WARNING: FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES Marqibo is for intravenous use only and is fatal if given by other routes. Death has occurred with intrathecal administration [see Warnings and Precautions ( 5.1 )] . Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vinCRIStine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 )] . WARNING: FOR INTRAVENOUS USE ONLY – FATAL IF GIVEN BY OTHER ROUTES See full prescribing information for complete boxed warning. Marqibo is for intravenous use only and is fatal if given by other routes. Death has occurred with intrathecal use. ( 5.1 ) Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vinCRIStine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage. ( 2.1 , 5.1 )
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 1 · 1 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Extravasation Tissue Injury: Extravasation causes tissue injury. If suspected, discontinue infusion immediately and consider local treatment measures ( 5.2 ) Neurologic Toxicity: Monitor patients for peripheral motor and sensory, central and autonomic neuropathy. Patients with preexisting severe neuropathy should be treated with Marqibo only after careful risk-benefit assessment. Interrupt, dose reduce, or discontinue Marqibo based on severity ( 2.3 , 5.3 ) Myelosuppression: Neutropenia, thrombocytopenia, or anemia may occur. Monitor blood counts prior to each dose of Marqibo. Consider Marqibo dose delay or reduction, as well as supportive care measures for grade 3 or 4 reactions ( 5.4 ) Tumor Lysis Syndrome: Anticipate, monitor for, and manage ( 5.5 ) Constipation and Bowel Obstruction : Institute a prophylactic bowel regimen to prevent potential constipation, bowel obstruction, and/or paralytic ileus. Use additional laxative products as needed ( 5.6 ) Fatigue : Severe fatigue can occur. Consider dose delay, reduction or discontinuation as appropriate ( 5.7 ) Hepatic Toxicity: Fatal liver toxicity and increased AST occurred. Monitor hepatic function tests. Interrupt or dose reduce as appropriate ( 5.8 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception ( 5.9 , 8.1 , 8.3 ) 5.1 For Intravenous Use Only: Fatal if Given by Other Routes Fatal if given by other routes. Death has occurred with intrathecal use. Marqibo (vinCRIStine sulfate LIPOSOME injection) has different dosage recommendations than vinCRIStine sulfate injection. Verify drug name and dose prior to preparation and administration to avoid overdosage [see Dosage and Administration ( 2.1 )]. 5.2 Extravasation Tissue Injury Extravasation can occur with Marqibo and extravasation causes tissue injury. Only administer through a secure and free-flowing venous access line. If extravasation is suspected, discontinue infusion immediately and consider local treatment measures 5.3 Neurologic Toxicity Sensory and motor neuropathies are common and are cumulative. Monitor patients for symptoms of peripheral motor and sensory, central and autonomic neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, hyporeflexia, areflexia, neuralgia, jaw pain, decreased vibratory sense, cranial neuropathy, ileus, burning sensation, arthralgia, myalgia, muscle spasm, or weakness, both before and during treatment. Orthostatic hypotension may occur. The risk of neurologic toxicity is greater if Marqibo is administered to patients with preexisting neuromuscular disorders or when other drugs with risk of neurologic toxicity are being given. In the studies of relapsed and/or refractory adult ALL patients, Grade ≥ 3 neuropathy events occurred in 32.5% of patients. Patients with preexisting severe neuropathy should be treated with Marqibo only after careful risk-benefit assessment. Interrupt, reduce the dose, or discontinue Marqibo based on severity [see Dosage and Administration ( 2.3 )]. 5.4 Myelosuppression Neutropenia, thrombocytopenia, or anemia may occur with Marqibo. Monitor complete blood counts prior to each dose of Marqibo. For Grade 3 or 4 neutropenia, thrombocytopenia, or anemia, consider Marqibo dose delay or reduction, as well as supportive care measures. 5.5 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) may occur in patients with ALL receiving Marqibo. Anticipate, monitor for, and manage as appropriate. 5.6 Constipation and Bowel Obstruction Ileus, bowel obstruction, and colonic pseudo obstruction have occurred. Marqibo can cause constipation [see Adverse Reactions ( 6 )]. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and paralytic ileus. Consider adequate dietary fiber intake, hydration, and stool softeners. Use additional laxative products as needed. 5.7 Fatigue Marqibo can cause severe fatigue. Consider dose delay, reduction, or discontinuation of Marqibo as appropriate. 5.8 Hepatic Toxicity Fatal hepatic toxicity and increased aspartate aminotransferase (AST) occurred. Grade ≥3 increased AST occurred in 6% to 11% of patients in clinical trials. Monitor hepatic function tests. Interrupt or reduce the dose of Marqibo as appropriate. 5.9 Embryo-fetal Toxicity Based on findings from nonclinical studies and the mechanism of action, Marqibo can cause fetal harm when administered to a pregnant woman. In toxicology studies in rats, vincristine sulfate liposome injection was teratogenic and caused embryo fetal mortality at exposures less than those reported in patients at the recommended dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Marqibo and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Marqibo and for 3 months after the last dose [see Use in Specific Populations ( 8.1, 8.3 )].
