Alectinib

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

EMA approved medicines: Human medicine

This chemical does not meet GHS hazard criteria for 66.7% (2 of 3) of all reports.

Warning

H341 (33.3%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

P203, P260, P280, P318, P319, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In preregistration trials of alectinib, ALT elevations occurred in up to 60% of patients, but values above 5 times the upper limit of normal (ULN) were found in only 1% to 5%. Alectinib therapy was also associated with frequent elevations in alkaline phosphatase (47%) and bilirubin (39%), but these abnormalities were usually transient, asymptomatic, and mild-to-moderate in degree. Clinically apparent liver injury with jaundice was rare, but cases were reported and at least 2% of alectinib treated subjects discontinued therapy early because of liver test abnormalities. In subsequent controlled trials, liver test abnormalities arose in 41% of alectinib treated patients and were above five times ULN in 8%, leading to early discontinuation in 4%, and 3 patients were judged to have drug induced liver injury.

L01XE36

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Both alectinib and its major active metabolite M4 demonstrate similar in vivo and in vitro activity against multiple mutant forms of ALK.

Alectinib is metabolized by CYP3A4 to its major active metabolite M4. M4 is then further metabolized by CYP3A4. Both alectinib and M4 demonstrate similar in vivo and in vitro activity. In vitro studies suggest that alectinib is not a substrate for P-gp while M4 is.

LIJ4CT1Z3Y

ALECTINIB

Established Pharmacologic Class [EPC] - Kinase Inhibitor

Mechanisms of Action [MoA] - Kinase Inhibitors

Alectinib is a Kinase Inhibitor. The mechanism of action of alectinib is as a Kinase Inhibitor.

Alectinib reached maximal concentrations at 4 hours following administration of 600 mg twice daily under fed conditions in patients with ALK-positive NSCLC. The absolute bioavailability was 37% in the fed state. A high-fat, high-calorie meal increased the combined exposure of alectinib and its major metabolite M4 by 3.1-fold following oral administration of a single 600 mg dose.

When radioactively labeled, 98% of radioactivity was found in feces with 84% of that amount excreted as unchanged alectinib and 6% as M4. Less than 0.5% was found to be recovered in urine.

4016 L

The apparent clearance is 81.9L/hr for alectinib and 217 L/hr for M4.