Generic Name: Oprelvekin
Class: Hematopoietic Agents
VA Class: BL400
Chemical Name: 2-178-Interleukin 11 (human clone pXM/IL-11)
Molecular Formula: C854H1411N253O235S2
CAS Number: 145941-26-0
Uses for Neumega
Neumega Dosage and Administration
Do not rub injection sites.2
Initiate oprelvekin 6–24 hours following completion of chemotherapy.1 Safety and efficacy of administering immediately prior to or concurrently with chemotherapy, or at the time of the expected platelet nadir, not established.1
If a dose is missed, resume next scheduled dose at the appropriate time; do not double a dose.2
Intended for use under the guidance and supervision of a clinician, but may be self-administered if clinician determines that patient and/or caregiver is competent to prepare and safely administer the drug.1
50 mcg/kg daily.1 3 Administer first dose 6–24 hours following completion of chemotherapy and continue until platelet counts ≥50,000/mm3.1 3 Do not exceed 21 days of treatment per chemotherapy cycle.1 3 17
Discontinue oprelvekin at least 2 days prior to next cycle of chemotherapy.1
Limited experience with doses >50 mcg/kg; may be associated with increased risk of cardiovascular events.1 (See Cardiovascular Effects under Cautions.)
Recommended maximum duration of therapy for each course of treatment is 21 days.1
Reduce dosage to 25 mcg/kg daily in patients with severe renal impairment (Clcr<30 mL/minute, as estimated from Scr).1 (See Absorption: Special Populations, under Pharmacokinetics.)
Cautions for Neumega
Known hypersensitivity to oprelvekin or any ingredient in the formulation.1
Fluid retention, usually a result of increased sodium and water retention, reported.1 3 7 10 12 15 Clinical manifestations range from mild to moderate peripheral edema to more severe conditions (e.g., pulmonary edema, capillary leak syndrome, atrial arrhythmias, development or exacerbation of pleural or pericardial effusion).1 2 3 5 6 7 10 14 15 Fluid retention usually develops within first few weeks of therapy and may continue for the duration of therapy.1 6 In most cases, edema is self-limiting and resolves within several days after drug discontinuance.1 2 6
Serious, sometimes fatal, cases of fluid retention reported in patients who received oprelvekin following bone marrow transplantation.1 3 17 Do not use oprelvekin in patients undergoing myeloablative chemotherapy.1
Use with caution in patients with CHF or who may be susceptible to developing CHF (e.g., history of heart failure even if well compensated and receiving appropriate medical management).1 3 10 Also use caution in those with other conditions or treatments that may precipitate or exacerbate fluid retention (e.g., pleural effusions, aggressive hydration, concomitant drugs known to cause edema).1 10 14 Closely monitor fluid status and initiate appropriate treatment if fluid imbalance occurs.1 14 Monitor preexisting fluid collections (e.g., pericardial effusions, ascites) and consider drainage if indicated.1
Monitor fluid and electrolyte status carefully in patients receiving maintenance therapy with diuretics.10 12 14 Sudden death has occurred in at least 2 patients who developed severe hypokalemia (<3 mEq/L) while receiving diuretic therapy concomitantly with ifosfamide and oprelvekin.1 3
Moderate decreases in hemoglobin, hematocrit, and RBCs reported, principally because of fluid retention and hemodilution.1 6 12 16 (See Fluid Retention under Cautions.) Usually manifests within 3–5 days following initiation of therapy and reverses over approximately 1 week upon drug discontinuance.1 3 Monitor CBC prior to chemotherapy and periodically during therapy.1
Reversible increases in plasma fibrinogen (e.g., twofold increase), haptoglobin, and other acute-phase reactants (e.g., C-reactive protein) observed.1 6 16 17 Increased concentrations of Von Willebrand factor (with normal multimer pattern) also reported in healthy individuals who received oprelvekin.1
Atrial arrhythmias (fibrillation or flutter) reported in about 10–15% of patients, in some cases resulting in stroke.1 5 7 10 14 15 17 Such arrhythmias are usually transient and convert to normal sinus rhythm spontaneously or with rate-control therapy.1 14 Cardiac arrest also reported, but causal relationship to drug uncertain.1
Use with caution in patients with a history of cardiac arrhythmias, including atrial and ventricular arrhythmias.1 3 Carefully consider potential risks versus benefits of therapy.1 Doses >50 mcg/kg may increase risk of adverse cardiovascular effects.1
Possible development or worsening of papilledema.1 2 3 11 13 14 Generally resolves upon drug discontinuance.1 3 11 13 14 17 Risk may increase with high dosages (e.g., >50 mcg/kg daily).11 13 Higher incidence of papilledema observed in children (16%) compared with adults (1%) in clinical trials.1 3 13 (See Pediatric Use under Cautions.) Use with caution in patients with preexisting papilledema or CNS tumors.1 3
Renal failure reported during postmarketing experience in patients who received oprelvekin following bone marrow transplantation.1 Do not use oprelvekin in patients undergoing myeloablative chemotherapy.1
Serious hypersensitivity reactions, including anaphylaxis and shock, reported during postmarketing experience.1 (See Boxed Warning.) Reported reactions include edema of the face, tongue, or larynx; dyspnea; wheezing; chest pain; hypotension (including shock); dysarthria; loss of consciousness; mental status changes; rash; urticaria; flushing; and fever.1 Such reactions can occur after initial administration or at any time during therapy.1 3 Take appropriate precautionary measures in case of hypersensitivity reactions (e.g., immediate availability of antihistamines, epinephrine, oxygen, corticosteroids).3
Advise patient regarding potential manifestations of hypersensitivity for which they should seek immediate medical attention.1 (See Advice to Patients.) Permanently discontinue therapy if allergic or hypersensitivity-type reactions occur.1 3
Perform CBC prior to chemotherapy and at regular intervals during therapy.1 (See Hematologic Effects under Cautions.)
