Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1539
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Neumega (Kit)
|
| dailymed-instance:dosage |
The recommended dose of Neumega in adults without
severe renal impairment is 50��g/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). A
safe and effective dose has not been established in children . The recommended dose of Neumega
in adults with severe renal impairment (creatinine clearance<30
mL/min) is 25��g/kg. An estimate of the patient's creatinine
clearance (CLcr) in mL/min is required. CLcr in mL/min may be estimated
from a spot serum creatinine (mg/dL) determination using the following
formula: Dosing should be initiated six 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/��L.
In controlled clinical trials, 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 two days before starting the next
planned cycle of chemotherapy.<br/>Preparation of Neumega:
|
| dailymed-instance:descripti... |
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 technology. 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 formulated in
single-use vials containing 5 mg of oprelvekin (specific activity
approximately 8 x 10Units/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.
|
| dailymed-instance:clinicalP... |
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 trials 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. Non-hematopoietic pathologic changes observed in
animals include fibrosis of tendons and joint capsules, periosteal
thickening, papilledema, and embryotoxicity (see PRECAUTIONS, Pediatric Use and PRECAUTIONS,
Pregnancy Category C). 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)<br/>Pharmacokinetics: The pharmacokinetics of Neumega have been evaluated
in studies of healthy, adult subjects and cancer patients receiving
chemotherapy. In a study in which a single 50��g/kg subcutaneous
dose was administered to eighteen healthy men, the peak serum concentration
(C) of 17.4��5.4 ng/mL (mean��S.D.)
was reached at 3.2��2.4 hrs (T) following
dosing. The terminal half-life was 6.9��1.7 hrs. In
a second study in which single 75��g/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��g/kg
were administered to cancer patients receiving chemotherapy, Neumega
did not accumulate and clearance of Neumega was not impaired following
multiple doses. In a dose escalation Phase
1 study, Neumega was also administered to 43 pediatric patients (ages
8 months to 18 years) and 1 adult patient receiving ICE (ifosfamide,
carboplatin, etoposide) chemotherapy. Administered doses ranged from
25 to 125��g/kg. Analysis of data from 40 pediatric
patients showed that C, T, and terminal
half-life were comparable to that in adults. The mean area under the
concentration-time curve (AUC) for pediatric patients (8 months to
18 years), receiving 50��g/kg was approximately half that
achieved in healthy adults receiving 50��g/kg. Available
data suggest that clearance of oprelvekin decreases with increasing
age in children. In another study, a single
50��g/kg dose of Neumega was administered subcutaneously to 48
healthy adults (24 women) aged 20 to 79 years. The half-life was generally
lower for subjects less than 40 years of age (t= 5.4
hr), as compared to subjects greater than 75 years of age (t= 8.0 hr). This change in tis not considered
to be clinically relevant. In preclinical trials
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 of 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<30 mL/min).
The mean��S.D. values for Cand 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 Cwas 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. A second
clinical study of 24 subjects with varying degrees of renal function
was also performed and confirmed the results observed in the first
study. Single 50��g/kg subcutaneous and intravenous doses were
administered in a randomized fashion. As the degree of renal impairment
increased, the Neumega AUC increased, although half-life remained
unchanged. In the six patients with severe impairment, the mean��S.D. Cand AUC were 23.6��6.7 ng/mL and 373��55.2 ng*hr/mL, respectively, compared with 13.1��3.8 ng/mL
and 195��49.3 ng*hr/mL, respectively, in the six subjects with
normal renal function. A comparable increase in exposure was observed
after intravenous administration of Neumega. The pharmacokinetic studies suggest that overall exposure to oprelvekin
increases as renal function decreases, indicating that a 50% dose
reduction of Neumega is warranted for patients with severe renal impairment
(see PRECAUTIONS,
Use in Patients with Renal Impairment and DOSAGE AND ADMINISTRATION). No dosage reduction is required for smaller changes
in renal function.<br/>Pharmacodynamics: 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 five and nine
days after the start of dosing with Neumega. After cessation of treatment,
platelet counts continued to increase for up to seven 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.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Neumega is contraindicated in patients with a history
of hypersensitivity to Neumega or any component of the product (see WARNINGS, Allergic Reactions
Including Anaphylaxis).
|
| dailymed-instance:supply |
Neumega is supplied as a sterile, white, preservative-free,
lyophilized powder in vials containing 5 mg oprelvekin. Neumega
is available in boxes containing one single-dose Neumega vial and
one 1-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 1-mL vials of diluent for Neumega (Sterile Water for
Injection, USP) - NDC 58394-004-02.<br/>Storage: Lyophilized Neumega and diluent should be stored
in a refrigerator at 2��C to 8��C (36��F to 46��F).
