peginesatide

(redirected from Omontys)

peginesatide

Omontys

Pharmacologic class: Erythropoiesis-stimulating agent (ESA)

Therapeutic class: Hematologic agent

Pregnancy risk category C

FDA Box Warning

Warning: ESAs increase risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence.

• In controlled trials, patients experienced greater risk of death, serious adverse CV reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dl.

• No trial has identified a hemoglobin target level, ESA dosage, or dosing strategy that doesn't increase these risks.

• Use the lowest dosage sufficient to reduce the need for RBC transfusions.

Action

Binds to and activates human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro; increases reticulocyte count, followed by increases in hemoglobin. Rate of hemoglobin increase varies among patients and is dependent on peginesatide dosage.

Availability

Solution for injection: 2 mg/0.5 ml, 3 mg/0.5 ml, 4 mg/0.5 ml, 5 mg/0.5 ml, 6 mg/0.5 ml in single-use vials; 1 mg/0.5 ml, 2 mg/0.5 ml, 3 mg/0.5 ml, 4 mg/0.5 ml, 5 mg/0.5 ml, 6 mg/0.5 ml in prefilled syringes; 10 mg/ml, 20 mg/2 ml in multi-use vials

Indications and dosages

Anemia caused by chronic kidney disease in patients on dialysis

Adults: Initially when hemoglobin level is less than 10 g/dl, 0.4 mg/kg subcutaneously or I.V. once monthly. When converting from another ESA, give once monthly based on total weekly epoetin or darbepoetin alfa dose at time of conversion.

Dosage adjustment

• Based on hemoglobin level

Contraindications

• Uncontrolled hypertension

Precautions

Use cautiously in:
• patients with chronic kidney disease and an insufficient hemoglobin response
• patients with chronic kidney disease not on dialysis
• coexistent CV disease and stroke, controlled hypertension
• anemia due to cancer chemotherapy (not indicated)
• patients undergoing coronary artery bypass graft surgery or orthopedic procedures
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Don't dilute drug or administer with other drug solutions.
• Evaluate transferrin saturation and serum ferritin level before starting drug; administer supplemental iron therapy when serum ferritin level is less than 100 mcg/L or when serum transferrin saturation is less than 20%, as prescribed. Be aware that other causes of anemia (such as vitamin deficiency, metabolic or chronic inflammatory conditions, or bleeding) should be corrected or excluded before initiating drug.
• Monitor hemoglobin level at least every 2 weeks until stable. When adjusting therapy, consider hemoglobin rate of rise, rate of decline, ESA responsiveness, and hemoglobin variability; be aware that a single hemoglobin excursion may not require a dosing change. Don't increase dosage more frequently than once every 4 weeks.

Be aware that for patient who doesn't respond adequately over a 12-week escalation period, increasing dosage further is unlikely to improve response and may increase risks. Drug should be used at the lowest dosage that will maintain a hemoglobin level sufficient to reduce need for RBC transfusions. Discontinue drug if responsiveness doesn't improve.

Be aware that using ESAs to target a hemoglobin level greater than 11 g/dl increases risk of serious adverse CV reactions and hasn't been shown to provide additional benefits. Ensure that patient's hypertension is under control before starting treatment. Reduce dosage or withhold drug if blood pressure becomes difficult to control.

Be aware that patients with cancer receiving ESAs or patients undergoing coronary artery bypass graft surgery may be at increased risk for serious CV adverse reactions or death; patients undergoing orthopedic procedures may be at risk for deep vein thrombosis; and patients with chronic kidney disease not on dialysis may be at increased risk for CV events.
• Be aware that the presence of peginesatide-specific binding antibodies is associated with declining hemoglobin levels and may require increased drug dosages to maintain hemoglobin levels or transfusion for anemia of chronic kidney disease.

Discontinue drug and administer appropriate therapy if a serious allergic reaction occurs.

Adverse reactions

CNS: headache, seizures, stroke

CV: procedural hypotension, hypotension, hypertension, congestive heart failure (CHF), myocardial infarction (MI)

GI: nausea, vomiting, diarrhea

Hematologic: thromboembolism

Metabolic: hyperkalemia

Musculoskeletal: muscle spasms, extremity pain, back pain, arthralgia

Respiratory: dyspnea, cough, upper respiratory tract infection

Other: arteriovenous fistula-site complications, pyrexia, peginesatide-specific binding antibodies, allergic reactions, increased mortality

Interactions

Drug-diagnostic tests.Potassium: increased level

Patient monitoring

• Continue to monitor hemoglobin level at least monthly provided hemoglobin level remains stable.
• Continue to evaluate transferrin saturation and serum ferritin level during treatment and to administer supplemental iron as prescribed.

During first several months after drug initiation, closely monitor patient for neurologic symptoms; appropriately control hypertension; and watch for such CV events as stroke, MI, and CHF.
• Be aware that patient receiving peginesatide may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis.

