Fruquintinib

Breast Feeding; Lactation; Milk, Human; Antineoplastic Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; Signal Transduction Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Warning

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In the prelicensure trials of fruquintinib, liver test abnormalities were common with its use as occurs frequently with the multikinase inhibitors. In the two large placebo controlled trials, serum ALT or AST elevations arose in 39% and 44% of fruquintinib-recipients compared to 27% and 30% of placebo-recipients. Aminotransferase levels exceeded 5 times the ULN in 6% and 4% of treated vs 3% and 2% of placebo participants. Serum aminotransferase elevations with jaundice arose only in one treated patient who developed an ALT of 270 U/L, AST 131 U/L, and a total bilirubin of 4.8 mg/dL 58 days after stopping therapy. The delay in onset was interpreted as the abnormalities being unrelated to therapy. There were no life threatening episodes of liver injury and no liver related deaths among the 1101 patients in the two controlled trials. Thus, clinically apparent liver injury was not observed with fruquintinib therapy, but ALT, AST, and bilirubin elevations were common during therapy, although not always due to the fruquintinib in these patients with advanced colorectal cancer. Furthermore, several other inhibitors of VEGF receptors have been implicated in instances of acute liver injury with symptoms and jaundice (pazopanib, regorafenib, sorafenib). Since approval and more widespread use of fruquintinib, there have been no published case reports of clinically apparent liver injury with jaundice.

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation, while in vivo studies demonstrated fruquintinib-mediated tumor growth inhibition in a tumor xenograft mouse model of colon cancer. Inhibition of VEGF-induced VEGFR-2 phosphorylation was illustrated in both in vitro and in vivo studies. Fruquintinib exposure-response relationships and the time course of pharmacodynamic response are unknown. A mean increase in QTc interval >20 milliseconds (ms) was not observed at the approved recommended dosage.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES.

The fruquintinib steady-state geometric mean (% coefficient of variation [CV]) maximum concentration (Cmax) is 300 ng/mL (28%) and the area under the concentration-time curve for the dosing interval (AUC0-24h) is 5880 ng∙h/mL (29%) at the recommended dosage. The fruquintinib Cmax and AUC0-24h are dose-proportional across the dosage range of 1 to 6 mg (0.2 to 1.2 times the recommended dosage). Fruquintinib steady state is achieved after 14 days with a mean AUC0-24h accumulation of 4-fold. The fruquintinib median (min, max) time to Cmax is approximately 2 hours (0, 26 hours). No clinically significant differences in fruquintinib pharmacokinetics were observed following administration of a high-fat meal (800 to 1000 calories, 50% fat).