Monitor platelet counts at time of expected nadir and continue monitoring until platelet counts recover to ≥50,000/mm3.1
Monitor fluid status.1 (See Fluid Retention under Cautions.)
Evaluated in a limited number of patients 8 months to 18 years of age.1 13 Pharmacokinetic studies suggest higher than recommended dosages may be necessary to achieve therapeutic effect in children and adolescents; however, dosages >50 mcg/kg daily have been associated with increased risk of adverse effects (i.e., papilledema, periosteal bone changes.)1 3 13 (See Absorption: Special Populations, under Pharmacokinetics.)
Long-term effects of oprelvekin on bone growth and development in children not established.1 Limited data in animals suggest possible adverse effects on bone, joints, and tendons (e.g., thickening of femoral and tibial growth plates, joint and tendon fibrosis, periosteal hyperostosis).1
Possible increased serum concentrations and systemic exposure to oprelvekin.1 (See Absorption: Special Populations, under Pharmacokinetics.) Reduce dosage in patients with severe renal impairment (Clcr <30 mL/minute).1 (See Dosage in Renal Impairment under Dosage and Administration.)
A substantial decrease in hemoglobin observed on day 2 of oprelvekin therapy in patients with any degree of renal impairment.1 (See Hematologic Effects under Cautions.)
Effects of oprelvekin on fluid retention in patients with renal impairment not established; carefully monitor fluid balance in such patients.1 (See Fluid Retention under Cautions.)
Common Adverse Effects
Adverse effects reported in at least 10% of patients receiving oprelvekin in clinical trials and significantly more often than with placebo1 3 include edema,1 7 10 14 16 17 tachycardia,1 7 10 palpitations,1 7 atrial fibrillation/flutter,1 5 7 10 14 15 17 oral moniliasis,1 dyspnea,1 7 10 14 pleural effusions,1 10 14 and conjunctival injection.1 12 14
Interactions for Neumega
Closely monitor electrolytes1
In patients with severe renal impairment (Clcr <30 mL/minute), mean AUC and peak plasma concentrations are approximately 2.6- and 2.2-fold higher, respectively, than in individuals with normal renal function.1 Clearance in severe renal impairment approximately 40% of that observed in individuals with normal renal function.1 No substantial change in pharmacokinetic parameters observed in patients with mild or moderate renal impairment compared with those with normal renal function.1
In infants, children, and adolescents 8 months to 18 years of age receiving a 50 mcg/kg dose, mean AUC approximately half that observed in adults.1 13 Limited data suggest children <12 years of age may not achieve adequate plasma concentrations with recommended dosages (50 mcg/kg daily).11 (See Pediatric Use under Cautions.)
