ZINPLAVA (Bezlotoxumab)
Monoclonal antibody for prevention of recurrent Clostridioides difficile infection
Quick facts about ZINPLAVA
Key takeaways about ZINPLAVA
- Not an antibiotic: ZINPLAVA does not treat active CDI. It must be given alongside standard antibiotics (vancomycin, fidaxomicin, or metronidazole) to prevent recurrence
- Single-dose convenience: Only one intravenous infusion is needed, administered over approximately 60 minutes during the current CDI treatment course
- Proven efficacy: Clinical trials (MODIFY I and MODIFY II) demonstrated that bezlotoxumab reduced CDI recurrence by approximately 40% compared to placebo over 12 weeks
- Targets toxin B: Works by neutralizing C. difficile toxin B, the primary driver of colonic damage and symptom recurrence
- Use with caution in heart failure: Patients with a history of congestive heart failure should be monitored, as heart failure events were reported more frequently in clinical trials
What Is ZINPLAVA and What Is It Used For?
ZINPLAVA (bezlotoxumab) is a human monoclonal antibody administered as a single intravenous infusion to prevent recurrence of Clostridioides difficile infection (CDI) in adults and children from 1 year of age who are at high risk of CDI coming back. It works by binding to and neutralizing toxin B, the main toxin responsible for colonic damage in CDI.
Clostridioides difficile infection is one of the most significant healthcare-associated infections worldwide. CDI causes inflammation of the colon (colitis), leading to symptoms that range from mild diarrhea to severe, life-threatening pseudomembranous colitis, toxic megacolon, and bowel perforation. The burden of CDI is particularly high among hospitalized patients, elderly individuals, and those who have recently received antibiotic therapy.
When a patient develops CDI, standard treatment involves antibiotics such as vancomycin, fidaxomicin, or metronidazole. While these antibiotics are effective at resolving the acute infection, a major challenge is that CDI recurs in approximately 20-30% of patients within 2-8 weeks after completing antibiotic treatment. Patients who have already experienced one recurrence face an even higher risk, with subsequent recurrence rates of 40-65%. This cycle of recurrence creates a significant clinical and economic burden.
ZINPLAVA addresses this problem through a novel mechanism. Bezlotoxumab is a fully human IgG1 monoclonal antibody that specifically binds to C. difficile toxin B (TcdB) with high affinity. Toxin B is the primary virulence factor responsible for the mucosal damage, inflammation, and fluid secretion that characterize CDI. By neutralizing toxin B, bezlotoxumab prevents the toxin from binding to host colonic epithelial cells and causing further tissue damage, thereby reducing the likelihood of symptomatic recurrence.
It is critical to understand that ZINPLAVA is not an antibiotic. It does not kill C. difficile bacteria or treat the active infection. Instead, it provides passive immunization against the effects of the toxin. ZINPLAVA must always be administered in conjunction with ongoing antibacterial drug treatment for CDI. The European Medicines Agency (EMA) approved bezlotoxumab in January 2017, and the U.S. Food and Drug Administration (FDA) granted approval in October 2016, making it the first monoclonal antibody specifically approved for reducing CDI recurrence.
How ZINPLAVA Works
The mechanism of action of bezlotoxumab is elegantly targeted. C. difficile produces two main exotoxins: toxin A (TcdA) and toxin B (TcdB). While both toxins contribute to disease, toxin B is considered the primary driver of colonic pathology. Toxin B binds to receptors on the surface of colonic epithelial cells, is internalized, and then disrupts the cell cytoskeleton by inactivating Rho family GTPases. This leads to cell rounding, loss of tight junctions, fluid secretion, and ultimately cell death and mucosal inflammation.
Bezlotoxumab binds to two specific epitopes on toxin B, effectively blocking the toxin's ability to attach to host cell receptors. The antibody neutralizes toxin B from multiple C. difficile ribotypes, including the hypervirulent BI/NAP1/027 strain, which has been associated with more severe disease and higher recurrence rates. By maintaining circulating anti-toxin B antibodies for several weeks after administration (the half-life is approximately 19 days), bezlotoxumab provides sustained protection during the vulnerable period when CDI recurrence is most likely to occur.
What Should You Know Before Taking ZINPLAVA?
Before receiving ZINPLAVA, inform your doctor about any allergies, heart conditions (especially congestive heart failure), pregnancy, or breastfeeding status. ZINPLAVA should not be given to patients allergic to bezlotoxumab or any of its excipients, and it should not be used in children under 1 year of age.
