What side effects may Capivasertib cause?

Capivasertib (trade name: Truqap) is the world’s first approved AKT inhibitor targeted drug, currently indicated primarily for combination therapy with fulvestrant in the treatment of advanced HR-positive/HER2-negative breast cancer with specific gene mutations.

What side effects may Capivasertib cause?

Besides its intended therapeutic effects, this medication may cause certain adverse reactions. While not all of these side effects may occur, medical attention may be required if they do appear. Seek immediate medical advice if you experience any of the following side effects:

Common symptoms include agitation, black tarry stools, blistering, peeling or loosening of the skin; blurred vision, chest pain, chills, cloudy urine; coma, confusion, cough, decreased urine output; depression, diarrhea, dizziness, dry mouth; fever, flushing and dryness of the skin, fruity-smelling breath; headache, hostility, increased appetite, intensified thirst; increased urination, irritability, itching, joint or muscle pain; drowsiness, muscle twitching, nausea, painful or difficult urination; rapid weight gain, redness and inflammation of the eyes, as well as redness, swelling or pain of the skin; peeling of the skin on hands and feet, sore throat, sores, ulcers or white spots in the mouth or on the lips; stomach pain, sweating, swelling of the face, ankles or hands; swollen glands, tingling sensation in hands and feet, difficulty breathing; skin ulceration, unexplained weight loss, or abnormal bleeding and bruising, along with unusual tiredness or weakness and vomiting.

Mechanism of Action of Capivasertib

Capivasertib is an inhibitor of all three isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3), which inhibits the phosphorylation of downstream AKT substrates. Activation of AKT in tumors results from the activation of upstream signaling pathways, AKT1 mutations, loss-of-function of phosphatase and tensin homolog (PTEN), and mutations in phosphatidylinositol 3-kinase catalytic subunit alpha (PI3KCA)⁴.

Pharmacokinetics of Capivasertib

The steady-state area under the plasma concentration-time curve (AUC) of capivasertib is 8,069 h·ng/mL (coefficient of variation: 37%), and the steady-state peak plasma concentration (Cmax) is 1,371 ng/mL (coefficient of variation: 30%). Steady-state plasma concentrations are expected to be achieved on the 3rd and 4th dosing days of each week starting from the 2nd week of treatment.

During non-dosing days, the plasma concentration of capivasertib is approximately 0.5% to 15% of the steady-state peak plasma concentration.

Within the dose range of 80 mg to 800 mg (equivalent to 0.2 to 2 times the approved recommended dose), the AUC and Cmax of capivasertib are proportional to the dose.

The time to reach peak plasma concentration (Tmax) is approximately 1–2 hours. The absolute bioavailability is 29%.

No clinically significant differences in the pharmacokinetic parameters of capivasertib were observed when administered with a high-fat meal (approximately 1,000 kcal, 60% fat content) or a low-fat meal (approximately 400 kcal, 26% fat content).