Interleukin eleven (IL-11) is a thrombopoietic growth factor that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. IL-11 is a member of a family of human growth factors which includes human growth hormone, granulocyte colony-stimulating factor (G-CSF), and other growth factors.
Oprelvekin, the active ingredient in Neumega, is produced in Escherichia coli ( E. coli ) by recombinant DNA methods. The protein has a molecular mass of approximately 19,000 daltons, and is non-glycosylated. The polypeptide is 177 amino acids in length and differs from the 178 amino acid length of native IL-11 only in lacking the amino-terminal proline residue. This alteration has not resulted in measurable differences in bioactivity either in vitro or in vivo .
Neumega is available for subcutaneous administration in single-use vials containing 5 mg of Oprelvekin (specific activity approximately 8 × 10 6 Units/mg) as a sterile, lyophilized powder with 23 mg Glycine, USP, 1.6 mg Dibasic Sodium Phosphate Heptahydrate, USP, and 0.55 mg Monobasic Sodium Phosphate Monohydrate, USP. When reconstituted with 1 mL of Sterile Water for Injection, USP, the resulting solution has a pH of 7.0 and a concentration of 5 mg/mL.
The primary hematopoietic activity of Neumega is stimulation of megakaryocytopoiesis and thrombopoiesis. Neumega has shown potent thrombopoietic activity in animal models of compromised hematopoiesis, including moderately to severely myelosuppressed mice and nonhuman primates. In these models, Neumega improved platelet nadirs and accelerated platelet recoveries compared to controls.
Preclinical studies have shown that mature megakaryocytes which develop during in vivo treatment with Neumega are ultrastructurally normal. Platelets produced in response to Neumega were morphologically and functionally normal and possessed a normal life-span.
IL-11 has also been shown to have non-hematopoietic activities in animals including: the regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), the inhibition of adipogenesis, the induction of acute phase protein synthesis, inhibition of pro-inflammatory cytokine production by macrophages, and the stimulation of osteoclastogenesis and neurogenesis.
IL-11 is produced by bone marrow stromal cells and is part of the cytokine family that shares the gp130 signal transducer. Primary osteoblasts and mature osteoclasts express mRNAs for both IL-11 receptor (IL-11R alpha) and gp130. Both bone-forming and bone-resorbing cells are potential targets of IL-11. (1)
The pharmacokinetics of Neumega have been evaluated in studies in healthy, adult subjects and oncology patients receiving chemotherapy. In a study in which a single 50 µg/kg subcutaneous dose was administered to eighteen men, the peak serum concentration (Cmax) of 17.4±5.4 ng/mL (mean ± S.D.) was reached at 3.2±2.4 hrs (Tmax) following dosing. The terminal half life was 6.9±1.7 hrs. In a second study in which single 75 µg/kg subcutaneous and intravenous doses were administered to twenty-four healthy subjects, the pharmacokinetic profiles were similar between men and women. The absolute bioavailability of Neumega was >80%. In a study in which multiple, subcutaneous doses of both 25 and 50 µg/kg were administered to cancer patients receiving chemotherapy, Neumega did not accumulate and clearance of Neumega was not impaired following multiple doses.
Neumega was also administered to twenty-eight infants, children, and adolescents receiving ICE (ifosfamide, carboplatin, etoposide) chemotherapy. Analysis of data from twenty-three pediatric patients showed that Cmax and Tmax were comparable to the adult population. The mean ± S.D. area under the concentration-time curve (AUC) for pediatric patients (8 months to 17 years), receiving 50 µg/kg or 100 µg/kg was 137±56 ng*hr/mL or 237±20 ng*hr/mL, respectively, compared with 189±41 ng*hr/mL in adults receiving 50 µg/kg. Available data suggest that clearance of IL-11 decreases with patient age, and that clearance in infants and children (8 months to 11 years) is approximately 1.2 to 1.6 fold higher than adults and adolescents (ages 12 and over).
