Capivasertib is an AKT kinase inhibitor that was approved for marketing in the United States in 2023. It is indicated for the treatment of locally advanced or metastatic breast cancer that is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and harbors PIK3CA/AKT1/PTEN gene mutations.

How to Use Capivasertib

Recommended Dosage and Administration Regimen

Standard Dosage: 400mg orally, twice daily (approximately 12 hours apart). Administer continuously for 4 days followed by a 3-day drug holiday, forming a weekly cycle.

Administration Method: Swallow the tablets whole; do not chew or break them. If a dose is missed and the time elapsed is ≤4 hours, take the missed dose as soon as possible. If more than 4 hours have passed, skip the missed dose. Do not take an additional dose to make up for a vomiting episode.

Combination Therapy: Administration should be performed with reference to the package insert of fulvestrant. Premenopausal/perimenopausal women should receive concurrent treatment with a luteinizing hormone-releasing hormone (LHRH) agonist.

Dosage Adjustment of Capivasertib

Adjustment Based on Adverse Reactions

Hyperglycemia: Discontinue Capivasertib if fasting blood glucose >160mg/dL. If blood glucose returns to normal within 28 days, resume treatment at the original dosage; otherwise, reduce the dosage. Permanently discontinue the drug if fasting blood glucose >500mg/dL or if life-threatening hyperglycemia occurs.

Diarrhea: For grade 2 diarrhea, suspend treatment until symptoms resolve; reduce the dosage if grade 2 diarrhea recurs for the first time. For grade 3 diarrhea, reduce the dosage after symptom resolution. Permanently discontinue the drug for grade 4 diarrhea.

Skin Reactions: For grade 2 skin reactions, resume treatment at the original dosage after suspension. If grade 2 reactions recur frequently, reduce the dosage. For grade 3 skin reactions, reduce the dosage after symptom resolution. Permanently discontinue the drug for grade 4 skin reactions.

Adjustment Due to Drug Interactions

Strong CYP3A Inhibitors: Avoid concurrent use. If coadministration is necessary, reduce the Capivasertib dosage to 320mg twice daily.

Moderate CYP3A Inhibitors: Concurrently reduce the Capivasertib dosage to 320mg twice daily.

CYP3A Inducers: Concurrent use is prohibited, as they can significantly decrease Capivasertib concentrations.

Capivasertib Use in Special Populations

Patients with Hepatic or Renal Impairment

Mild to Moderate Hepatic Impairment: No dosage adjustment is required, but close monitoring for adverse reactions is recommended.

Severe Hepatic Impairment: No data support safe use; avoid administration.

Renal Impairment: No dosage adjustment is needed for patients with mild to moderate renal impairment (creatinine clearance [CLcr] ≥30mL/min). Data on use in patients with severe renal impairment (CLcr 15-29mL/min) are unavailable.

Elderly Patients

Caution is advised in patients aged 65 years and older. Clinical data show that this population has a higher incidence of adverse reactions and requires more frequent dosage adjustments.

Pregnancy and Lactation

Pregnant Women: Capivasertib has embryofetal toxicity. Strict contraception is required until 1 month after the last dose (for women) or 4 months after the last dose (for men).

Lactation: Animal studies indicate that Capivasertib is excreted into breast milk. It is recommended to avoid breastfeeding during treatment and until the drug is discontinued.