Adverse Reactions Observed in Clinical Trials

The safety of XOSPATA was evaluated in 292 patients treated with XOSPATA 120 mg daily1

  • All adverse reactions were grouped by events that were reported under different terms but were represented by the same phenomenon (eg, transaminase increased included: AST increased, ALT increased, transaminases increased, liver function test increased, hepatic failure, hepatocellular injury, and hepatotoxicity)1
    • Similarly, adverse reactions reported in more than one body system that appeared to represent a common pathophysiologic event were grouped together

Adverse Reactions Reported in ≥10% (Any Grade) or ≥5% (Grades 3-5) of Patients With Relapsed or Refractory AML Who Received XOSPATA 120 mg Daily (N=292)1
Adverse Reaction Any Grade
 n (%) 		Grade ≥3*
 n (%)
Musculoskeletal and Connective
Tissue Disorders		    
Myalgia/arthralgia 123 (42) 13 (5)
Investigations    
Transaminase increased 121 (41) 47 (16)
Bilirubin increase 31 (11) 14 (5)
General Disorders and
Administration Site Conditions		    
Fatigue/malaise 116 (40) 14 (5)
Fever 103 (35) 13 (5)
Edema 100 (34) 5 (2)
Noninfectious diarrhea 99 (34) 8 (3)
Constipation 80 (27) 2 (<1)
Nausea 78 (27) 4 (1)
Stomatitis 77 (26) 11 (4)
Vomiting 58 (20) 3 (1)
Respiratory, Thoracic,
and Mediastinal Disorders		    
Dyspnea 98 (34) 36 (12)
Cough 74 (25) 1 (<1)
Skin and Subcutaneous
Tissue Disorders		    
Rash 87 (30) 8 (3)
Infections and Infestations    
Pneumonia 89 (30) 66 (23)
Sepsis 43 (15) 41 (14)
Vascular Disorders    
Hypotension 60 (21) 21 (7)
Hypertension 30 (10) 17 (6)
Nervous System Disorders    
Headache 60 (21) 4 (1)
Dizziness 57 (20) 1 (<1)
Dysgeusia 31 (11) 0
Renal and Urinary Disorders    
Renal impairment 54 (19) 11 (4)
Gastrointestinal Disorders    
Abdominal pain 50 (17) 5 (2)
Metabolism and
Nutrition Disorders		    
Decreased appetite 44 (15) 6 (2)
Psychiatric Disorders    
Insomnia 42 (14) 1 (<1)

*Grades 3 to 5 include serious, life-threatening, and fatal adverse reactions.1

ALT=alanine aminotransferase; AML=acute myeloid leukemia; AST=aspartate aminotransferase.


Adverse reactions1
Most Common Adverse Reactions (≥20%)1
  • 42% myalgia/arthralgia
  • 41% transaminase increased
  • 40% fatigue/malaise
  • 35% fever
  • 34% noninfectious diarrhea
  • 34% dyspnea
  • 34% edema
  • 30% rash
  • 30% pneumonia
  • 27% nausea
  • 26% stomatitis
  • 25% cough
  • 21% headache
  • 21% hypotension
  • 20% dizziness
  • 20% vomiting

  • The most frequent nonhematological serious adverse reactions (≥5%) reported in patients were:
    • 19% pneumonia
    • 13% sepsis
    • 13% fever
    • 7% dyspnea
    • 5% renal impairment
  • Other clinically significant adverse reactions occurring in ≤10% of patients included:
    • 7% prolonged QT interval
    • 4% cardiac failure†
    • 3% pericardial effusion
    • 2% pericarditis
    • 1% differentiation syndrome
    • 1% anaphylactic reaction
    • 1% PRES

†Grouped terms: cardiac failure, cardiac failure congestive, cardiomyopathy, cardiomegaly, chronic left ventricular failure, and ejection fraction decreased.1


Discontinuation rate1

8%

of patients treated with XOSPATA permanently discontinued treatment due to an adverse reaction (n=22/292)

  • The most common adverse reactions (>1%) leading to treatment discontinuation were:
    • 2% pneumonia
    • 2% sepsis
    • 1% dyspnea

PRES=posterior reversible encephalopathy syndrome; QT=cardiac ventricular repolarization.

Laboratory Abnormalities Observed in Clinical Trials

Most Common (>20%) Laboratory Abnormalities Reported Post Baseline in Patients With Relapsed or Refractory AML Who Received XOSPATA 120 mg Daily (N=292)1
Parameter Any Grade
 n (%) 		Grade ≥3‡
 n (%)
Creatinine increased 273 (94) 10 (3)
Hyperglycemia 252 (86) 26 (9)
Hypertriglyceridemia 237 (81) 18 (6)
ALT increased 229 (78) 35 (12)
AST increased 228 (78) 28 (10)
Alkaline phosphatase increased 189 (65) 3 (1)
Hypocalcemia 179 (61) 15 (5)
Hypoalbuminemia 169 (58) 10 (3)
Creatine kinase increased 157 (54) 14 (5)
Hypophosphatemia 141 (48) 36 (12)
Hypokalemia 103 (35) 25 (9)
Hyponatremia 93 (32) 36 (12)

‡Grades 3 to 5 include serious, life-threatening, and fatal adverse reactions.1

Drug Interactions With XOSPATA

Effect of Other Drugs on XOSPATA1
Co-administered drugs Effect on XOSPATA Recommendation
Combined P-gp and strong CYP3A inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases the exposure of XOSPATA, which may decrease the efficacy of XOSPATA Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers
Strong CYP3A inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases the exposure of XOSPATA
  • Consider alternative therapies that are not strong CYP3A inhibitors
  • If concomitant use of strong CYP3A inhibitors is considered essential for the care of the patient, monitor the patient more frequently for adverse reactions with XOSPATA
  • Interrupt and reduce dose of XOSPATA in patients with serious or life-threatening toxicity
Effect of XOSPATA on Other Drugs1
Co-administered drugs Effect on other drugs Recommendation
Drugs that target the 5HT2B receptor or the sigma nonspecific receptor Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (eg, escitalopram, fluoxetine, sertraline) Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient

5HT2B=5-hydroxytryptamine receptor 2B; CYP3A=cytochrome P450 family 3 subfamily A; P-gp=P-glycoprotein.