openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings
WARNINGS Allergic Reactions Allergic-type reactions occurring on initial or subsequent treatment have been reported in less than 1 in 4000 patients treated with NEUPOGEN ® . These have generally been characterized by systemic symptoms involving at least 2 body systems‚ most often skin (rash‚ urticaria‚ facial edema)‚ respiratory (wheezing‚ dyspnea)‚ and cardiovascular (hypotension‚ tachycardia). Some reactions occurred on initial exposure. Reactions tended to occur within the first 30 minutes after administration and appeared to occur more frequently in patients receiving NEUPOGEN ® IV. Rapid resolution of symptoms occurred in most cases after administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine. Symptoms recurred in more than half the patients who were rechallenged. SPLENIC RUPTURE SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED FOLLOWING THE ADMINISTRATION OF NEUPOGEN ® . INDIVIDUALS RECEIVING NEUPOGEN ® WHO REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE. Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) has been reported in patients receiving NEUPOGEN ® , and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving NEUPOGEN ® who develop fever, lung infiltrates, or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, NEUPOGEN ® should be withheld until resolution of ARDS or discontinued. Patients should receive appropriate medical management for this condition. Alveolar Hemorrhage and Hemoptysis Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization has been reported in healthy donors undergoing peripheral blood progenitor cell (PBPC) mobilization. Hemoptysis resolved with discontinuation of NEUPOGEN ® . The use of NEUPOGEN ® for PBPC mobilization in healthy donors is not an approved indication. Sickle Cell Disorders Severe sickle cell crises, in some cases resulting in death, have been associated with the use of NEUPOGEN ® in patients with sickle cell disorders. Only physicians qualified by specialized training or experience in the treatment of patients with sickle cell disorders should prescribe NEUPOGEN ® for such patients, and only after careful consideration of the potential risks and benefits. Patients With Severe Chronic Neutropenia The safety and efficacy of NEUPOGEN ® in the treatment of neutropenia due to other hematopoietic disorders (eg‚ myelodysplastic syndrome [MDS]) have not been established. Care should be taken to confirm the diagnosis of SCN before initiating NEUPOGEN ® therapy. MDS and AML have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. 17 Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with NEUPOGEN ® for SCN. Based on available data including a postmarketing surveillance study, the risk of developing MDS and AML appears to be confined to the subset of patients with congenital neutropenia (see ADVERSE REACTIONS ). Abnormal cytogenetics and MDS have been associated with the eventual development of myeloid leukemia. The effect of NEUPOGEN ® on the development of abnormal cytogenetics and the effect of continued NEUPOGEN ® administration in patients with abnormal cytogenetics or MDS are unknown. If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing NEUPOGEN ® should be carefully considered.
ADVERSE REACTIONS Clinical Trial Experience Cancer Patients Receiving Myelosuppressive Chemotherapy In clinical trials involving over 350 patients receiving NEUPOGEN ® following nonmyeloablative cytotoxic chemotherapy‚ most adverse experiences were the sequelae of the underlying malignancy or cytotoxic chemotherapy. In all phase 2 and 3 trials‚ medullary bone pain‚ reported in 24% of patients‚ was the only consistently observed adverse reaction attributed to NEUPOGEN ® therapy. This bone pain was generally reported to be of mild-to-moderate severity‚ and could be controlled in most patients with non-narcotic analgesics; infrequently‚ bone pain was severe enough to require narcotic analgesics. Bone pain was reported more frequently in patients treated with higher doses (20 to 100 mcg/kg/day) administered IV‚ and less frequently in patients treated with lower SC doses of NEUPOGEN ® (3 to 10 mcg/kg/day). In the randomized‚ double-blind‚ placebo-controlled trial of NEUPOGEN ® therapy following combination chemotherapy in patients (n = 207) with small cell lung cancer‚ the following adverse events were reported during blinded cycles of study medication (placebo or NEUPOGEN ® at 4 to 8 mcg/kg/day). Events are reported as exposure-adjusted since patients remained on double-blind NEUPOGEN ® a median of 3 cycles versus 1 cycle for placebo. % of Blinded Cycles With Events NEUPOGEN ® N = 384 Patient Cycles Placebo N = 257 Patient Cycles Event Nausea/Vomiting 