ZINPLAVA™

(bezlotoxumab) injection

Professional Resources

Facts and figures about CDI

Clostridium difficile: 1 of 3 pathogens designated as an urgent threat by the CDC1

  • A threat is categorized as “urgent” when it requires more monitoring and prevention activities and because of significant associated risks, including clinical impact and incidence.1
  • Rates of CDI have increased in the United States over the past decade,2 and there were an estimated 453,000 cases of CDI in 2011.3
  • While CDI is traditionally considered a hospital-acquired infection,4 community-acquired CDI is a growing public health threat.5
  • The risk of getting CDI is 7 to 10 times higher in people taking antibiotics.6

The risk of CDI recurrence is substantial7,8

Risk of rCDI increases proportionally with each subsequent episode7

  • After an initial CDI episode, more than 25% of patients have a second episode.
    • More than 40% of patients with a previous history of CDI experience additional episodes.

CDI can have potentially serious clinical consequences8

  • The characteristic symptom of CDI is CDAD.8 Dehydration and electrolyte disorders are observed in more than 80% of patients with CDI.9
  • CDI is not merely a case of nuisance diarrhea. Some cases of CDI are severe. In rare cases, it can lead to colonic ileus, pseudomembranous colitis, or death.8,10

Definitions

CDAD = Clostridium difficile–associated diarrhea 

CDC = Centers for Disease Control and Prevention 

CDI = Clostridium difficile infection

References

1. Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2013.

2. Butler M, Olson A, Drekonja D, et al. Early Diagnosis, Prevention, and Treatment of Clostridium difficile: Update. Comparative Effectiveness Review No. 172. Rockville, MD: Agency for Healthcare Research and Quality; 2016. AHRQ publication 16-EHC012-EF.

3. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(9):825–834. doi:10.1056/NEJMoa1408913.

4. Deadly diarrhea: C. difficile causes immense suffering, death. Centers for Disease Control and Prevention website. www.cdc.gov/HAI/organisms/cdiff/Cdiff_infect.html. Accessed July 14, 2017.

5. Gupta A, Khanna S. Community-acquired Clostridium difficile infection: an increasing public health threat. Infect Drug Resist. 2014;7:63–72. doi:10.2147/IDR.S46780.

6. Hensgens MP, Goorhuis A, Dekkers OM, et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67(3):742–748. doi:10.1093/jac/dkr508. 

7. Wilcox MH et al. N Engl J Med. 2017;376(4):305–317.

8. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–455. doi:10.1086/651706.

9. Lucado J, Gould C, Elixhauser A. Clostridium difficile Infections (CDI) in Hospital Stays, 2009. Rockville, MD: Agency for Healthcare Research and Quality; 2012. H•CUP Statistical Brief #124.

10. Drug trials snapshots: Zinplava. US Food and Drug Administration website. http://www.fda.gov/Drugs/InformationOnDrugs/ucm528793.htm. Accessed July 11, 2017.

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 is also available.

AINF-1245982-000007/18