Contraindications
ZINPLAVA is contraindicated in patients with a known hypersensitivity to bezlotoxumab or to any of the excipients in the formulation. These excipients include citric acid monohydrate, diethylenetriaminepentaacetic acid, polysorbate 80, sodium chloride, sodium citrate dihydrate, water for injections, and sodium hydroxide (for pH adjustment). While true allergic reactions to monoclonal antibodies are uncommon, infusion-related reactions can occur and healthcare providers should be prepared to manage them.
Warnings and Precautions
The most important warning associated with ZINPLAVA relates to heart failure. In the pivotal MODIFY I and MODIFY II clinical trials, heart failure was reported more frequently among bezlotoxumab-treated patients who had a baseline history of congestive heart failure (CHF) compared to placebo-treated patients with CHF. During the 12-week follow-up period, serious adverse cardiac events occurred in 12.7% of bezlotoxumab-treated patients with baseline CHF versus 4.8% in the placebo group. Deaths also occurred at a higher rate in this subgroup. Therefore, ZINPLAVA should be reserved for patients in whom the benefit of reducing CDI recurrence outweighs the risk, and patients with a history of CHF should be carefully monitored.
ZINPLAVA is not a treatment for CDI. It has no antibacterial activity and will not resolve an active C. difficile infection on its own. Patients must continue their prescribed antibiotic regimen for CDI as directed by their physician. Additionally, ZINPLAVA should not be administered as an intravenous push or bolus injection; it must be given as a slow intravenous infusion over approximately 60 minutes.
In clinical trials, heart failure occurred more frequently in ZINPLAVA-treated patients with a history of congestive heart failure. If you have heart failure, your doctor will carefully assess whether the benefits of ZINPLAVA outweigh the risks before prescribing this medication.
Use in Children
ZINPLAVA is approved for use in children aged 1 year and older who are at high risk of CDI recurrence. The dosage is weight-based (10 mg/kg), the same as for adults. ZINPLAVA should not be given to children under 1 year of age, as the safety and efficacy in this age group have not been established. Pediatric CDI is increasingly recognized as a clinical problem, particularly in children with underlying conditions or those who have received prolonged courses of antibiotics.
Pregnancy and Breastfeeding
The effects of ZINPLAVA during pregnancy have not been adequately studied in humans. As a monoclonal antibody of the IgG1 subclass, bezlotoxumab is expected to cross the placental barrier, particularly during the second and third trimesters. Animal studies have not demonstrated direct harm to the fetus, but the relevance of animal data to humans is uncertain. The decision to use ZINPLAVA during pregnancy should be made jointly by the patient and their healthcare provider, carefully weighing the potential benefits against the potential risks.
It is not known whether bezlotoxumab is excreted in human breast milk. Human IgG antibodies are known to be present in breast milk, particularly in the early postpartum period. The potential effects of bezlotoxumab on a breastfed infant or on milk production have not been studied. As with pregnancy, the decision to use ZINPLAVA during breastfeeding should involve a careful benefit-risk assessment.
Sodium Content
ZINPLAVA contains up to 182.8 mg of sodium per vial, which is equivalent to approximately 9.1% of the WHO-recommended maximum daily sodium intake for adults. This should be taken into account for patients on a controlled sodium diet, although the single-dose nature of the medication means this is a one-time exposure rather than a chronic concern.
Driving and Operating Machinery
ZINPLAVA has no or negligible effect on the ability to drive or use machines. There are no specific restrictions on driving or operating machinery following administration of bezlotoxumab.
How Does ZINPLAVA Interact with Other Drugs?
No clinically significant drug interactions have been identified with ZINPLAVA. As a monoclonal antibody, bezlotoxumab is not metabolized by cytochrome P450 enzymes and is not expected to interact with drugs that are substrates, inducers, or inhibitors of these enzymes. It can be safely used alongside CDI antibiotics such as vancomycin, metronidazole, and fidaxomicin.
Formal drug interaction studies have not been conducted with bezlotoxumab. However, based on its pharmacological properties, clinically meaningful interactions are not expected. Monoclonal antibodies are large protein molecules that are eliminated through intracellular catabolism (broken down into amino acids) rather than by hepatic metabolism via cytochrome P450 pathways. This means that bezlotoxumab does not compete with, induce, or inhibit the metabolism of other medications processed by the liver.
