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Vafseo has a well-studied safety profile1
Vafseo was studied in ~2000 patients on dialysis with anemia due to CKD1,2
Vafseo was similar to an ESA† in time to first occurrence of MACE1,*
Noninferiority of Vafseo to darbepoetin alfa was established because the upper-bound of the 95% CI for the MACE hazard ratio was less than the prespecified, noninferiority margin of 1.25.1
Time to first MACE* in the pooled safety population of both dialysis trials2
TAP TO EXPAND
ROTATE DEVICE FOR LARGEST VIEW
MACE in the INNO2VATE trials (ITT analyses)1,‡
| Vafseo N=1947, PY=3134.4 | Darbepoetin alfa N=1955, PY=3164.0 | |
|---|---|---|
| First occurrence of MACE | 355 | 377 |
| All-cause mortality, n | 253 | 253 |
| Nonfatal myocardial infarction, n | 76 | 87 |
| Nonfatal stroke, n | 26 | 37 |
| MACE hazard ratio§ (95% CI) | 0.96 (0.83, 1.11) | |
| MACE incidence rate per 100 PY | 11.3 | 11.9 |
Adverse reactions (≥5%) in patients with anemia due to CKD on dialysis during the Incident Dialysis Trial (INNO2VATE-1) and Prevalent Dialysis Trial (INNO2VATE-2)1
| Adverse reactions | Vafseo N=1947 (%) | Darbepoetin alfa N=1955 (%) |
|---|---|---|
| Hypertension|| | 14 | 17 |
| Diarrhea | 13 | 10 |
| Headache|| | 9 | 8 |
| Nausea | 8 | 8 |
| Fatigue|| | 8 | 5 |
| Abdominal pain | 7 | 7 |
| Vomiting|| | 7 | 7 |
| GI erosion|| | 6 | 5 |
| Dizziness|| | 6 | 5 |
| Dyspnea|| | 6 | 7 |
| AV fistula thrombosis | 6 | 5 |
| Dialysis-related complication | 5 | 7 |
- Permanent treatment discontinuations due to
an adverse reaction1
- 4.9% of patients treated with Vafseo
- 1.1% of patients treated with darbepoetin alfa
- Gastrointestinal symptoms (nausea, vomiting, and diarrhea) resulted in permanent treatment discontinuation in 1.8% of patients treated with Vafseo1
||Grouped terms1:
- Hypertension includes hypertensive crisis, pre-eclampsia, and hypertensive encephalopathy
- Headache includes occipital neuralgia
- Fatigue includes asthenia, lethargy, and malaise
- Vomiting includes hematemesis
- Gastrointestinal erosion includes duodenal ulcers and perforation, gastrointestinal ulcers and perforation, esophageal ulcers and perforation, and unspecified site or hematemesis, gastrointestinal hemorrhage, helicobacter duodenitis and gastritis, melaena, and gastric hemorrhage
- Dizziness includes labyrinthitis, vertigo, vestibular neuronitis, and presyncope
- Dyspnea includes orthopnea and respiratory distress
AV=arteriovenous; CKD=chronic kidney disease; GI=gastrointestinal; PY=person years.
Vafseo clinical trials examined other safety outcomes including thrombotic vascular events1
Adjudicated thrombotic vascular events in adult patients
with CKD on dialysis
(fatal and nonfatal events)
in a pooled analysis1,¶
| Vafseo (N=1947) | Darbepoetin alfa (N=1955) | |
|---|---|---|
| Event | Rate per 100 PY# | Rate per 100 PY# |
| Vascular access thrombosis | 4.8 | 3.9 |
| Myocardial infarction | 2.9 | 2.8 |
| Stroke | 1.1 | 1.4 |
| Deep vein thrombosis | 0.5 | 0.6 |
| Pulmonary embolism | 0.2 | 0.3 |
| Arterial thrombosis | 0.2 | 0.1 |
- Adjudicated fatal and nonfatal thrombotic vascular events were observed in 9.0 per 100 PY of patients in the pooled Vafseo arm and in 8.7 per 100 PY of patients in the pooled darbepoetin alfa arm1
Meet Victor, a 65-year-old patient with anemia due to CKD who has been undergoing in-center dialysis for 6 months and whose Hb levels are not achieving the target range
“I am doing everything I can with my doctor to maintain my hemoglobin level, but it remains low.”
9.1 g/dL
Transferrin saturation=23% Serum ferritin=746 ng/mL
Hypothetical patient profile. Not an actual patient.
CKD=chronic kidney disease; ESA=erythropoiesis-stimulating agent; Hb=hemoglobin; IV=intravenous.
WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS
THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS.
VAFSEO increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE).
Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels.
