Abiraterona
Abiraterona Uses, Dosage, Side Effects, Food Interaction and all others data.
Abiraterona is an orally active inhibitor of the steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). It inhibits CYP17A1 in a selective and irreversible manner via covalent binding mechanism. CYP17A1 is an enzyme that catalyzes the biosynthesis of androgen and is highly expressed in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone (DHEA) by the enzyme CYP17A1 to decrease serum levels of testosterone and other androgens.
Abiraterona is associated with decreases in PSA levels, tumor shrinkage (as evaluated by RECIST criteria), radiographic regression of bone metastases and improvement in pain. Levels of adrenocorticotropic hormones increased up to 6-fold but this can be suppressed by dexamethasone.
Trade Name | Abiraterona |
Availability | Prescription only |
Generic | Abiraterone |
Abiraterone Other Names | Abiraterona, Abiraterone |
Related Drugs | estradiol, Premarin, Xtandi, Casodex, Zytiga, Lynparza |
Type | |
Formula | C24H31NO |
Weight | Average: 349.509 Monoisotopic: 349.240564619 |
Protein binding | >99% protein bound to alpha-1-acid glycoprotein and albumin. |
Groups | Approved |
Therapeutic Class | Cytotoxic Chemotherapy |
Manufacturer | |
Available Country | |
Last Updated: | September 19, 2023 at 7:00 am |
Uses
Abiraterona is a CYP17 inhibitor used for combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.
Abiraterona is also used to associated treatment for these conditions: Metastatic Castration Resistant Prostate Cancer
How Abiraterona works
Abiraterona is an orally active inhibitor of the steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). It inhibits CYP17A1 in a selective and irreversible manner via covalent binding mechanism. CYP17A1 is an enzyme that catalyzes the biosynthesis of androgen and is highly expressed in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone (DHEA) by the enzyme CYP17A1 to decrease serum levels of testosterone and other androgens.
Dosage
Abiraterona dosage
The recommended dose of Abiraterona is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Abiraterona must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Abiraterona is taken and for at least one hour after the dose of Abiraterona is taken. The tablets should be swallowed whole with water. Do not crush or chew tablets.
Side Effects
Hypertension, Hypokalemia, and Fluid Retention due to Mineralocorticoid Excess, Adrenocortical Insufficiency Hepatotoxicity
Toxicity
Toxicity is related to the blockade of 17α-hydroxylase activity. Blockade results in the accumulation of upstream mineralocorticoids like 11-deoxycorticosterone leading to secondary hyperaldosteronism. Signs of hydroaldosteronism include fluid retention and hypokalemia. Mineralocorticoid receptor antagonists may be used to treat signs and symptoms.
Precaution
Abiraterona may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. In the two randomized clinical trials, grade 3 to 4 hypertension occurred in 2% of patients, grade 3 to 4 hypokalemia in 4% of patients, and grade 3 to 4 edema in 1% of patients treated with Abiraterona.
Food Interaction
- Exercise caution with St. John's Wort. This herb induces CYP3A4 and may increase the serum levels of abiraterone.
- Take on an empty stomach. Take at least 1 hour before or 2 hours after eating as food may increase exposure to abiraterone by 4-fold.
[Moderate] ADJUST DOSING INTERVAL: Food may significantly increase the oral bioavailability of abiraterone acetate.
Compared to administration in the fasted state, abiraterone peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat; 300 calories) and approximately 17- and 10-fold higher, respectively, when it was administered with a high-fat meal (57% fat; 825 calories).
Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures.
The safety of these increased exposures during multiple dosing has not been assessed.
MANAGEMENT: Abiraterona acetate must be taken on an empty stomach.
No food should be consumed for at least two hours before and one hour after the abiraterone acetate dose.
Abiraterona Drug Interaction
Moderate: tamsulosin, metoprololUnknown: charcoal, naproxen, fexofenadine, aspirin, ubiquinone, rosuvastatin, sodium iodide, insulin glargine, leuprolide, leuprolide, omeprazole, bioflavonoids, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, denosumab
Abiraterona Disease Interaction
Volume of Distribution
Vdss= 19,669 ± 13,358 L
Elimination Route
Abiraterona itself is poorly absorbed and is susceptible to hydrolysis by esterases. The salt form, abiraterone acetate, is a prodrug which has a much higher oral bioavailability and is also esterase resistant. Peak drug concentrations of abiraterone were reached in 1.5 - 4 hours. Abiraterona acetate was rapidly and completely deacetylated into abiraterone-the parent salt form was not detectable in early pharmacokinetic studies. Food and high fat meals increases absorption 4.4-fold.
Half Life
Terminal elimination half-life = 5-14 hours
Elimination Route
Excreted via feces (~88%) and urine (~5%)
Pregnancy & Breastfeeding use
There are no human data on the use of Abiraterona in pregnancy and it is not for use in women of childbearing potential. Maternal use of a CYP17 inhibitor is expected to produce changes in hormone levels that could affect development of the foetus.
Pregnancy: Abiraterona is not for use in women. Abiraterona acetate is contraindicated in women who are or may potentially by pregnant (see Pharmacology: Toxicology: Preclinical Safety Data under Actions and Contraindications).
Breast feeding: Abiraterona is not for use in women. It is not known if either abiraterone acetate or its metabolites are excreted in human milk
Contraindication
Hypersensitivity to the Abiraterona acetate or to any of the excipients of Abiraterona. Women who may potentially be pregnant.
Acute Overdose
There have been no reports of overdose during clinical studies. There is no specific antidote. In the event of an overdose, administration should be withheld and general supportive measures undertaken, including monitoring for arrhythmias, hypokalaemia and for signs and symptoms of fluid retention. Liver function also should be assessed.
Storage Condition
Store below 30°C.
Innovators Monograph
You find simplified version here Abiraterona
Abiraterona contains Abiraterone see full prescribing information from innovator Abiraterona Monograph, Abiraterona MSDS, Abiraterona FDA label