Abiraterone

Name: Abiraterone

What should I discuss with my healthcare provider before taking abiraterone?

You should not use abiraterone if you are allergic to it, or if you have ever had:

  • severe liver disease.

To make sure abiraterone is safe for you, tell your doctor if you have:

  • liver disease;

  • heart disease, high blood pressure;

  • problems with your adrenal gland or pituitary gland;

  • low levels of potassium in your blood;

  • fluid retention;

  • a heart attack; or

  • if you take medicine to treat seizures, tuberculosis, HIV or AIDS.

While you are taking abiraterone and for at least 1 week after your treatment ends:

  • If your sexual partner is pregnant--Use a condom to prevent transfer of this medication to her.

  • If your sexual partner could become pregnant--Use a condom plus another form of effective birth control to prevent pregnancy.

Although abiraterone is not for use by women, this medicine can harm an unborn baby or cause birth defects. Abiraterone tablets should not be handled by a woman who is pregnant or who may become pregnant. If this cannot be avoided, the woman should wear latex gloves.

It is not known whether abiraterone passes into breast milk or if it could harm a nursing baby. Abiraterone should not be used by a woman who is breast-feeding a baby.

Abiraterone is not approved for use by anyone younger than 18 years old.

How should I take abiraterone?

Abiraterone is usually taken once per day while also taking prednisone two times per day. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Your prednisone dosage needs may change if you have surgery, are ill, or are under stress. Do not change your medication dose or schedule without your doctor's advice.

Take abiraterone on an empty stomach. Do not eat anything for at least 2 hours before you take abiraterone and for at least 1 hour after you have taken the medicine.

Do not crush, chew, or break an abiraterone tablet. Swallow it whole with a full glass of water.

Your blood pressure will need to be checked often, and you may need frequent blood tests at your doctor's office.

You should not stop using abiraterone or prednisone suddenly. Follow your doctor's instructions about tapering your prednisone dose.

Store at room temperature away from moisture and heat.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

abiraterone Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Bladder pain
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • bloody or cloudy urine
  • blurred vision
  • bone fracture
  • chest pain or discomfort
  • convulsions
  • decreased urine
  • difficult, burning, or painful urination
  • dizziness
  • dry mouth
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • feeling of warmth
  • frequent urge to urinate
  • headache
  • increased need to urinate
  • increased thirst
  • increased urge to urinate during the night
  • lightheadedness, dizziness, or fainting
  • loss of appetite
  • lower back or side pain
  • mood changes
  • muscle pain or cramps
  • nausea or vomiting
  • nervousness
  • numbness or tingling in the hands, feet, or lips
  • pain or swelling in the arms or legs without any injury
  • passing urine more often
  • pounding in the ears
  • rapid weight gain
  • redness of the face, neck, arms, and occasionally, upper chest
  • slow heartbeat
  • sudden sweating
  • swelling
  • swelling with pits or depressions on the skin
  • unusual tiredness or weakness
  • unusual weight gain or loss
  • waking to urinate at night
Less common
  • Abdominal or stomach pain or tenderness
  • arm, back, or jaw pain
  • chest tightness or heaviness
  • clay colored stools
  • cool, sweaty skin
  • dark urine
  • decreased appetite
  • decreased urine output
  • difficulty with breathing
  • dilated neck veins
  • extreme fatigue
  • fever
  • headache
  • irregular breathing
  • itching skin or rash
  • sweating
  • swelling of the face, fingers, feet, or lower legs
  • weakness
  • weight gain
  • yellow eyes or skin
Rare
  • Darkening of the skin
  • diarrhea
  • mental depression

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Acid or sour stomach
  • belching
  • body aches or pain
  • chills
  • cough
  • difficulty with moving
  • ear congestion
  • heartburn
  • indigestion
  • joint pain
  • loss of voice
  • muscle cramps or spasms
  • muscle or bone pain
  • muscle stiffness
  • nasal congestion
  • runny nose
  • sneezing
  • sore throat
  • stomach discomfort or upset
  • swelling or stiffness of the joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What side effects can this medication cause?

Abiraterone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • joint swelling or pain
  • hot flashes (a sudden wave of mild or intense body heat)
  • diarrhea
  • heartburn

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

  • dizziness
  • feeling faint or lightheaded
  • headache
  • confusion
  • fast or irregular heartbeats
  • muscle weakness or aches
  • leg pain
  • swelling of the hands, feet, ankles, or lower legs
  • unusual bruising or bleeding
  • extreme tiredness
  • lack of energy
  • nausea
  • loss of appetite
  • pain in the upper right part of the stomach
  • yellowing of the skin or eyes
  • flu-like symptoms
  • difficult, painful or frequent urination

Abiraterone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Abiraterone Precautions

Abiraterone may cause serious side effects including:

  • high blood pressure, low blood potassium levels, and fluid retention. 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. This may occur if you stop taking prednisone, get an infection, or are under stress.
  • liver problems. Your healthcare provider will do blood tests to check your liver before treatment with abiraterone and during treatment with abiraterone.

