Summary of the safety profile The safety profile of ZINPLAVA was assessed in two Phase 3 clinical studies in adults. 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.
5 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. 5 % of subjects receiving ZINPLAVA 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. 1) in which all patients received a single dose. Paediatric population The safety of ZINPLAVA was assessed in one Phase 3 clinical trial (MODIFY III) in which 107 paediatric patients 1 to < 18 years of age (4 patients 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 ZINPLAVA.
The safety profile in paediatric patients was consistent with that in adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.