Abiraterone

Name: Abiraterone

What should I avoid while taking abiraterone?

Avoid eating for at least 2 hours before you take abiraterone and for at least 1 hour after your dose. Food can increase the amount of abiraterone your body absorbs.

Avoid taking an herbal supplement containing St. John's wort at the same time you are taking abiraterone.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Uses For abiraterone

Note: Women of childbearing potential should not use or handle abiraterone tablets without protection (eg, gloves).

Abiraterone is used in combination with prednisone to treat patients with metastatic castration-resistant prostate cancer (prostate cancer that is resistant to medical or surgical treatments that lower testosterone and has already spread to other parts of the body). abiraterone is used in patients who have received cancer treatments, such as docetaxel.

abiraterone is available only with your doctor's prescription.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Abiraterone Drug Class

Abiraterone is part of the drug class:

  • Other hormone antagonists and related agents

Abiraterone Food Interactions

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of abiraterone there are no specific foods that you must exclude from your diet when receiving abiraterone.

Abiraterone and Lactation

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if abiraterone passes into your breast milk. You and your healthcare provider should decide if you will take abiraterone or breastfeed. You should not do both. 

Abiraterone Dosage

Take abiraterone exactly as prescribed. Follow the directions on your prescription label carefully.

The recommended dose of abiraterone is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Abiraterone must be taken on an empty stomach. No food should be consumed for at least 2 hours before the dose of abiraterone is taken and for at least 1 hour after the dose of abiraterone is taken. The tablets should be swallowed whole with water.

 

 

Pharmacology

Mechanism of Action

Androgen biosynthesis inhibitor that inhibits 17 alpha-hydroxylase/C17,20-lyase (CYP17); this enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis

Pharmacokinetics

Peak Plasma Time: 2 hr

Peak Plasma Concentration: 226 ng/mL ± 178 ng/mL (at steady state)

AUC: 1173 ± 690 ng.hr/mL; increases up to 10-fold when administered with food

Protein Bound: >99% (albumin, alpha-1 acid glycoprotein)

Vd: 19,669 ± 13,358 L (at steady state)

Not a substrate of P-glycoprotein

Excretion: feces (88%), urine (5%)

Half-life: 12 ± 5 hr (prolonged by hepatic impairment to 18-19 hr)

Metabolism

  • Metabolism: Abiraterone acetate is hydrolyzed to abiraterone (active metabolite); hydrolysis is likely via esterase activity and is not CYP mediated; CYP3A4 and SULT2A1 enzymes are involved in the formation of 2 inactive metabolites, N-oxide abiraterone sulphate and abiraterone sulphate
  • Enzyme inhibition: Strong inhibitor of CYP1A2 and CYP2D6; moderate inhibitor of CYP2C9, CYP2C19, and CYP3A4

In Summary

Commonly reported side effects of abiraterone include: decreased serum potassium, increased serum aspartate aminotransferase, increased serum triglycerides, fluid retention, and hypokalemia. Other side effects include: hypertension. See below for a comprehensive list of adverse effects.

Abiraterone Dosage and Administration

Recommended Dosage

The recommended dose of Abiraterone acetate is 1,000 mg (four 250 mg tablets) administered orally once daily in combination with prednisone 5 mg administered orally twice daily. Abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of Abiraterone acetate is taken and for at least one hour after the dose of Abiraterone acetate is taken [see Clinical Pharmacology (12.3)]. The tablets should be swallowed whole with water. Do not crush or chew tablets.

Dose Modification Guidelines in Hepatic Impairment and Hepatotoxicity

Hepatic Impairment

In patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the recommended dose of Abiraterone acetate to 250 mg once daily. A once daily dose of 250 mg in patients with moderate hepatic impairment is predicted to result in an area under the concentration curve (AUC) similar to the AUC seen in patients with normal hepatic function receiving 1,000 mg once daily. However, there are no clinical data at the dose of 250 mg once daily in patients with moderate hepatic impairment and caution is advised. In patients with moderate hepatic impairment monitor ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. If elevations in ALT and/or AST greater than 5× upper limit of normal (ULN) or total bilirubin greater than 3× ULN occur in patients with baseline moderate hepatic impairment, discontinue Abiraterone acetate and do not re-treat patients with Abiraterone acetate [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Do not use Abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C).

Hepatotoxicity

For patients who develop hepatotoxicity during treatment with Abiraterone acetate (ALT and/or AST greater than 5× ULN or total bilirubin greater than 3× ULN), interrupt treatment with Abiraterone acetate [see Warnings and Precautions (5.3)]. Treatment may be restarted at a reduced dose of 750 mg once daily following return of liver function tests to the patient's baseline or to AST and ALT less than or equal to 2.5× ULN and total bilirubin less than or equal to 1.5× ULN. For patients who resume treatment, monitor serum transaminases and bilirubin at a minimum of every two weeks for three months and monthly thereafter.

If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted at a reduced dose of 500 mg once daily following return of liver function tests to the patient's baseline or to AST and ALT less than or equal to 2.5× ULN and total bilirubin less than or equal to 1.5× ULN.

If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment with Abiraterone acetate. The safety of Abiraterone acetate re-treatment of patients who develop AST or ALT greater than or equal to 20× ULN and/or bilirubin greater than or equal to 10× ULN is unknown.

Permanently discontinue Abiraterone acetate for patients who develop a concurrent elevation of ALT greater than 3 × ULN and total bilirubin greater than 2 × ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation [see Warnings and Precautions (5.3)].

Dose Modification Guidelines for Strong CYP3A4 Inducers

Avoid concomitant strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) during Abiraterone acetate treatment. Although there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inducers, because of the potential for an interaction, if a strong CYP3A4 inducer must be co-administered, increase the Abiraterone acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Abiraterone Description

Abiraterone acetate, the active ingredient of Abiraterone acetate is the acetyl ester of Abiraterone. Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each Abiraterone acetate tablet contains 250 mg of Abiraterone acetate. Abiraterone acetate is designated chemically as (3β)-17-(3-pyridinyl) androsta-5,16-dien-3-yl acetate and its structure is:

Abiraterone acetate is a white to off-white, non-hygroscopic, crystalline powder. Its molecular formula is C26H33NO2 and it has a molecular weight of 391.55. Abiraterone acetate is a lipophilic compound with an octanol-water partition coefficient of 5.12 (Log P) and is practically insoluble in water. The pKa of the aromatic nitrogen is 5.19.

Inactive ingredients in the tablets are colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, and Impairment of Fertility

A two-year carcinogenicity study was conducted in rats at oral Abiraterone acetate doses of 5, 15, and 50 mg/kg/day for males and 15, 50, and 150 mg/kg/day for females. Abiraterone acetate increased the combined incidence of interstitial cell adenomas and carcinomas in the testes at all dose levels tested. This finding is considered to be related to the pharmacological activity of Abiraterone. Rats are regarded as more sensitive than humans to developing interstitial cell tumors in the testes. Abiraterone acetate was not carcinogenic in female rats at exposure levels up to 0.8 times the human clinical exposure based on AUC. Abiraterone acetate was not carcinogenic in a 6-month study in the transgenic (Tg.rasH2) mouse.

Abiraterone acetate and Abiraterone did not induce mutations in the microbial mutagenesis (Ames) assay and was not clastogenic in both the in vitro cytogenetic assay using primary human lymphocytes and in the in vivo rat micronucleus assay.

Abiraterone acetate has the potential to impair reproductive function and fertility in humans based on findings in animals. In repeat-dose toxicity studies in male rats (13- and 26-weeks) and monkeys (39-weeks), atrophy, aspermia/hypospermia, and hyperplasia in the reproductive system were observed at ≥50 mg/kg/day in rats and ≥250 mg/kg/day in monkeys and were consistent with the antiandrogenic pharmacological activity of Abiraterone [see Nonclinical Toxicology (13.2)]. These effects were observed in rats at systemic exposures similar to humans and in monkeys at exposures approximately 0.6 times the AUC in humans.

In fertility studies in rats, reduced organ weights of the reproductive system, sperm counts, sperm motility, altered sperm morphology and decreased fertility were observed in males dosed for 4 weeks at ≥30 mg/kg/day. Mating of untreated females with males that received 30 mg/kg/day Abiraterone acetate resulted in a reduced number of corpora lutea, implantations and live embryos and an increased incidence of pre-implantation loss. Effects on male rats were reversible after 16 weeks from the last Abiraterone acetate administration. Female rats dosed for 2 weeks until day 7 of pregnancy at ≥30 mg/kg/day had an increased incidence of irregular or extended estrous cycles and pre-implantation loss (300 mg/kg/day). There were no differences in mating, fertility, and litter parameters in female rats that received Abiraterone acetate. Effects on female rats were reversible after 4 weeks from the last Abiraterone acetate administration. The dose of 30 mg/kg/day in rats is approximately 0.3 times the recommended dose of 1,000 mg/day based on body surface area.

Animal Toxicology and/or Pharmacology

In 13- and 26-week studies in rats and 13- and 39-week studies in monkeys, a reduction in circulating testosterone levels occurred with Abiraterone acetate at approximately one half the human clinical exposure based on AUC. As a result, decreases in organ weights and toxicities were observed in the male and female reproductive system, adrenal glands, liver, pituitary (rats only), and male mammary glands. The changes in the reproductive organs are consistent with the antiandrogenic pharmacological activity of Abiraterone acetate. A dose-dependent increase in cataracts was observed in rats at 26 weeks starting at ≥50 mg/kg/day (similar to the human clinical exposure based on AUC). In the 39-week monkey study, no cataracts were observed at higher doses (2 times greater than the clinical exposure based on AUC). All other toxicities associated with Abiraterone acetate reversed or were partially resolved after a 4-week recovery period.

Patient Counseling Information

See FDA-approved patient labeling (Patient Information)

  • Patients should be informed that Abiraterone acetate and prednisone are used together and that they should not interrupt or stop either of these medications without consulting their physician.
  • Patients receiving GnRH agonists should be informed that they need to maintain this treatment during the course of treatment with Abiraterone acetate and prednisone.
  • Patients should be informed that Abiraterone acetate should not be taken with food and that no food should be consumed for at least two hours before the dose of Abiraterone acetate is taken and for at least one hour after the dose of Abiraterone acetate is taken. They should be informed that the tablets should be swallowed whole with water without crushing or chewing. Patients should be informed that taking Abiraterone acetate with food causes increased exposure and this may result in adverse reactions.
  • Patients should be informed that Abiraterone acetate is taken once daily and prednisone is taken twice daily according to their physician's instructions.
  • Patients should be informed that in the event of a missed daily dose of Abiraterone acetate or prednisone, they should take their normal dose the following day. If more than one daily dose is skipped, patients should be told to inform their physician.
  • Patients should be apprised of the common side effects associated with Abiraterone acetate, including peripheral edema, hypokalemia, hypertension, elevated liver function tests, and urinary tract infection. Direct the patient to a complete list of adverse reactions in PATIENT INFORMATION.
  • Patients should be advised that their liver function will be monitored using blood tests.
  • Patients should be informed that Abiraterone acetate may harm a developing fetus; thus, women who are pregnant or women who may be pregnant should not handle Abiraterone acetate without protection, e.g., gloves. Patients should also be informed that it is not known whether Abiraterone or its metabolites are present in semen and they should use a condom if having sex with a pregnant woman. The patient should use a condom and another effective method of birth control if he is having sex with a woman of child-bearing potential. These measures are required during and for one week after treatment with Abiraterone acetate.

Manufactured by:
Patheon Inc.
Mississauga, Canada

Manufactured for:
Janssen Biotech, Inc.
Horsham, PA 19044

Distributed by:
Patriot Pharmaceuticals, LLC
Horsham, PA 19044

© 2017 Patriot Pharmaceuticals, LLC
Revised: May 2017

PATIENT INFORMATION

Abiraterone Acetate
Tablets
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: May 2017
Read this Patient Information that comes with Abiraterone acetate before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.
What is Abiraterone acetate?
Abiraterone acetate is a prescription medicine that is used along with prednisone. Abiraterone acetate is used to treat men with castration-resistant prostate cancer (prostate cancer that is resistant to medical or surgical treatments that lower testosterone) that has spread to other parts of the body.
Abiraterone acetate is not for use in women.
It is not known if Abiraterone acetate is safe or effective in children.

Who should not take Abiraterone acetate?
Do not take Abiraterone acetate if you are pregnant or may become pregnant. Abiraterone acetate may harm your unborn baby.
Women who are pregnant or who may become pregnant should not touch Abiraterone acetate without protection, such as gloves.

What should I tell my healthcare provider before taking Abiraterone acetate?
Before you take Abiraterone acetate, tell your healthcare provider if you:
  • have heart problems
  • have liver problems
  • have a history of adrenal problems
  • have a history of pituitary problems
  • have any other medical conditions
  • plan to become pregnant. See "Who should not take Abiraterone acetate?"
  • are breastfeeding or plan to breastfeed. It is not known if Abiraterone acetate passes into your breast milk. You and your healthcare provider should decide if you will take Abiraterone acetate or breastfeed. You should not do both. See "Who should not take Abiraterone acetate?"
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Abiraterone acetate can interact with many other medicines.
You should not start or stop any medicine before you talk with the healthcare provider that prescribed Abiraterone acetate.
Know the medicines you take. Keep a list of them with you to show to your healthcare provider and pharmacist when you get a new medicine.
How should I take Abiraterone acetate?
  • Take Abiraterone acetate and prednisone exactly as your healthcare provider tells you.
  • Take your prescribed dose of Abiraterone acetate 1 time a day.
  • Your healthcare provider may change your dose if needed.
  • Do not stop taking your prescribed dose of Abiraterone acetate or prednisone without talking with your healthcare provider first.
  • Take Abiraterone acetate on an empty stomach. Do not take Abiraterone acetate with food. Taking Abiraterone acetate with food may cause more of the medicine to be absorbed by the body than is needed and this may cause side effects.
  • No food should be eaten 2 hours before and 1 hour after taking Abiraterone acetate.
  • Swallow Abiraterone acetate tablets whole. Do not crush or chew tablets.
  • Take Abiraterone acetate tablets with water.
  • Men who are sexually active with a pregnant woman must use a condom during and for 1 week after treatment with Abiraterone acetate. If their female partner may become pregnant, a condom and another form of birth control must be used during and for 1 week after treatment with Abiraterone acetate. Talk with your healthcare provider if you have questions about birth control.
  • If you miss a dose of Abiraterone acetate or prednisone, take your prescribed dose the following day. If you miss more than 1 dose, tell your healthcare provider right away.
  • Your healthcare provider will do blood tests to check for side effects.
What are the possible side effects of Abiraterone acetate?
Abiraterone acetate may cause serious side effects including:
  • High blood pressure (hypertension), low blood potassium levels (hypokalemia) and fluid retention (edema). Tell your healthcare provider if you get any of the following symptoms:
 
  • dizziness
  • fast heartbeats
  • feel faint or lightheaded
  • headache
 
  • confusion
  • muscle weakness
  • pain in your legs
  • swelling in your legs or feet
  • Adrenal problems may happen if you stop taking prednisone, get an infection, or are under stress.
  • Liver problems. You may develop changes in liver function blood test. Your healthcare provider will do blood tests to check your liver before treatment with Abiraterone acetate and during treatment with Abiraterone acetate. Liver failure may occur, which can lead to death. Tell your healthcare provider if you notice any of the following changes:
    • yellowing of the skin or eyes
    • darkening of the urine
    • severe nausea or vomiting
The most common side effects of Abiraterone acetate include:
  • weakness
  • joint swelling or pain
  • swelling in your legs or feet
  • hot flushes
  • diarrhea
  • vomiting
  • cough
  • high blood pressure
  • shortness of breath
  • urinary tract infection
  • bruising
  • low red blood cells (anemia) and low blood potassium levels
  • high blood sugar levels, high blood cholesterol and triglycerides
  • certain other abnormal blood tests
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Abiraterone acetate. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Abiraterone acetate?
  • Store Abiraterone acetate at room temperature between 68°F to 77°F (20°C to 25°C).
Keep Abiraterone acetate and all medicines out of the reach of children.
General information about Abiraterone acetate.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Abiraterone acetate for a condition for which it was not prescribed. Do not give Abiraterone acetate to other people, even if they have the same symptoms that you have. It may harm them.
This leaflet summarizes the most important information about Abiraterone acetate. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Abiraterone acetate that is written for health professionals.
For more information, call Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN).
What are the ingredients of Abiraterone acetate?
Active ingredient: Abiraterone acetate
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, and sodium lauryl sulfate.
Manufactured by: Patheon Inc., Mississauga, Canada
Manufactured for: Janssen Biotech, Inc., Horsham, PA 19044
Distributed by: Patriot Pharmaceuticals, LLC, Horsham, PA 19044
© 2017 Patriot Pharmaceuticals, LLC
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