Protect from light. Do not freeze. Reconstituted Neumega must be used within 3 hours of reconstitution
and can be stored in the vial either at 2��C to 8��C (36��F
to 46��F) or at room temperature up to 25��C (77��F).
|
| dailymed-instance:genericDr... | |
| dailymed-instance:boxedWarn... |
Allergic Reactions Including Anaphylaxis: Neumega has caused allergic or hypersensitivity reactions,
including anaphylaxis. Administration of Neumega should be permanently
discontinued in any patient who develops an allergic or hypersensitivity
reaction .
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
General: 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 or initiated at the time of expected nadir have not been
established (see DOSAGE
AND ADMINISTRATION). The
effectiveness of Neumega has not been evaluated in patients receiving
chemotherapy regimens of greater than five days duration or regimens
associated with delayed myelosuppression (eg, nitrosoureas, mitomycin-C).<br/>Chronic Administration: Neumega has been administered safely using the recommended
dosage schedule for up to six cycles
following chemotherapy. The safety and efficacy of chronic administration
of Neumega have not been established. Continuous dosage (two to 13
weeks) in nonhuman primates produced joint capsule and tendon fibrosis
and periosteal hyperostosis . The
relevance of these findings to humans is unclear.<br/>Information for Patients: Neumega should be used under the guidance and supervision
of a health care professional. However, 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). 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 serious and most common adverse reactions
associated with Neumega administration, including those symptoms related
to allergic or hypersensitivity reactions . Patients
should be advised to immediately seek medical attention if any of
the following signs or symptoms develop: swelling of the face, tongue,
or throat; difficulty breathing, swallowing or talking; shortness
of breath; wheezing; chest pain; throat tightness; lightheadedness;
loss of consciousness; confusion; drowsiness; rash; itching; hives;
flushing and/or fever. 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 (see ADVERSE
REACTIONS and WARNINGS, Fluid Retention). Most
patients who receive Neumega develop anemia. Patients should be advised
to contact their physician if symptoms attributable to atrial arrhythmia
develop. Female patients of childbearing potential should be advised
of the possible risks to the fetus of Neumega .<br/>Laboratory Monitoring: A complete blood count should be obtained prior to
chemotherapy and at regular intervals during Neumega therapy . Platelet counts should be monitored during the time
of the expected nadir and until adequate recovery has occurred (post-nadir
counts���50,000/��L).<br/>Drug Interactions: Most patients in trials evaluating Neumega were treated
concomitantly with filgrastim (G-CSF) with no adverse effect of Neumega
on the activity of G-CSF. No information is available on the clinical
use of sargramostim (GM-CSF) with Neumega in human subjects. 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.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: 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 two
to 20 times the human dose, no effects on fertility have been
observed in rats treated with Neumega at doses up to 1000��g/kg/day.<br/>Pregnancy Category C: 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, early embryonic development, and pre- and postnatal 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 two to 20 times the human dose (���100��g/kg/day)
in the rat and at 0.02 to 2.0 times the human dose (���1��g/kg/day)
in the rabbit. Findings in pregnant rats consisted of transient hypoactivity
and dyspnea after administration (maternal toxicity), 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 (ie, retarded fetal
development) occurred in rats at 20 times the human dose. Findings
in pregnant rabbits consisted of decreased fecal/urine eliminations
(the only toxicity noted at 1��g/kg/day in dams) as well
as decreased food consumption, body weight loss, abortion, increased
embryonic and fetal deaths, and decreased numbers of live fetuses.
No teratogenic effects of Neumega were observed in rabbits at doses
up to 0.6 times the human dose (30��g/kg/day). Adverse effects in the first generation offspring of rats
given Neumega at maternally toxic doses���2 times the human
dose (���100��g/kg/day) during both gestation and
lactation included increased newborn mortality, decreased viability
index on day 4 of lactation, and decreased body weights during lactation.
