ce between daptomycin and particular reagents used in some assays of prothrombin time/international normalised ratio (PT/INR) have been reported. This interference led to a false prolongation of PT and elevation of INR. If unexplained abnormalities of PT/INR are observed in patients taking daptomycin, consideration should be given to a possible in vitro interaction with the laboratory test. The possibility of erroneous results may be minimised by drawing samples for PT or INR testing near the time of trough plasma concentrations of daptomycin (see section 4.4).
4.6 Pregnancy and lactation
Pregnancy
No clinical data on pregnancies are available for daptomycin. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).
Cubicin should not be used during pregnancy unless clearly necessary i.e., only if the potential benefit outweighs the possible risk.
Breast-feeding
In a single case study, Cubicin was administered daily for 28 days to a nursing mother at a dose of 500 mg/day, and samples of the patient's breast milk were collected over a 24-hour period on day 27. The highest measured concentration of daptomycin in the breast milk was 0.045 µg/ml, which is a low concentration. Therefore, until more experience is gained, breast-feeding should be discontinued when Cubicin is administered to nursing women.
Fertility
No clinical data on fertility are available for daptomycin. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
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.
On the basis of reported adverse drug reactions, Cubicin is presumed to be unlikely to produce an effect on the ability to drive or use machinery.
4.8 Undesirable effects
In clinical studies, 2,011 subjects received Cubicin. Within these trials, 1,221 subjects received a daily dose of 4 mg/kg, of whom 1,108 were patients and 113 were healthy volunteers; 460 subjects received a daily dose of 6 mg/kg, of whom 304 were patients and 156 were healthy volunteers. Adverse reactions (i.e. considered by the investigator to be possibly, probably, or definitely related to the medicinal product) were reported at similar frequencies for Cubicin and comparator regimens.
The following adverse reactions were reported during therapy and during follow-up with frequencies corresponding to very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data):
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1 Adverse reactions from clinical studies and post-marketing reports
System organ class
Frequency
Adverse reactions
Infections and infestations
Common:
Fungal infections, urinary tract infection, candida infection
Uncommon:
Fungaemia
Not known*:
Clostridium difficile-associated diarrhoea**
Blood and lymphatic system disorders
Common:
Anaemia
Uncommon:
Thrombocythaemia,
