Included as part of the PRECAUTIONS section.
Increased Mortality, Myocardial Infarction, Stroke, and
- In controlled clinical trials of other ESAs in patients
with CKD comparing higher hemoglobin targets (13 - 14 g/dL) to lower targets (9
- 11.3 g/dL) (see Table 2), increased risk of death, myocardial infarction,
stroke, congestive heart failure, thrombosis of hemodialysis vascular access,
and other thromboembolic events was observed in the higher target groups.
- Using ESAs to target a hemoglobin level of greater than
11 g/dL increases the risk of serious adverse cardiovascular reactions and has
not been shown to provide additional benefit. Use caution in patients with
coexistent cardiovascular disease and stroke [see DOSAGE AND ADMINISTRATION].
Patients with CKD and an insufficient hemoglobin response to ESA therapy may be
at even greater risk for cardiovascular reactions and mortality than other
patients. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may
contribute to these risks.
- In controlled clinical trials of ESAs in patients with
cancer, increased risk for death and serious adverse cardiovascular reactions
was observed. These adverse reactions included myocardial infarction and
- In controlled clinical trials, ESAs increased the risk of
death in patients undergoing coronary artery bypass graft surgery (CABG) and
deep venous thrombosis (DVT) was observed in patients undergoing orthopedic
The design and overall results of 3 large trials
comparing higher and lower hemoglobin targets are shown in Table 2 (Normal
Hematocrit Study (NHS), Correction of Hemoglobin Outcomes in Renal
Insufficiency (CHOIR) and Trial to Reduce Cardiovascular Events with Aranesp® Therapy (TREAT)).
Table 2 : Adverse Cardiovascular Outcomes in
Randomized Controlled Trials Comparing Higher and Lower Hemoglobin Targets in
Patients with CKD
(N = 1265)
(N = 1432)
(N = 4038)
|Time Period of Trial
||1993 to 1996
||2003 to 2006
||2004 to 2009
||Patients with CKD on hemodialysis with coexisting CHF or CAD, hematocrit 30 ± 3% on epoetin alfa
||Patients with CKD not on dialysis with hemoglobin
||Patients with CKD not on dialysis with type II diabetes, hemoglobin ? 11 g/dL
|Hemoglobin Target; Higher vs. Lower (g/dL)
||14.0 vs. 10.0
||13.5 vs. 11.3
||13.0 vs. ? 9.0
|Median (Q1, Q3) Achieved Hemoglobin level (g/dL)
||12.6 (11.6, 13.3) vs. 10.3 (10.0, 10.7)
||13.0 (12.2, 13.4) vs. 11.4 (11.1, 11.6)
||12.5 (12.0, 12.8) vs. 10.6 (9.9, 11.3)
||All-cause mortality or non-fatal MI
||All-cause mortality, MI, hospitalization for CHF, or stroke
||All-cause mortality, MI, myocardial ischemia, heart failure, and stroke
|Hazard Ratio or Relative Risk (95% CI)
||1.28 (1.06 – 1.56)
||1.34 (1.03 – 1.74)
||1.05 (0.94 – 1.17)
|Adverse Outcome for Higher Target Group
|Hazard Ratio or Relative Risk (95% CI)
||1.27 (1.04 – 1.54)
||1.48 (0.97 – 2.27)
||1.92 (1.38 – 2.68)
Patients with Chronic Kidney
Disease Not on Dialysis
OMONTYS is not indicated and is
not recommended for the treatment of anemia in patients with CKD who are not on
A higher percentage of patients
(22%) who received OMONTYS experienced a composite cardiovascular safety
endpoint event compared to 17% who received darbepoetin alfa in two randomized,
active-controlled, open-label, multi-center trials of 983 patients with anemia
due to CKD who were not on dialysis. The trials had a pre-specified, prospective
analysis of a composite safety endpoint consisting of death, myocardial
infarction, stroke, or serious adverse events of congestive heart failure,
unstable angina or arrhythmia (hazard ratio 1.32, 95% CI: 0.97, 1.81).
