Bezlotoxumab (Zinplava) with MAYO Clinic

Bezlotoxumab (Zinplava) with MAYO ClinicGroup 4 Rafi Saadallah, Anthony Hill, Alex Nedved, Angel WithrowBezlotoxumab (Zinplava)BLT with MAYO Clinic Pharmacy and Therapeutic committeeDrug Evaluation Monograph Generic anticipateBezlotoxumabBrand Name ZinplavaManufacturerMERCK SHARP DOHMETherapeutic Category 8004 Antitoxins and Immune GlobulinsClassification J06BB Specific ImmunoglobulinsFDA Classification Approved (rating not specified)Status Rx unaccompaniedSimilar Agents on Market NoneSummaryZinplava is the first and only monoclonal antibody FDA approved for bar of continual C. Diff infections. It is expenditured as an add on therapy to decrease risk of recurrent C. Diff. Zinplava is currently the only drug in its class because its currently the only drug in the market that prevents the recurrence of CDI alternatively of treating the actual infection. The drugs mechanisms of action is unique due to its ability to inhibit Toxin B and stopping its effects on the cell. After looki ng at the trials, its hard to carry out any side effects that can prevent muckle from taking this drug. Most of the Zinplavas side effects were nausea, headaches, and infusion problems. It is recommended to not use this drug with people who have congestive total failure.RecommendationsIt is recommended to add Zinplava to the drug formulary for add on therapy. It is usefull for those patients that are at especially high risk of a recurrent C. Diff infection. Zinplava currently addresss $4,560.00 per vial and while it has been proven to reduce the risk of recurrent zinplava the use of this medication can only be justified in patients that meet criteria that would put them at high risk of recurrent C. Difff. With other options ready(prenominal) to prevent recurrent C. Diff it can only be justified to use zinplava in a particular group of patients that cannot tolerate alternative medical interventions and are at an increased risk of recurrent C. Diff.Pharmacological Data weapon of action A monoclonal antibody that inhibits Toxin B (does not bind to Toxin A) and stops the effect on Mammalian cells. This drug should not be used alone, alternatively it needs to be used in conjunction with other antibiotics to treat recurrence cases of C.Diff.Therapeutic Indications FDA approved on June 9th, 2016 for the prevention and treatment of recurrent C.diff in patients 18 years of age that are undergoing germicide therapy for the treatment of C. Diff.Evidence Based Guidelines Zinplava was approved in October 2016 and its place in guideline therapy has not til now been determined. It is the first monoclonal antibody approved for the prevention of recurrent C. Diff. and guidelines do not yet reflect therapy with zinplava for the prevention of primary or recurrent C. Diff. All guidelines available are only for the treatment of C.diff and do not yet include zinplava.Clinical StudiesThe safety of Zinplava was evaluated in two placebo- lateralityled Phase 3 trials. Patients received a single Zinplava acid with antimicrobial treatment for C. diff infection. Between the experimental group and placebo group, mortality rates were slightly lower in the experimental group at 7.1% compared to 7.6% at a 12 week follow-up. Common side effects noted were nausea, pyrexia, and headache. Heart failure was listed as a serious adverse reaction, as it occurred in 2.3% of the experimental group compared to 1% in the placebo group. Infusion related reactions were reported in 10% of patients treated with Zinplava compared to 8% of placebo patients.In terms of recurrence prevention efficacy, Trial 1 had 386 patients in the Zinplava group and 395 patients in the control group. Disease recurrence was found in 67 patients (17.4%) treated with Zinplava and in 109 patients (27.6%) of the control group. In Trial 2, there were 395 patients in the Zinplava group and 378 patients in the control group. Disease recurrence was found in 62 patients (15.7%) treated with Zinplava and in 97 patients (25.7%) of the control group. There was no statistical significanceMerck Sharp Dohme Corp. A study of MK-3415, MK-6072, and MK-3415A in participants receiving antibiotic therapy for clostridium difficile infection (MK-3415A-001) (MODIFY I). NLM Identifier NCT01241552. Last updated November 30, 2015. Available at https//www.clinicaltrials.gov/ct2/show/NCT01241552?term=NCT01241552rank=1.Merck