In rats given 20 times the human dose (1000��g/kg/day)
during both gestation and lactation, maternal toxicity and growth
retardation of the first generation offspring resulted in an increased
rate of fetal death of the second generation offspring.<br/>Nursing Mothers: 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 Neumega,
taking into account the importance of the drug to the mother.<br/>Pediatric Use: A safe and effective dose of Neumega has not been
established in children. In a Phase 1, single arm, dose-escalation
study, 43 pediatric patients were treated with Neumega at doses ranging
from 25 to 125��g/kg/day following ICE chemotherapy.
All patients required platelet transfusions and the lack of a comparator
arm made the study design inadequate to assess efficacy. The projected
effective dose (based on comparable AUC observed for the effective
dose in healthy adults) in children appears to exceed the maximum
tolerated pediatric dose of 50��g/kg/day . Papilledema was dose-limiting and occurred in 16% of
children (see WARNINGS,
Papilledema). The most
common adverse events seen in pediatric studies included tachycardia
(84%), conjunctival injection (57%), radiographic and echocardiographicevidence of cardiomegaly (21%) and periosteal changes (11%). These
events occurred at a higher frequency in children than adults. The
incidence of other adverse events was generally similar to those observed
using Neumega at a dose of 50��g/kg in the randomized studies
in adults receiving chemotherapy . Studies in animals were predictive of the effect of Neumega on developing
bone in children. In growing rodents treated with 100, 300, or 1000��g/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 two to 13 weeks at doses of 10 to 1000��g/kg
showed partially reversible joint capsule and tendon fibrosis and
periosteal hyperostosis. An asymptomatic, laminated periosteal reaction
in the diaphyses of the femur, tibia, and fibula has been observed
in one patient during pediatric studies involving multiple courses
of Neumega treatment. The relationship of these findings to treatment
with Neumega is unclear. No studies have been performed to assess
the long-term effects of Neumega on growth and development.<br/>Geriatric Use: In a multicenter, double-masked, placebo-controlled
trial, 141 subjects were randomized (35 subjects were���65 years
of age) to evaluate Neumega (50��g/kg) in the prevention of
severe chemotherapy-induced thrombocytopenia when administered subcutaneously
daily for 14 days starting after chemotherapy was completed. No overall
differences in safety and efficacy were observed between subjects���65 years of age and subjects<65 years of age.<br/>Use in Patients with Renal Impairment: Neumega is eliminated primarily by the kidneys. The
pharmacokinetics of Neumega were studied in subjects with varying
degrees of renal dysfunction. AUC, C, and absolute bioavailability were significantly increased in subjects
with severe renal impairment (creatinine clearance<30 mL/min)
. There were no significant changes in the pharmacokinetic
parameters in subjects with mild or moderate impairment. A significant
decrease in the hemoglobin concentration was noted on Day 2 after
a single dose of Neumega in subjects with all degrees of renal impairment.
By Day 14, the hemoglobin was decreased only in patients with severe
renal impairment. 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 .
|
| dailymed-instance:overdosag... |
Doses of Neumega above 125��g/kg have
not been administered to humans. While clinical experience is limited,
doses of Neumega greater than 50��g/kg may be associated
with an increased incidence of cardiovascular events in adult patients
(see WARNINGS, Fluid
Retention and Cardiovascular Events). If an overdose
of Neumega is administered, Neumega should be discontinued, and the
patient should be closely observed for signs of toxicity . Reinstitution of Neumega therapy should be based upon
individual patient factors (eg, evidence of toxicity, continued need
for therapy).
|
| dailymed-instance:genericMe... |
Oprelvekin
|
| dailymed-instance:fullName |
Neumega (Kit)
|
| dailymed-instance:adverseRe... |
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical
studies of a drug cannot be directly compared to rates in the clinical
studies of another drug and may not reflect the rates observed in
practice. The adverse reaction information from clinical trials does,
however, provide a basis for identifying the adverse events that appear
to be related to drug use and for approximating rates. Three hundred twenty-four subjects, with ages ranging
from eight months to 75 years, have been exposed to Neumega treatment
in clinical studies. Subjects have received up to six (eight in pediatric
patients) sequential courses of Neumega treatment, with each course
lasting from one 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��g/kg
and placebo groups. The most frequently reported serious adverse events
were neutropenic fever, syncope, atrial fibrillation, fever and pneumonia.