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: For Intravenous Use Only [see Warnings and Precautions ( 5.1 )] Extravasation Tissue Injury [see Warnings and Precautions ( 5.2 )] Neurologic Toxicity [see Warnings and Precautions ( 5.3 )] Myelosuppression [see Warnings and Precautions ( 5.4 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )] Constipation and Bowel Obstruction [see Warnings and Precautions ( 5.6 )] Fatigue [see Warnings and Precautions ( 5.7 )] Hepatic Toxicity [see Warnings and Precautions ( 5.8 )] Most common adverse reactions (incidence ≥ 30%) are constipation, nausea, pyrexia, fatigue, peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, and insomnia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma LLC at 1-888 292 9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Acute Lymphoblastic Leukemia Relapsed or Refractory Philadelphia Chromosome Negative ALL The safety of Marqibo was evaluated in a total of 83 adults in two trials: study 1 and study 2. Patients received Marqibo 2.25 mg/m2 once every seven days. Adverse reactions were observed in 100% of patients. The most common adverse reactions (>30%) were constipation (57%), nausea (52%), pyrexia (43%), fatigue (41%), peripheral neuropathy (39%), febrile neutropenia (38%), diarrhea (37%), anemia (34%), decreased appetite (33%), and insomnia (32%). Adverse reactions of Grade 3 or greater were reported in 96% of patients. Adverse reactions of Grade 3 or greater and occurring in ≥ 5% of patients are summarized in Table 2. Table 2 Most Commonly Reported (> 5%) Grade 3 a or Greater Adverse Reactions among 83 Patients Receiving the Clinical Dosing Regimen Adverse Reactions Grade ≥ 3 Study 1 and 2 (N=83) n(%) Blood and Lymphatic System Disorders 47 (56.6) Febrile Neutropenia 26 (31.3) Neutropenia 15 (18.1) Anemia 14 (16.9) Thrombocytopenia 14 (16.9) Infections 33 (39.8) Pneumonia 7 (8.4) Septic Shock 5 (6.0) Staphylococcal Bacteremia 5 (6.0) Neuropathyb 27 (32.5) Peripheral Sensory and Motor Neuropathy 14 (16.7) Constipation 4 (4.8) Ileus, Colonic Pseudo-Obstruction 5 (6.0) Asthenia 4 (4.8) Muscular Weakness 1 (1.2) Respiratory Thoracic and Mediastinal Disorders 17 (20.5) Respiratory Distress 5 (6.0) Respiratory Failure 4 (4.8) General Disorders and Administration Site Condition 31 (37.3) Pyrexia 12 (14.5) Fatigue 10 (12.0) Pain 7 (8.4) Gastrointestinal Disorders 21 (25.3) Abdominal Pain 7 (8.4) Investigations 20 (24.1) Aspartate Aminotransferase Increased 6 (7.2) Vascular Disorders 8 (9.6) Hypotension 5 (6.0) Psychiatric Disorders 9 (10.8) Mental Status Changes 3 (3.6) Cardiac Disorders 9 (10.8) Cardiac Arrest 5 (6.0) Renal and Urinary Disorders 6 (7.2) Musculoskeletal and Connective Tissue Disorders 7 (8.4) a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. b Including neuropathy-associated adverse reactions. A total of 76% of patients experienced serious adverse reactions during the studies. The most frequent serious adverse reactions included febrile neutropenia (20%), pyrexia (13%), hypotension (7%), respiratory distress (6%), and cardiac arrest (6%). Twenty-eight percent of patients experienced adverse reactions leading to treatment discontinuation. The most frequent adverse reactions that caused treatment discontinuation were peripheral neuropathy (10%), leukemia related (7%), and tumor lysis syndrome (2%). Dose reduction, delay, or omission occurred in 53% of patients. Adverse reactions related to neuropathy and leading to treatment discontinuation were decreased vibratory sense, facial palsy, hyporeflexia, constipation, asthenia, fatigue, and musculoskeletal pain, each reported in at least 1 patient. Deaths occurred in 23% of patients in study 1. The non-leukemia related causes of deaths were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multi system organ failure (2), pneumonia and septic shock (3), respiratory failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1).