Effect of fidaxomicin on P-gp substrates 

Fidaxomicin may be a mild to moderate inhibitor of intestinal P-gp.

Fidaxomicin (200 mg twice daily) had a small but not clinically relevant effect on digoxin exposure. However, a larger effect on P-gp substrates with lower bioavailability more sensitive to intestinal P-gp inhibition such as dabigatran etexilat cannot be excluded.

Effect of fidaxomicin on other transporters 

Fidaxomicin does not have a clinically significant effect on the exposure of rosuvastatin, a substrate for the transporters OATP2B1 and BCRP. Co-administration of 200 mg fidaxomicin twice daily with a single dose of 10 mg rosuvastatin to healthy subjects did not have a clinically significant effect on the AUCinf of rosuvastatin. 

4.6 Fertility, pregnancy and lactation

Pregnancy 

There are no data available from the use of fidaxomicin in pregnant women. Animal studies did not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of DIFICLIR during pregnancy.

Breast-feeding 

It is unknown whether fidaxomicin and its metabolites are excreted in human milk. Although no effects on the breastfed newborns/infants are anticipated since the systemic exposure to fidaxomicin is low, a risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from DIFICLIR therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. 

Fertility 

Fidaxomicin had no effects on fertility when eva luated in rats (see section 5.3).

4.7 Effects on ability to drive and use machines

DIFICLIR has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Summary of the safety profile 

The most common adverse reactions are vomiting, nausea and constipation.

Tabulated summary of adverse reactions 

Table 1 displays adverse reactions associated with twice daily administration of fidaxomicin in the treatment of C. difficile infection, reported in at least two patients, presented by system organ class.

The frequency of adverse reactions is defined as follows: 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, adverse reactions are presented in order of decreasing seriousness.

Table 1: Summary of adverse reactions by MedDRA system organ class 

MedDRA system organ class 

Common 

Uncommon 

Frequency not known 

Immune system disorders

rash, pruritus

hypersensitivity reactions (angioedema, dyspnea)

Metabolism and nutrition disorders

decreased appetite