Powder for Injection
A thrombopoietic growth factor structurally and functionally similar to endogenous human interleukin-11 (IL-11); lacks only amino-terminal proline residue of endogenous IL-11.1 8 9 10 No measurable difference in biologic activity in vivo or in vitro compared with endogenous IL-11.1 8 10
Stimulates multiple stages of the hematopoietic pathway.5 6 10 16 Binds directly to IL-11 receptors on myeloid progenitor cell surfaces and stimulates production of erythrocytes, platelets, neutrophils, and macrophages within the bone marrow.5 6 10 16 18
Principally affects megakaryocytopoiesis.1 3 10 Produces a dose-dependent increase in platelet counts by stimulating the proliferation and differentiation of megakaryocyte progenitor cells in synergy with other growth factors (e.g., interleukin-3 [IL-3], thrombopoietin [TPO], stem cell factor [SCF]).1 3 5 6 7 10 12 13 14 15 16 18
Non-hematologic effects include regulation of intestinal epithelium growth, inhibition of adipogenesis, stimulation of synthesis of acute phase reactants, modulation (e.g., inhibition) of pro-inflammatory cytokines, and stimulation of osteoclastogenesis and neurogenesis.1 6 10 12 16
Advice to Patients
Risk of fluid retention; importance of immediately informing clinician if swelling in hands or feet, rapid weight gain, shortness of breath, or difficulty breathing occurs; importance of informing clinician of preexisting heart failure or concurrent therapy with medications that can cause fluid retention.1 2
Importance of recognizing symptoms of allergic or hypersensitivity reactions (e.g., swelling of the face, tongue, or throat; tightness in throat; difficulty breathing, swallowing, or talking; shortness of breath; wheezing; chest pain; lightheadedness; loss of consciousness; confusion; drowsiness; rash; itching; hives; flushing; fever), and immediately informing clinician if any of these symptoms occur.1 2
Importance of informing clinician if any swelling or bruising persists at injection site.2
Importance of providing copy of manufacturer's patient information if drug is being self-administered.2 Instruct patient and/or caregiver regarding proper dosage and administration of oprelvekin, including use of aseptic technique and safe disposal of needles and syringes (e.g., using puncture-resistant container).1 2
Importance of not taking a double dose to make up for a missed dose but instead taking the next scheduled dose at appropriate time.2
Importance of informing clinicians of existing or contemplated concomitant therapy (e.g., diuretics), including prescription and OTC drugs as well as any concomitant illnesses (e.g., CHF, renal impairment, papilledema).1 2
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection, for subcutaneous use only
Neumega (preservative-free; available with 1 mL sterile water for injection diluent)
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions December 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
1. Wyeth. Neumega (oprelvekin) for injection prescribing information. Philadelphia, PA; 2006 Sep.
2. Wyeth. Neumega (oprelvekin) for injection patient information. Philadelphia, PA; 2006 Sep.
3. Wyeth, Philadelphia, PA: Personal communication.
4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site. Accessed 2008 Feb 14.
5. Demetri GD. Targeted approaches for the treatment of thrombocytopenia.Oncologist. 2001; 6 (Suppl 5):15-23. [PubMed 11700388]
6. Gordon MS, McCaskill-Stevens WJ, Battiato LA et al. A phase I trial of recombinant interleukin-11 (Neumaga rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.Blood. 1996; 87:3615-24. [PubMed 8611685]
7. Tepler I, Elias L, Smith JW II et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy.Blood. 1996; 87:3607-14. [PubMed 8611684]
8. Aoyama K, Uchida T, Takanuki F et al. Pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male subjects.Br J Clin Pharmacol. 1997; 43:571-8. [PubMed 9205816]
9. Oprelvekin. In: Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005: 1211-2.
10. Adams VR, Brenner TL. Oprelvekin (Neumega).J Oncol Pharm Practice. 1999; 5:117-24.
11. Marder HK. Dear healthcare professional letter regarding important change to the safety information for Neumega(oprelvekin) use in the pediatric population. Philadelphia, PA: Wyeth; 2001.
12. Dykstra KH, Rogge H, Stone A et al. Mechanism and amelioration of recombinant human interleukin-11 (rhIL-11)-induced anemia in healthy subjects.J Clin Pharmacol. 2000; 40:880-8. [PubMed 10934673]
13. Cairo MS, Davenport V, Bessmertny O et al. Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study.Br J Haematol. 2005; 128:49-58. [PubMed 15606549]
14. Isaacs C, Robert NJ, Bailey FA et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin.J Clin Oncol. 1997; 15:3368-77. [PubMed 9363868]
15. Anon. New biotech product approved to reduce need for chemotherapy-related platelet transfusions. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 1997 Nov 25.
16. Du X, Williams DA. Interleukin-11: Review of molecular, cell biology, and clinical use.Blood. 1997; 89:3897-908. [PubMed 9166826]
17. Bhatia M, Davenport V, Cairo SM. The role of interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with solid tumors, lymphoma, acute myeloid leukemia and bone marrow failure syndromes.Leuk Lymphoma. 2007; 48:9-15. [PubMed 17325843]
18. Weich NS, Wang A, Fitzgerald M et al. Recombinant human interleukin-11 directly promotes megakaryocytopoiesis in vitroBlood. 1997; 90:3893-902.