecycline in recommended dosage did not affect the rate or extent of absorption, or clearance of digoxin (0.5 mg followed by 0.25 mg daily) when administered in healthy adults. Digoxin did not affect the pharmacokinetic profile of tigecycline. Therefore, no dosage adjustment is necessary when tigecycline is administered with digoxin.
In in vitro studies, no antagonism has been observed between tigecycline and other commonly used antibiotic classes.
Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.
4.6 Pregnancy and lactation
Pregnancy
There are no adequate data from the use of tigecycline in pregnant women. Results from animal studies have shown tigecycline may cause foetal harm when administered during pregnancy (see section 5.3). The potential risk for humans is unknown. As it is known for tetracycline class antibiotics, tigecycline may also induce permanent dental defects (discolouration and enamel defects) and a delay in ossification processes in foetuses, exposed in utero during the last half of gestation, and in children under eight years of age due to the enrichment in tissues with a high calcium turnover and formation of calcium chelate complexes (see section 4.4). Tigecycline should not be used during pregnancy unless clearly necessary.
Breastfeeding
It is not known whether this medicinal product is excreted in human milk. In animal studies tigecycline is excreted into milk of lactating rats. Because a potential risk to the breast-feeding infant cannot be ruled out, when treating with tigecycline, caution should be exercised and interruption of breast-feeding should be considered (see section 5.3).
Fertility
Tigecycline did not affect mating or fertility in rats at exposures up to 4.7 times the human daily dose based on AUC. In female rats, there were no compound-related effects on ovaries or oestrus cycles at exposures up to 4.7 times the human daily dose based on AUC.
4.7 Effects on ability to drive and use machines
No studies on the effects of tigecycline on the ability to drive and use machines have been performed. Dizziness may occur and this may have an effect on driving and use of machines (see section 4.8).
4.8 Undesirable effects
a. Summary of safety profile
The total number of patients treated with tigecycline in Phase 3 clinical studies was 1415. Adverse reactions were reported in approximately 41 % of patients treate |
