ZINPLAVA SIDE EFFECTS
- Generic Name: bezlotoxumab injection
- Brand Name: Zinplava
- Drug Class: Monoclonal Antibodies
SIDE EFFECTS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of ZINPLAVA was evaluated in two placebo-controlled, Phase 3 trials (Trial 1 n= 390 and Trial 2 n= 396). Patients received a single 10 mg/kg intravenous infusion of ZINPLAVA and concomitant standard of care antibacterial drugs (metronidazole, vancomycin or fidaxomicin) for CDI (SoC). Adverse reactions reported within the first 4 weeks after ZINPLAVA was administered are described for the pooled Phase 3 trial population of 786 patients. The median age of patients receiving ZINPLAVA was 65 years (range 18 to 100), 50% were age 65 years or older, 56% were female, and 83% were white.
The most common adverse reactions following treatment with ZINPLAVA (reported in ≥ 4% of patients within the first 4 weeks of infusion and with a frequency greater than placebo) were nausea, pyrexia, and headache (see Table 1).
Table 1: Adverse Reactions Reported in ≥ 4% of ZINPLAVA-Treated Patients with CDI and at a Frequency Greater than Placebo in Trial 1 and Trial 2*,†
| Adverse Reaction | ZINPLAVA with SoC‡ N=786 % |
Placebo with SoC‡ N=781 % |
| Gastrointestinal disorders | ||
| Nausea | 7% | 5% |
| General disorders and administration site conditions | ||
| Pyrexia | 5% | 3% |
| Nervous system disorders | ||
| Headache | 4% | 3% |
| * All patients as treated population, defined as all randomized patients who received a dose of study medication, by treatment received † Adverse reactions reported within 4 weeks of administration of ZINPLAVA or placebo ‡ SoC = Standard of Care antibacterial drugs (metronidazole or vancomycin or fidaxomicin) for CDI |
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Serious adverse reactions occurring within 12 weeks following infusion were reported in 29% of ZINPLAVA-treated patients and 33% of placebo-treated patients. Heart failure was reported as a serious adverse reaction in 2.3% of the ZINPLAVA-treated patients and 1.0% of the placebo-treated patients.
One patient discontinued the ZINPLAVA infusion due to ventricular tachyarrhythmia that occurred 30 minutes after the start of the infusion.
Mortality rates were 7.1% and 7.6% in ZINPLAVA-treated patients and placebo-treated patients, respectively, during the 12-week follow-up period.
Infusion Related Reactions
Overall, 10% of ZINPLAVA-treated patients experienced one or more infusion specific adverse reactions on the day of, or the day after, the infusion compared to 8% of placebo-treated patients. Infusion specific adverse reactions reported in ≥ 0.5% of patients receiving ZINPLAVA and at a frequency greater than placebo were nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnea (1%) and hypertension (1%). Of these patients, 78% and 20% of patients experienced mild and moderate adverse reactions, respectively. These reactions resolved within 24 hours following onset.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity following administration of ZINPLAVA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to bezlotoxumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Following treatment with ZINPLAVA in Trial 1 and Trial 2, none of the 710 evaluable patients tested positive for treatment-emergent anti-bezlotoxumab antibodies.
SRC: NLM .