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Abiraterone Acetate - Uses, Dosage, and Side Effects

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Abiraterone acetate is used as an antineoplastic agent. Along with Prednisolone, it is used to treat metastatic castration-resistant prostate cancer.

Medically reviewed by

Dr. Rajesh Gulati

Published At January 20, 2023
Reviewed AtMay 26, 2023

Overview:

Abiraterone is used to reduce androgen production in the body. Androgens are the male hormones that cause overgrowth or cancerous growth in the prostate gland. It is used along with the steroid Prednisolone to treat the cancerous prostate gland growth, which spreads to other parts. It is used in male patients who cannot be treated with surgery or medicines.

What Are the Indications and Usage of Abiraterone Acetate?

Abiraterone acetate is a CYP17 inhibitor indicated to be used along with Prednisolone to treat metastatic castration-resistant prostate cancer.

What Is the Dosage and Administration of the Abiraterone Acetate?

Dosage Form: Tablet.

Dosage Strength: 250 milligrams.

Recommended Dosage: Abiraterone acetate is administered as 1000 milligrams in four equal doses of 250 milligrams given orally, and Prednisolone is given in 5 milligrams orally twice daily. Abiraterone acetate is given on an empty stomach. Therefore, the patient should avoid consuming the food for at least two hours before and one hour after having the dose.

Hepatic Impairment Patients: The recommended dose is 250 milligrams, once daily.

What Are the Contraindications of Abiraterone Acetate?

Abiraterone acetate is contraindicated in cases where the woman is pregnant or can become pregnant.

Warning and Precautions:

  • Mineralocorticoid Excess: Abiraterone acetate should be used cautiously in patients with cardiovascular disease or heart failure. Hypertension and hypokalemia are controlled before starting the treatment or dosage. The blood pressure and other symptoms are also monitored.

  • Adrenocortical Insufficiency: The symptoms of adrenocortical insufficiency are observed in the patient after using Abiraterone acetate. The steroidal dose is made to increase on observing the stressful condition.

  • Hepatotoxicity: If the patient suffers from increased liver enzymes, the Abiraterone acetate must be modified or discontinued.

  • Food Effects: Abiraterone acetate is used on an empty stomach because it can increase its effects if taken with meals.

Special Considerations:

  • Pregnancy: Abiraterone acetate can cause fetal harm if taken during pregnancy, and also, it is specified to men, so contraindicated in females. Although no specific and adequate studies have been reported till now to evaluate its effects on pregnant women, the studies done in pregnant rats have reported developmental toxicity.

  • Nursing Mothers: There are no relevant studies on nursing mothers as it is specified to men and contraindicated in females. It is unclear whether Abiraterone acetate is excreted in human milk. So, it is not indicated in nursing mothers, and if recommended, the patient should discontinue breastfeeding until Abiraterone acetate is taken.

  • Pediatric Use: The safety and effectiveness of Abiraterone acetate have not been established in child patients.

  • Geriatric Use: There are no concluded adequate results to studies performed, so the overall safety and effectiveness were not observed in the elderly patients.

  • Patients with Hepatic Impairments: There are no requirements for dosage adjustments for patients with mild hepatic impairments. But for moderate hepatic impairments, the patient is recommended to decrease its dosage to 250 milligrams, which is not recommended for patients with severe hepatic impairments. But if the patient develops hepatotoxicity during treatment, the drug is discontinued, or dosage adjustment is made for the concerned patients.

  • Patients with Renal Impairments: There are no dosage adjustments for patients with renal impairments.

Adverse Reactions:

The adverse reactions related to Abiraterone acetate are:

  • Fatigue.

  • Joint swelling.

  • Edema.

  • Hot flush.

  • Diarrhea.

  • Vomiting.

  • Cough.

  • Hypertension.

  • Dyspnea.

  • Urinary tract infection.

  • Contusion.

  • Anemia.

  • High levels of alkaline phosphatase.

  • Hypertriglyceridemia.

  • Hypokalemia.

  • Increased levels of AST and ALT.

  • Hyperglycemia.

  • Lymphopenia.

