Download Zytiga and Xtandi Prior Authorization

JOHNS HOPKINS HEALTHCARE
PHARMACY DEPARTMENT POLICY AND PROCEDURE
Policy Number:
MEDS78
TITLE OF POLICY: Zytiga and Xtandi
LOB: PP, EHP
Effective Date: 07/17/2013
Review Date: n/a
LOB: PPMCO, EHP
Page 1 of 2
POLICY:
Zytiga (abiraterone acetate) and Xtandi (enzalutamide) will require prior authorization. The process for
initiating a prior authorization request can be found in policy PHARM 20.
POLICY CRITERIA:
Zytiga will be approved for the following:
• Men with metastatic castration-resistant prostate cancer in combination with prednisone.
• A quantity limit of 120 tablets per 30 days.
Xtandi will be approved for the following:
• Men with metastatic castration-resistant prostate cancer who have previously received docetaxel AND
• Failed or have a contraindication to Zytiga
• A quantity limit of 120 tablets per 30 days.
AUTHORIZATION PERIOD
• Authorization for the initial course of therapy may be given for up to 12 months.
• Reauthorization for continued therapy may be given for up to 12 month.
EXCLUSIONS:
For Zytiga
• Dose greater than the FDA approved dose of 1000mg daily.
• AST>5xULN
• Total Bilirubin >3x ULN
• Patients with left ventricular ejection fraction < 50% or
• Class II to IV of New York Heart Association (NYHA) classification
For Xtandi
• Individuals who have seizures/ a low seizure threshold
• Dose greater than the FDA approved dose of160 mg daily.
Both
• Women who are pregnant or may become pregnant
• There are currently no studies that evaluate the effectiveness and safety in other types of cancer, however,
cases may be reviewed on an individual basis.
BACKGROUND AND DEFINITION OF TERMS:
Zytiga is approved in combination with prednisone for the treatment of patients with metastatic castrationresistant prostate cancer. It inhibits androgen biosynthesis by inhibiting 17 α‑ hydroxylase/C17,20-lyase
(CYP17 ). CYP17 is responsible for the catalysis of necessary precursors for the formation of testosterone.
CYP17 is expressed in testicular, adrenal, and prostate tumor tissues. Unlike GnRH agonists, that inhibit the
production of testosterone in the testes only, Zytiga is able to inhibit the androgen production in multiple sites
due to the inhibition of CYP17.
JOHNS HOPKINS HEALTHCARE
PHARMACY DEPARTMENT POLICY AND PROCEDURE
Policy Number:
MEDS78
TITLE OF POLICY: Zytiga and Xtandi
LOB: PP, EHP
Effective Date: 07/17/2013
Review Date: n/a
LOB: PPMCO, EHP
Page 2 of 2
As a result of the inhibition of CYP17, not only are the androgen levels low, but there may also be an increase
in mineralocorticoid production. The overproduction may contribute to hypertension, hypokalemia, and edema.
Those individuals with heart disease should be monitored very closely while on Zytiga, due to potential increase
in blood pressure, fluid retention, and hypokalemia. Cardiac failure occurred more commonly among Zytiga
users, than those using placebo.
In addition to cardiac concerns, there were also incidences of hepatotoxicity (ALT and/or AST greater than 5X
ULN or total bilirubin greater than 3X ULN). For some individuals, their treatment was discontinued
permanently; for others, once the patient’s baseline or AST and ALT were less than or equal to 2.5X ULN and
total bilirubin was less than or equal to 1.5X ULN, treatment was restarted at 750mg. If they had to be
discontinued again due to hepatotoxicity, and then restarted again, they were dosed at 500mg daily.
Zytiga is also a strong inhibitor of CYP2D6 and CYP2C8, avoidance of their substrates or reduction in dose
may be necessary, if use of Zytiga is required. Zytiga is a substrate of CYP3A4, so caution or avoidance should
be used for those required to take Zytiga. Zytiga should be taken on an empty stomach as a once daily dose of
four (250 mg ) tablets.
Xtandi (enzalutamide) has been approved for castration-resistant prostate cancer, in patients who have
previously received docetaxel. It is an androgen receptor inhibitor that competitively binds to the androgen
receptor and prevents androgen nuclear translocation and DNA interaction.
A significant adverse reaction that caused discontinuation of therapy during clinical trials was seizure activity.
Consequently, individuals with a known history of seizures, or low seizure threshold (e.g., transient ischemic
attack, cerebrovascular accident, brain metastases) or using medications (e.g.,varenicline, bupropion, etc.) that
lowers seizure threshold should avoid Xtandi.
Administration of Xtandi should be avoided with strong CYP2C8 inhibitors when possible. If concomitant
administration is required, the dose of Xtandi should be reduced to one-half the daily dose. Xtandi is an strong
inducer of CYP3A4, CYP2C9, and CYP2C19 ; hence, those substrates with a narrow therapeutic window
should be avoided. Xtandi is to be taken as a once daily dose of 4 (160mg) tablets.
POLICY APPROVED BY:
Signature on file at JHHC
REFERENCES:
Johns Hopkins HealthCare Pharmacy Policy PHARM20, Step Therapy, Prior Authorization and Quantity Limits
Xtandi® [package insert]. Horsham, PA: Janssen Biotech Inc.; 2012 December.
Zytiga® [package insert]. Northbrook, IL: Astellas Pharma US, Inc.; 2012 August.