ZINPLAVA™

(bezlotoxumab) injection 25 mg/mL

Safety Profile

Selected adverse reactions

  • The most common adverse reactions occurring within 4 weeks of infusion with a frequency greater than placebo and reported in ≥4% of patients treated with ZINPLAVA and Standard of Care (SoC) CDI antibacterial drug therapy vs placebo and SoC antibacterial drug therapy were nausea (7% vs 5%), pyrexia (5% vs 3%), and headache (4% vs 3%).
  • 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 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 similar across treatment arms (7.1% with ZINPLAVA and 7.6% with SoC CDI antibiotics alone) during the 12-week follow-up period.
  • Infusion-related reactions: Following treatment with ZINPLAVA, 10% of patients experienced ≥1 infusion-specific adverse reactions the day of or the day after treatment, compared with 8% of those receiving placebo.
    • 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%).
    • For patients experiencing infusion-related adverse reactions, 78% were mild and 20% were moderate, and all resolved within 24 hours following onset.

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Warnings & Precautions / Drug Interactions

Indication

ZINPLAVA is a human monoclonal antibody that binds to Clostridium difficile toxin B indicated to reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at high risk for CDI recurrence.

ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not an antibacterial drug. ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.

Selected Safety Information

  • In patients with a history of congestive heart failure (CHF), ZINPLAVA should be used when the benefit outweighs the risk. Heart failure was reported more commonly in the two Phase 3 clinical trials in ZINPLAVA-treated patients compared to placebo-treated patients. In patients with a history of CHF, 12.7% (n=15/118) of ZINPLAVA-treated patients and 4.8% (n=5/104) of placebo-treated patients had the serious adverse reaction of heart failure during the 12-week study period. During the same period, for patients with a history of CHF, there were more deaths in ZINPLAVA-treated patients 19.5% (n=23/118) than in placebo-treated patients 12.5% (n=13/104). The causes of death varied and included cardiac failure, infections, and respiratory failure.
  • The most common adverse reactions occurring within 4 weeks of infusion with a frequency greater than placebo and reported in ≥4% of patients treated with ZINPLAVA and Standard of Care (SoC) antibacterial drug therapy vs placebo and SoC antibacterial drug therapy were nausea (7% vs 5%), pyrexia (5% vs 3%), and headache (4% vs 3%).
  • 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 placebo-treated patients.
  • In ZINPLAVA-treated patients, 10% experienced one or more infusion specific adverse reactions compared to 8% of placebo-treated patients, on the day of or the day after, the infusion. 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% experienced mild adverse reactions, and 20% experienced moderate adverse reactions. These reactions resolved within 24 hours following onset.
  • 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. Comparison of the incidence of antibodies to bezlotoxumab in the two Phase 3 studies (MODIFY I and II) with the incidence of antibodies in other studies or to other products may be misleading. In MODIFY I and II, none of the 710 evaluable ZINPLAVA-treated patients tested positive for treatment-emergent anti-bezlotoxumab antibodies.

Before prescribing ZINPLAVATM (bezlotoxumab), please read the Prescribing Information. The Patient Information also is available.

US-MKB-0069503/23