Increased Mortality and/or
Increased Risk of Tumor Progression or Recurrence in Patients with Cancer
OMONTYS is not indicated and is
not recommended for reduction of RBC transfusions in patients receiving
treatment for cancer and whose anemia is not due to CKD because ESAs have shown
harm in some settings and the benefit-risk factors for OMONTYS in this setting
have not been evaluated.
The safety and efficacy of OMONTYS have not been
established for use in patients with anemia due to cancer chemotherapy. Results
from clinical trials of ESAs in patients with anemia due to cancer therapy
showed decreased locoregional control, progression-free survival and/or
decreased overall survival. The findings were observed in clinical trials of
other ESAs administered to patients with: breast cancer receiving chemotherapy,
advanced head and neck cancer receiving radiation therapy, lymphoid malignancy,
cervical cancer, non-small cell lung cancer, and with various malignancies who
were not receiving chemotherapy or radiotherapy.
OMONTYS is contraindicated in patients with uncontrolled
Appropriately control hypertension prior to initiation of
and during treatment with OMONTYS. Reduce or withhold OMONTYS if blood pressure
becomes difficult to control. Advise patients of the importance of compliance
with antihypertensive therapy and dietary restrictions [see PATIENT INFORMATION].
Serious Allergic Reactions
Serious allergic reactions, including anaphylactic
reactions, hypotension, bronchospasm, angioedema and generalized pruritus, may
occur in patients treated with OMONTYS. Immediately and permanently discontinue
OMONTYS and administer appropriate therapy if a serious allergic reaction
Lack or Loss of Response to OMONTYS
For lack or loss of hemoglobin response to OMONTYS,
initiate a search for causative factors (e.g., iron deficiency, infection,
inflammation, bleeding). If typical causes of lack or loss of hemoglobin
response are excluded, evaluate the patient for the presence of antibodies to
peginesatide. In the absence of antibodies to peginesatide, follow dosing
recommendations for management of patients with an insufficient hemoglobin
response to OMONTYS therapy [see DOSAGE AND ADMINISTRATION].
Contact Affymax, Inc. (1-855-466-6689) to perform assays
for binding and neutralizing antibodies.
Patients may require adjustments in their dialysis
prescriptions after initiation of OMONTYS. Patients receiving OMONTYS may
require increased anticoagulation with heparin to prevent clotting of the
extracorporeal circuit during hemodialysis.
Evaluate transferrin saturation and serum ferritin prior
to and during OMONTYS treatment. Administer supplemental iron therapy when
serum ferritin is less than 100 mcg/L or when serum transferrin saturation is
less than 20% [see DOSAGE AND ADMINISTRATION]. The majority of patients
with CKD will require supplemental iron during the course of ESA therapy.
Following initiation of therapy and after each dose adjustment, monitor
hemoglobin every 2 weeks until the hemoglobin is stable and sufficient to
minimize the need for RBC transfusion. Thereafter, hemoglobin should be monitored
at least monthly provided hemoglobin levels remain stable.
Patient Counseling Information
See FDA-approved patient
labeling (Medication Guide).
Prior to treatment, inform
patients of the risks and benefits of OMONTYS.
- To read the Medication Guide and to review and discuss
any questions or concerns with their healthcare provider before starting
OMONTYS and at regular intervals while receiving OMONTYS.
- Of the increased risks of
mortality, serious cardiovascular reactions, thromboembolic reactions, stroke, and tumor progression [see WARNINGS AND
- To undergo regular blood
pressure monitoring, adhere to prescribed anti-hypertensive regimen and follow
recommended dietary restrictions.
- To seek medical care
immediately if they experience any symptoms of
an allergic reaction with use of OMONTYS [see WARNINGS AND
- To contact their healthcare
provider for new-onset neurologic symptoms or change in seizure frequency.
- Of the need to have regular
laboratory tests for hemoglobin.