In the MODIFY clinical trials, bezlotoxumab was administered alongside various CDI antibiotic regimens, including oral vancomycin, oral metronidazole, and oral fidaxomicin. No evidence of interactions between bezlotoxumab and these antibiotics was observed. Patients in the trials were also receiving a wide range of concomitant medications for their comorbid conditions, and no new safety signals attributable to drug interactions were identified.
| Drug / Drug Class | Interaction Level | Clinical Significance |
|---|---|---|
| Vancomycin (oral) | None identified | Safe to use together; standard CDI combination |
| Fidaxomicin | None identified | Safe to use together; standard CDI combination |
| Metronidazole (oral) | None identified | Safe to use together; standard CDI combination |
| CYP450 substrates | None expected | Bezlotoxumab not metabolized via CYP450 |
| Other IV medications | Physical incompatibility | Do not co-infuse through the same IV line |
ZINPLAVA should not be administered simultaneously with other medications through the same intravenous line. While no pharmacological drug interactions have been identified, physical compatibility with other IV solutions (other than 0.9% sodium chloride and 5% dextrose) has not been established.
What Is the Correct Dosage of ZINPLAVA?
ZINPLAVA is given as a single intravenous infusion at a dose of 10 mg/kg body weight. The infusion is administered over approximately 60 minutes. This is a one-time dose; no repeat doses are required. The dose is the same for adults and children aged 1 year and older.
Adults
The recommended dose of ZINPLAVA for adults is 10 mg/kg administered as a single intravenous infusion over approximately 60 minutes. The dose is calculated based on the patient's body weight in kilograms. The concentrated solution (25 mg/mL) must be diluted before administration using either 0.9% sodium chloride solution or 5% dextrose solution, to achieve a final concentration of 1 to 10 mg/mL. ZINPLAVA should be administered during the course of antibacterial treatment for CDI.
Adult Dosage Example
For a 70 kg patient: 10 mg/kg × 70 kg = 700 mg bezlotoxumab. This equates to 28 mL of the 25 mg/mL concentrate, which is then diluted in a compatible IV solution and infused over 60 minutes.
Children (1 Year and Older)
The dosage for pediatric patients aged 1 year and older is the same as for adults: 10 mg/kg body weight as a single intravenous infusion over approximately 60 minutes. The dose is weight-based, ensuring appropriate dosing across different ages and sizes. ZINPLAVA should not be used in children under 1 year of age.
Elderly Patients
No dose adjustment is required for elderly patients. In the MODIFY clinical trials, a substantial proportion of patients were aged 65 years or older, reflecting the higher incidence of CDI in this population. The safety and efficacy profile of bezlotoxumab was consistent across age groups, and no specific dose modifications were necessary for older adults.
Renal and Hepatic Impairment
No dose adjustment is required for patients with renal impairment or hepatic impairment. Bezlotoxumab is not eliminated by the kidneys or metabolized by the liver. As a monoclonal antibody, it is catabolized through intracellular proteolysis. Population pharmacokinetic analyses did not identify renal or hepatic function as significant covariates affecting bezlotoxumab clearance.
| Patient Group | Dose | Route | Notes |
|---|---|---|---|
| Adults | 10 mg/kg | IV infusion over 60 min | Single dose during CDI antibiotic course |
| Children (≥1 year) | 10 mg/kg | IV infusion over 60 min | Same as adult dosing; weight-based |
| Elderly (≥65 years) | 10 mg/kg | IV infusion over 60 min | No dose adjustment required |
| Renal impairment | 10 mg/kg | IV infusion over 60 min | No dose adjustment required |
| Hepatic impairment | 10 mg/kg | IV infusion over 60 min | No dose adjustment required |
Missed Dose
If you miss your scheduled appointment for the ZINPLAVA infusion, contact your healthcare provider or the hospital as soon as possible to arrange a new appointment. Because ZINPLAVA is given as a single dose, it is important not to miss this administration. The infusion should ideally be given during the course of your CDI antibiotic treatment to maximize its protective effect against recurrence.
Overdose
There is limited experience with overdose of bezlotoxumab in clinical settings. In clinical studies, single doses of up to 20 mg/kg were administered intravenously without dose-limiting toxicity. In the event of an overdose, the patient should be monitored for signs and symptoms of adverse effects, and appropriate supportive care should be initiated. There is no specific antidote for bezlotoxumab overdose.
What Are the Side Effects of ZINPLAVA?