The most commonly reported adverse events were edema, dyspnea, tachycardia,
conjunctival injection, palpitations, atrial arrhythmias, and pleural
effusions. The most frequently reported adverse reactions resulting
in clinical intervention (eg, discontinuation of Neumega, adjustment
in dosage, or the need for concomitant medication to treat an adverse
reaction symptom) were atrial arrhythmias, syncope, dyspnea, congestive
heart failure, and pulmonary edema (see WARNINGS, Fluid Retention and WARNINGS, Cardiovascular
Events). Selected adverse events that occurred
in���10% of Neumega-treated patients are listed in Table 3. The following adverse events also occurred more
frequently in cancer patients receiving Neumega than in those receiving
placebo: blurred vision, paresthesia, dehydration, skin discoloration,
exfoliative dermatitis, and eye hemorrhage. Other than a higher incidence
of severe asthenia in Neumega treated patients (10 [14%] in Neumega
patients versus two [3%] in placebo patients), the incidence of severe
or life-threatening adverse events was comparable in the Neumegaand
placebo treatment groups. Two patients with
cancer treated with Neumega experienced sudden death that 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
(see WARNINGS, Cardiovascular
Events). Other serious
events associated with Neumega were papilledema and cardiovascular
events including atrial arrhythmias and stroke. In addition, cardiomegaly
was reported in children. 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. The incidence
of fever, neutropenic fever, flu-like symptoms, thrombocytosis, thrombotic
events, the average numberof units of red blood cells transfused
per patient, and the duration of neutropenia<500 cells/��L
were similar in the Neumega 50��g/kg and placebo groups.<br/>Immunogenicity: In clinical studies that evaluated the immunogenicity
of Neumega, two of 181 patients (1%) developed antibodies to
Neumega. In one of these two patients, neutralizing antibodies to
Neumega were detected in an unvalidated assay. The clinical relevance
of the presence of these antibodies is unknown. In the post-marketing
setting, cases of allergic reactions, including anaphylaxis have been
reported (see WARNINGS,
Allergic Reactions Including Anaphylaxis). The
presence of antibodies to Neumega was not assessed in these patients. The data reflect the percentage of patients whose test
results were considered positive for antibodies to Neumega and are
highly dependent on the sensitivity and specificity of the assay.
Additionally the observed incidence of antibody positivity in an assay
may be influenced by several factors including sample handling, concomitant
medications, and underlying disease. For these reasons, comparisons
of the incidence of antibodies to Neumega with incidence of antibodies
to other products may be misleading.<br/>Abnormal Laboratory Values: 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 . The increase in plasma volume is also associated with
a decrease in the serum concentration of albumin and several other
proteins (eg, 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.<br/>Post-marketing Reports: Because these reactions are reported voluntarily
from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship
to drug exposure. Decisions to include these reactions in labeling
are typically based on one or more of the following factors: (1) seriousness
of the reactions, (2) frequency of reporting, or (3) strength of causal
connection to Neumega. The following adverse
reactions have been reported during the post-marketing use of Neumega: .