Patient teaching

• If patient will self-administer drug, tell him to follow exact directions for injection, storage, and proper disposal of needles and syringes.

Advise patient to immediately report allergic reactions; new-onset seizures, premonitory symptoms, or change in seizure frequency; and CV signs and symptoms.
• Advise patient of importance of having blood tests and blood pressure checks, and of compliance with antihy-pertensive therapy, iron supplements, and dietary restrictions.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.

peginesatide

(peg-in-es-a-tide ) ,

Omontys

(trade name)

Classification

Therapeutic: antianemics
Pharmacologic: temporary class
Pregnancy Category: C

Indications

Treatment of anemia due to chronic kidney disease (CKD) in adults who are currently being dialyzed. Should not be used to treat other causes of anemia or as substitute for RBC transfusions in acute situations.

Action

Binds to/activates the human erythropoietin receptor, stimulating production of RBC precursors.

Therapeutic effects

Increased reticulocyte count and hemoglobin with decreased need for RBC transfusions.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability. 46% absorbed following subcutaneous administration.
Distribution: Unknown.
Metabolism and Excretion: Not metabolized, excreted in urine.
Half-life: Healthy subjects—25 hr, dialysis patients—48 hr.

Time/action profile

ROUTEONSETPEAK†DURATION‡
IV, Subcutunknown48 hr1 mo
† Following subcutaneous administration.‡ Effects on Hgb.

Contraindications/Precautions

Contraindicated in: Uncontrolled hypertension;Hypersensitivity.
Use Cautiously in: Hypertension (control prior to and during treatment); Other causes of anemia (exclude and/or treat), evaluate/maintain iron repletion; History of cancer; History seizures; Lactation: Use with extreme caution in nursing women; Obstetric: Use during pregnancy only if potential benefit justifies potential risk to the fetus; Pediatric: safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • seizures (life-threatening)
  • headache (most frequent)

Respiratory

  • cough (most frequent)
  • dyspnea

Cardiovascular

  • myocardial infarction (life-threatening)
  • stroke (life-threatening)
  • thromboembolism (life-threatening)
  • hypotension
  • vascular access thrombosis

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis, hypotension, bronchospasm, angioedema, and pruritis
  • arteriovenous fistula site complication (most frequent)
  • tumor progression/recurrence

Interactions

Drug-Drug interaction

Need for heparin in the extracorporeal circuit may be ↑.

Route/Dosage

Intravenous Subcutaneous (Adults) 0.04 mg/kg once monthly; initiate only when hemoglobin is <10 g/dL; use lowest possible dose shown to ↓ the need for RBC transfusions. Doses should not be altered more often than once monthly. If Hgb ↑ by more than 1 g/dL in the 2 wk before a dose or more than 2g/dL in the 4 wk prior to a dose, dose should be ↓ by 25% or more as required to ↓ rapid response. If Hgb ≥11 g/dL, interrupt or reduce treatment to 25% or previous dose. If Hgb has not ↑ by >1 g/dL after 4 wk of treatment, dose may be ↑ 25%, if no improvement in seen in 12 wk of treatment, other causes of anemia should be investigated.

Availability

Injection for intavenous or subcutaneous injection: Single use vials 2 mg/0.5 mL, 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, 6 mg/0.5 mL, Single use pre-filled syringes 1 mg/0.5 mL, 2 mg/0.5 mL, 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, 6 mg/0,5 mL, Multiple-use vials 10 mg/mL, 20 mg/mL (contains preservative)

Nursing implications

Nursing assessment

  • Monitor BP before and during therapy. Inform health care professional if severe hypertension is present or if BP begins to increase. Additional antihypertensive therapy may be required during initiation of therapy. Reduce or withhold therapy if BP becomes difficult to control.
  • Monitor for signs and symptoms of anaphylaxis (hypotension, bronchospasm, angioedema, generalized pruritus). Permanently discontinue therapy and treat symptomatically if symptoms occur.
  • Monitor for symptoms of anemia (fatigue, dyspnea, pallor).
  • Monitor dialysis shunts (thrill and bruit) and status of artificial kidney during hemodialysis. Heparin dose may need to be increased to prevent clotting. Monitor patients with underlying vascular disease for impaired circulation.
  • Lab Test Considerations: Monitor hemoglobin levels at least every 2 wks until stable, then at least monthly. Do not ↑ dose more frequently than once every 4 wks. If hemoglobin rises >1 g/dL in the 2 wks prior to dose or more than 2 g/dL in 4 wks, ↓ dose by 25% or more as needed to reduce rapid response. If hemoglobin level approaches or exceeds 11 g/dL, ↓ or interrupt dose of peginesatide. After dose withheld and hemoglobin ↓, may restart at a dose 25% below previously administered dose. If hemoglobin does not ↑ by >1 g/dL after 4 wks of therapy, ↑ dose by 25%. If inadequate response after 12 wks, increasing dose further is unlikely to improve response and may increase risks. Use lowest dose that will maintain Hgb level sufficient to reduce need for transfusions.
    • May cause ↑ in WBCs and platelets. May ↓ bleeding times.
    • Monitor serum ferritin, transferrin, and iron levels to assess need for concurrent iron therapy. Correct other causes of anemia before initiating peginesatide. Transferrin saturation should be at least 20% and ferritin should be at least 100 ng/mL.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • When converting from epoetin or darbepoetin, dose of peginesatide is based on previous dose of epoetin or darbepoetin (see manufacturer's guide). For patients previously receiving epoetin, administer first dose of peginesatide 1 wk after last dose of epoetin. For patients previously receiving darbepoetin, administer first dose of peginesatide at the next scheduled dose in place of darbepoetin.
    • If a dose is missed, administer as soon as possible and restart peginesatide at monthly dose frequency.
  • Subcut: Do not dilute or administer with other solutions. Solution should be colorless to slightly yellow; do not administer solution that is discolored or contains particulate matter. Pre-filled syringes and single vials are single use; discard unused portion. Multi-use vials may be stored in refrigerator for 28 days after first use.