In preclinical studies in rats, radiolabeled Neumega was rapidly cleared from the serum and distributed to highly perfused organs. The kidney was the primary route of elimination. The amount if intact Neumega in urine was low, indicating that the molecule was metabolized before excretion. In a clinical study, a single dose of Neumega was administered to subjects with severely impaired renal function (creatinine clearance < 15 mL/min). The mean ± S.D. values for Cmax and AUC were 30.8 ± 8.6 ng/mL and 373 ± 106 ng*hr/mL, respectively. When compared with control subjects in this study with normal renal function, the mean Cmax was 2.2 fold higher and the mean AUC was 2.6 fold (95% confidence interval 1.7-3.8) higher in the subjects with severe renal impairment. In the subjects with severe renal impairment, clearance was approximately 40% of the value seen in subjects with normal renal function. The average terminal half-life was similar in subjects with severe renal impairment and those with normal renal function.
In a study in which Neumega was administered to non-myelosuppressed cancer patients, daily subcutaneous dosing for 14 days with Neumega increased the platelet count in a dose-dependent manner. Platelet counts began to increase relative to baseline between 5 and 9 days after the start of dosing with Neumega. After cessation of treatment, platelet counts continued to increase for up to 7 days then returned toward baseline within 14 days. No change in platelet reactivity as measured by platelet activation in response to ADP, and platelet aggregation in response to ADP, epinephrine, collagen, ristocetin and arachidonic acid has been observed in association with Neumega treatment.
In a randomized, double-blind, placebo-controlled study in normal volunteers, subjects receiving Neumega had a mean increase in plasma volume of >20%, and all subjects receiving Neumega had at least a 10% increase in plasma volume. Red blood cell volume decreased similarly (due to repeated phlebotomy) in the Neumega and placebo groups. As a result, whole blood volume increased approximately 10% and hemoglobin concentration decreased approximately 10% in subjects receiving Neumega compared with subjects receiving placebo. Mean 24 hour sodium excretion decreased, and potassium excretion did not increase, in subjects receiving Neumega compared with subjects receiving placebo.
Two randomized, double-blind, placebo-controlled trials studied Neumega for the prevention of severe thrombocytopenia following single or repeated sequential cycles of various myelosuppressive chemotherapy regimens.
One study evaluated the effectiveness of Neumega in eliminating the need for platelet transfusions in patients who had recovered from an episode of severe chemotherapy-induced thrombocytopenia (defined as a platelet count </=20,000/µL), and were to receive one additional cycle of the same chemotherapy without dose reduction. Patients had various underlying non-myeloid malignancies, and were undergoing dose-intensive chemotherapy with a variety of regimens. Patients were randomized to receive Neumega at a dose of 25 µg/kg or 50 µg/kg, or placebo. The primary endpoint was whether the patient required one or more platelet transfusions in the subsequent chemotherapy cycle. Ninety-three patients were randomized. Five patients withdrew from the study prior to receiving study drug. As a result, eighty-eight patients were included in a modified intent-to-treat analysis. The results for the Neumega 50 µg/kg and placebo groups are summarized in Table 1. The placebo group includes one patient who underwent chemotherapy dose reduction and who avoided platelet transfusions.
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In the primary efficacy analysis, more patients avoided platelet transfusion in the Neumega 50 µg/kg arm than in the placebo arm (p=0.04, Fisher' Exact test, 2-tailed). The difference in the proportion of patients avoiding platelet transfusions in the Neumega 50 µg/kg and placebo groups was 21% (95% confidence interval 2 to 40%). The results observed in patients receiving 25 µg/kg of Neumega were intermediate between those of the placebo and the 50 µg/kg groups.
A second study evaluated the effectiveness of Neumega in eliminating platelet transfusions over two dose-intensive chemotherapy cycles in breast cancer patients who had not previously experienced severe chemotherapy-induced thrombocytopenia. All patients received the same chemotherapy regimen (cyclophosphamide 3,200 mg/m 2 and doxorubicin 75 mg/m 2 ). All patients received concomitant Filgrastim (G-CSF) in all cycles. The patients were stratified by whether or not they had received prior chemotherapy, and randomized to receive Neumega 50 µg/kg or placebo. The primary endpoint was whether or not a patient required one or more platelet transfusions in the two study cycles. Seventy-seven patients were randomized. Thirteen patients failed to complete both study cycles--eight of these had insufficient data to be evaluated for the primary endpoint. The results of this trial are summarized in Table 2.
