Abiret

Abiraterone Acetate is used for the treatment of specific types of advanced prostate cancer in adult men.

● Metastatic Castration-Resistant Prostate Cancer (mCRPC):
Abiraterone Acetate is indicated in combination with prednisone or prednisolone for adult men with metastatic prostate cancer that continues to progress despite castration-level testosterone. Approved for use:
– Before chemotherapy in patients with minimal or no symptoms after androgen deprivation therapy (ADT) 
– After chemotherapy in patients whose disease has progressed following treatment with docetaxel 

● Metastatic Castration-Sensitive Prostate Cancer (mCSPC):
Abiraterone Acetate is indicated in combination with prednisone or prednisolone and androgen deprivation therapy (ADT) for adult men with newly diagnosed, high-risk, metastatic prostate cancer that is still sensitive to hormonal therapy.

Abiraterone Acetate should be taken exactly as directed for the treatment of advanced prostate cancer in adult men.

◆ Abiraterone Acetate Dosage
▪ 1000 mg orally once daily
▪ Must be taken on an empty stomach
– No food should be consumed for at least  2 hours before and 1 hour after the dose

◆ Prednisone or Prednisolone (to be taken with Abiraterone Acetate)
▪ For mCRPC (metastatic castration-resistant prostate cancer): 5 mg twice daily
▪ For mCSPC (metastatic castration-sensitive prostate cancer): 5 mg once daily

◆ Additional Instructions
▪ Continue GnRH analog therapy in patients not surgically castrated
▪ Administer the medication at the same time each day

⚙️ Mechanism of Action (MOA)

Abiraterone Acetate is a selective and irreversible inhibitor of the enzyme CYP17A1 (17α-hydroxylase/C17,20-lyase), which is crucial for the production of androgens.
By inhibiting CYP17A1, Abiraterone Acetate reduces the synthesis of testosterone and other androgens in the testes, adrenal glands, and prostate tumor tissue, thereby slowing or stopping the growth of androgen-sensitive prostate cancer.

🧪 Pharmacokinetics

• Absorption: Peak plasma concentration is reached in about 2 hours when taken on an empty stomach.
• Bioavailability: Increased up to 10-fold when taken with food. Therefore, it must be taken on an empty stomach for optimal absorption.
• Distribution: Highly protein-bound (>99%).
• Metabolism: Primarily metabolized in the liver via CYP3A4, with further metabolism via SULT2A1.
• Elimination: Excreted mainly in feces (~88%), with less than 5% eliminated via urine.
• Half-life: Approximately 12 ± 5 hours.

🧬 Therapeutic Class

Hormonal Antineoplastic Agent
(Androgen Biosynthesis Inhibitor)

Abiraterone Acetate can interact with other drugs, potentially affecting their effectiveness or increasing the risk of side effects.

• CYP2D6 Substrates
  Effect: Increased plasma concentrations
  Details: Abiraterone may increase the levels of drugs metabolized by CYP2D6, such as metoprolol, risperidone, haloperidol, and codeine. Dose adjustments may be required.
• CYP3A4 Substrates
  Effect: Decreased plasma concentrations
  Details: As a weak CYP3A4 inducer, abiraterone may reduce the effectiveness of drugs metabolized by CYP3A4, including midazolam, fentanyl, and cyclosporine. Monitor closely.
• P-gp Substrates
  Effect: Variable
  Details: Abiraterone may affect the therapeutic levels of P-glycoprotein (P-gp) substrates like digoxin. Regular monitoring of therapeutic levels is advised.
• Warfarin & Vitamin K Antagonists
  Effect: Increased INR/bleeding risk
  Details: Co-administration with warfarin or Vitamin K antagonists may increase the INR and risk of bleeding. Monitor INR closely.
• Strong CYP3A4 Inhibitors (e.g., ketoconazole, ritonavir)
  Effect: Increased abiraterone levels
  Details: Co-administration with strong CYP3A4 inhibitors may increase abiraterone levels, increasing the risk of side effects. Monitor for adverse effects.
• Strong CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine)
  Effect: Decreased abiraterone levels
  Details: Strong inducers of CYP3A4 may lower abiraterone levels, reducing its effectiveness. Monitor closely and adjust the dose as necessary.

Spironolactone
Effect: Antagonistic effects
Details: Spironolactone has androgenic activity, which may counteract the effects of abiraterone. Avoid co-administration.

Abiraterone Acetate is contraindicated in women who are or may become pregnant, as it may cause fetal harm based on its mechanism of action and findings from animal studies. It is not intended for use in women, particularly during pregnancy or breastfeeding. The drug’s safety in lactation is unknown, and due to the potential for serious adverse effects in a nursing infant, breastfeeding is not recommended during treatment and for at least 3 weeks after the last dose. Male patients with female partners of reproductive potential should use effective contraception during treatment and for 3 weeks following discontinuation of Abiraterone Acetate.

·  Store Abiraterone Acetate at room temperature (between 20°C to 25°C or 68°F to 77°F).

  Keep the medication in its original container, tightly closed, and protected from moisture.

  Do not store the medication in the bathroom or near sinks.

  Keep out of reach of children and dispose of any unused medication properly, according to local regulations.