Abirtega

The standard adult dosage for Abiraterone acetate depends on the specific formulation being used and the condition being treated.

• For Metastatic Castration-Resistant Prostate Cancer (mCRPC): The typical dose is 1,000 mg (either four 250 mg tablets or two 500 mg tablets) administered orally once daily. This must be taken in combination with prednisone 5 mg orally twice daily.
• For Metastatic High-Risk Castration-Sensitive Prostate Cancer (mCSPC): The typical dose is 1,000 mg orally once daily, combined with prednisone 5 mg orally once daily.

Some newer formulations of abiraterone (such as Yonsa) use a micronized technology that allows for a lower dose (e.g., 500 mg daily) because the drug is absorbed more efficiently. It is critical to confirm which formulation you have been prescribed, as they are not interchangeable on a milligram-for-milligram basis.

Abiraterone is not indicated for use in the pediatric population. Prostate cancer is a disease of adult males, and the safety and efficacy of this medication in children or adolescents have not been established. It should not be administered to individuals under the age of 18.

Renal Impairment

For patients with pre-existing kidney disease (renal impairment), no initial dosage adjustment is typically necessary. The drug is not significantly cleared by the kidneys.

Hepatic Impairment

Because Abiraterone is metabolized by the liver, patients with liver issues require careful monitoring:

• Mild Hepatic Impairment (Child-Pugh Class A): No dosage adjustment is usually required.
• Moderate Hepatic Impairment (Child-Pugh Class B): The recommended dose is often reduced to 250 mg once daily. If liver enzymes (ALT/AST) rise significantly during treatment, the drug may need to be discontinued.
• Severe Hepatic Impairment (Child-Pugh Class C): Abiraterone is contraindicated and should not be used.

Elderly Patients

No specific dosage adjustments are required based solely on age; however, elderly patients may be more susceptible to cardiac side effects or complications from fluid retention and should be monitored closely.

1. 1The Empty Stomach Rule: This is the most critical instruction. Abiraterone must be taken on an empty stomach. You should not eat anything for at least two hours before taking your dose and for at least one hour after taking your dose. Taking Abiraterone with food causes the body to absorb too much of the drug, which can lead to severe side effects.
2. 2Swallow Whole: Do not crush, chew, or break the tablets. Swallow them whole with a full glass of water.
3. 3Consistency: Take your dose at the same time every day to maintain steady levels in your blood.
4. 4Prednisone Co-administration: Do not stop taking your prescribed prednisone or prednisolone unless directed by your doctor. These steroids are necessary to prevent a condition called mineralocorticoid excess, which causes high blood pressure and low potassium.
5. 5Storage: Store the tablets at room temperature (68°F to 77°F or 20°C to 25°C) in a dry place away from moisture and heat.

If you miss a dose of Abiraterone, skip the missed dose and take your usual dose the following day. Do not take two doses at once to make up for a missed one. If you miss more than one dose, contact your healthcare provider immediately for instructions.

There is no specific antidote for an Abiraterone overdose. If an overdose occurs, stop taking the medication and seek emergency medical attention or contact a poison control center. Treatment will focus on supportive care, including monitoring liver function and heart rhythm.

> Important: Follow your healthcare provider's dosing instructions precisely. Do not adjust your dose or stop the medication without medical guidance, as this could cause your cancer to progress or lead to adrenal complications.

Most patients taking Abiraterone will experience some level of side effects, many of which are related to the hormonal changes the drug induces. Common effects include:

• Fluid Retention (Edema): Swelling in the legs, ankles, or feet. This occurs because the drug can cause the body to hold onto salt and water.
• Hypokalemia (Low Potassium): This can cause muscle weakness, leg cramps, or a fluttering heart (palpitations).
• Hypertension (High Blood Pressure): New or worsening high blood pressure is common and requires regular monitoring.
• Hot Flashes: A sudden feeling of warmth, often most intense over the face and neck, similar to menopause symptoms.
• Fatigue: A general feeling of tiredness or lack of energy that does not improve with rest.
• Joint Swelling or Pain (Arthralgia): Discomfort in the joints is frequently reported.
• Diarrhea or Digestive Upset: Mild nausea or changes in bowel habits may occur during the first few weeks of treatment.

• Urinary Tract Infections (UTIs): Patients may experience increased frequency of urination or burning during urination.
• Anemia: A decrease in red blood cells, which can contribute to fatigue and shortness of breath.
• Increased Triglycerides: Changes in blood lipid levels may be observed in routine blood tests.
• Fractures: Because the drug lowers androgen levels, it can lead to bone thinning (osteoporosis) over time, increasing the risk of broken bones.