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This study showed a trend in favor of Neumega, particularly in the subgroup of patients with prior chemotherapy. Open-label treatment with Neumega has been continued for up to four consecutive chemotherapy cycles without evidence of any adverse effect on the rate of neutrophil recovery or red blood cell transfusion requirements. Some patients continued to maintain platelet nadirs >20,000 cells/µL for at least four sequential cycles of chemotherapy without the need for transfusions, chemotherapy dose reduction, or changes in treatment schedules.
Platelet activation studies done on a limited number of patients showed no evidence of abnormal spontaneous platelet activation, or an abnormal response to ADP. In an unblinded, retrospective analysis of the two placebo-controlled studies, 19 of 69 patients (28%) receiving Neumega 50 µg/kg and 34 of 67 patients (51%) receiving placebo reported at least one hemorrhagic adverse event which involved bleeding.
In a randomized, double-blind, placebo-controlled, phase 2 study conducted in patients who received autologous bone marrow transplantation following myeloablative chemotherapy, the incidence of platelet transfusions and time to neutrophil and platelet engraftment were similar in the Neumega and placebo-treated arms.
In long term follow-up of patients, the distribution of survival and progression-free survival times was similar between patients randomized to Neumega therapy and those randomized to receive placebo.
Neumega is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia. Efficacy was demonstrated in patients who had experienced severe thrombocytopenia following the previous chemotherapy cycle. Neumega is not indicated following myeloablative chemotherapy.
Neumega is contraindicated in patients with a history of hypersensitivity to Neumega or any component of the product.
Neumega is known to cause fluid retention (see : Pharmacodynamics ), and it should be used with caution in patients with clinically evident congestive heart failure, patients who may be susceptible to developing congestive heart failure, and patients with a history of heart failure who are well-compensated and receiving appropriate medical therapy (see PRECAUTIONS : Fluid Retention ).
Close monitoring of fluid and electrolyte status should be performed in patients receiving chronic diuretic therapy. Sudden deaths have occurred in Oprelvekin-treated patients receiving chronic diuretic therapy and ifosfamide who developed severe hypokalemia (see ADVERSE REACTIONS ).
Dosing with Neumega should begin 6 to 24 hours following the completion of chemotherapy dosing. The safety and efficacy of Neumega given immediately prior to or concurrently with cytotoxic chemotherapy have not been established (see DOSAGE AND ADMINISTRATION ).
Neumega has not been evaluated in patients receiving chemotherapy regimens of greater than 5 days duration or regimens associated with delayed myelosuppression (e.g., nitrosoureas, mitomycin-C).
The parenteral administration of Neumega should be attended by appropriate precautions in case allergic reactions occur (see CONTRAINDICATIONS ).
Patients receiving Neumega have commonly experienced mild to moderate fluid retention as indicated by peripheral edema or dyspnea on exertion. Weight gain has been uncommon. The fluid retention is reversible within several days following discontinuation of Neumega. In some patients, preexisting pleural effusions have increased during administration of Neumega. Preexisting fluid collections, including pericardial effusions or ascites, should be monitored. Drainage should be considered if medically indicated. Capillary leak syndrome has not been observed following treatment with Neumega.
Moderate decreases in hemoglobin concentration, hematocrit, and red blood cell count (~10-15%) without a decrease in red blood cell mass have been observed. These changes are predominantly due to an increase in plasma volume (dilutional anemia) that is primarily related to renal sodium and water retention. The decrease in hemoglobin concentration typically begins within 3-5 days of the initiation of Neumega, and is reversible over approximately a week following discontinuation of Neumega.
During dosing with Neumega, fluid balance should be monitored and appropriate medical management is advised. If a diuretic is used, fluid and electrolyte balance should be carefully monitored. Neumega should be used with caution in patients who may develop fluid retention as a result of associated medical conditions or whose medical condition may be exacerbated by fluid retention.
