ic or renal transporters.
Bezlotoxumab-mediated drug-drug interactions are unlikely as the target of bezlotoxumab is an exogenous toxin.
Concomitant oral standard of care (SoC) antibacterial therapy for CDI was given together with ZINPLAVA.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited data from the use of bezlotoxumab in pregnant women. Animal studies do not indicate reproductive toxicity (see section 5.3). ZINPLAVA should not be used during pregnancy unless the clinical condition of the woman requires treatment with bezlotoxumab.
Breast-feeding
It is unknown whether bezlotoxumab is secreted in human milk. Because monoclonal antibodies may be excreted in human milk, a decision should be made whether to discontinue breast-feeding or to not administer ZINPLAVA, taking into account the importance of ZINPLAVA to the mother.
Fertility
No clinical data are available on the possible effects of bezlotoxumab on fertility. Fertility studies have not been conducted in animals. There was no binding of bezlotoxumab to reproductive tissue in tissue cross reactivity studies, and no notable effects in the male and female reproductive organs in repeat dose toxicity studies in mice (see section 5.3).
4.7 Effects on ability to drive and use machines
Bezlotoxumab has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
The safety profile of ZINPLAVA was assessed in two Phase 3 clinical studies. The most common adverse reactions following treatment with ZINPLAVA (reported in ≥ 4 % of patients within the first 4 weeks of infusion) were nausea, diarrhoea, pyrexia and headache. These adverse reactions were reported at a similar frequency in placebo treated patients compared with ZINPLAVA treated patients.
Tabulated list of adverse reactions
Table 1 presents the adverse reactions reported within 4 weeks of infusion in ZINPLAVA-treated patients and listed 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 frequency.
Table 1: Adverse Reactions with ZINPLAVA
MedDRA System Organ Class
Frequency
Adverse Reaction(s)
Nervous system disorders
Common
Headache
Gastrointestinal disorders
Common
Nausea, diarrhoea
General disorders and administration site conditions
Common
Pyrexia
Injury, poisoning and procedural complications
Common
Infusion related reactions†
† See Description of selected adverse reactions below.
Description of selected adverse reactions
Serious adverse reactions
In clinical studies, serious adverse reactions occurring within 12 weeks following infusion were reported in 29 % of ZINPLAVA-treated patients and 33 % in patients receiving placebo.
Infusion related reactions
Overall, 10 % of subjects in the ZINPLAVA group experienced one or more infusion specific adverse reactions on the day of, or the day after, the infusion compared to 8 % in the placebo group. Infusion specific adverse reactions reported in ≥ 0.5 % of subjects receiving ZINPLAVA and at a frequency greater than placebo were nausea (3 %), fatigue (1 %), pyrexia (1 %), dizziness (1 %), h |