• Adrenal Insufficiency: If the accompanying steroid (prednisone) is stopped suddenly or if the body is under extreme stress (like surgery or infection), the adrenal glands may fail to produce enough hormones.
• Severe Hepatotoxicity: Rare but serious liver failure has been reported.
• Fulminant Myocarditis: Rare inflammation of the heart muscle.

> Warning: Stop taking Abiraterone and call your doctor immediately if you experience any of the following serious symptoms:

• Signs of Liver Toxicity: Yellowing of the skin or eyes (jaundice), dark urine, severe nausea, or pain in the upper right side of the stomach area.
• Severe Hypertension: Sudden, severe headache, blurred vision, or confusion.
• Cardiac Events: Chest pain, shortness of breath while resting, or a very fast/irregular heartbeat.
• Severe Hypokalemia: Extreme muscle weakness, inability to move the legs, or significant heart palpitations.
• Allergic Reaction: Swelling of the face, lips, or tongue; hives; or difficulty breathing.

Prolonged use of Abiraterone can lead to cumulative effects on the body:

• Bone Mineral Density Loss: Long-term androgen deprivation increases the risk of osteoporosis. Your doctor may recommend bone-strengthening medications or Vitamin D/Calcium supplements.
• Metabolic Changes: Increased risk of weight gain, changes in blood sugar (hyperglycemia), and increased cholesterol levels.
• Muscle Loss: A gradual decrease in muscle mass (sarcopenia) is common with long-term hormone therapy.

Currently, Abiraterone does not carry an FDA Black Box Warning. However, it does carry significant 'Warnings and Precautions' regarding hepatotoxicity (liver toxicity) and mineralocorticoid excess. The FDA requires regular monitoring of liver function tests (ALT, AST, and bilirubin) before starting treatment and every two weeks for the first three months of therapy.

Report any unusual symptoms to your healthcare provider immediately. Early detection of side effects often allows for dose adjustments that can keep you on the medication safely.

Abiraterone is a potent medication that requires careful medical supervision. The most critical safety concern is the risk of liver damage and the potential for severe cardiovascular strain due to hormonal shifts. Patients must adhere to all scheduled blood tests and blood pressure checks to ensure the drug is being processed safely by the body.

No FDA black box warnings for Abiraterone. However, the FDA-approved labeling includes strong warnings regarding Hepatotoxicity and Adrenocortical Insufficiency.

• Hepatotoxicity (Liver Damage): Abiraterone can cause significant elevations in liver enzymes, which may indicate liver injury. In rare cases, this has led to liver failure or death. Liver function must be assessed via blood tests (ALT, AST, and bilirubin) prior to starting, every two weeks for the first three months, and monthly thereafter.
• Mineralocorticoid Excess: Because Abiraterone inhibits the CYP17 enzyme, it can cause an increase in mineralocorticoids. This leads to hypertension (high blood pressure), hypokalemia (low potassium), and fluid retention. This risk is why Abiraterone must be taken with prednisone.
• Adrenocortical Insufficiency: This condition occurs when the body cannot produce enough cortisol. It is especially risky if the patient stops taking their prednisone suddenly or experiences a major stressor like surgery or a severe infection. Symptoms include dizziness, severe fatigue, and low blood pressure.
• Cardiovascular Disease: Use with caution in patients with a history of heart failure, recent heart attack, or ventricular arrhythmias. The fluid retention caused by the drug can worsen pre-existing heart conditions.
• Blood Sugar Changes: In patients with diabetes, Abiraterone may affect blood glucose levels. More frequent monitoring of blood sugar may be required.

Patients on Abiraterone require a rigorous monitoring schedule:

• Liver Function Tests (LFTs): ALT, AST, and bilirubin every 2 weeks for the first 12 weeks, then monthly.
• Potassium Levels: Checked monthly or more frequently if the patient is at risk for hypokalemia.
• Blood Pressure: Should be measured at least once a month.
• PSA Levels: Prostate-Specific Antigen (PSA) is monitored to determine if the cancer is responding to the treatment.

Abiraterone is not known to cause significant impairment of the central nervous system. However, because fatigue is a very common side effect, patients should assess their level of alertness before driving or operating heavy machinery.

