Indikasjoner

Zinplava is a CDI antitoxin B indicated to prevent recurrence in adults at high risk for recurrence of CDI3

Despite treatment with antibiotics for CDI…

The risk of CDI recurrence remains a cause for concern1,2

Epidemiologic data from the US has shown that...

People who are at risk for CDI recurrence include

  • Age ≥65 years4–6
  • History of CDI in the past 6 months5–7
  • Recent antibiotic use6,8
  • Immunocompromised9
  • Severe CDI10
  • Inadequate immune response to toxins6,11

CDI antibiotics may not be enough to reduce the risk of CDI recurrence for high-risk patients8,12

  • While CDI antibiotics may target bacteria and resolve the infection, they may also perpetuate disruption of the gut microbiota and increase the risk for CDI recurrence due to persistent vegetative C difficile and germination of remaining spores.

An inadequate immune response to C difficile toxins is a contributing factor to CDI recurrence13

Role of the body’s adaptive immune response to C difficile toxins6

 

  • Most patients have an adequate immune response and are able to create antibodies against CDI toxins, which limits damage to the gut epithelium and helps prevent CDI recurrence.6
    • However, some patients are unable to mount an adequate immune response to toxins, which contributes to the recurrence risk.6

ZINPLAVA: CDI antitoxin B that may prevent recurrence in adults at high risk for recurrence of CDI3

Now, you have an option to prevent CDI recurrence in high-risk patients

Non-antibiotic mechanism of action targets toxin B3,14

  • ZINPLAVA is a selective, fully human monoclonal antibody that binds with high affinity to toxin B.3

ZINPLAVA enhances the immune response against toxin B3

  • Neutralizes toxin B activity.

Referanser

  • 1.

    McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standardantibiotics for Clostridium difficile disease. JAMA. 1994;271(24):1913–1918.

  • 2.

    McFarland LV, Elmer GW, Surawicz CM. Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am Coll Gastroenterol. 2002;97(7):1769–1775.

  • 3.

    SPC Zinplava september 2017, avsnitt 4.1, 4.2, 4.8, 5.1.

  • 4.

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

  • 5.

    Debast SB, Bauer MP, Kuijper EJ. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(2):1–26.

  • 6.

    Gupta SB, Mehta V, Dubberke ER, et al. Antibodies to toxin B are protective against Clostridium difficile infection recurrence. Clin Infect Dis. 2016;63(6):730–734. doi:10.1093/cid/ciw364.

  • 7.

    Kelly CP, LaMont JT. Clostridium difficile—more difficult than ever. N Engl J Med. 2008;359:1932–1940. doi:10.1056/NEJMra0707500.

  • 8.

    Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313(4):398–408.doi:10.1001/jama.2014.17103.

  • 9.

    Huang AM, Marini BL, Frame D, Aronoff DM, Nagel JL. Risk factors for recurrent Clostridium difficile infection in hematopoietic stem cell transplantrecipients. Transpl Infect Dis. 2014;16(5):744–750.

  • 10.

    Eyre DW, Walker AS, Wyllie D, et al. Predictors of first recurrence of Clostridium difficile infection: implications for initial management. Clin Infect Dis. 2012;55(S2):S77–S87.

  • 11.

    Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(6):21–27.

  • 12.

    Britton RA, Young VB. Role of the intestinal microbiota in resistance to colonization byClostridium difficile. Gastroenterology. 2014;146:1547–1553.

  • 13.

    Bauer MP, Nibbering PH, Poxton IR, et al. Humoral immune response as predictor of recurrence in Clostridium difficile infection. Clin Microbiol Infect. 2014;20(12):1323–1328. doi:10.1111/1469-0691.12769.

  • 14.

    Orth P, Xiao L, Hernandez LD, et al. Mechanism of action and epitopes of Clostridium difficile toxin-B-neutralizing antibody bezlotoxumab revealed by x-ray crystallography. J Biol Chem. 2014;289(26):18008–18021. doi:10.1074/jbc.M114.560748.

INFC-1247832-0003 May 2018

Dosering og administrasjon

In addition to CDI antibiotics...

ZINPLAVA: One-time, one-hour infusion1

  • The recommended dose of ZINPLAVA is 10 mg/kg based on patient body weight administered as an intravenous infusion over 60 minutes as a single dose.

ZINPLAVA works together with CDI antibiotics for CDI recurrence prevention

  • ZINPLAVA must be administered during the course of antibiotic treatment for CDI.
  • ZINPLAVA is not an antibiotic and is not indicated for the treatment of an acute episode of CDI.
  • ZINPLAVA should be administered using a sterile, nonpyrogenic, low protein binding 0.2 micron to 5 micron in-line or add-on filter.
    • ZINPLAVA can be infused via a central line or peripheral catheter.
    • ZINPLAVA should not be administered as an intravenous push or bolus.
    • Do not coadminister other drugs simultaneously through the same infusion line.

Referanser

  • 1.

    SPC Zinplava september 2017, avsnitt 4.1, 4.2, 4.8, 5.1.