Do not take abiraterone if you:

  • are allergic to abiraterone or to any of its ingredients
  • are pregnant or may become pregnant. Abiraterone may harm your unborn baby.

Abiraterone Overdose

If you take too much abiraterone, call your local Poison Control Center or seek emergency medical attention right away.

If abiraterone is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Administration

Oral Administration

Take on empty stomach, at least 1 hr ac or 2 hr pc

Food increases AUC up to 10-fold

Swallow tablets whole with water; do not chew, crush, or split

Usual Adult Dose for Prostate Cancer

1,000 mg orally once a day on an empty stomach (in combination with prednisone 5 mg orally 2 times a day)

Comments: No food should be consumed for at least 2 hours before the dose and for at least 1 hour after the dose of this drug.

Use: Treatment of metastatic castration-resistant prostate cancer

Other Comments

Administration Advice:
-This drug should be swallowed whole with water.
-Drug tablets should not be crushed or chewed.
-Pregnant women should not handle this drug without protection (e.g., gloves).
-In the event of a missed dose, the missed dose should be skipped and treatment should be resumed the following day with the usual daily dose.

General:
-Patients already receiving a gonadotropin-releasing hormone (GnRH) agonist should continue to take that drug during abiraterone treatment.

Monitoring:
-Cardiovascular: Cardiac function
-Endocrine: Blood pressure, serum potassium, fluid retention, signs/symptoms of adrenocortical insufficiency
-Hepatic: ALT, AST, bilirubin
-Metabolic: Blood sugar (in diabetic patients)

Indications and Usage for Abiraterone

Abiraterone acetate is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

Use in specific populations

Pregnancy

Pregnancy Category X [see Contraindications (4.1)].

Abiraterone acetate can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no adequate and well-controlled studies with Abiraterone acetate in pregnant women and Abiraterone acetate is not indicated for use in women, it is important to know that maternal use of a CYP17 inhibitor could affect development of the fetus. Abiraterone acetate caused developmental toxicity in pregnant rats at exposures that were lower than in patients receiving the recommended dose. Abiraterone acetate is contraindicated in women who are or may become pregnant while receiving the drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. Advise females of reproductive potential to avoid becoming pregnant during treatment with Abiraterone acetate.

In an embryo-fetal developmental toxicity study in rats, Abiraterone acetate caused developmental toxicity when administered at oral doses of 10, 30 or 100 mg/kg/day throughout the period of organogenesis (gestational days 6–17). Findings included embryo-fetal lethality (increased post implantation loss and resorptions and decreased number of live fetuses), fetal developmental delay (skeletal effects) and urogenital effects (bilateral ureter dilation) at doses ≥10 mg/kg/day, decreased fetal ano-genital distance at ≥30 mg/kg/day, and decreased fetal body weight at 100 mg/kg/day. Doses ≥10 mg/kg/day caused maternal toxicity. The doses tested in rats resulted in systemic exposures (AUC) approximately 0.03, 0.1 and 0.3 times, respectively, the AUC in patients.

Nursing Mothers

Abiraterone acetate is not indicated for use in women. It is not known if Abiraterone acetate is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Abiraterone acetate, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Abiraterone acetate in pediatric patients have not been established.

Geriatric Use

Of the total number of patients receiving Abiraterone acetate in Phase 3 trials, 73% of patients were 65 years and over and 30% were 75 years and over. No overall differences in safety or effectiveness were observed between these elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Hepatic Impairment

The pharmacokinetics of Abiraterone were examined in subjects with baseline mild (N=8) or moderate (N=8) hepatic impairment (Child-Pugh Class A and B, respectively) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of Abiraterone after a single oral 1,000 mg dose of Abiraterone acetate increased by approximately 1.1-fold and 3.6-fold in subjects with mild and moderate baseline hepatic impairment, respectively compared to subjects with normal hepatic function.

In another trial, the pharmacokinetics of Abiraterone were examined in subjects with baseline severe (N=8) hepatic impairment (Child-Pugh Class C) and in 8 healthy control subjects with normal hepatic function. The systemic exposure (AUC) of Abiraterone increased by approximately 7-fold and the fraction of free drug increased 2-fold in subjects with severe baseline hepatic impairment compared to subjects with normal hepatic function.

No dosage adjustment is necessary for patients with baseline mild 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. Do not use Abiraterone acetate in patients with baseline severe hepatic impairment (Child-Pugh Class C). If elevations in ALT or AST >5× ULN or total bilirubin >3× ULN occur in patients with baseline moderate hepatic impairment, discontinue Abiraterone acetate treatment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

For patients who develop hepatotoxicity during treatment, interruption of treatment and dosage adjustment may be required [see Dosage and Administration (2.2), Warnings and Precautions (5.3), and Clinical Pharmacology (12.3)].

Patients with Renal Impairment

In a dedicated renal impairment trial, the mean PK parameters were comparable between healthy subjects with normal renal function (N=8) and those with end stage renal disease (ESRD) on hemodialysis (N=8) after a single oral 1,000 mg dose of Abiraterone acetate. No dosage adjustment is necessary for patients with renal impairment [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

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