Neumega should be used with caution in patients with a history of atrial arrhythmia, and only after consideration of the potential risks in relation to anticipated benefit. Transient atrial arrhythmias (atrial fibrillation or atrial flutter) have occurred in approximately 10% of patients following treatment with Neumega. In some patients this may be due to increased plasma volume associated with fluid retention (See PRECAUTIONS : Fluid Retention ); Neumega has been shown not to be directly arrhythmogenic. Arrhythmias have usually been brief in duration and usually without clinical sequelae; however sequelae including stroke have been observed in patients receiving Neumega who experienced atrial arrhythmias. Conversion to sinus rhythm typically occurred spontaneously or after rate-control drug therapy. Most patients have continued to receive Neumega without recurrence of atrial arrhythmia. A retrospective analysis of data from clinical studies of Neumega suggests that advancing age and other conditions associated with an increased risk of atrial arrhythmias such as use of cardiac medications and a history of doxorubicin exposure are risk factors for the development of atrial fibrillation or atrial flutter in patients receiving Neumega. Ventricular arrhythmias have not been attributed to the use of Neumega.
Transient, mild visual blurring has occasionally been reported by patients treated with Neumega. Papilledema has been reported in approximately 1.5% of patients treated with Neumega following repeated cycles of exposure. Nonhuman primates treated with Neumega at a dose of 1,000 µg/kg SC once daily for 4 to 13 weeks developed papilledema which was not associated with inflammation or any other histologic abnormality and was reversible after dosing was discontinued. Neumega should be used with caution in patients with preexisting papilledema, or with tumors involving the central nervous system since it is possible that papilledema could worsen or develop during treatment.
A small proportion (1%) of patients receiving Neumega in clinical studies developed antibodies to Oprelvekin and transient rashes were occasionally observed at the injection site following Neumega administration. The presence of these antibodies or injection site reactions have not been correlated with clinical symptoms such as anaphylactoid reactions or a loss of clinical response to Neumega. No anaphylactoid or other severe adverse allergic reactions were reported in clinical studies following single or repeated doses of Neumega.
Neumega has been administered safely using the recommended dosing schedule (see DOSAGE AND ADMINISTRATION ) for up to 6 cycles following chemotherapy. The safety and efficacy of chronic administration of Neumega have not been established. Continuous dosing (2-13 weeks) in nonhuman primates produced joint capsule and tendon fibrosis and periosteal hyperostosis (see PRECAUTIONS : Pediatric Use ). The relevance of these findings to humans is unclear.
In situations when the physician determines that Neumega may be used outside of the hospital or office setting, persons who will be administering Neumega should be instructed as to the proper dose, and the method for reconstituting and administering Neumega (See DOSAGE AND ADMINISTRATION and Patient Information at the end of this insert). If home use is prescribed, patients should be instructed in the importance of proper disposal and cautioned against the reuse of needles, syringes, drug product, and diluent. A puncture resistant container should be used by the patient for the disposal of used needles.
Patients should be informed of the most common adverse reactions associated with Neumega administration, including those symptoms related to fluid retention (see ADVERSE REACTIONS and PRECAUTIONS ). Mild to moderate peripheral edema and shortness of breath on exertion can occur within the first week of treatment and may continue for the duration of administration of Neumega. Patients who have preexisting pleural or other effusions or a history of congestive heart failure should be advised to contact their physician for worsening of dyspnea. Most patients who receive Neumega develop some anemia. Patients who are older or who have other risk factors for the development of atrial arrhythmias should be cautioned to contact their physician if symptoms attributable to atrial arrhythmia develop and are not transient. Female patients of childbearing potential should be advised of the possible risks to the fetus of Neumega (see PRECAUTIONS : Pregnancy).
A complete blood count should be obtained prior to chemotherapy and at regular intervals during Neumega therapy (see DOSAGE AND ADMINISTRATION). Platelet counts should be monitored during the time of the expected nadir and until adequate recovery has occurred (post-nadir counts >/=50,000).
Most patients in trials evaluating Neumega were treated concomitantly with Filgrastim (granulocyte colony-stimulating factor[G-CSF]) with no adverse effect of Neumega on the activity of G-CSF. No information is available on the clinical use of Sargramostim (granulocyte-macrophage colony-stimulating factor [GM-CSF]) with Neumega. However, in a study in nonhuman primates in which Neumega and GM-CSF were coadministered, there were no adverse interactions between Neumega and GM-CSF and no apparent difference in the pharmacokinetic profile of Neumega.
Drug interactions between Neumega and other drugs have not been fully evaluated. Based on in vitro and nonclinical in vivo evaluations of Neumega, drug-drug interactions with known substrates of P450 enzymes would not be predicted.
No studies have been performed to assess the carcinogenic potential of Neumega. In vitro , Neumega did not stimulate the growth of tumor colony-forming cells harvested from patients with a variety of human malignancies. Neumega has been shown to be non-genotoxic in in vitro studies. These data suggest that Neumega is not mutagenic. Although prolonged estrus cycles have been noted at 2 to 20 times the human dose, no effects on fertility have been observed in rats treated with Neumega at doses up to 1000 µg/kg/day.
Neumega has been shown to have embryocidal effects in pregnant rats and rabbits when given in doses of 0.2 to 20 times the human dose. There are no adequate and well-controlled studies of Neumega in pregnant women. Neumega should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Neumega has been tested in studies of fertility and early embryonic development in rats and in studies of organogenesis (teratogenicity) in rats and rabbits. Parental toxicity has been observed when Neumega is given at doses of 2 to 20 times the human dose (>/=100 µg/kg/day) in the rat and when given in doses of 0.02 to 2.0 times the human dose (>/=1 µg/kg/day) in the rabbit. Findings in the rat consisted of transient hypoactivity and dyspnea after administration, as well as prolonged estrus cycle, increased early embryonic deaths and decreased numbers of live fetuses. In addition, low fetal body weights and a reduced number of ossified sacral and caudal vertebrae (i.e., retarded fetal development) occurred in rats at 20 times the human dose, but no long-term behavioral or developmental abnormalities were evident. Findings in the rabbits consisted of decreased (fecal/urine) eliminations (the only toxicity noted at 1 µg/kg/day) as well as decreased food consumption, body weight loss, abortion, increased embryonic and fetal deaths, and decreased numbers of live fetuses. There have been no teratogenic effects of Neumega observed in rabbits.
It is not known if Neumega is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Neumega, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Efficacy trials have not been conducted in a pediatric population. Preliminary data are available from an ongoing pharmacokinetic study in twenty-eight patients ages 8 months to 17 years who have been treated with Neumega at doses of 25 to 100 µg/kg following ICE (ifosfamide, etoposide, carboplatin) chemotherapy. Neumega treatment was given once daily for a maximum of 28 days in up to eight cycles. Based upon this study, a dose of 75 to 100 µg/kg in the pediatric population will produce plasma levels consistent with those obtained in adults given 50 µg/kg (see CLINICAL PHARAMACOLOGY : ).
Adverse events in this pediatric open-label, non-comparative study were generally similar to those observed using Neumega at a dose of 50 µg/kg in the randomized chemotherapy studies in adults. Most adverse events that were associated with Neumega in adults occurred either with similar or lower frequency in the pediatric study compared with adults. The incidences of tachycardia (46% [13/28]) and conjunctival injection (50% [14/28]) in the pediatric study were higher than in adults (see ADVERSE REACTIONS). There was no evidence of a dose-response relationship for any of the Neumega-associated adverse events among the pediatric patients.
No studies have been performed to assess the long-term effects of Neumega on growth and development. In growing rodents treated with 100, 300, or 1000 µg/kg/day for a minimum of 28 days, thickening of femoral and tibial growth plates was noted, which did not completely resolve after a 28-day non-treatment period. In a nonhuman primate toxicology study of Neumega, animals treated for 2 to 13 weeks at doses of 10 to 1000 µg/kg showed partially reversible joint capsule and tendon fibrosis and periosteal hyperostosis. The clinical significance of these findings is not known. An asymptomatic, laminated periosteal reaction in the diaphyses of the femur, tibia and fibula has been observed in one patient during pediatric trials involving multiple courses of Neumega treatment. The relationship of these findings to treatment with Neumega is unclear.