  • Hypercholesterolemia.

For Patients:

Why Is Abiraterone Acetate Used?

Abiraterone acetate is used to treat certain types of prostate cancer that can spread to different body parts, but it is used in combination with Prednisolone. Ideally, Abiraterone is classified under androgens biosynthesis inhibitors, and these act by lowering the number of certain hormones in the body.

How Is Abiraterone Acetate Taken?

Abiraterone acetate is taken orally by mouth as it comes in the form of a tablet and an empty stomach with water. It is taken two hours after meals or one hour before going for a meal. It is taken once or twice a day as recommended by the doctor. The medicine is swallowed with the help of water without chewing or crushing it. The medicine should only be withdrawn by consulting the doctor.

What Are the Precautions While Having Abiraterone Acetate?

Precautions while taking Abiraterone acetate medicine are

  • The patient should inform the doctor if the patient has an allergy to Abiraterone acetate.

  • The patient should inform about the other medication the patient takes, like Dextromethorphan or Carbamazepine.

  • The patient should also inform the doctor about the infection, stress, or low levels of potassium if the patient suffers.

  • Abiraterone is used in men only; hence it is contraindicated in pregnant women and nursing mothers.

  • If the male patient takes Abiraterone, then the female partner is on contraception for three weeks, as birth control is best. But the patient should consult the doctor for the right choices.

  • The doctor should inform the patient about infertility occurring due to Abiraterone.

What if the Patient Forgets the Dose?

If the patient needs to remember or miss one dose, they should take it regularly the next day. And if the patient misses the dose for more than one day, then the patient should consult the doctor.

What Are the Dietary Instructions the Patient Follows While Going on Abiraterone Acetate?

The patient should continue to follow the regular diet unless the doctor recommends any supplemental diet.

What Are the Side Effects of Abiraterone Acetate Medicine?

Side effects of Abiraterone acetate are

  • Joint swelling or pain.

  • Groin pain.

  • Diarrhea.

  • Hot flashes.

  • Heartburn.

  • Cough.

  • Difficulty in falling asleep.

Sometimes, the patient can also suffer serious side effects. Some of them are

  • Dizziness.

  • Feeling faint.

  • Lightheadedness.

  • Headaches.

  • Confusion.

  • Irregular heartbeat.

  • Muscle weakness.

  • Leg pains.

  • Swelling of hands, feet, ankles, or legs.

  • Rash.

  • Unusual bruising.

  • Unusual bleeding.

  • Extreme tiredness.

  • Lack of energy.

  • Vomiting.

  • Nausea.

  • Loss of appetite.

  • Pain in the upper right part of the stomach.

  • Yellowing of skin or eyes.

  • Flu-like symptoms.

  • Blood in the urine.

  • Difficulty in urination.

  • Bone fracture.

How to Store and Dispose of the Medicine?

The medicine is kept in tightly closed containers and at room temperature, away from excess moisture and heat. The medicine is kept away from children. The unneeded medicine is disposed of in a particular way as recommended by the FDA (Food and Drug Administration), that have provided take-back programs so that no animals or pet, children, or people take medicine unknowingly.

For Doctors:

Abiraterone Acetate:

Abiraterone is an inhibitor of CYP17. It has a chemical name (3beta)-17-(3-pyridinyl) androsta-5,16-dien-3-yl acetate and a molecular formula of C26H33NO22 with a molecular weight of 391.55. It is a lipophilic compound also with an octanol-water partition coefficient of 5.12 (Log P). Abiraterone acetate is available as a white to off-white, non-hygroscopic, crystalline powder, which is insoluble in water. The active ingredient in Abiraterone acetate is the acetyl ester of Abiraterone. Its inactive ingredient is colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate. It has a pKa of aromatic nitrogen of 5.19.

What Is the Clinical Pharmacology of Abiraterone Acetate?

