Pegnisatide an update

Pegnisatide an update

• 1.
  DR.JITENDRA AGRAWAL SECOND YEARRESIDENT
• 2.
   Synthetic PegylatedErythropoesis Stimulating Agent  Dimeric Peptide having two identical 21-amino acid chains covalently bonded to a linker derived from iminodiacetic acid and β-alanine.  The dimeric peptide is covalently linked to a single lysine- branched bis-(methoxypoly(ethylene glycol)) (PEG)  Amino acid sequence is defferent from Erythropoetine
• 3.
   Recently approvedas treatment of anemia associated with chronic kidney disease (CKD) in adult patients on dialysis by US FDA on 27th March 2012
• 4.
  Binds to humanerythropoietin receptor Activates receptor Stimulates erythropoesis in human red cell precursor
• 5.
   Following IV/ SC route:  Maximal plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increase with dose  Following SC injection  Maximum plasma concentration reach within 48 hrs  Bioavailability – approximately 46%  Not metabolized  Excreted predominantly through kidney
• 6.
  Half life: Route Healthy CKD individual(hrs) (hrs) IV 25.0 7.6 47.9 16.5 SC 53.0 17.7 53.0 17.7
• 7.
   No accumulationevery 4 weeks following intravenous or subcutaneous administration  The pharmacokinetics of patients with CKD on dialysis are not altered by age, gender or race
• 8.
   Increases thereticulocyte count followed by increases in hemoglobin  The rate of hemoglobin increase varies among patients and is dependent on the dose.  No effect on QTc Interval
• 9.
   No formaldrug/drug interaction studies have been performed.  Peginesatide does not bind to serum albumin or lipoproteins as demonstrated in in vitro protein binding studies in rat, monkey and human sera.  In vitro studies conducted with human hepatocytes or microsomes have shown no potential for peginesatide to induce or inhibit CYP450 enzymes.
• 10.
   Treatment ofanaemia due to chronic kidney disease (CKD) in adult patients on dialysis.  Not indicated :  Who are not on dialysis  Receiving treatment for cancer  Substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia.
• 11.
   Uncontrolled hypertension
• 12.
   First evaluateiron store and nutritional factor  Individualize dosing and use the lowest dose sufficient to reduce the need for RBC transfusions  Initiate treatment when the hemoglobin level is less than 10 g/dL
• 13.
  If patient notreceived any ESA previously Initial dose 0.04 mg/kg body weight, IV or SC Once monthly
• 14.
   If thepatient is previously on : Epoetin alfa Darbepoetin alfa 1st dose should be 1st dose should be administered one administered at week after the last the next scheduled epoetin alfa dose dose in place of was administered darbepoetin alfa.
• 15.
   Replaced Dose? Previous Total Weekly Previous Weekly PEGNISATIDE Dose Epoetin Alfa Dose Darbepoetin Alfa Dose Once Monthly (mg/month) (U/week) (mcg/week) Less than 2,500 Less than 12 2 2,500 to 4,300 12 to 18 3 4,300 to 6,500 18 to 25 4 6,500 to 8,900 25 to 35 5 8,900 to 13,000 35 to 45 6 13,000 to 19,000 45 to 60 8 19,000 to 33,000 60 to 95 10 33,000 to 68,000 95 to 175 15 greater than or equal to greater than or equal to 175 20 68,000
• 16.
   Monitor Hblevels at least every 2 weeks until stable, then monitor at least monthly.  Do not increase the dose more frequently than once every 4 weeks.  If the Hb rises rapidly (e.g., more than 1 g/dL in the 2 weeks prior to the dose or more than 2 g/dL in 4 weeks), reduce the dose 25% or more as needed to reduce rapid responses.
• 17.
   If theHb level approaches or exceeds 11 g/dL, reduce or interrupt the dose.  After a dose has been withheld and once the hemoglobin begins to decrease, restart at a dose approximately 25% below the previously administered dose.  Patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%.  If a dose of is missed, administer the missed dose as soon as possible
• 18.
   Serious AdverseDrug Reactions  Myocardial Infarction  Stroke  Thromboembolism  Hypertension
• 19.
   Gastrointestinal  Musculoskeletal Diarrhoea (18.4%) Muscle Spasms (15.3%) Nausea (17.4%) Pain in Extremity (10.9%) Vomitting (15.3%) Back Pain (10.9%) Arthralgia (10.7%)  Respiratory Dyspnea (18.4%) Cough (15.9%)  Metabolic Hyperkalemia (11.4%0  CNS Headache (15.4%)  Procedural Arteriovenous Fistula Site Complication (16.1%)  CVS Hypotension (10.9%) Hypotension (14.2%) Hypertension (13.2%)
• 20.
   Immunogenicity  Only 1.2% patients developed detectable levels of peginesatide-specific binding antibodies  More incidence in SC administered patients  presence of antibodies associated with declining hemoglobin levels  The requirement of dose increases to maintain Hb level
• 21.
   Novel ESA which is synthetic and unrelated to Erythropoietin  No added advantage over Epoetin alfa and Darbepoetin alfa in adverse drug reactions  Administered once a month rather than once a Weekly that of Epoetin alfa and Darbepoetin alfa  Does not cause Pure Red Cell Aplasia
• 22.
  1. Kenneth Kaushansky , Thomas Kipps.Hematopoietic Agents: Growth factors, Minerals and Vitamins. In: Brunton L, editor.Goodman & Gillman’s The Pharmacological Basis of Therapeutics, 12th ed. New York: Mcgraw Hill; 2011.p.1068-73. 2. Andrew Wagner, Ramy Arnaout, George Demetri. Pharmacology of Hematopoiesis and Immunomodulation. In: David Golan, editor. Principles of Pharmacology, The Pathophysiological Basis of Drug Therapy, 3rd ed. Philadelphia: Lippincott Williams and Wilkins Publications; 2012.p.779-83. 3. OMONTYS® (Peginasatide) for Injection. US Prescribing Information. April 2012.[ cited April 30, 2012]. Available from: www.accessdata.fda.gov/drugsatfda_docs/label/.../202799s000lbl.pdf 4. Richard B Stead et al.Evaluation of the safety and pharmacodynamics of Hematide, a novel erythropoietic agent, in a phase 1, double-blind, placebo- controlled, dose-escalation study in healthy volunteers. Blood, 15 September 2006, Vol. 108, No. 6, pp. 1830-1834. 5. FDA approves Omontys to treat anemia in adult patients on dialysis, Press Announcement. [cited April 29, 2012]. Available From: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm297 464.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=w ebsite&utm_term=peginesatide&utm_content=6