capivasertib

Action and Spectrum

Actions and spectrum: 

capivasertib is a potent & selective inhibitor of protein kinase B (AKT). It acts by targeting the AKT signalling pathway, involved in cell growth, survival, and metabolism. By inhibiting AKT, capivasertib can disrupt the signalling cascades that promote tumor cell proliferation and survival. 

The spectrum of capivasertib’s activity is primarily focused on cancers that exhibit dysregulation of the AKT pathway, such as hormone receptor-positive, HER2-negative breast cancer and certain types of solid tumors. It is being investigated as a targeted therapy in combination with other anti-cancer agents for the treatment of various malignancies. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

There is no black box warning specifically associated with capivasertib 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

capivasertib is contraindicated in individuals with known hypersensitivity or allergy to the drug or any of its components. It is also contraindicated in pregnant women due to the potential risk to the fetus. Additionally, capivasertib should not be used in severe hepatic impairment or severe renal impairment. Contraindications may vary depending on the specific indication and the accompanying medications. It is important to consult the prescribing information and healthcare professionals for a comprehensive list of contraindications before initiating treatment with capivasertib.  

Caution: 

• Cardiac events: capivasertib may increase the risk of cardiac events such as QT prolongation and ventricular arrhythmias. It should be used with caution in patients with a history of or risk factors for cardiac disorders. 
• Diabetes: capivasertib can cause hyperglycemia and may worsen glycemic control in patients with diabetes. Regular monitoring of blood glucose levels is recommended, and appropriate management of diabetes should be implemented. 
• Interactions with other medications: capivasertib may interact with other drugs, including those metabolized by CYP3A4 enzymes. Close monitoring and potential dose adjustments may be required when capivasertib is co-administered with other medications. 

Comorbidities: 

• Cardiovascular disease: Cancer patients may have a higher risk of cardiovascular conditions such as heart disease, hypertension, and arrhythmias. 
• Diabetes: Diabetes is a common comorbidity in cancer patients. capivasertib can affect glucose metabolism and may require monitoring and adjustments in diabetic patients. 
• Renal impairment: capivasertib can affect renal function, and patients with pre-existing renal impairment may require close monitoring during treatment. 
• Hepatic impairment: Liver dysfunction may be present in cancer patients, and capivasertib may have an impact on liver function. Close monitoring of liver enzymes is recommended. 
• Immunodeficiency: Cancer and its treatments can weaken the immune system, making more susceptible to infections and other complications. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

capivasertib is a selective inhibitor of the protein kinase enzyme called AKT (protein kinase B). AKT is involved in cellular processes, including cell survival, growth, and proliferation, making it a potential target for cancer therapy. By inhibiting AKT, capivasertib interferes with the signalling pathways that promote cancer cell growth and survival. 

The pharmacology of capivasertib is primarily focused on its ability to selectively target AKT and disrupt the signalling pathways involved in cancer cell growth and survival. By doing so, it aims to inhibit tumor growth and potentially enhance the effectiveness of other cancer treatments.  

Pharmacodynamics: 

The pharmacodynamics of capivasertib involves its interaction with the target protein kinase AKT (protein kinase B) and its downstream signalling pathways. capivasertib selectively inhibits AKT, preventing its activation and subsequent phosphorylation of downstream targets involved in cell survival, proliferation, and metabolism. 

By inhibiting AKT, capivasertib disrupts the PI3K/AKT/mTOR signalling pathway, which is commonly dysregulated in various cancer types. This pathway plays a critical role in promoting cell growth, survival, and resistance to apoptosis. By blocking AKT activity, capivasertib can inhibit the growth and proliferation of cancer cells. 

The pharmacodynamic effects of capivasertib can be assessed through various biomarkers, including levels of phosphorylated AKT and downstream signalling molecules. Changes in these biomarkers can indicate the inhibition of AKT signalling and the potential therapeutic response to capivasertib. 

Pharmacokinetics: 

Absorption 

capivasertib is administered orally as a tablet. After oral ingestion, it is absorbed from the gastrointestinal tract and enters the systemic circulation. 

Distribution 

Once absorbed, capivasertib is distributed throughout the body. It binds extensively to plasma proteins, such as albumin. The drug may cross blood-brain barrier and enter the central nervous system. 

Metabolism 

capivasertib undergoes extensive metabolism in the liver through various enzymatic pathways, including oxidation and glucuronidation. The primary metabolites formed are inactive or have minimal pharmacological activity. 

Elimination and excretion 

The metabolites of capivasertib are primarily eliminated through the feces (via biliary excretion) and urine (via renal excretion). The exact proportions of excretion routes are not well-established. 

Adminstartion

Administration: 

capivasertib is typically administered orally as a tablet. The exact dosage and administration schedule may vary depending on the specific indication and the patient’s individual characteristics. It is important to follow the instructions provided by the healthcare provider or the prescribing information. 

capivasertib tablets should be taken with water, and they can be taken with or without food. It is recommended to swallow the tablet whole and not chew, crush, or split it. 

The dosing regimen, including the number of tablets to be taken and the frequency of administration is determined by the physician based on factors such as the patient’s condition, overall health, and response to treatment.

It is important to adhere to the prescribed dosage and administration schedule to ensure the optimal therapeutic effect of capivasertib. If a dose of capivasertib is missed, it is advised to take the next scheduled dose at the regular time. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: capivasertib 

Pronounced: (ca-pi-va-SER-tib)  

Why do we use capivasertib? 

• Breast Cancer: capivasertib is being studied as a treatment for hormone receptor-positive, HER2-negative breast cancer, particularly in combination with endocrine therapy. 
• Prostate Cancer: capivasertib is being investigated as a therapeutic option for advanced prostate cancer, especially in patients with mutations in the PTEN gene or alterations in the PI3K/AKT pathway. 
• Solid Tumors: capivasertib is also being explored as a potential treatment for other solid tumors, including bladder cancer, ovarian cancer, and head & neck squamous cell carcinoma.