Mechanism of Action: Abiraterone acetate gets converted to Abiraterone, an androgen biosynthesis inhibitor that inhibits CYP17. The enzyme is present in the adrenal, testicular, and prostatic tumors and is used by androgen biosynthesis. CYP17 enzyme is used in reactions as a catalyst to convert pregnenolone and progesterone to 17 alpha-hydroxy derivatives by 17 alpha-hydroxylase and dehydroepiandrosterone (DHEA) and androstenedione formation by the C17 and 20 lyase activity, which are the precursor of testosterone. Abiraterone decreases serum testosterone levels and the serum prostate-specific antigen.

Pharmacokinetics:

  • Absorption: The systemic exposure of Abiraterone is increased if taken with food. It is taken at 100 mg orally. After Abiraterone consumption, the patient should avoid food for two hours before and one hour after the dosage. The medicine is taken as a whole with water.

  • Distribution: Abiraterone is bound to plasma proteins, albumin, and alpha-1 acid glycoprotein. The volume of distribution of Abiraterone is 13,358 L.

  • Metabolism: After the oral administration of Abiraterone acetate as a capsule. It got hydrolyzed to Abiraterone. It also has two metabolites in human plasma, Abiraterone sulfate and N-oxide Abiraterone sulfate; both contribute about 43% and are inactive. The enzymes required for their formation are CYP3A4 and SULT2A1.

  • Excretion: Abiraterone acetate is excreted 88% in feces and 5% in urine. Among this, 88% is present in feces, the unchanged Abiraterone acetate is present in 55%, and Abiraterone contributed nearly 22% of the administered dose. The mean half-life of Abiraterone in plasma is 12 hours.

  • Patients with Hepatic Impairments: A single dose of 1000 milligrams administered in fasting conditions increases the folds by 1.1 and 3.6 in the mild and moderate hepatic impairments patients, respectively. In these patients, the mean half-life increases to 18 hours in mild hepatic impairments, and moderates have 19 hours mean half-life. But in severe cases, there is a two-fold increase in free drugs present in patients.

  • Patients with Renal Impairments: After 1000 milligrams single dose, fasting for one hour after dialysis in patients with end-stage renal impairments.

Dosage and Administration:

Abiraterone is recommended at 1000 milligrams orally, which is taken in 250 milligrams in four doses in combination with Prednisolone, 5 milligrams twice daily administered orally. It is taken on an empty stomach. The patient should consume no food for at least two hours before and at least one hour after the dosage. And the tablets are swallowed without crushing or chewing them.

  • Dose Modification in Hepatic Impairments: Moderate hepatic impairment patient is recommended Abiraterone acetate 250 mg once daily but with caution. And if the moderate hepatic impairment patient has bilirubin levels greater with an increase in AST, then discontinue Abiraterone acetate. Severely impaired are not recommended to have Abiraterone acetate.

  • Dose Modifications for Hepatotoxicity: The patient who suffers from hepatotoxicity while treated with Abiraterone acetate is recommended to discontinue the treatment, and if they restart, then start with 750 milligrams from 1000 milligrams after finding the liver function tests in which the AST and ALT less than or equal to 2.5X ULN, along with serum bilirubin less than or equal to 1.5X ULN. and if soon hepatotoxicity reoccurs then interrupt the treatment and restart with 500-milligram dose.

  • Dose modifications for strong CYP3A4 Inducers: Abiraterone acetate with the CYP3A4 inducers is avoided. If they are co-administered, then the Abiraterone acetate dose frequency is increased to twice a day by taking 1000 milligrams two times a day. And after discontinuing the CYP3A4 inducers, the twice dose is also withdrawn to once a day 1000 milligram dose.

  • Dose Strength: 250-milligram dosage tablets are available in a white to off-white color and present in an oval shape.

Overdosage:

There is no antidote for Abiraterone acetate overdose effects. It is managed by discontinuing the Abiraterone acetate and taking supportive measures like monitoring arrhythmias, cardiac failure, and liver function tests.

What Are the Drug Interactions of Abiraterone Acetate?

Studies have suggested that Abiraterone can inhibit CYP1A2, CYP2D6, and CYP2C8.

  • The drug-to-drug interaction has shown that Dextromethorphan 30 milligrams, when administered with Abiraterone acetate 1000 milligrams, have formed an active metabolite of Dextromethorphan which is Dextrorphan and has increased 1.3 fold.

