Capivasertib

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

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

This chemical does not meet GHS hazard criteria for 20% (1 of 5) of reports.

Danger

H302 (60%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P264, P270, P280, P301+P317, P318, P319, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 5 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

In the prelicensure trials of capivasertib in combination with fulvestrant as therapy of advanced or metastatic breast cancer, liver test abnormalities were frequent, with elevations in ALT levels in 23% compared to 13% of those on placebo and fulvestrant. However, the enzyme elevations were usually transient, mild-to-moderate in severity and not associated with symptoms or jaundice. ALT elevations above 5 times the upper limit of normal (ULN) arose in 3% of patients on capivasertib vs 0% with placebo. Because capivasertib was always given in combination with a hormonal agent, it was not always possible to attribute the liver test abnormalities to capivasertib alone. There were no discontinuations of capivasertib because of liver test abnormalities and no episodes of clinically apparent liver injury or deaths from liver failure. Since approval and clinical availability of capivasertib, there have been no published case reports of clinically apparent liver injury with jaundice, but clinical experience with its use has been limited.

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

In vitro, capivasertib reduced the growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor-positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN. The exposure-response relationship and time course of pharmacodynamic response for the effectiveness of capivasertib has not been fully characterized. Exposure-response relationships were observed for diarrhea (CTCAE Grade 2 to 4), rash (CTCAE Grade 2 to 4), and hyperglycemia (CTCAE Grades 3 or 4) at doses of 80 to 800 mg (0.2 to 2 times the approved recommended dosage). At the recommended capivasertib dose, a mean increase in the QTc interval > 20 ms was not observed.

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2, and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function, and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA).

Substances that inhibit or prevent the proliferation of NEOPLASMS.

Agents that inhibit PROTEIN KINASES.