rs of reproductive potential to use effective contraception during treatment withXOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnantwhile receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to thefetus [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling:
• Posterior reversible encephalopathy [see Warnings and Precautions (5.1)]
• Prolonged QT interval [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trialsof a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observedin practice.
The safety eva luation of XOSPATA is based on 292 patients with relapsed or refractory AML treated with 120 mggilteritinib daily. The median duration of exposure to XOSPATA was 3 months (range 0.1 to 42.8 months).
The most frequent nonhematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis(13%), fever (13%), dyspnea (7%) and renal impairment (5%).
Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The mostcommon adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). Themost common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise(40%), fever (35%), noninfectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea(27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).
Table 2: Adverse Reactions Reported in ≥10% (Any Grade) or ≥5% (Grade 3-5) of Patients withRelapsed or Refractory AML
Body System
Adverse Reaction
XOSPATA (120 mg daily)
N=292
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)
Edemaþ 100 (34) 5 (2)
Noninfectious diarrheaß 99 (34) 8 (3)
Constipation 80 (27) 2 (<1)
Nausea 78 (27) 4 (1)
Stomatitisà 77 (26) 11 (4)
Vomitingè 58 (20) 3 (1)
Respiratory, Thoracic and Mediastinal Disorders
Dyspneað 98 (34) 36 (12)
Cough 74 (25) 1 (<1)
Skin and subcutaneous tissue disorders
Rashø 87 (30) 8 (3)
Infections and Infestations
Pneumoniaý 89 (30) 66 (23)
Sepsis₤ 43 (15) 41 (14)
Vascular disorders
Hypotension¥ 60 (21) 21 (7)
HypertensionΠ30 (10) 17 (6)
Nervous System Disorders
Headacheɶ 60 (21) 4 (1)
DizzinessÐ 57 (20) 1 (<1)
Dysgeusia 31 (11) 0
Renal and urinary disorders
Renal impairmentA 54 (19) 11 (4)
Gastrointestinal Disorders
Abdominal painB 50 (17) 5 (2)
Metabolism and Nutrition disorders
Decreased appetite 44 (15) 6 (2)
Psychiatric Disorders
Insomnia 42 (14) 1 (<1)
*Grade 3-5 |
