Neumega

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).

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.

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 (see ADVERSE REACTIONS).

Pre-existing fluid collections, including pericardial effusions or ascites, should be monitored. Drainage should be considered if medically indicated.

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 (see WARNINGS, Fluid Retention).

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 mcg/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 (see WARNINGS, Fluid Retention).

In the post-marketing setting, ventricular arrhythmias have been reported, generally occurring within two to seven days of initiation of treatment.

Stroke has been reported in the setting of patients who develop atrial fibrillation/flutter while receiving Neumega (see WARNINGS, Cardiovascular Events). Patients with a history of stroke or transient ischemic attack may also be at increased risk for these events.

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 mcg/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 (see ADVERSE REACTIONS). Changes in visual acuity and/or visual field defects ranging from blurred vision to blindness can occur in patients with papilledema taking Neumega.