Adverse reactions : תופעות לוואי

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 Common                 Pyrexia site conditions
Injury, poisoning and procedural               Common       Infusion related reactions† complications
† 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 %), 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; see section 5.1) in which all patients received a single dose.

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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form.
http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.go v.il