Administer OMONTYS under the
direct supervision of a healthcare provider or, in situations where a patient
has been trained to administer OMONTYS at home, provide instruction on the
proper use of OMONTYS, including instructions to:
- Carefully review the Medication Guide and the Instructions for Use
- Avoid the reuse of needles,
syringes, or unused portions of the OMONTYS single use vials or single use
pre-filled syringes and properly dispose of these items
- Always keep a puncture-proof disposal container available for the disposal of used
syringes and needles.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Peginesatide was not carcinogenic in a 2-year study in
rats at doses up to 0.25 mg/kg administered every 3 weeks by intravenous
injection. This dose is approximately 14% the human exposure (AUC) at a dose of
0.35 mg/kg in patients on dialysis. Peginesatide was not carcinogenic in a
26-week study in rasH2 transgenic mice when administered by intravenous
injection at doses of 0.1, 0.25, or 0.5 mg/kg/dose every 3 weeks.
Peginesatide was not mutagenic or clastogenic in the in
vitro Ames assay, in vitro mammalian chromosome aberration assay, and an
vivo mouse erythrocyte micronucleus assay.
When peginesatide was administered intravenously to male
and female rats at weekly intervals prior to and during mating, and treated
rats mated, fertility was reduced at ≥ 0.1 mg/kg (approximately 5% of the
dose of 0.35 mg/kg in patients) and was most evident at doses ≥ 1.0 mg/kg
of peginesatide. Adverse effects in males included reduced weight of seminal
vesicles and prostate. Decreased viable fetuses at ≥ 0.1 mg/kg in females
appeared to be due to pre- and post-implantation losses. There was no apparent
drug-related effect on estrous cycles or number of corpora lutea.
Use In Specific Populations
Pregnancy Category C
There are no adequate and
well-controlled studies in pregnant women. Peginesatide was teratogenic and
caused embryofetal lethality when administered to pregnant animals at doses
and/or exposures that resulted in polycythemia. OMONTYS should be used during
pregnancy only if the potential benefit justifies the potential risk to the
Administration of peginesatide
by intravenous injection to rats and rabbits during organogenesis was
associated with embryofetal toxicity and malformations. Dosing was every third
day in rats for a total of 5 doses and every fifth day in rabbits for a
total of 3 doses (0.01 to 50 mg/kg/dose). In rats and rabbits, adverse
embryofetal effects included reduced fetal weight, increased resorption,
embryofetal lethality, cleft palate (rats only), sternum anomalies,
unossification of sternebrae and metatarsals, and reduced ossification of some
bones. Embryofetal toxicity was evident in rats at peginesatide doses of ≥
1 mg/kg and the malformations (cleft palate and sternoschisis, and variations
in blood vessels) were mostly evident at doses of ≥ 10 mg/kg. The dose of
1 mg/kg results in exposures (AUC) comparable to those in humans after
intravenous administration at a dose of 0.35 mg/kg in patients on dialysis. In
a separate embryofetal developmental study in rats, reduced fetal weight and
reduced ossification were seen at a lower dose of 0.25 mg/kg. Reduced fetal
weight and delayed ossification in rabbits were observed at ≥ 0.5
mg/kg/dose of peginesatide. In a separate embryofetal developmental study in
rabbits, adverse findings were observed at lower doses and included increased
incidence of fused sternebrae at 0.25 mg/kg. The effects in rabbits were
observed at doses lower (5% - 50%) than the dose of 0.35 mg/kg in patients.
It is not known whether peginesatide is excreted in human
milk. Because many drugs are excreted into human milk, caution should be
exercised when OMONTYS is administered to a nursing woman.
The safety and efficacy of OMONTYS in pediatric patients
have not been established.
Of the total number of dialysis patients in Phase 3
clinical studies of OMONTYS, 32.5% were age 65 and over, while 13% were age 75
and over. No overall differences in safety or effectiveness were observed
between these subjects and younger subjects.