There is no direct contraindication between alcohol and Abiraterone; however, alcohol can strain the liver. Given that Abiraterone has a risk of hepatotoxicity, it is generally advised to limit alcohol consumption while on this medication. Discuss your alcohol intake with your oncologist.

Do not stop taking Abiraterone or Prednisone abruptly. If Abiraterone is stopped, the cancer may begin to grow more rapidly. If Prednisone is stopped suddenly, you may experience a life-threatening adrenal crisis. If the medication must be stopped, your doctor will provide a specific tapering schedule.

> Important: Discuss all your medical conditions, especially liver disease, heart problems, or a history of diabetes, with your healthcare provider before starting Abiraterone.

While there are few absolute contraindications, Abiraterone should not be used with certain drugs that drastically alter its concentration or where the combined toxicity is too high:

• Strong CYP3A4 Inducers (e.g., Rifampin, Phenytoin): These medications can significantly decrease the levels of Abiraterone in your blood, making it ineffective against your cancer. If a strong inducer must be used, a dose adjustment of Abiraterone may be required, but avoid the combination if possible.
• Live Vaccines: Because the combination of Abiraterone and prednisone can suppress the immune system, live vaccines (like the yellow fever vaccine) should generally be avoided.

• CYP2D6 Substrates (e.g., Thioridazine, Dextromethorphan, Venlafaxine): Abiraterone is an inhibitor of the CYP2D6 enzyme. It can increase the concentration of drugs metabolized by this enzyme, potentially leading to toxicity. For drugs with a narrow therapeutic index (like thioridazine), this interaction can be dangerous.
• CYP2C8 Substrates (e.g., Pioglitazone, Repaglinide): Abiraterone can increase the levels of these medications, increasing the risk of side effects like hypoglycemia (low blood sugar).

• Warfarin: Abiraterone may affect the metabolism of blood thinners. Patients on Warfarin should have their INR (clotting time) monitored more frequently when starting or stopping Abiraterone.
• Digoxin: There is a potential for Abiraterone to increase digoxin levels, necessitating closer monitoring of heart rate and digoxin blood levels.

• High-Fat Meals: As previously noted, food—especially high-fat food—massively increases the absorption of Abiraterone. This can lead to unpredictable and dangerously high drug levels. Abiraterone must be taken on an empty stomach.
• Grapefruit and Grapefruit Juice: Grapefruit can inhibit the CYP3A4 enzyme, which breaks down Abiraterone. This could lead to increased levels of the drug in your system. It is best to avoid grapefruit products during treatment.

• St. John's Wort: This herbal supplement is a potent inducer of CYP3A4 and can significantly reduce the effectiveness of Abiraterone. It should not be used during treatment.
• Kava Kava/Comfrey: These herbs are known for potential liver toxicity and should be avoided to prevent additive strain on the liver while taking Abiraterone.

• PSA (Prostate-Specific Antigen): Abiraterone will ideally cause PSA levels to drop. However, an increase in PSA while on the drug may indicate that the cancer is becoming resistant to the treatment.
• Liver Function Tests: Abiraterone frequently causes elevations in AST and ALT, which can interfere with the interpretation of other medical conditions.

For each major interaction, the mechanism usually involves the Cytochrome P450 enzyme system. When Abiraterone inhibits an enzyme (like CYP2D6), other drugs that need that enzyme to be cleared stay in the body longer, leading to toxicity. Conversely, when another drug induces an enzyme (like CYP3A4), Abiraterone is cleared too quickly, leading to treatment failure.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and vitamins.

Conditions where Abiraterone must NEVER be used include:

1. 1Pregnancy: Abiraterone is strictly contraindicated in women who are or may become pregnant. The drug is classified as Pregnancy Category X (or equivalent). It can cause severe fetal harm or death. Furthermore, pregnant women should not even handle the tablets without gloves, as the drug can be absorbed through the skin.
2. 2Severe Hepatic Impairment (Child-Pugh Class C): Because the liver is responsible for metabolizing the drug, those with severe liver failure cannot process it, leading to toxic accumulation.
3. 3Hypersensitivity: Any patient with a known severe allergic reaction to abiraterone acetate or any of the inactive ingredients in the tablet should not take the medication.

Conditions requiring careful risk-benefit analysis by a specialist:

• Moderate Hepatic Impairment (Child-Pugh Class B): Requires a significant dose reduction and weekly liver monitoring. If LFTs worsen, the drug must be stopped.
• Severe Cardiovascular Disease: Patients with NYHA Class III or IV heart failure or those with a very recent history of myocardial infarction (heart attack) should only use Abiraterone if the benefits clearly outweigh the risks of fluid retention and cardiac strain.
• Uncontrolled Hypertension: High blood pressure must be brought under control with medication before starting Abiraterone, as the drug will likely increase blood pressure further.
• Hypokalemia: Low potassium levels must be corrected before starting treatment to avoid dangerous heart arrhythmias.