The most commonly reported side effects of ZINPLAVA in clinical trials include nausea, diarrhea, fever (pyrexia), headache, dizziness, fatigue, high blood pressure (hypertension), and shortness of breath (dyspnea). These effects occurred in up to 1 in 10 patients and were generally mild to moderate in severity.
Like all medicines, ZINPLAVA can cause side effects, although not everyone experiences them. The safety profile of bezlotoxumab has been evaluated in the pivotal MODIFY I and MODIFY II clinical trials, which together enrolled over 2,500 patients. In these studies, the overall incidence of adverse events was similar between the bezlotoxumab and placebo groups, reflecting the generally well-tolerated nature of the medication.
The following side effects have been reported from clinical studies. It is important to note that because ZINPLAVA is administered as a single dose, side effects are typically transient and occur within the first few days after the infusion.
Common Side Effects
- Nausea – feeling of queasiness or urge to vomit
- Diarrhea – loose or watery stools (note: may be difficult to distinguish from CDI symptoms)
- Fever (pyrexia) – elevated body temperature
- Headache – mild to moderate head pain
- Dizziness – feeling lightheaded or unsteady
- Fatigue – unusual tiredness or lack of energy
- Hypertension – elevated blood pressure
- Dyspnea – shortness of breath or difficulty breathing
Infusion-related reactions, including nausea, fatigue, fever, dizziness, headache, and dyspnea, have been observed during or shortly after the bezlotoxumab infusion. These reactions were generally mild and self-limiting. In rare cases, slowing or temporarily stopping the infusion may be necessary to manage symptoms.
As mentioned in the warnings section, heart failure events were more frequent among patients with baseline congestive heart failure who received ZINPLAVA compared to placebo. This is a known risk that is taken into consideration when prescribing bezlotoxumab for patients with pre-existing cardiac conditions. Patients with a history of heart failure should be closely monitored during and after the infusion.
Tell your doctor or healthcare provider if you experience any of the side effects listed above, particularly if they are severe or persistent. If you experience chest pain, significant breathing difficulties, swelling in your legs or ankles, or rapid weight gain after receiving ZINPLAVA, seek medical attention promptly, as these could be signs of heart failure.
How Should You Store ZINPLAVA?
ZINPLAVA should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F), protected from light, and must not be frozen. The diluted solution can be stored at room temperature for up to 16 hours or refrigerated for up to 24 hours. As a hospital-administered medication, storage is typically managed by healthcare professionals.
The unopened vials of ZINPLAVA concentrate should be stored in a refrigerator at 2°C to 8°C. The vials must not be frozen. To protect from light, vials should be kept in the outer carton until ready for use. The vial may be removed from refrigeration and stored at room temperature, protected from light, for up to 24 hours before dilution.
Once the concentrated solution has been diluted for infusion, the prepared solution can be stored either at room temperature for up to 16 hours or in a refrigerator at 2°C to 8°C for up to 24 hours. If the diluted solution has been refrigerated, the infusion bag should be brought to room temperature before administration. The diluted solution must not be frozen.
Any unused solution remaining in the vial or infusion bag should be discarded in accordance with local requirements for disposal of pharmaceutical waste. ZINPLAVA does not contain any preservatives, and any unused portions should not be saved for later use. Do not use the medication after the expiration date printed on the carton and vial (indicated by "EXP"), which refers to the last day of the stated month.
Keep all medicines out of the sight and reach of children.
What Does ZINPLAVA Contain?
Each milliliter of ZINPLAVA concentrate contains 25 mg of bezlotoxumab as the active ingredient. It is available in 40 mL vials (1,000 mg) and 25 mL vials (625 mg). The solution is clear to moderately opalescent, colorless to pale yellow.
Active Ingredient
The active substance is bezlotoxumab, a fully human monoclonal antibody of the IgG1 subclass produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Each mL of concentrate contains 25 mg of bezlotoxumab. The 40 mL vial contains 1,000 mg of bezlotoxumab, and the 25 mL vial contains 625 mg of bezlotoxumab.
Inactive Ingredients (Excipients)
The other ingredients in ZINPLAVA are:
- Citric acid monohydrate (E330)
- Diethylenetriaminepentaacetic acid (DTPA)
- Polysorbate 80 (E433)
- Sodium chloride
- Sodium citrate dihydrate (E331)
- Water for injections
- Sodium hydroxide (E524) – for pH adjustment
Appearance and Packaging
ZINPLAVA concentrate for solution for infusion is a clear to moderately opalescent (with a slight pearlescent sheen), colorless to pale yellow liquid. It is supplied in glass vials, packaged individually in cartons. Do not use the product if the solution appears discolored or contains visible particles.
