1. DR.JITENDRA AGRAWAL
SECOND YEAR RESIDENT

2.  Synthetic Pegylated Erythropoesis 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 approved as treatment of anemia associated
with chronic kidney disease (CKD) in adult patients on
dialysis by US FDA on 27th March 2012

4. Binds to human erythropoietin 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 accumulation every 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 the reticulocyte 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 formal drug/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 of anaemia 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 evaluate iron 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 not received any ESA previously
Initial dose
0.04 mg/kg body weight, IV or SC
Once monthly

14.  If the patient 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 Hb levels 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 the Hb 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 Adverse Drug 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