There is no established cross-sensitivity with other common drugs, though patients who have had severe reactions to other steroid-synthesis inhibitors should be monitored closely for similar hypersensitivity reactions.

> Important: Your healthcare provider will evaluate your complete medical history, including liver health and cardiac status, before prescribing Abiraterone.

Abiraterone is not for use in women. It is highly teratogenic (causes birth defects). According to FDA labeling, Abiraterone is contraindicated in pregnancy. There are no human data on the use of Abiraterone in pregnant women, but its mechanism of action—blocking androgen synthesis—is essential for normal fetal development. Male patients with female partners of reproductive potential must use effective contraception (such as condoms) during treatment and for three weeks after the final dose, as the drug may be present in semen.

Abiraterone is not indicated for use in women. It is unknown if the drug or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in a nursing infant, the drug is not to be used by breastfeeding mothers.

The safety and effectiveness of Abiraterone in pediatric patients have not been established. It is not used in children. There is a theoretical risk that the drug could interfere with normal puberty and growth due to its profound effect on sex hormones.

The majority of patients in clinical trials for Abiraterone were 65 years of age and older (over 70% in some studies). No overall differences in safety or effectiveness were observed between these elderly patients and younger adult patients. However, older patients are more likely to have pre-existing heart conditions or be taking multiple other medications (polypharmacy), which increases the risk of drug interactions and fluid-retention-related complications like congestive heart failure.

In clinical studies, no significant difference in the pharmacokinetics of abiraterone was observed between subjects with normal kidney function and those with end-stage renal disease on dialysis. Therefore, no dose adjustment is necessary for patients with renal impairment. It is not removed by hemodialysis.

The liver is the primary site of metabolism for Abiraterone. In patients with moderate hepatic impairment (Child-Pugh Class B), the systemic exposure (AUC) of the drug increases by nearly four-fold. Consequently, the dose is reduced to 250 mg once daily. For those with severe impairment (Class C), the exposure increases even more, making the drug unsafe for use.

> Important: Special populations, particularly those with liver or heart disease, require individualized medical assessment and more frequent laboratory monitoring.

Abiraterone acetate is an orally active inhibitor of the enzyme CYP17 (17α-hydroxylase/C17,20-lyase). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues. It is required for the biosynthesis of androgens. Specifically, CYP17 catalyzes two sequential reactions: the conversion of pregnenolone and progesterone into their 17α-hydroxy derivatives, and the subsequent formation of the androgen precursors dehydroepiandrosterone (DHEA) and androstenedione. By inhibiting these steps, Abiraterone reduces the levels of circulating testosterone and other androgens to near-zero levels.

The primary pharmacodynamic effect of Abiraterone is the reduction of serum testosterone. In clinical trials, the administration of 1,000 mg daily resulted in a decrease of serum testosterone to below the limit of detection (typically <1 ng/dL) within days. Because it also blocks cortisol synthesis, there is a compensatory rise in Adrenocorticotropic Hormone (ACTH), which can drive mineralocorticoid excess. This is why co-administration of prednisone is pharmacodynamically necessary to suppress ACTH and maintain cortisol-like activity.

| Parameter | Value |

|---|---|

| Bioavailability | <10% (Fasted); Increases up to 10x with food |

| Protein Binding | >99% (Albumin and Alpha-1 acid glycoprotein) |

| Half-life | 12 - 15 hours |

| Tmax | 2 hours |

| Metabolism | Hepatic (CYP3A4 and SULT2A1) |

| Excretion | Fecal ~88%, Renal ~5% |

• Molecular Formula: C26H33NO2 (as acetate)
• Molecular Weight: 391.55 g/mol
• Solubility: Practically insoluble in water; soluble in organic solvents like methanol and ethanol.
• Structure: It is a steroidal compound, specifically a pyridine derivative of pregnenolone acetate.

Abiraterone is classified as a CYP17 enzyme inhibitor. It is part of the broader category of 'Next-Generation Anti-Androgens' or 'Androgen Synthesis Inhibitors.' It is distinct from 'Androgen Receptor Antagonists' like Enzalutamide, which block the receptor rather than the production of the hormone itself.