INTEGRATED SAFETY SET

Adverse Reactions Observed in Clinical Trials

  • The safety of XOSPATA was evaluated on the basis of 319 patients with relapsed or refractory AML treated with XOSPATA 120 mg daily in 3 clinical trials1
  • The median duration of exposure to XOSPATA was 3.6 months (range: 0.1 to 43.4 months)1
  • Fatal adverse reactions occurred in 2% of patients who received XOSPATA, including cardiac arrest (1%) and 1 case each of differentiation syndrome and pancreatitis1
  • The most frequent (≥5%) nonhematological serious adverse reactions reported in patients treated with XOSPATA were1:
    • 13% fever
    • 9% dyspnea
    • 8% renal impairment
    • 6% transaminase increased
    • 5% noninfectious diarrhea

7%

of patients treated with XOSPATA permanently discontinued treatment due to an adverse reaction (n=22/319)1

  • The most common adverse reactions (>1%) leading to treatment discontinuation in the XOSPATA arm were AST increased (2%) and ALT increased (2%)1
  • Dose interruption due to an adverse reaction occurred in 29% of patients treated with XOSPATA (n=91/319)1
    • The most common adverse reactions leading to dose interruption were AST increased (6%), ALT increased (6%), and fever (4%)
  • Dose reduction due to an adverse reaction occurred in 6% of patients in the XOSPATA arm (n=20/319)1
Most Frequent (≥10%) Nonhematological Adverse Reactions (All Grades) Reported in Patients Treated With XOSPATA1
  • 51% transaminase increased
  • 50% myalgia/arthralgia
  • 44% fatigue/malaise
  • 41% fever
  • 41% mucositis
  • 40% edema
  • 36% rash
  • 35% noninfectious diarrhea
  • 35% dyspnea
  • 30% nausea
  • 28% cough
  • 28% constipation
  • 25% eye disorders
  • 24% headache
  • 22% dizziness
  • 22% hypotension
  • 21% vomiting
  • 21% renal impairment
  • 18% abdominal pain
  • 18% neuropathy
  • 15% insomnia
  • 11% dysgeusia
  • The most frequent (≥5%) Grade ≥3 nonhematological adverse reactions reported in patients treated with XOSPATA were1:
    • 21% transaminase increased
    • 12% dyspnea
    • 7% hypotension
    • 7% mucositis
    • 7% myalgia/arthralgia
    • 6% fatigue/malaise
  • Other clinically significant adverse reactions occurring in ≤10% of patients included1:
    • 9% prolonged QT interval
    • 8% hypersensitivity*
    • 5% pancreatitis*
    • 4% cardiac failure*
    • 4% pericardial effusion
    • 3% acute febrile neutrophilic dermatosis
    • 3% differentiation syndrome
    • 2% pericarditis/myocarditis*
    • 1% large intestine perforation
    • 1% PRES
  • Shifts to Grades 3 to 4 nonhematologic laboratory abnormalities included1:
    • 14% phosphate decreased
    • 13% ALT increased
    • 12% sodium decreased
    • 10% AST increased
    • 6% calcium decreased
    • 6% creatine kinase increased
    • 6% triglycerides increased
    • 3% creatinine increased
    • 2% alkaline phosphatase increased

*Grouped terms: cardiac failure (cardiac failure, cardiac failure congestive, cardiomegaly, cardiomyopathy, chronic left ventricular failure, and ejection fraction decreased), hypersensitivity (anaphylactic reaction, angioedema, dermatitis allergic, drug hypersensitivity, erythema multiforme, hypersensitivity, and urticaria), pancreatitis (amylase increased, lipase increased, pancreatitis, pancreatitis acute), pericarditis/myocarditis (myocarditis, pericardial hemorrhage, pericardial rub, and pericarditis).1

ALT=alanine aminotransferase; AML=acute myeloid leukemia; AST=aspartate aminotransferase; PRES=posterior reversible encephalopathy syndrome; QT=cardiac ventricular repolarization.

ADMIRAL TRIAL SAFETY

Safety Profile of XOSPATA vs Salvage Chemotherapy in Preselected Low-Intensity Chemotherapy Subgroup

Adverse reactions reported in the first 30 days of treatment in the ADMIRAL trial were evaluated according to whether patients were preselected for high-intensity chemotherapy or low-intensity chemotherapy.1

  • 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, blood alkaline phosphatase increased, and transaminases increased)1
    • Similarly, adverse reactions reported in more than one body system that appeared to represent a common pathophysiologic event were grouped together
Adverse Reactions Adverse Reactions Adverse Reactions Adverse Reactions Adverse Reactions

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

Safety Profile of XOSPATA vs Salvage Chemotherapy in Preselected High-Intensity Chemotherapy Subgroup

  • All adverse reactions were grouped by events that were reported under different terms but were represented by the same phenomenon (eg, myalgia/arthralgia included: arthralgia, back pain, bone pain, flank pain, limb discomfort, medial tibial stress syndrome, myalgia, muscle twitching, musculoskeletal discomfort, musculoskeletal pain, muscle spasms, neck pain, noncardiac chest pain, pain, and pain in extremity)1
    • Similarly, adverse reactions reported in more than one body system that appeared to represent a common pathophysiologic event were grouped together
Adverse Reactions Adverse Reactions Adverse Reactions Adverse Reactions Adverse Reactions

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

ADMIRAL TRIAL SAFETY

Laboratory Abnormalities by Preselected High-Intensity and Low-Intensity Chemotherapy in the First 30 Days of ADMIRAL Trial

Selected post-baseline laboratory values were observed in the first 30 days of treatment in the ADMIRAL trial.1

Laboratory Abnormalities Chart Laboratory Abnormalities Chart Laboratory Abnormalities Chart

Drug Interactions With XOSPATA

Effect of Other Drugs on XOSPATA Chart Effect of XOSPATA on Other Drugs Chart Effect of XOSPATA on Other Drugs Chart Effect of XOSPATA on Other Drugs Chart
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

‡Refer to Section 12.3 in the Full Prescribing Information for more information on concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer (eg, rifampin) or strong CYP3A inhibitors (eg, itraconazole).1

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