Indications
Brigatinib is used to treat adults with ALK-positive (anaplastic lymphoma kinase) metastatic Non-small cell lung cancer (NSCLC). It is meant for people whose disease has progressed while on Crizotinib, or who can't tolerate Crizotinib.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Brigatinib is a tyrosine kinase inhibitor. In laboratory tests, at concentrations that can be reached in patients, it was active against several kinases, including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R) and FLT-3, as well as EGFR deletion and point mutations. In in-vitro and in vivo assays, it blocked autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2 and S6. It also blocked the in vitro proliferation of cell lines expressing EML4-ALK and NPM ALK fusion proteins, and in mice it slowed the growth of EML4-ALK-positive NSCLC xenografts in a dose-dependent way. The exposure-response relationships and the time course of the pharmacodynamic response are unknown.
Absorption: After single oral doses of 30 to 240 mg, the median time to peak concentration (Tmax) ranged from 1 to 4 hours.
Distribution: Brigatinib is 66% bound to human plasma proteins, and in vitro this binding does not depend on concentration. The blood to plasma concentration ratio is 0.69. With 180 mg taken once daily, the mean apparent volume of distribution (Vz/F) at steady-state was 153 L.
Elimination: With 180 mg taken once daily, the mean apparent oral clearance (CL/F) at steady-state is 12.7 L/h, and the mean plasma elimination half-life is 25 hours.
Metabolism: In vitro, Brigatinib is mainly metabolized by CYP2C8 and CYP3A4. Healthy subjects were given a single 180 mg oral dose of radiolabeled Brigatinib. In them, N-demethylation and cysteine conjugation were the two major metabolic pathways. The main circulating radioactive components were unchanged Brigatinib (92%) and its primary metabolite, AP26123 (3.5%). In patients, the steady-state AUC of AP26123 was less than 10% of the AUC of Brigatinib exposure. In vitro, AP26123 inhibited ALK with approximately 3-fold lower potency than Brigatinib.
Excretion: After healthy subjects took a single 180 mg oral dose of radiolabeled Brigatinib, 65% of the dose was recovered in feces and 25% in urine. Unchanged Brigatinib made up 41% of the total radioactivity in feces and 86% in urine.
Pregnancy & Breastfeeding
Pregnancy: There are no clinical data on the use of Brigatinib in pregnant women. If the medicine is used during pregnancy, or if the patient becomes pregnant while taking it, she should be told about the potential risk to the fetus.
Lactation: No data are available on whether Brigatinib passes into human milk, or on its effects on a breastfed infant or on milk production. Because breastfed infants could have adverse reactions, women who are breastfeeding should be advised not to breastfeed during treatment with Brigatinib and for 1 week after the final dose.
Females of reproductive potential: These women should be advised to use effective non-hormonal contraception during treatment and for at least 4 months after the final dose. They should be counselled to choose a non-hormonal method, since Brigatinib can make some hormonal contraceptives ineffective.
Males of reproductive potential: Brigatinib has the potential for genotoxicity, so males with female partners of reproductive potential should be advised to use effective contraception during treatment and for at least 3 months after the final dose.
Infertility: Animal findings in the male reproductive organs suggest that Brigatinib may reduce fertility in males.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.
Side Effects & Interactions
Side Effects
No side-effect data recorded yet.