Sharp Dohme Corp. A study of MK-6072 and MK-3415A in participants receiving antibiotic therapy for clostridium difficile infection (MK-3415A-002) (MODIFY 11). NLM Identifier NCT01513239. Last updated October 29, 2015. Available at https//www.clinicaltrials.gov/ct2/show/NCT01513239?term=NCT01513239rank=1.Pharmacokinetics and Bioavailability submergenceImmediately and 100% bioavailableDistributionVd is 7.33 LMetabolismBy CatabolismExcretion Primarily by CatabolismDosage FormsDrugBezlotoxumab conceptualizationSolutionStrength constant of gravitation mg/40 ml (25 mg/ml)Storage 2-8 C (Do not freeze)Special considerationsSolutions diluted for infusion may be stored at room temperature for up to 16 hours or under refrigeration for up to 24 hours.Administration Infusion over a 60 delicate period through a sterile, low protein binding 0.2 to 5 micro line or add on filter. Can be administered through a central line or a peripheral catheter.Dosage Range AdultsIV 10 mg/kg (single dose)ChildrenOnly studied in 18 years or olderElderlySame as adult dosingHepatic FailureNo dose adjustmentsRenal Impairment No dose adjustmentsAdverse EffectsAdverse Effects Nausea, Pyrexia, Headache, Infusion related reactions, ImmunogenicitySerious Congestive Heart Failure exacerbationSpecial Precautions In congestive heart failure patients, Bezlotoxumab should be reserved for patients where benefit outweighs the risk in order to reduce risk of worsening heart failure.Contraindications NoneDrug Interactions -Belimumab Monoclonal Antibodies may enhance the adverse/toxic effect of Belimuma b(Brand name Benlysta).Drug Food interactions None.Drug Laboratory Test interactions None.Patient Safety -Zinplava has a good side effect profile with the most common side effect being nausea. The patient should tell their doctor if they have or have had a chronicle of congestive heart failure, as it can be a serious side effect of the zinplava.Monitoring Guidelines Monitor for signs and symptoms of adverse reactions.Patient Information -Zinplava doesnt say the place of their antibacterial treatment for CDI. Patient must continue to take their treatment regimen as directed. You will need to have a doctors employment to receive Zinplava. Administration will take one hour via IV route. If you miss an appointment, contact your doctor right away.Cost Comparison Drug (Strength) perfunctory Dose/DosingAWPZinplava 1000 mg/40 mL (25 mg/mL)10 mg/kg infusion over 1 hour$4560.00( per vial 1000 mg/40 ml)vancomycin HCL in dextrose IV-1g/200ml-500 mg/100 ml-750 mg/150 ml$27.65$7.92$14.50Vanco mycin HCL in NaCl IV-1g/200 ml-500 mg/100 ml-750 mg/150 ml$28.55$8.82$15.40Vancomycin HCL IV10 g500 mg750 mg1000 mg5000 mg$206.40$8.40$11.63$15.60$85.50Pharmacoeconomic AnalysisProblem definition -The objective of this analysis is to determine if Zinplava should be used as an add on to antimicrobial therapy.Perspective -Will be from the perspective of the institution.Specific treatment alternatives and outcomes -Zinplava can only be used as an add on to antimicrobial therapy for the treatment and prevention of recurrent Clostridium Difficile. The treatment options are either antimicrobial therapy without zinplava and antimicrobial therapy with zinplava.Pharmacoeconomic model Number need to treat with zinplava will be used in order to detail the effects that zinplava has in order to make a realistic judgement as to whether or not zinplava is worth the extra cost to add on therapy in terms of determining if adding on zinplava can be justified from an economic perspective. .-NNT (Vanco mycin and Zinplava) = 5.5Drugs Average Cost Vancomycin$25.6 (per 1 gram)Vancomycin + Zinplava$25.6 (per 1 gram) + $4,560 (1000mg/40 ml) = $4,585.6Note to reader Number needed to treat data was extrapolated from a randomized, double blind controlled study using 200 patients during a phase angle 2 trial. Recurrence of C. Diff. (measured after 84 days) between the monoclonal antibody and placebo group was 7% and 25%, respectively with a 95% confidence interval and a p-value Presented by Rafi Saadallah, Anthony Hill, Alex Nedved, Angel Withrow to the Pharmacy and Therapeutics committee on March 10th, 2017Reference Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD, Jr., Leney M, Sloan S, Hay CA, Ambrosino DM Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med 2010, 362197-205.(Economic analysis refrence)