bserved in patients with relapsed or refractory AML areshown in Table 3.
Table 3: Most common (>20%) Laboratory Abnormalities Reported in Patients with Relapsed or
Refractory AML
Parameter
XOSPATA (120 mg daily)
N=292
Any Grade
n (%)
Grade ≥3*
n (%)
Creatinine increased 273 (94) 10 (3)
Hyperglycemia 252 (86) 26 (9)
Hypertriglyceridemia 237 (81) 18 (6)
Alanine aminotransferase increased 229 (78) 35 (12)
Aspartate aminotransferase 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)
*Grade 3-5 includes serious, life-threatening and fatal adverse reactions.
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on XOSPATA
Combined P-gp and Strong CYP3A Inducers
Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure whichmay decrease XOSPATA efficacy [see Clinical Pharmacology (12.3)]. Avoid concomitant use of XOSPATA withcombined P-gp and strong CYP3A inducers.
Strong CYP3A InhibitorsConcomitant use of XOSPATA with a strong CYP3A inhibitor increases gilteritinib exposure [see Clinical Pharmacology(12.3)]. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors isconsidered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions.
Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity [see Dosage andAdministration (2.3)].
7.2 Effect of XOSPATA on Other Drugs
Drugs that Target 5HT2B Receptor or Sigma Nonspecific ReceptorConcomitant use of gilteritinib may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecificreceptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their useis considered essential for the care of the patient [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on findings from animal studies (see Data) and its mechanism of action, XOSPATA can cause fetal harm whenadministered to a pregnant woman [see Clinical Pharmacology (12.1)].
There are no available data on XOSPATA use in pregnant women to inform a drug-associated risk of adversedevelopmental outcomes. In animal reproduction studies, administration of gilteritinib to pregnant rats duringorganogenesis caused adverse developmental outcomes including embryo-fetal lethality, suppressed fetal growth, andteratogenicity at maternal exposures (AUC24) approximately 0.4 times the AUC24 in patients receiving the recommendeddose (see Data). Advise pregnant women of the potential risk to a fetus.
Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The backgroundrisk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, theestimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%20%, respectively.
Data
Animal Data
In an embryo-fetal development study in rats, pregnant animals received oral doses of gilteritinib of 0, 0.3, 3, 10, and30 mg/kg/day during the period o |