|
| dailymed-instance:warning |
Allergic Reactions Including Anaphylaxis: In the post-marketing setting, Neumega has caused
allergic or hypersensitivity reactions, including anaphylaxis. The
administration of Neumega should be attended by appropriate precautions
in case allergic reactions occur. In addition, patients should be
counseled about the symptoms for which they should seek medical attention
(see PRECAUTIONS,
Information for Patients). Signs and symptoms
reported included edema of the face, tongue, or larynx; shortness
of breath; wheezing; chest pain; hypotension (including shock); dysarthria;
loss of consciousness; mental status changes; rash; urticaria; flushing
and fever. Reactions occurred after the first dose or subsequent doses
of Neumega. Administration of Neumega should be permanently discontinued
in any patient who develops an allergic or hypersensitivity reaction
(see BOXED WARNING, CONTRAINDICATIONS, ADVERSE
REACTIONS, and ADVERSE REACTIONS, Immunogenicity).<br/>Increased Toxicity Following Myeloablative Therapy: Neumega is not indicated following myeloablative
chemotherapy. In a randomized, placebo-controlled Phase 2 study, the
effectiveness of Neumega was not demonstrated (see CLINICAL STUDIES, Study in
Patients Following Myeloablative Chemotherapy). In this study, a statistically significant increased incidence
in edema, conjunctival bleeding,hypotension, and tachycardia was
observed in patients receiving Neumega as compared to placebo. The following severe or fatal adverse reactions have been
reported in post-marketing use in patients who received Neumega following
bone marrow transplantation: fluid retention or overload (eg, facial
edema, pulmonary edema), capillary leak syndrome, pleural and pericardial
effusion, papilledema and renal failure.<br/>Fluid Retention: Neumega is known to cause serious fluid retention
that can result in peripheral edema, dyspnea on exertion, pulmonary
edema, capillary leak syndrome, atrial arrhythmias, and exacerbation
of pre-existing pleural effusions. Severe fluid retention, some cases
resulting in death, was reported following recent bone marrow transplantation
in patients who have received Neumega. Neumega is not indicated following
myeloablative chemotherapy (see CLINICAL PHARMACOLOGY, Pharmacodynamics; WARNINGS, Increased
Toxicity Following Myeloablative Therapy; WARNINGS, Cardiovascular Events; and WARNINGS,
Dilutional Anemia). It should be used with caution
in patients with clinically evident congestive heart failure, patients
who may be susceptible to developing congestive heart failure, patients
receiving aggressive hydration, patients with a history of heart failure
who are well-compensated and receiving appropriate medical therapy,
and patients who may develop fluid retention as a result of associated
medical conditions or whose medical condition may be exacerbated by
fluid retention. Fluid retention is reversible
within several days following discontinuation of Neumega. During dosing
with Neumega, fluid balance should be monitored and appropriate medical
management is advised. 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 . Pre-existing
fluid collections, including pericardial effusions or ascites, should
be monitored. Drainage should be considered if medically indicated.<br/>Dilutional Anemia: Moderate decreases in hemoglobin concentration, hematocrit,
and red blood cell count (~10% to 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 three to five days of the
initiation of Neumega, and is reversible over approximately a week
following discontinuation of Neumega .<br/>Cardiovascular Events: Neumega use is associated with cardiovascular events
including arrhythmias and pulmonary edema. Cardiac arrest has been
reported, but the causal relationship to Neumega is uncertain. Use
with caution in patients with a history of atrial arrhythmias, and
only after consideration of the potential risks in relation to anticipated
benefit. In clinical trials, cardiac events including atrial arrhythmias
(atrial fibrillation or atrial flutter) occurred in 15% (23/157) of
patients treated with Neumega at doses of 50��g/kg. Arrhythmias
were usually brief in duration; conversion to sinus rhythm typically
occurred spontaneously or after rate-control drug therapy. Approximately
one-half (11/24) of the patients who were rechallenged had recurrent
atrial arrhythmias. Clinical sequelae, including stroke, have been
reported in patients who experienced atrial arrhythmias while receiving
Neumega. The mechanism for induction of arrhythmias
is not known. Neumega was not directly arrhythmogenic in animal models.
In some patients, development of atrial arrhythmias may be due to
increased plasma volume associated with fluid retention . In the post-marketing setting,
ventricular arrhythmias have been reported, generally occurring within
two to seven days of initiation of treatment.<br/>Nervous System Events: Stroke has been reported in the setting of patients
who develop atrial fibrillation/flutter while receiving Neumega . Patients with a history of stroke or transient ischemic
attack may also be at increased risk for these events.<br/>Papilledema: Papilledema has been reported in 2% (10/405) of patients
receiving Neumega in clinical trials following repeated cycles of
exposure. The incidence was higher, 16% (7/43) in children than in
adults, 1% (3/362). Nonhuman primates treated with Neumega at a dose
of 1,000��g/kg SC once daily for four to 13 weeks developed
papilledema that 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 pre-existing
papilledema, or with tumors involving the central nervous system since
it is possible that papilledema could worsen or develop during treatment
. Changes in visual acuity and/or visual field defects
ranging from blurred vision to blindness can occur in patients with
papilledema taking Neumega.
|
| dailymed-instance:indicatio... |
Neumega is indicated for the prevention of severe
thrombocytopenia and the reduction of the need for platelet transfusions
following myelosuppressive chemotherapy in adult 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 (see WARNINGS, Increased Toxicity Following Myeloablative
Therapy). The safety and effectiveness of Neumega
have not been established in pediatric patients.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Neumega
|