Drug Information

Drug Interaction:

ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzyme CYP2D6.

Avoid co-administration of ZYTIGA with CYP2D6 substrates that have

a narrow therapeutic index. If an alternative treatment cannot be used,

exercise caution and consider a dose reduction of the concomitant CYP2D6 substrate.

Indication:

ZYTIGAR (abiraterone acetate) Tablets For Oral Administration

Initial U.S. Approval 2011

Drug Name- Zytiga

Active Ingredient - Abiraterone acetate

In combination with prednisolone ( steroid) to treat patients with late-stage

(metastatic) castration-resistent prostrate cancer who have received prior

docetaxel (chemotherapy)

Indication-

In combination with prednisolone ( steroid) to treat patients with late-stage

(metastatic) castration-resistent prostrate cancer who have received prior

docetaxel (chemotherapy)

Approved by FDA on 28-4-2011 (Ref- FDA approved List- 2011)

New drugs approved For Marketing by Drug Controller General of India(DCGI )

during the period January 1988 to November 2014

(Ref- IDMA Annual Publication 2015)

Name of Drug Indication Date of Approval

1.Abiraterone acetate tablets 250mg 16-12-2011

In combination with prednisone for the treatment of patients with metastatic-

castration-resistent prostrate cancer and who have received prior chemotherapy

containing docetaxel

Prostrate cancer-

Metastatic castration resistent prostrate cancer

Adverse Reaction:

The most common adverse reactions ( 5%) are joint swelling or discomfort,

hypokalemia, edema, muscle discomfort, hot flush, diarrhea, urinary tract infection,

cough, hypertension, arrhythmia, urinary frequency, nocturia, dyspepsia,

fractures and upper respiratory tract infection.

Contra-Indications:

CONTRAINDICATIONS

ZYTIGA is contraindicated in women who are or may become pregnant.

WARNINGS AND PRECAUTIONS

Mineralocorticoid excess: Use ZYTIGA with caution in patients with a history

of cardiovascular disease. The safety of ZYTIGA in patients with LVEF < 50%

or NYHA Class III or IV heart failure is not established.

Control hypertension and correct hypokalemia before treatment.

Monitor blood pressure, serum potassium and symptoms of fluid retention at least monthly.

Adrenocortical insufficiency: Monitor for symptoms and signs of adrenocortical

insufficiency. Increased dosage of corticosteroids may be indicated before,

during and after stressful situations.

Hepatotoxicity: Increases in liver enzymes have led to drug interruption,

dose modification and/or discontinuation. Monitor liver function and modify

interrupt, or discontinue ZYTIGA dosing as recommended.

Food Effect: ZYTIGA must be taken on an empty stomach.

Exposure (area under the curve) of abiraterone increases up to 10 fold

when abiraterone acetate is taken with meals.

Dosages/ Overdosage Etc:

INDICATIONS AND USAGE

ZYTIGA is a CYP17 inhibitor indicated for use in combination with prednisone

for the treatment of patients with metastatic castration-resistant prostate cancer

who have received prior chemotherapy containing docetaxel.

DOSAGE AND ADMINISTRATION

Recommended dose: ZYTIGA 1,000 mg (four 250 mg tablets) administered

orally once daily in combination with prednisone 5 mg administered

orally twice daily.

ZYTIGA must be taken on an empty stomach.

No food should be consumed for at least two hours before the dose of

ZYTIGA is taken and for at least one hour after the dose of ZYTIGA is taken.

The tablets should be swallowed whole with water.

Do not crush or chew tablets.

For patients with baseline moderate hepatic impairment (Child-Pugh Class

B), reduce the ZYTIGA starting dose to 250 mg once daily.

„h For patients who develop hepatotoxicity during treatment, hold ZYTIGA until recovery.

Retreatment may be initiated at a reduced dose.

ZYTIGA should be discontinued if patients develop severe hepatotoxicity.

DOSAGE FORMS AND STRENGTHS

Tablet 250 mg

Patient Information:

PATIENT COUNSELING INFORMATION

1.Patients should be informed that ZYTIGA and prednisone are used together and that

they should not interrupt or stop either of these medications without consulting their physician.

2. Patients receiving GnRH agonists should be informed that they need to maintain

this treatment during the course of treatment with ZYTIGA and prednisone.

3. Patients should be informed that ZYTIGA must not be taken with food and

that no food should be consumed for at least two hours before the dose of ZYTIGA

is taken and for at least one hour after the dose of ZYTIGA 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 ZYTIGA with

food causes increased exposure and this may result in adverse reactions.

4.Patients should be informed that ZYTIGA is taken once daily and prednisone

is taken twice daily according to their physician¡¦s instructions.

5.Patients should be informed that in the event of a missed daily dose of

ZYTIGA 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.

6. Patients should be apprised of the common side effects associated with ZYTIGA,

including peripheral edema, hypokalemia, hypertension and urinary tract infection.

Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION.

7. Patients should be advised that their liver function will be monitored using blood tests.

8. Patients should be informed that ZYTIGA may harm a developing fetus; thus, women

who are pregnant or women who may be pregnant should not handle ZYTIGA

without protection, e.g., gloves.

9..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 ZYTIGA.

Pharmacology/ Pharmacokinetics:

1. Mechanism of Action

Abiraterone acetate (ZYTIGA) is converted in vivo to abiraterone, an androgen

biosynthesis inhibitor, that inhibits 17 á-hydroxylase/C17,20-lyase (CYP17).

This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues

and is required for androgen biosynthesis

2. Pharmacokinetics

Following administration of abiraterone acetate, the pharmacokinetics of abiraterone

and abiraterone acetate have been studied in healthy subjects and in patients

with metastatic castration-resistant prostate cancer (CRPC). In vivo, abiraterone

acetate is converted to abiraterone. In clinical studies, abiraterone acetate

plasma concentrations were below detectable levels (< 0.2 ng/mL) in > 99%

of the analyzed samples.

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy

Pregnancy Category X

ZYTIGA 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, the patient should be apprised of the potential hazard to

the fetus and the potential risk for pregnancy loss. Women of childbearing potential

should be advised to avoid becoming pregnant during treatment with ZYTIGA.

2. Nursing Mothers

ZYTIGA 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

rom ZYTIGA, a decision should be made to either discontinue nursing,

or discontinue the drug taking into account the importance of the drug to the mother.

3. Pediatric Use

ZYTIGA is not indicated in children.

4. Geriatric Use

Of the total number of patients in a phase 3 trial of ZYTIGA, 71% of patients

were 65 years and over and 28% were 75 years and over.

No overall differences in safety or effectiveness were observed between

these elderly patients and younger patients.

1/11.Abiraterone Acetate - Zytiga -@- Carcino-chemotherapeutic Drugs (Apr 2011)

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation