Xbira

Xbira Uses, Dosage, Side Effects, Food Interaction and all others data.

Xbira 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.

Xbira 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 Xbira
Availability Prescription only
Generic Abiraterone
Abiraterone Other Names Abiraterona, Abiraterone
Related Drugs estradiol, Premarin, Xtandi, Casodex, Zytiga, Lynparza
Type Tablet
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 Cipla Limited
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Xbira
Xbira

Uses

Xbira is a CYP17 inhibitor used for combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

Xbira is also used to associated treatment for these conditions: Metastatic Castration Resistant Prostate Cancer

How Xbira works

Xbira 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

Xbira dosage

The recommended dose of Xbira is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Xbira must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Xbira is taken and for at least one hour after the dose of Xbira 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

Xbira 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 Xbira.

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: Xbira 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.

Xbira Disease Interaction

Major: hepatic impairmentModerate: CVD

Volume of Distribution

Vdss= 19,669 ± 13,358 L

Elimination Route

Xbira 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. Xbira 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 Xbira 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: Xbira is not for use in women. Xbira acetate is contraindicated in women who are or may potentially by pregnant (see Pharmacology: Toxicology: Preclinical Safety Data under Actions and Contraindications).

Breast feeding: Xbira 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 Xbira acetate or to any of the excipients of Xbira. 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 Xbira

Xbira contains Abiraterone see full prescribing information from innovator Xbira Monograph, Xbira MSDS, Xbira FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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