XPOVIO can cause severe gastrointestinal toxicities [see Adverse Reactions (6.1)]. In patients with DLBCL (n=134), gastrointestinal toxicity occurred in 80% of patients with Grade 3 or 4 in 13%. 

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. 

In patients with DLBCL (SADAL, n=134) with use of antiemetic prophylaxis, nausea occurred in 57% of patients and Grade 3 nausea occurred in 6% of patients. Vomiting occurred in 28% of patients and Grade 3 vomiting occurred in 1.5% of patients. The median time to first onset was 3 days for nausea and 7 days for vomiting. 

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 (2.5)]. 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. 

In patients with DLBCL (SADAL, n=134), diarrhea occurred in 37% of patients and Grade 3 diarrhea occurred in 3% of patients treated with XPOVIO. The median time to onset of the first event was 12 days. 

Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration (2.5)]. 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. 

In patients with DLBCL (SADAL, n=134), anorexia was reported as an adverse reaction in 37% of patients and Grade 3 anorexia occurred in 3.7% of patients treated with XPOVIO. Weight loss (Grade 1-2) was reported as an adverse reaction in 30% of patients. 

Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first three months of treatment. Interrupt, reduce dose or permanently discontinue based on severity of adverse reaction [see Dosage and Administration (2.5)]. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.