  • Studies have also suggested that the Abiraterone acetate 1000 milligrams daily and a single 100 milligram of CYP1A2 substrate Theophylline have not increased the exposure of Theophylline.

  • The use of CYP34A substrate Abiraterone with the strong inducer of CYP34A inducer like Rifampicin 600 milligrams for six days daily administered with the Abiraterone acetate 1000 milligram as a single dose, decreased the mean plasma concentration by 55%.

  • The co-administration of Ketoconazole with Abiraterone acetate has no effects on the pharmacokinetics of Abiraterone.

  • Using Pioglitazone with Abiraterone acetate has increased the Pioglitazone by 46%.

  • Abiraterone and primary metabolites have been shown to inhibit the hepatic uptake of transporter OATP1B1.

QT Prolongation:

Abiraterone is taken at 1000 milligrams, single dose daily, with Prednisolone at 5 milligrams twice daily has presented the reports with a slight increase in QT intervals.

Nonclinical Toxicology:

  • Carcinogenesis: The studies on rats were done to diagnose Abiraterone acetate carcinogenesis. The male rats have shown interstitial cell tumors in the testes, whereas female rats have no effects of Abiraterone on them. The use of Abiraterone has shown carcinogenic effects.

  • Mutagenesis: Abiraterone acetate showed no mutagenic effects when microbial mutagenesis Ames assay was performed.

  • Impairments of Fertility: The studies performed on animals like rats and monkeys have presented the case with atrophy, hyperplasia, and hypothermia of the reproductive organs. The effects on implantation and live embryos were also expressed. There are no relevant studies for the Abiraterone acetate done on humans.

Clinical Studies:

The safety and efficacy of Abiraterone acetate were evaluated in patients who had metastatic castration-resistant prostate cancer (CRPC). Androgens deprivation therapy was demonstrated in two random studies, with placebo-controlled phase 3 clinical trials. The study excluded patients with a history of adrenal gland or pituitary disorders and those with prostate cancer treatment with Ketoconazole.

  • Patients With Metastatic CRPC and Who Have Docetaxel Chemotherapy Prior: 1195 patients were administered Abiraterone acetate orally with 1000 milligrams taken once daily along with Prednisolone 5 milligrams which taken twice daily or instead a placebo once daily was given with Prednisolone 5 milligrams orally. The median age of the patient was 69 years. Among them, 89% of the patients had a 0 to 1 score in ECOG performance, and 45% had more than four scores in Brief Pain Inventory-Short Form Score. 90% have metastasis in bone and 30% visceral involvement. 70% of the patients have a cytotoxic chemotherapy regimen and the remaining 30% in two regimens. In an interim analysis conducted among the patients, 552 deaths were reported in a patient with Abiraterone than a placebo control.

  • Patients With Metastatic CRPC Who Had Not Received Prior Cytotoxic Chemotherapy:1088 patients were administered Abiraterone 1000 milligrams once a day or a placebo once a day along with Prednisolone 5 milligrams given twice daily. The patients who have pain or metastases were omitted. The median age was 70 years of the patients. The ECOG performance status is 76% of the patients have zero scores, and 24% have one score. The pain assessments were 0 to 1 for 66% of patients and 2 to 3 for 26% of patients, conducted by the Brief Pain Inventory-Short Form. The final analysis was on 741 patients who showed a death rate when treated with Abiraterone acetate than placebo-treated patients. 65% were given Abiraterone acetate, and 78% were given a placebo for the CRPC. But it was used as a subsequent therapy for 13% in Abiraterone acetate and 44% of the patient for placebo. One hundred fifty patients were treated with Abiraterone acetate, and 251 patients were on placebo, have shown radiographic progressiveness.

Primary Efficacy Endpoints - The time of cytotoxic chemotherapy was 25.2 for the Abiraterone acetate patients and 16.8 months for the placebo-treated patients. The time opiates used supported a delay in patients' pain progression for Abiraterone acetate, whereas the placebo had 23.7 months.

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Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician

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