Neumega is eliminated primarily by the kidneys. The pharmacokinetics of Neumega have not been studied in patients with mild or moderate renal impairment (creatinine clearance >/= 15 mL/min). Fluid retention associated with Neumega treatment has not been studied in patients with renal impairment, but fluid balance should be carefully monitored in these patients (See PRECAUTIONS : Fluid Retention ).
Three hundred eight subjects, with ages ranging from 8 months to 75 years, have been exposed to Neumega treatment. Subjects have received up to six (eight in pediatric patients) sequential courses of Neumega treatment, with each course lasting from 1 to 28 days. Apart from the sequelae of the underlying malignancy or cytotoxic chemotherapy, most adverse events were mild or moderate in severity and reversible after discontinuation of Neumega dosing.
In general, the incidence and type of adverse events were similar between Neumega 50 µg/kg and placebo groups. The following adverse events, occurring in >/=10% of patients, were observed at equal or greater frequency in placebo-treated patients: asthenia, pain, chills, abdominal pain, infection, anorexia, constipation, dyspepsia, ecchymosis, myalgia, bone pain, nervousness, and alopecia. Selected adverse events that occurred in Neumega-treated patients are listed in Table 3.
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The following adverse events also occurred more frequently in cancer patients receiving Neumega than in those receiving placebo: amblyopia, paresthesia, dehydration, skin discoloration, exfoliative dermatitis, and eye hemorrhage; a statistically significant association of Neumega to these events has not been established. Other than a higher incidence of severe asthenia in Neumega treated patients (10 [14%] in Neumega patients versus 2 [3%] in placebo patients), the incidence of severe or life-threatening adverse events was comparable in the Neumega and placebo treatment groups.
The incidence of fever, neutropenic fever, flu-like symptoms, thrombocytosis, thrombotic events, the average number of units of red blood cells transfused per patient, and the duration of neutropenia <500 cells/µL were similar in the Neumega 50 µg/kg and placebo groups.
Two patients with cancer treated with Neumega experienced sudden death which the investigator considered possibly or probably related to Neumega. Both deaths occurred in patients with severe hypokalemia (<3.0 mEq/L) who had received high doses of ifosfamide and were receiving daily doses of a diuretic. The relationship of these deaths to Neumega remains unclear.
The most common laboratory abnormality reported in patients in clinical trials was a decrease in hemoglobin concentration predominantly as a result of expansion of the plasma volume (see PRECAUTIONS : Fluid Retention ). The increase in plasma volume is also associated with a decrease in the serum concentration of albumin and several other proteins (e.g., transferrin and gamma globulins). A parallel decrease in calcium without clinical effects has been documented.
After daily SC injections, treatment with Neumega resulted in a two-fold increase in plasma fibrinogen. Other acute-phase proteins also increased. These protein levels returned to normal after dosing with Neumega was discontinued. Von Willebrand factor (vWF) concentrations increased with a normal multimer pattern in healthy subjects receiving Neumega.
Doses of Neumega above 100 µg/kg have not been administered to humans. While clinical experience is limited, doses of Neumega greater than 50 µg/kg may be associated with an increased incidence of cardiovascular events in adult patients (see PRECAUTIONS : Fluid Retention / Cardiovascular ). If an overdose of Neumega is administered. Neumega should be discontinued, and the patient should be closely observed for signs of toxicity (see PRECAUTIONS and ADVERSE REACTIONS ). Reinstitution of Neumega therapy should be based upon individual patient factors (e.g., evidence of toxicity, continued need for therapy).
The recommended dose of Neumega in adults is 50 µg/kg given once daily. Neumega should be administered subcutaneously as a single injection in either the abdomen, thigh, or hip (or upper arm if not self-injecting). Based upon a pharmacokinetic study, a dose of 75 to 100 µg/kg in the pediatric population will produce plasma levels consistent with those obtained in adults given 50 µg/kg (see : ).