No trial has identified a hemoglobin target level, dose of VAFSEO, or dosing strategy that does not increase these risks.
Use the lowest dose of VAFSEO sufficient to reduce the need for red blood cell transfusions.
CONTRAINDICATIONS
- Known hypersensitivity to VAFSEO or any of its components
- Uncontrolled hypertension
WARNINGS AND PRECAUTIONS
- Increased Risk of Death, Myocardial Infarction (MI), Stroke, Venous Thromboembolism, and Thrombosis of Vascular AccessA rise in hemoglobin (Hb) levels greater than 1 g/dL over 2 weeks can increase these risks. Avoid in patients with a history of MI, cerebrovascular event, or acute coronary syndrome within the 3 months prior to starting VAFSEO. Targeting a Hb level of greater than 11 g/dL is expected to further increase the risk of death and arterial and venous thrombotic events. Use the lowest effective dose to reduce the need for red blood cell (RBC) transfusions. Adhere to dosing and Hb monitoring recommendations to avoid excessive erythropoiesis.
- HepatotoxicityHepatocellular injury attributed to VAFSEO was reported in less than 1% of patients, including one severe case with jaundice. Elevated serum ALT, AST, and bilirubin levels were observed in 1.8%, 1.8%, and 0.3% of CKD patients treated with VAFSEO, respectively. Measure ALT, AST, and bilirubin before treatment and monthly for the first 6 months, then as clinically indicated. Discontinue VAFSEO if ALT or AST is persistently elevated or accompanied by elevated bilirubin. Not recommended in patients with cirrhosis or active, acute liver disease.
- HypertensionWorsening of hypertension was reported in 14% of VAFSEO and 17% of darbepoetin alfa patients. Serious worsening of hypertension was reported in 2.7% of VAFSEO and 3% of darbepoetin alfa patients. Cases of hypertensive crisis, including hypertensive encephalopathy and seizures, have also been reported in patients receiving VAFSEO. Monitor blood pressure. Adjust anti-hypertensive therapy as needed.
- SeizuresSeizures occurred in 1.6% of VAFSEO and 1.6% of darbepoetin alfa patients. Monitor for new-onset seizures, premonitory symptoms, or change in seizure frequency.
- Gastrointestinal (GI) ErosionGastric or esophageal erosions occurred in 6.4% of VAFSEO and 5.3% of darbepoetin alfa patients. Serious GI erosions, including GI bleeding and the need for RBC transfusions, were reported in 3.4% of VAFSEO and 3.3% of darbepoetin alfa patients. Consider this risk in patients at increased risk of GI erosion. Advise patients about signs of erosions and GI bleeding and urge them to seek prompt medical care if present.
- Serious Adverse Reactions in Patients with Anemia Due to CKD and Not on DialysisThe safety of VAFSEO has not been established for the treatment of anemia due to CKD in adults not on dialysis and its use is not recommended in this setting. In large clinical trials in adults with anemia of CKD who were not on dialysis, an increased risk of mortality, stroke, MI, serious acute kidney injury, serious hepatic injury, and serious GI erosions was observed in patients treated with VAFSEO compared to darbepoetin alfa.
- MalignancyVAFSEO has not been studied and is not recommended in patients with active malignancies. Malignancies were observed in 2.2% of VAFSEO and 3.0% of darbepoetin alfa patients. No evidence of increased carcinogenicity was observed in animal studies.
ADVERSE REACTIONS
- The most common adverse reactions (occurring at ≥ 10%) were hypertension and diarrhea.
DRUG INTERACTIONS
- Iron supplements and iron-containing phosphate binders: Administer VAFSEO at least 1 hour before products containing iron.
- Non-iron-containing phosphate binders: Administer VAFSEO at least 1 hour before or 2 hours after non-iron-containing phosphate binders.
- BCRP substrates: Monitor for signs of substrate adverse reactions and consider dose reduction.
- Statins: Monitor for statin-related adverse reactions. Limit the daily dose of simvastatin to 20 mg and rosuvastatin to 5 mg.
USE IN SPECIFIC POPULATIONS
- Pregnancy: May cause fetal harm.
- Lactation: Breastfeeding not recommended until two days after the final dose.
- Hepatic Impairment: Not recommended in patients with cirrhosis or active, acute liver disease
VAFSEO is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months.
Limitations of Use
- VAFSEO has not been shown to improve quality of life, fatigue, or patient well-being.
- VAFSEO is not indicated for use:
- As a substitute for red blood cell transfusions in patients who require immediate correction of anemia.
- In patients with anemia due to CKD not on dialysis.
Please note that this information is not comprehensive. Please click here for the Full Prescribing Information, including BOXED WARNING and Medication Guide.