57 64 Skeletal Pain 22 11 Alopecia 18 27 Diarrhea 14 23 Neutropenic Fever 13 35 Mucositis 12 20 Fever 12 11 Fatigue 11 16 Anorexia 9 11 Dyspnea 9 11 Headache 7 9 Cough 6 8 Skin Rash 6 9 Chest Pain 5 6 Generalized Weakness 4 7 Sore Throat 4 9 Stomatitis 5 10 Constipation 5 10 Pain (Unspecified) 2 7 In this study‚ there were no serious‚ life-threatening‚ or fatal adverse reactions attributed to NEUPOGEN ® therapy. Specifically‚ there were no reports of flu-like symptoms‚ pleuritis‚ pericarditis‚ or other major systemic reactions to NEUPOGEN ® . Spontaneously reversible elevations in uric acid‚ lactate dehydrogenase‚ and alkaline phosphatase occurred in 27% to 58% of 98 patients receiving blinded NEUPOGEN ® therapy following cytotoxic chemotherapy; increases were generally mild-to-moderate. Transient decreases in blood pressure (less than 90/60 mmHg)‚ which did not require clinical treatment‚ were reported in 7 of 176 patients in phase 3 clinical studies following administration of NEUPOGEN ® . Cardiac events (myocardial infarctions‚ arrhythmias) have been reported in 11 of 375 cancer patients receiving NEUPOGEN ® in clinical studies; the relationship to NEUPOGEN ® therapy is unknown. No evidence of interaction of NEUPOGEN ® with other drugs was observed in the course of clinical trials (see PRECAUTIONS ). There has been no evidence for the development of antibodies or of a blunted or diminished response to NEUPOGEN ® in treated patients‚ including those receiving NEUPOGEN ® daily for almost 2 years. Patients With Acute Myeloid Leukemia In a randomized phase 3 clinical trial, 259 patients received NEUPOGEN ® and 262 patients received placebo postchemotherapy. Overall, the frequency of all reported adverse events was similar in both the NEUPOGEN ® and placebo groups (83% vs 82% in Induction 1; 61% vs 64% in Consolidation 1). Adverse events reported more frequently in the NEUPOGEN ® -treated group included: petechiae (17% vs 14%), epistaxis (9% vs 5%), and transfusion reactions (10% vs 5%). There were no significant differences in the frequency of these events. There were a similar number of deaths in each treatment group during induction (25 NEUPOGEN ® vs 27 placebo). The primary causes of death included infection (9 vs 18), persistent leukemia (7 vs 5), and hemorrhage (6 vs 3). Of the hemorrhagic deaths, 5 cerebral hemorrhages were reported in the NEUPOGEN ® group and 1 in the placebo group. Other serious nonfatal hemorrhagic events were reported in the respiratory tract (4 vs 1), skin (4 vs 4), gastrointestinal tract (2 vs 2), urinary tract (1 vs 1), ocular (1 vs 0), and other nonspecific sites (2 vs 1). While 19 (7%) patients in the NEUPOGEN ® group and 5 (2%) patients in the placebo group experienced severe or fatal hemorrhagic events, overall, hemorrhagic adverse events were reported at a similar frequency in both groups (40% vs 38%). The time to transfusion-independent platelet recovery and the number of days of platelet transfusions were similar in both groups. Cancer Patients Receiving Bone Marrow Transplant In clinical trials‚ the reported adverse effects were those typically seen in patients receiving intensive chemotherapy followed by bone marrow transplant (BMT). The most common events reported in both control and treatment groups included stomatitis, nausea, and vomiting‚ generally of mild-to-moderate severity and were considered unrelated to NEUPOGEN ® . In the randomized studies of BMT involving 167 patients who received study drug‚ the following events occurred more frequently in patients treated with Filgrastim than in controls: nausea (10% vs 4%)‚ vomiting (7% vs 3%)‚ hypertension (4% vs 0%)‚ rash (12% vs 10%)‚ and peritonitis (2% vs 0%). None of these events were reported by the investigator to be related to NEUPOGEN ® . One event of erythema nodosum was reported moderate in severity and possibly related to NEUPOGEN ® . Generally‚ adverse events observed in nonrandomized studies were similar to those seen in randomized studies‚ occurred in a minority of patients, and were of mild-to-moderate severity. In one study (n = 45)‚ 3 serious adverse events reported by the investigator were considered possibly related to NEUPOGEN ® . These included 2 events of renal insufficiency and 1 event of capillary leak syndrome. The relationship of these events to NEUPOGEN ® remains unclear since they occurred in patients with culture-proven infection with clinical sepsis who were receiving potentially nephrotoxic antibacterial and antifungal therapy. Cancer Patients Undergoing Peripheral Blood Progenitor Cell Collection and Therapy In clinical trials‚ 126 patients received NEUPOGEN ® for PBPC mobilization. In this setting‚ NEUPOGEN ® was generally well tolerated. Adverse