"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
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 (oprelvekin) treatment in clinical studies. Subjects have received up to six (eight in pediatric patients) sequential courses of Neumega (oprelvekin) 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 (oprelvekin) dosing.
In general, the incidence and type of adverse events were similar between Neumega (oprelvekin) 50 µg/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 (oprelvekin) , 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 (oprelvekin) -treated patients are listed in Table 3.
TABLE 3: SELECTED ADVERSE EVENTS
|Body System Adverse Event||Placebo
|Body as a Whole|
|Edema *||10 (15)||41 (59)|
|Neutropenic fever||28 (42)||33 (48)|
|Headache||24 (36)||28 (41)|
|Fever||19 (28)||25 (36)|
|Tachycardia*||2 (3)||14 (20)|
|Vasodilatation||6 (9)||13 (19)|
|Palpitations*||2 (3)||10 (14)|
|Syncope||4 (6)||9 (13)|
|Atrial fibrillation/flutter*||1 (1)||8 (12)|
|Digestive S ystem|
|Nau sea/vomiting||47 (70)||53 (77)|
|Mucositis||25 (37)||30 (43)|
|Diarrhea||22 (33)||30 (43)|
|Oral moniliasis*||1 (1)||10 (14)|
|Nervous Sy stem|
|Dizziness||19 (28)||26 (38)|
|Insomnia||18 (27)||23 (33)|
|Dy spnea *||15 (22)||33 (48)|
|Rhinitis||21 (31)||29 (42)|
|Cough increased||15 (22)||20 (29)|
|Phary ngitis||11 (16)||17 (25)|
|Pleural effusions*||0 (0)||7 (10)|
|Skin and Appendages|
|Rash||11 (16)||17 (25)|
|Conjunctival Injection*||2 (3)||13 (19)|
|*Occurred in significantly more Neumega-treated patients than in placebo-treated patients.|
The following adverse events also occurred more frequently in cancer patients receiving Neumega (oprelvekin) 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 (oprelvekin) treated patients (10 [14%] in Neumega (oprelvekin) patients versus two [3%] in placebo patients), the incidence of severe or life-threatening adverse events was comparable in the Neumega (oprelvekin) and placebo treatment groups.
Two patients with cancer treated with Neumega (oprelvekin) experienced sudden death that the investigator considered possibly or probably related to Neumega (oprelvekin) . 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 (oprelvekin) 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 number of units of red blood cells transfused per patient, and the duration of neutropenia < 500 cells/µL were similar in the Neumega (oprelvekin) 50 µg/kg and placebo groups.
In clinical studies that evaluated the immunogenicity of Neumega (oprelvekin) , two of 181 patients (1%) developed antibodies to Neumega (oprelvekin) . In one of these two patients, neutralizing antibodies to Neumega (oprelvekin) 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 (oprelvekin) was not assessed in these patients.
The data reflect the percentage of patients whose test results were considered positive for antibodies to Neumega (oprelvekin) 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 byseveral factors including sample handling, concomitant medications, and underlying disease. Forthese reasons, comparisons of the incidence of antibodies to Neumega (oprelvekin) with incidence ofantibodies to other products may be misleading.
Abnormal Laboratory Values
The most common laboratory abnormality reported in patients in clinical trials was a decrease inhemoglobin concentration predominantly as a result of expansion of the plasma volume (see WARNINGS, Fluid Retention). The increase in plasma volume is also associated with adecrease in the serum concentration of albumin and several other proteins (eg, transferrin andgamma globulins). A parallel decrease in calcium without clinical effects has been documented.
After daily SC injections, treatment with Neumega (oprelvekin) resulted in a two-fold increase in plasmafibrinogen. Other acute-phase proteins also increased. These protein levels returned to normalafter dosing with Neumega (oprelvekin) was discontinued. Von Willebrand factor (vWF) concentrationsincreased with a normal multimer pattern in healthy subjects receiving Neumega (oprelvekin) .
Because these reactions are reported voluntarily from a population of uncertain size, it is notalways possible to reliably estimate their frequency or establish a causal relationship to drugexposure. Decisions to include these reactions in labeling are typically based on one or more ofthe following factors: (1) seriousness of the reactions, (2) frequency of reporting, or (3) strengthof causal connection to Neumega (oprelvekin) .
The following adverse reactions have been reported during the post-marketing use of Neumega (oprelvekin) :
- allergic reactions and anaphylaxis/anaphylactoid reactions
- visual disturbances ranging from blurred vision to blindness
- optic neuropathy
- ventricular arrhythmias
- capillary leak syndrome
- renal failure
- injection site reactions (dermatitis, pain, and discoloration)
Read the Neumega (oprelvekin) Side Effects Center for a complete guide to possible side effects
Most patients in trials evaluating Neumega (oprelvekin) were treated concomitantly with filgrastim (G-CSF) with no adverse effect of Neumega (oprelvekin) on the activity of G-CSF. No information is available on the clinical use of sargramostim (GM-CSF) with Neumega (oprelvekin) in human subjects. However, in a study in nonhuman primates in which Neumega (oprelvekin) and GM-CSF were coadministered, there were no adverse interactions between Neumega (oprelvekin) and GM-CSF and no apparent difference in the pharmacokinetic profile of Neumega (oprelvekin) .
Drug interactions between Neumega (oprelvekin) and other drugs have not been fully evaluated. Based on in vitro and nonclinical in vivo evaluations of Neumega (oprelvekin) , drug-drug interactions with known substrates of P450 enzymes would not be predicted.
Last reviewed on RxList: 10/21/2008
This monograph has been modified to include the generic and brand name in many instances.
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