xpovio

Important safety information

Thrombocytopenia : Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care ( 2.4 , 5.1 ). Neutropenia : Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony-stimulating factors ( 2.4 , 5.2 ). Gastrointestinal Toxicity : Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care ( 2.4 , 5.3 ). Hyponatremia : Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care ( 2.4 , 5.4 ). Serious Infection : Monitor for infection and treat promptly ( 5.2 , 5.5 ). Neurological Toxicity : Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes ( 5.6 ). Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception ( 5.7 , 8.1 , 8.3 ). Cataract : Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract ( 5.8 ). 5.1 Thrombocytopenia XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia is the leading cause of dosage modifications [see Adverse Reactions ( 6.1 )] . In patients with multiple myeloma who received XPOVIO 100 mg once weekly (BOSTON, n=195), thrombocytopenia was reported in 92% of patients and severe (Grade 3-4) thrombocytopenia was reported in 43% of patients. The median time to first onset was 22 days for any grade thrombocytopenia and 43 days for Grade 3 or 4 thrombocytopenia. Bleeding occurred in 16% of patients with thrombocytopenia, clinically significant bleeding (Grade ≥3 bleeding) occurred in 4% of patients with thrombocytopenia, and fatal hemorrhage occurred in 2% of patients with thrombocytopenia. Permanent discontinuations of XPOVIO due to thrombocytopenia occurred in 2% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM, n=202), thrombocytopenia was reported as an adverse reaction in 74% of patients and severe (Grade 3-4) thrombocytopenia was reported in 61% of patients. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, clinically significant bleeding occurred in 5% of patients with thrombocytopenia, and fatal hemorrhage occurred in <1% of patients. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first three months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )]. 5.2 Neutropenia XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection [see Adverse Reactions ( 6.1 )] . In patients with multiple myeloma who received XPOVIO 100 mg once weekly (BOSTON, n=195), neutropenia was reported in 48% of patients and severe neutropenia (Grade 3-4) was reported in 12% of patients. The median time to onset of the first event was 23 days for any grade neutropenia and 40 days for Grade 3-4 neutropenia. Febrile neutropenia was reported in <1% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM, n=202), neutropenia was reported as an adverse reaction in 34% of patients and severe (Grade 3-4) neutropenia was reported in 21% of patients. The median time to onset of the first event was 25 days. Febrile neutropenia was reported in 3% of patients. Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first three months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )]. 5.3 Gastrointestinal Toxicity XPOVIO can cause severe gastrointestinal toxicities [see Adverse Reactions ( 6.1 )] . Nausea/Vomiting In patients with multiple myeloma who received XPOVIO once weekly (BOSTON, n=195) with use of antiemetic prophylaxis (88% of patients), nausea was reported in 50% of patients and Grade 3 nausea was reported in 8% of patients. The median time to onset of the first event was 6 days. Vomiting was reported in 21% of patients and Grade 3 vomiting was reported in 4.1% of patients. The median time to onset of the first event was 8 days. Permanent discontinuation due to nausea occurred in 3.1% of patients and due to vomiting occurred in 2.1% of patients. In patients with multiple myeloma receiving XPOVIO 80 mg twice weekly (STORM, n=202) with use of antiemetic prophylaxis, nausea was reported as an adverse reaction in 72% of patients and Grade 3 nausea occurred in 9%. The median time to first onset of nausea was 3 days. Vomiting was reported in 41% of patients and Grade 3 vomiting occurred in 4% of patients. The median time to first onset of vomiting was 5 days. Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )] . Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated. Diarrhea In patients with multiple myeloma who received XPOVIO once weekly (BOSTON, n=195), diarrhea was reported in 32% of patients and Grade 3 diarrhea was reported in 6% of patients. The median time to onset of the first event was 50 days. Permanent discontinuation due to diarrhea occurred in 1% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM, n=202), diarrhea was reported as an adverse reaction in 44% of patients and Grade 3 diarrhea occurred in 6% of patients. The median time to onset of diarrhea was 15 days. Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration ( 2.4 )] . Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated. Anorexia/Weight Loss In patients with multiple myeloma who received XPOVIO 100 mg once weekly (BOSTON, n=195), anorexia was reported in 35% of patients and Grade 3 anorexia was reported in 3.6% of patients. The median time to onset of the first event was 35 days. Permanent discontinuations due to anorexia occurred in 2.1% of patients. Weight loss was reported in 26% of patients and Grade 3 weight loss was reported in 2.1% of patients. The median time to onset of the first event was 58 days. Permanent discontinuation due to weight loss occurred in 1% of patients. In patients with multiple myeloma who received XPOVIO 80 mg twice weekly (STORM n=202), anorexia was reported as an adverse reaction in 53% of patients and Grade 3 anorexia occurred in 5% of patients. The median time to onset of anorexia was 8 days. Weight loss was reported as an adverse reaction in 47% of patients and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days. Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first…