Dosing should be initiated 6 to 24 hours after the completion of chemotherapy. Platelet counts should be monitored periodically to assess the optimal duration of therapy. Dosing should be continued until the post-nadir platelet count is >/=50,000 cells/µL. In controlled clinical studies, doses were administered in courses of 10 to 21 days. Dosing beyond 21 days per treatment course is not recommended.
Treatment with Neumega should be discontinued at least 2 days before starting the next planned cycle of chemotherapy.
Neumega is supplied as a sterile, white, preservative-free, lyophilize powder in vials containing 5 mg Oprelvekin. Neumega is available in boxes containing one single-dose Neumega vial and one 5-mL vial of diluent for Neumega (Sterile Water for Injection, USP) - NDC 58394-004-01; and boxes containing seven single-dose Neumega vials and seven 5-mL vials of diluent for Neumega (Sterile Water for Injection, USP) - NDC 58394-004-02.
Lyophilized Neumega and diluent should be stored in a refrigerator at 2 to 8°C (36 to 46°F). DO NOT FREEZE. Reconstituted Neumega must be used within 3 hours of reconstitution and can be stored in the vial either at 2 to 8°C (36 to 46°F) or at room temperature up to 25°C (77°F).
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(1) Du, X, and Williams, D., Interleukin 11: Review of Molecular, Cell Biology and Clinical Use. Blood. 89(11): 3897-3908, 1997.
GENETICS INSTITUTE
Genetics Institute, Inc.
Cambridge, MA 02140-2387, USA
US License Number 1163
Telephone: 1-888-446-3344
IL1131.00 Rev. 12/97
(Oprelvekin)
General Information
Neumega is intended for use under the guidance and supervision of a health care professional. If, however, your physician recommends self-injection, you should be instructed in the preparation of Neumega, the proper method for self-injection, and the correct dose to use. You should not try self-administration until you are certain that you understand your health care professional's instructions. Each dose should be given at about the same time each day. If you miss a dose, continue with the next scheduled dose.
Possible Side Effects
As with any medication, use of Neumega may be associated with side effects. In clinical studies, these effects were generally mild or moderate and stopped after treatment. The most common side effects seen in studies of Neumega were edema (swelling) of the arms and/or legs, shortness of breath when moving about, and anemia. These side effects are probably related to water retention. Edema and shortness of breath on exertion can occur within the first week of treatment and may continue for the duration of administration of Neumega. It is also possible that you may experience irregular heartbeats. If you experience chest pain, shortness of breath, fatigue, blurred vision, or an irregular pulse that persists, contact your physician. If you have any other problems, whether or not you think they are related to Neumega, you should tell your doctor.
If you are a woman of child-bearing potential, you should be aware that use of Neumega poses possible risks of the fetus. If you become pregnant or wish to become pregnant during treatment with Neumega, consult your physician about continuing to use Neumega.
Dosage and Administration
The Neumega vial contains a powder which must be reconstituted prior to injection in 1 mL of Sterile Water for Injection, USP provided with Neumega. Powdered Neumega and Sterile Water for Injection, USP should be stored in a refrigerator at 2 to 8°C (36 to 46°F). DO NOT FREEZE.
A new vial of Neumega and Sterile Water for Injection, USP should be used to prepare each dose. Do not use Neumega or Sterile Water for Injection, USP beyond the expiration date printed on the vial. Any unused portion of reconstituted Neumega medication or Sterile Water for Injection, USP remaining in the vial should be discarded. Because neither Neumega powder for injection nor its accompanying Sterile Water for Injection, USP contain a preservative, the single-use vials should not be reentered or reused.
Neumega should be used as soon as possible following reconstitution and must be used within 3 hours of reconstitution. The reconstituted Neumega solution can be stored in the vial for up to 3 hours either at room temperature up to 25°C (77°F), or in the refrigerator at 2 to 8°C (36 to 46°F) THE RECONSTITUTED SOLUTION SHOULD NOT BE STORED IN A SYRINGE.
NOTE: Follow aseptic technique in reconstitution and administration as demonstrated by the health care professional.
Reconstituting Neumega
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Injecting Neumega
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Genetics Institute, Inc.
Rev. 12/97 Cambridge, MA 02140-2387, USA