Preparation for Infusion (Healthcare Professionals)
The concentrate must be diluted before administration. Healthcare professionals should withdraw the required volume from the vial(s) based on the patient's weight and transfer it to an intravenous infusion bag containing either 0.9% sodium chloride injection or 5% dextrose injection. The final concentration of the diluted solution should be between 1 and 10 mg/mL. The diluted solution is administered intravenously over 60 minutes using a sterile, non-pyrogenic, low-protein-binding 0.2 to 5 µm in-line or add-on filter.
Frequently Asked Questions About ZINPLAVA
ZINPLAVA (bezlotoxumab) is used to prevent recurrence of Clostridioides difficile infection (CDI) in adults and children aged 1 year and older who are at high risk of CDI coming back. It is given as a single intravenous infusion during the course of antibiotic treatment for an active CDI episode. ZINPLAVA is not an antibiotic and does not treat the active infection itself – it specifically targets and neutralizes toxin B produced by the bacteria to prevent recurrence.
In the two pivotal Phase 3 clinical trials (MODIFY I and MODIFY II), ZINPLAVA reduced CDI recurrence rates by approximately 38-40% compared to placebo over a 12-week follow-up period. In MODIFY I, the recurrence rate was 17.4% with bezlotoxumab versus 27.6% with placebo. In MODIFY II, recurrence was 15.7% versus 25.7%. The benefit was particularly pronounced in patients at highest risk of recurrence, such as those aged 65 or older, those with a history of prior CDI episodes, and those infected with the hypervirulent 027 ribotype.
Yes, ZINPLAVA has no known clinically significant drug interactions. It can be safely used alongside the antibiotics prescribed for CDI treatment (vancomycin, fidaxomicin, or metronidazole) as well as other medications you may be taking for other conditions. However, ZINPLAVA should not be infused through the same IV line as other medications at the same time. Always inform your healthcare team about all medications you are taking.
No, ZINPLAVA is not an antibiotic. It is a monoclonal antibody – a type of targeted protein therapy. Unlike antibiotics, which kill bacteria directly, ZINPLAVA works by binding to and neutralizing toxin B produced by C. difficile. This prevents the toxin from damaging the colon and triggering a recurrence of symptoms. You must continue taking your prescribed antibiotic for CDI treatment alongside ZINPLAVA.
ZINPLAVA should not be given to patients who are allergic to bezlotoxumab or any of its other ingredients. It should also not be used in children under 1 year of age. Patients with a history of congestive heart failure should discuss the risks and benefits carefully with their doctor, as heart failure events were reported more frequently in this subgroup during clinical trials. The decision to use ZINPLAVA should be individualized based on each patient's risk profile.
The ZINPLAVA infusion takes approximately 60 minutes. It is given as a single dose in a hospital or clinical setting by a trained healthcare professional. After the infusion, you may be monitored for a short period for any immediate reactions. Only one infusion is needed – there are no follow-up doses required.
References
- European Medicines Agency (EMA). ZINPLAVA (bezlotoxumab) – Summary of Product Characteristics. Available at: ema.europa.eu/EPAR/zinplava. Accessed January 2026.
- U.S. Food and Drug Administration (FDA). ZINPLAVA (bezlotoxumab) Prescribing Information. Approved October 2016.
- Wilcox MH, Gerding DN, Poxton IR, et al. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med. 2017;376(4):305-317. doi:10.1056/NEJMoa1602615.
- McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by IDSA and SHEA. Clin Infect Dis. 2018;66(7):e1-e48.
- van Prehn J, Reigadas E, Vogelzang EH, et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): updated guidance document on the treatment of Clostridioides difficile infection in adults. Clin Microbiol Infect. 2021;27(Suppl 2):S1-S21.
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd List (2023). Geneva: World Health Organization; 2023.
- Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73(5):e1029-e1044.
- 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.
Editorial Team
iMedic Medical Editorial Team – specialists in infectious disease, clinical pharmacology, and gastroenterology with documented academic backgrounds and clinical experience.
iMedic Medical Review Board – independent panel of medical experts who review all content according to international guidelines (WHO, EMA, FDA, IDSA/SHEA, ESCMID).
This article is based on Level 1A evidence from peer-reviewed randomized controlled trials and international clinical guidelines. All medical claims are supported by the references listed above. Content follows the GRADE evidence framework. No commercial funding was involved in the creation of this article.