Laboratory Abnormality 90 mg once daily
N= 109 90→180 mg once daily
N=110
All Grades
(%) Grades 3-4
(%) All Grades
(%) Grades 3-4
(%)
* Per CTCAE version 4.0 † Elevated blood insulin was also observed in both regimens
Chemistry
Increased aspartate aminotransferase 38 0.9 65 0
Hyperglycemia† 38 3.7 49 3.6
Increased creatine phosphokinase 27 2.8 48 12
Increased lipase 21 4.6 45 5.5
Increased alanine aminotransferase 34 0 40 2.7
Increased amylase 27 3.7 39 2.7
Increased alkaline phosphatase 15 0.9 29 0.9
Decreased phosphorous 15 1.8 23 3.6
Prolonged activated partial thromboplastin time 22 1.8 20 0.9
Hematology
Anemia 23 0.9 40 0.9
Lymphopenia 19 2.8 27 4.5CLOSE
7 DRUG INTERACTIONS
7.1 Drugs That May Increase Brigatinib Plasma Concentrations
Strong CYP3A Inhibitors
Coadministration of itraconazole, a strong CYP3A inhibitor, increased brigatinib plasma concentrations and may result in increased adverse reactions [see CLINICAL PHARMACOLOGY (12.3)]. Avoid the concomitant use of strong CYP3A inhibitors with ALUNBRIG, including but not limited to certain antivirals (e.g., boceprevir, cobicistat, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir), macrolide antibiotics (e.g., clarithromycin), antifungals (e.g., itraconazole, ketoconazole, posaconazole, voriconazole), and conivaptan. Avoid grapefruit or grapefruit juice as it may also increase plasma concentrations of brigatinib [see CLINICAL PHARMACOLOGY (12.3)]. If concomitant use of a strong CYP3A inhibitor cannot be avoided, reduce the dose of ALUNBRIG by approximately 50% [see DOSAGE AND ADMINISTRATION (2.3)].
7.2 Drugs That May Decrease Brigatinib Plasma Concentrations
Strong CYP3A Inducers
Coadministration of ALUNBRIG with rifampin, a strong CYP3A inducer, decreased brigatinib plasma concentrations and may result in decreased efficacy [see CLINICAL PHARMACOLOGY (12.3)]. Avoid the concomitant use of strong CYP3A inducers with ALUNBRIG, including but not limited to rifampin, carbamazepine, phenytoin, and St. John's Wort [see CLINICAL PHARMACOLOGY (12.3)].
7.3 Drugs That May Have Their Plasma Concentrations Altered by Brigatinib
CYP3A Substrates
Brigatinib induces CYP3A in vitro and may decrease concentrations of CYP3A substrates. Coadministration of ALUNBRIG with CYP3A substrates, including hormonal contraceptives, can result in decreased concentrations and loss of efficacy of CYP3A substrates [see USE IN SPECIFIC POPULATIONS (8.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to a pregnant woman [see DATA and CLINICAL PHARMACOLOGY (12.1)]. There are no clinical data on the use of ALUNBRIG in pregnant women. Administration of brigatinib to pregnant rats during the period of organogenesis resulted in dose-related skeletal anomalies at doses as low as 12.5 mg/kg/day (approximately 0.7 times the h |