Patient/Family Teaching

  • Advise patient to read the Medication Guide prior to initiating therapy and with each Rx refill in case of changes.
  • Explain rationale for BP control (monitoring, antihypertensive therapy, compliance with diet restrictions) and concurrent iron therapy (increased red blood cell production requires iron).
    • Discuss ways of preventing self-injury in patients at risk for seizures. Driving and activities requiring continuous alertness should be avoided.
    • Advise patient to notify health care professional immediately if signs of blood clots (chest pain, trouble breathing or shortness of breath, pain in the legs, with or without swelling; a cool or pale arm or leg, sudden confusion, trouble speaking or trouble understanding others’ speech, sudden numbness or weakness in the face, arm, or leg, especially on one side of the body, sudden trouble seeing, sudden trouble walking, dizziness, loss of balance or coordination, loss of consciousness or fainting, hemodialysis vascular access stops working) or anaphylaxis occur.
    • Advise patient to inform health care professional of medication prior to treatment or surgery.
    • Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
  • Anemia of Chronic Renal Failure: Stress importance of compliance with dietary restrictions, medications, and dialysis. Foods high in iron and low in potassium include liver, pork, veal, beef, mustard and turnip greens, peas, eggs, broccoli, kale, blackberries, strawberries, apple juice, watermelon, oatmeal, and enriched bread.
  • Home Care Issues: Home dialysis patients determined to be able to safely and effectively administer peginesatide should be taught proper dosage, administration technique, and disposal of equipment.

Evaluation/Desired Outcomes

  • Increase in hematocrit with improvement in symptoms of anemia in patients with chronic renal failure.
References in periodicals archive ?
The launch of three new pipeline drugs, ferric citrate, Omontys (peginesatide), and Nulojix (belatacept), is expected to boost the market.
and Takeda Pharmaceutical Company Limited (Takeda) announced today that their Omontys (peginesatide) product collaboration and license agreement will terminate effective September 10, 2014.
Recent recall of Omontys (erythropoietic agent) due to severe anaphylactic reactions serves a tragic example of lack of predictability of animal testing.
Drugmaker Affymax Inc said it was considering selling itself or filing for bankruptcy among a range of alternatives, as it struggles to stay afloat following the recent recall of its sole commercial product, the anemia drug Omontys.
Affymax is a California-based biopharmaceutical company whose primary drug offering is Omontys (peginesatide) Injection for the treatment of anemia in chronic kidney disease in adult patients on dialysis.
Peginesatide, which will be marketed as Omontys by Affymax, is administered once a month, intravenously or subcutaneously.
Affymax has developed Omontys (also known as peginesatide), an injection for the treatment of anemia due to chronic kidney disease in adult patients on dialysis.
The Omontys product partnership would be ended by Affymax Inc.
Enzon receives royalty revenues on seven marketed products that utilize its proprietary Customized PEGylation Linker Technology (Customized Linker Technology) platform, namely PegIntron, Sylatron, Macugen, CIMZIA, OMONTYS, Oncaspar and Adagen.
Finkelstein Thompson's investigation relates to the recent announcement by Affymax and partner Takeda Pharmaceutical that they were voluntarily recalling all lots of Omontys, Affymax's flagship anemia drug.
Following the Voluntary Recall of the ESA Omontys, Surveyed Nephrologists are Less Likely to Prescribe a New ESA Compared With Descriptions of Other Likely Future Renal Anemia Products, According to a New Report from BioTrends Research Group
Nasdaq: AFFY) violated state or federal laws when communicating serious side effects and the subsequent voluntary recall of its anemia drug, Omontys, in February 2013.