Abiraterone

BRAND NAMES: 

Yonsa® - It is in the dosage form of Abiraterone acetate 125mg combined with methylprednisolone. It is administered daily as YONSA® as a 500mg dose(125mg tablets) taken once daily, along with 4mg methylprednisolone twice daily.

ZYTIGA® - In Zytiga®, abiraterone was the main active ingredient used in men with prostate cancer.

MECHANISM OF ACTION:

CYP17 converts pregnenolone and progesterone into 17 α-hydroxy derivatives. It cleaves the C 20, 21-acetyl group, dehydroepiandrosterone, and androstenedione. DHEA and androstenedione are precursors to testosterone. Prostate cancer is caused by an overproduction of male hormones. Androgens are made by the testicles, adrenal glands, and metastatic cancer cells. Abiraterone acetate interacts with and inhibits CYP17A1, an enzyme that catalyzes the generation of androgens. Inhibiting this enzyme lowers the amount of androgen produced in the body.

PHARMACOKINETICS:

Absorption: Patients with metastatic castration-resistant prostate cancer who received abiraterone acetate orally had a median Tmax of two hours. When abiraterone acetate is taken with food, systemic exposure to abiraterone increases. When a single dosage of abiraterone acetate 500 mg was provided with a high-fat meal versus overnight fasting in healthy volunteers, abiraterone Cmax was roughly 6.5-fold higher, and AUC0 was 4.4-fold higher. Given the typical variety in the volume and composition of meals, taking abiraterone with meals may result in higher and highly varied exposures.

Distribution: The average apparent steady-state volume of distribution is 19,669 L. 

Metabolism : Esterases are believed to facilitate the conversion of abiraterone acetate to abiraterone, the active metabolite, albeit particular esterases have yet to be found. The two primary circulating metabolites in human plasma are abiraterone sulfate, which is produced by CYP3A4 and SULT2A1, and N-oxide abiraterone sulfate, which is produced by SULT2A1. These metabolites account for approximately 43% of abiraterone exposure but are pharmacologically inactive. 

Excretion: Following oral administration of C-abiraterone acetate, roughly 88% of the radioactive dosage is recovered in feces. The primary chemicals found in feces are unaltered abiraterone acetate and abiraterone, which account for approximately 55% and 22% of the provided dose, respectively. About 5% of the dosage is recovered in urine.

PHARMACODYNAMICS:

Abiraterone acetate is promptly hydrolyzed to abiraterone, which explains its pharmacological effects. Abiraterone lowers serum testosterone and other androgens. A change in serum prostate-specific antigen levels may be detected. 

DOSAGE AND ADMINISTRATION: 

Zytiga in the form of a tablet. The strengths of tablets are 250mg and 500mg. Yonsa is in the form of ultra-micronized tablets. The strength of the tablets is 125mg. Abiraterone is available as a tablet to be taken orally on an empty stomach with water, one hour before or two hours after consuming any food. It is normally taken once a day. Take abiraterone at roughly the same time every day.

CONTRAINDICATIONS:

Abiraterone acetate is contraindicated in pregnancy and should be used with caution with patients with cardiac disease. Because of the potential increase in blood pressure and fluid retention, abiraterone acetate should be used with caution in patients with heart failures and ventricular arrhythmias.

DRUG INTERACTIONS:

Although certain medications should never be combined, two separate medications may be combined even if an interaction occurs. In some circumstances, your doctor may wish to adjust the dosage or take other precautions while you are taking this medication. 

• Heart rhythm problems: quinidine, procainamide, amiodarone, sotalol 

• Methadone is a painkiller. 

• Antibiotic-moxifloxacin

• Herbal medications and antipsychotics 

FOOD INTERACTIONS:

Avoid taking abiraterone with food as it may cause side effects. Take abiraterone on an empty stomach, take it an hour before or 2 hours after food.

SIDE EFFECTS:

• A drug may have some undesirable side effects in addition to its intended effects. Side effects of abiraterone include 

• Fast or erratic heartbeat. 

• Severe headache and impaired vision 

• Anaemia causes pale skin, fatigue, and cold hands and feet. 

• Hypokalaemia symptoms include leg cramps, constipation, increased urination, and muscle weakness. 

• Liver disorders include jaundice, nausea, vomiting, and stomach pain. 

• Hypoglycemia causes dizziness, rapid heartbeat, and headaches. 

• Cold symptoms include nose, sneezing, coughing, and sore throat. 

OVERDOSE:

Overdose symptoms include 

• Fast or erratic heartbeat. 

• Feeling dizzy or fainting. 

• Having difficulty breathing 

• Swelling of the foot, ankles, and lower legs. 

• Weight loss.

TOXICITY:

The number of human overdoses with abiraterone is small. Abiraterone is available in generic 250mg and 500mg pills, as well as under the brand name Zytiga. The normal dose is 1000 mg per day, along with 5 mg of prednisone twice a day. Fatigue, nausea, vomiting, diarrhea, and abdominal discomfort are some of the most common adverse effects. Inhibition of CYP17 can also cause symptoms of mineralocorticoid excess, including hypotension, hypokalemia, and fluid retention. Adrenocortical insufficiency, hypoglycemia in diabetic patients, increased fractures, embryo-fetal toxicity, and hepatotoxicity are all rare but potentially serious adverse effects. 

STORAGE:

Keep the medicine in a tightly sealed container at room temperature, and keep away from heat, moisture, and direct light. Keep it out of the freezer. 

Maintain the temperature ranging from 20° to 25° C (68° to 77°).