events related to NEUPOGEN ® consisted primarily of mild-to-moderate musculoskeletal symptoms‚ reported in 44% of patients. These symptoms were predominantly events of medullary bone pain (33%). Headache was reported related to NEUPOGEN ® in 7% of patients. Transient increases in alkaline phosphatase related to NEUPOGEN ® were reported in 21% of the patients who had serum chemistries measured; most were mild-to-moderate. All patients had increases in neutrophil counts during mobilization‚ consistent with the biological effects of NEUPOGEN ® . Two patients had a WBC count greater than 100‚000/mm 3 . No sequelae were associated with any grade of leukocytosis. Sixty-five percent of patients had mild-to-moderate anemia and 97% of patients had decreases in platelet counts; 5 patients (out of 126) had decreased platelet counts to less than 50‚000/mm 3 . Anemia and thrombocytopenia have been reported to be related to leukapheresis; however‚ the possibility that NEUPOGEN ® mobilization may contribute to anemia or thrombocytopenia has not been ruled out. Patients With Severe Chronic Neutropenia Mild-to-moderate bone pain was reported in approximately 33% of patients in clinical trials. This symptom was readily controlled with non-narcotic analgesics. Generalized musculoskeletal pain was also noted in higher frequency in patients treated with NEUPOGEN ® . Palpable splenomegaly was observed in approximately 30% of patients. Abdominal or flank pain was seen infrequently, and thrombocytopenia (less than 50‚000/mm 3 ) was noted in 12% of patients with palpable spleens. Fewer than 3% of all patients underwent splenectomy‚ and most of these had a prestudy history of splenomegaly. Fewer than 6% of patients had thrombocytopenia (less than 50‚000/mm 3 ) during NEUPOGEN ® therapy‚ most of whom had a pre-existing history of thrombocytopenia. In most cases‚ thrombocytopenia was managed by NEUPOGEN ® dose reduction or interruption. An additional 5% of patients had platelet counts between 50‚000 and 100‚000/mm 3 . There were no associated serious hemorrhagic sequelae in these patients. Epistaxis was noted in 15% of patients treated with NEUPOGEN ®‚ but was associated with thrombocytopenia in 2% of patients. Anemia was reported in approximately 10% of patients‚ but in most cases appeared to be related to frequent diagnostic phlebotomy‚ chronic illness, or concomitant medications. Other adverse events infrequently observed and possibly related to NEUPOGEN ® therapy were: injection site reaction‚ rash‚ hepatomegaly‚ arthralgia‚ osteoporosis‚ cutaneous vasculitis‚ hematuria/proteinuria‚ alopecia‚ and exacerbation of some pre-existing skin disorders (eg‚ psoriasis). Cytogenetic abnormalities, transformation to MDS, and AML have been observed in patients treated with NEUPOGEN ® for SCN (see WARNINGS , PRECAUTIONS : Pediatric Use ). As of 31 December 1997, data were available from a postmarketing surveillance study of 531 SCN patients with an average follow-up of 4.0 years. Based on analysis of these data, the risk of developing MDS and AML appears to be confined to the subset of patients with congenital neutropenia. A life-table analysis of these data revealed that the cumulative risk of developing leukemia or MDS by the end of the 8th year of NEUPOGEN ® treatment in a patient with congenital neutropenia was 16.5% (95% C.I. = 9.8%, 23.3%); this represents an annual rate of approximately 2%. Cytogenetic abnormalities, most commonly involving chromosome 7, have been reported in patients treated with NEUPOGEN ® who had previously documented normal cytogenetics. It is unknown whether the development of cytogenetic abnormalities, MDS, or AML is related to chronic daily NEUPOGEN ® administration or to the natural history of congenital neutropenia. It is also unknown if the rate of conversion in patients who have not received NEUPOGEN ® is different from that of patients who have received NEUPOGEN ® . Routine monitoring through regular CBCs is recommended for all SCN patients. Additionally, annual bone marrow and cytogenetic evaluations are recommended in all patients with congenital neutropenia (see LABORATORY MONITORING ). Postmarketing Experience The following adverse reactions have been identified during postapproval of NEUPOGEN ® . 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. splenic rupture (see WARNINGS : Splenic Rupture ) acute respiratory distress syndrome (ARDS) (see WARNINGS : Acute Respiratory Distress Syndrome ) alveolar hemorrhage and hemoptysis (see WARNINGS : Alveolar Hemorrhage and Hemoptysis ) sickle cell crisis (see WARNINGS : Sickle Cell Disorders ) cutaneous vasculitis (see PRECAUTIONS : Cutaneous Vasculitis ) Sweet’s syndrome (acute febrile neutrophilic dermatosis)