INFC-1247832-0003 May 2018

Effekt og sikkerhet

ZINPLAVA + CDI antibiotics: Superior to CDI antibiotics alone in reducing C difficile recurrence 1

Percentage of patients with CDI recurrence 3

ZINPLAVA + CDI antibiotics significantly reduced the CDI recurrence rate vs CDI antibiotics alone through 12 weeks following administration of study infusion (P<0.0001). 1

  • Pooled data from 2 large-scale clinical trials. 1
  • Compared ZINPLAVA + CDI antibiotics vs CDI antibiotics alone (n=1,554). 1
  • Efficacy end point: the proportion of patients with recurrence of CDI through 12 weeks following administration of the study infusion. 1
  • 39% of all study participants received 1 or more systemic antibiotics (during the 12-week follow-up period). 1

Study design: The efficacy of ZINPLAVA was investigated in 2 randomized, double-blind, placebo-controlled, multicenter, Phase 3 trials in 1,554 patients. All patients received concomitant SOC antibiotics for CDI. Adult patients had a confirmed diagnosis of CDI, which was defined as diarrhea (passage of ≥3 loose bowel movements as defined in the Bristol stool chart as types 5 through 7 in ≤24 hours) and a positive stool test for toxigenic C difficile from a stool sample collected ≤7 days before study entry. Patients received a 10- to 14-day course of oral SOC antibiotics for CDI (metronidazole, vancomycin, or fidaxomicin, chosen by the investigator). Patients on oral vancomycin or oral fidaxomicin could have also received IV metronidazole. A single infusion of ZINPLAVA or placebo was administered prior to completion of antibiotics, and patients were followed for 12 weeks following the infusion. The day of the infusion of ZINPLAVA or placebo ranged from before starting antibiotics up to day 14 of treatment, with a median on day 3. The efficacy end point was the proportion of patients with recurrence of CDI through 12 weeks following administration of the study infusion. 1

IV=intravenous; RRR=relative risk reduction; SOC=standard-of-care.

ZINPLAVA + CDI antibiotics reduced recurrence vs CDI antibiotics alone in certain prespecified high-risk patients 1

Immunocompromised patients 1

In the pooled studies, 21% of patients were immunocompromised (medical conditions or medications that may result in immunosuppression).

Severe CDI patients 1

In the pooled studies, 16% of patients presented with clinically severe CDI (Zar score ≥2 a).

Age ≥ 65 years 1

In the pooled studies, 51% of patients were ≥ 65 years of age.

History of CDI 1

In the pooled studies, 28% of patients had a history of CDI within the 6 months prior to the episode under treatment.

  • Patients infected with a hypervirulent strain (027, 078, or 244 ribotypes) who received CDI antibiotics alone had a 32.2% (n=37/115) recurrence rate, while patients who received ZINPLAVA + CDI antibiotics had a 21.6% (n=22/102) recurrence rate (95% CI, -10.6 [-22.1, 1.3]).
  • Patients infected with 027 ribotype who received CDI antibiotics alone had a 34.0% (n=34/100) recurrence rate, while patients who received ZINPLAVA + CDI antibiotics had a 23.6% (n=21/89) recurrence rate (95% CI, -10.4 [-23.0, 2.6]).

a Zar severity assessment score for C difficile. Variables included aged >60 years, 1 point; albumin <2.5 mg/dL, 1 point; temperature >101°F, 1 point; white blood cell count >15 x 109/L, 1 point; intensive care unit admission, 2 points; and pseudomembranous colitis on colonoscopy, 2 points. Zar score was assessed at randomization, after antibiotics were already initiated. 2

ZINPLAVA + CDI antibiotics reduced recurrence vs CDI antibiotics alone in certain prespecified high-risk patients 1

Percentage of immunocompromised patients with CDI recurrence 3

Percentage of severe CDI patients with CDI recurrence 3

Percentage of patients age ≥65 years with CDI recurrence 16

Percentage of patients with a history of CDI and CDI recurrence 3

ZINPLAVA: CDI-related hospital readmissions

  • In a post hoc analysis of readmissions in 1,050 hospitalized patients, ZINPLAVA reduced CDI-associated hospital readmissions, including inpatients at high risk for CDI recurrence. 3

Adapted from Prabhu V S, Cornely O A, Golan Y et al.

Referanser

  • 1.

    SPC Zinplava september 2017, avsnitt 4.1, 4.2, 4.8, 5.1.

  • 2.

    Zar FA, Bakkanagari SR, Moorthi KMLST, et al. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302–307. doi:10.1086/519265.

  • 3.

    Prabhu V S, Cornely O A, Golan Y et al., Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment forClostridium difficileInfection, Clinical Infectious Diseases 2017;XX(00):1–4, DOI: 10.1093/cid/cix523

INFC-1247832-0003 May 2018

Virkningsmekanisme

Default Image

ZINPLAVA® TARGETS TOXIN B AND ENHANCES THE IMMUNE RESPONSE

Film lengde: 4 Minutter.

Zinplava (bezlotoxumab)

INDIKASJON:

ZINPLAVA er indisert til forebygging av tilbakefall av Clostridium difficile-infeksjon (CDI) hos voksne med høy risiko for tilbakefall av CDI

UTVALGT SIKKERHETSINFORMASJON:

Kontraindikasjoner:

Overfølsomhet overfor virkestoffet eller overfor noen av hjelpestoffene

Forsiktighet utvises ved:

ZINPLAVA er ikke en behandling mot CDI og har ingen effekt på den pågående CDI-episoden. ZINPLAVA skal administreres i løpet av antibiotikabehandlingen som gis mot CDI. Det finnes ingen data vedrørende effekt av ZINPLAVA dersom det gis etter de første 10-14 dagene av antibiotikabehandlingen mot CDI. ZINPLAVA skal ikke administreres som en intravenøs støt- eller bolusdose. Det er ingen erfaring med gjentatt administrering av ZINPLAVA hos pasienter med CDI. I kliniske studier fikk pasienter med CDI kun én enkelt dose av ZINPLAVA

Viktige bivirkninger:

De vanligste bivirkningene etter behandling med ZINPLAVA (rapportert hos ≥ 4 % av pasientene innen de første 4 ukene etter infusjon) var kvalme, diaré, feber og hodepine. Disse bivirkningene ble rapportert med tilsvarende frekvens hos pasienter behandlet med placebo.

Før forskrivning av Zinplava, se preparatomtalen.


CD-00087 03/19