he median time to onset of the first vomiting event was 5 days.
Provide prophylactic 5‐HT3 antagonists and/or other anti‐nausea agents, prior to and during treatment with XPOVIO. Manage nausea/vomiting by dose interruption, reduction, and/or discontinuation. Administerintravenous fluids and replace electrolytes to prevent dehydration in patients at risk. Use additional anti‐
nausea medications as clinically indicated [see Dosage and Administration (2.4)].
Diarrhea
Diarrhea was reported as an adverse reaction in 44% of patients, and Grade 3 diarrhea occurred in 6% ofpatients treated with XPOVIO. The median time to onset of diarrhea was 15 days.
Manage diarrhea by dose modifications and/or standard anti‐diarrheal agents; administer intravenous fluids to prevent dehydration in patients at risk [see Dosage and Administration (2.4)].
Anorexia/Weight Loss
Anorexia was reported as an adverse reaction in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. 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 patient weight at baseline, during treatment, and as clinically indicated. Monitor more frequentlyduring the first two months of treatment. Manage anorexia and weight loss with dose modifications, appetitestimulants, and nutritional support [see Dosage and Administration (2.4)].
5.4 Hyponatremia
XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO experienced hyponatremia, 22% ofpatients experienced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.
Monitor sodium level at baseline, during treatment, and as clinically indicated. Monitor more frequentlyduring the first two months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose>150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clinical guidelines (intravenous salineand/or salt tablets), including dietary review. Interrupt and/or reduce dose, or permanently discontinue basedon severity of adverse reaction [see Dosage and Administration (2.4) and Adverse Reactions (6.1)].
5.5 Infections
In patients receiving XPOVIO, 52% of patients experienced any grade of infection. Upper respiratory tractinfection of any grade occurred in 21%, pneumonia in 13%, and sepsis in 6% of patients. Grade ≥3 infectionswere reported in 25% of patients, and deaths resulting from an infection occurred in 4% of patients. The mostcommonly reported Grade ≥3 infections were pneumonia in 9% of patients, followed by sepsis in 6%. Themedian time to onset was 54 days for pneumonia and 42 days for sepsis. Most infections were not associatedwith neutropenia and were caused by non‐opportunistic organisms [see Adverse Reactions (6.1)].
5.6 Neurological Toxicity
Neurological toxicities occurred in patients treated with XPOVIO [see Adverse Reactions (6.1)].
Neurological adverse reactions including dizziness, syncope, depressed level of consciousness, and mentalstatus changes (including delirium and confusional state) occurred in 30% of patients, and severe events(Grade 3‐4) occurred in 9% of patients treated with XPOVIO. Median time to the first event was 15 days.
Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerb |
