Bezlotoxumab

There are limited data from the use of bezlotoxumab in pregnant women. Animal studies do not indicate reproductive toxicity. Bezlotoxumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with bezlotoxumab.

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 bezlotoxumab, taking into account the importance of bezlotoxumab 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.

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

Summary of the safety profile

The safety profile of bezlotoxumab was assessed in two Phase 3 clinical studies in adults. The most common adverse reactions following treatment with bezlotoxumab (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 bezlotoxumab-treated patients.

Tabulated list of adverse reactions

The table below presents the adverse reactions reported within 4 weeks of infusion in bezlotoxumab-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 decreas ing frequency.

Adverse Reactions with Bezlotoxumab:

^† 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 bezlotoxumab-treated patients and 33% in patients receiving placebo.

Infusion related reactions

Overall, 10% of subjects in the bezlotoxumab 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 bezlotoxumab and at a frequency greater than placebo were nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnoea (1%) and hypertension (1%). Of the patients who experienced an infusion specific adverse reaction, the majority reported a reaction with a maximum intensity of mild (78%) or moderate (20%), and the majority of reactions resolved within 24 hours following onset.

Immune-related adverse reactions

In a Phase 1 clinical trial, healthy subjects received two consecutive doses of 10 mg/kg of bezlotoxumab separated by 12 weeks. The adverse reactions after the second dose were not markedly different from those observed after the first dose, and are consistent with adverse reactions observed in the two Phase 3 trials (MODIFY I and MODIFY II) in which all patients received a single dose.

Paediatric population

The safety of bezlotoxumab was assessed in one Phase 3 clinical trial (MODIFY III) in which 107 paediatric patients 1 to <18 years of age (4 p atients 1 to <2 years, 33 patients 2 to <6 years, 26 patients 6 to <12 years, and 44 patients 12 to <18 years) received a single dose of 10 mg/kg of bezlotoxumab. The safety profile in paediatric patients was consistent with that in adults.