igher Incidence than in the Dacarbazine Arm (Between Arm Difference of ≥5% forAll Grades or ≥2% for Grades 3 and 4)a (Study 2)† Laboratory Abnormality Halaven Dacarbazine
All Grades Grades 3 - 4 All Grades Grades 3 – 4
Hematology
Anemia 70% 4.1% 52% 6%
Neutropenia 63% 32% 30% 8.9%
Chemistry
Increased alanine aminotransferase (ALT) 43% 2.3% 28% 2.3%
Increased aspartate aminotransferase (AST) 36% 0.9% 16% 0.5%
Hypokalemia 30% 5.4% 14% 2.8%
Hypocalcemia 28% 5% 18% 1.4%
Hypophosphatemia 20% 3.2% 11% 1.4%
aEach test incidence is based on the number of patients who had both baseline and at least one on-study measurement and at least 1 grade increase from baseline.Halaven group (range 221-222) and dacarbazine group (range 214-215)
†Laboratory results were graded per NCI CTCAE v4.03.
6.2 Postmarketing Experience The following adverse drug reactions have been identified during post-approval of HALAVEN. 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.
Blood and Lymphatic System Disorders: lymphopenia
Gastrointestinal Disorders: pancreatitis
Hepatobiliary Disorders: hepatotoxicity
Immune System Disorders: drug hypersensitivity
Infections and Infestations: pneumonia, sepsis/neutropenic sepsis
Metabolism and Nutrition Disorders: hypomagnesemia, dehydration
Respiratory, thoracic and mediastinal disorders: interstitial lung disease
Skin and Subcutaneous Tissue Disorders: pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. Clinically meaningful differences in exposure (AUC) were not observed in patients with advanced solid tumors when HALAVEN was administered with or without ketoconazole (a strong inhibitor of CYP3A4 and a P-gp inhibitor) and when HALAVEN was administered with or without rifampin (a CYP3A4 inducer) [see Clinical Pharmacology (12.3)].
7.2 Effect of HALAVEN on Other Drugs Eribulin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 enzymes or induce CYP1A2, CYP2C9, CYP2C19 or CYP3A4 enzymes at relevant clinical concentrations. Eribulin is not expected to alter the plasma concentrations of drugs that are substrates of these enzymes [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy Risk Summary
Based on findings from an animal reproduction study and its mechanism of action, HALAVEN can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of HALAVEN during pregnancy. In an animal reproduction study, eribulin mesylate caused embryo-fetal toxicity when administered to pregnant rats during organogenesis at doses below the recommended human dose [see Data]. Advise pregnant women of the potential risk to a fetus.
The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically-recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
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