MIFEPRISTONE tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

MIFEPRISTONE (UNII: 320T6RNW1F) (MIFEPRISTONE - UNII:320T6RNW1F)

Available from:

Actavis Pharma, Inc.

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Mifepristone is a cortisol receptor blocker indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery. LIMITATIONS OF USE: - Mifepristone tablets should not be used in the treatment of patients with type 2 diabetes unless it is secondary to Cushing’s syndrome. Mifepristone is contraindicated in: - Pregnancy [See Dosage and Administration (2.1), Use in Specific Populations (8.1, 8.3)] - Patients taking drugs metabolized by CYP3A such as simvastatin, lovastatin, and CYP3A substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, due to an increased risk of adverse events. [See Drug Interactions (7.1) and Clinical Pharmacology (12.3)] - Patients receiving systemic corticosteroids for lifesaving purposes (e.g., immunosuppression after organ transplantation) because mifepristone antagonizes the effect of glucocorticoids. - Women with a history of unexplained vaginal bleeding or with endometrial hyperplasia with atypia or endometrial carcinoma. - Patients with known hypersensitivity to mifepristone or to any of the product components. Risk Summary Mifepristone is contraindicated in pregnancy because the use of mifepristone results in pregnancy loss. There are no data that assess the risk of birth defects in women exposed to mifepristone during pregnancy. Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator (See Data) . Mifepristone administered to pregnant mice, rats, and rabbits during organogenesis caused pregnancy loss in all species at clinically relevant doses based on body surface area comparisons (See Data) .The inhibition of both endogenous and exogenous progesterone by mifepristone at the progesterone receptor results in pregnancy loss. If mifepristone is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. [See Contraindications (4)] The estimated risk of fetal loss is elevated in patients with active Cushing’s syndrome (24% to 30%), and the risk of major birth defects is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively. Data Human Data There are no data on long term exposure to mifepristone in pregnancy. Available data are limited to exposure to a single dose of mifepristone for pregnancy termination. In a prospective study in France of 46 pregnancies exposed to a single dose of mifepristone alone and 59 pregnancies exposed to a single dose of mifepristone and misoprostol, the overall major birth defect rate (4%) was greater than the general population background rate of 2% to 3% (2 birth defects in each group). There was no pattern of birth defects identified. Animal Data Reproductive studies were performed in mice, rats and rabbits at doses of 0.25 to 4.0 mg/kg (less than human exposure at the maximum clinical dose, based on body surface area). Because of the anti-progestational activity of mifepristone, fetal losses were much higher than in control animals. Skull deformities were detected in rabbit studies at less than human exposure, although mifepristone did not cause any adverse developmental effects in rats or mice during organogenesis. These deformities were most likely due to the mechanical effects of uterine contractions resulting from antagonism of the progesterone receptor. Risk Summary Mifepristone is present in human milk, however, there are no data on the amount of mifepristone in human milk, the effects on the breastfed infant, or the effects on milk production during long term use of mifepristone (see Data) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for mifepristone and any potential adverse effects on the breastfed child from mifepristone or from the underlying maternal condition. Clinical Considerations To minimize exposure to a breastfed infant, women who discontinue or interrupt mifepristone treatment may consider pumping and discarding milk during treatment and for 18 to 21 days (5 to 6 half-lives) after the last dose, before breastfeeding. Data Available published data based on intake of a single dose of 600 mg of mifepristone in 10 breastfeeding women who were 6 to 12 months postpartum showed a small amount in breast milk (the estimated relative infant dose was 0.5%). The half-life of mifepristone is longer with repeat dosing compared to a single dose; therefore, there may be greater exposure with long term use. Pregnancy Testing Due to its anti-progestational activity, mifepristone causes pregnancy loss. Perform pregnancy testing before the initiation of treatment with mifepristone or if treatment is interrupted for more than 14 days in females of reproductive potential. Contraception Recommend non-hormonal contraception for the duration of treatment and for one month after stopping treatment. Mifepristone interferes with the effectiveness of hormonal contraceptives. [See Drug Interactions (7.6)] Safety and effectiveness of mifepristone in pediatric patients have not been established. Clinical studies with mifepristone did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger people. The maximum dose should not exceed 600 mg per day in renally impaired patients [see Clinical Pharmacology (12.3)] . In patients with mild to moderate hepatic impairment, the maximum dose should not exceed 600 mg per day. The pharmacokinetics of mifepristone in patients with severe hepatic impairment has not been studied, and mifepristone should not be used in these patients [see Clinical Pharmacology (12.3)] .

Product summary:

Mifepristone tablets are supplied as follows: 300 mg – Each dark yellow to light brown, film-coated, oval-shaped tablet debossed with A33 on one side and plain on the other side contains 300 mg of mifepristone. Tablets are supplied in bottles of 28 (NDC 0591-4390-96) and bottles of 280 (NDC 0591-4390-35). Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

Actavis Pharma, Inc.
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MEDICATION GUIDE
Dispense with Medication Guide available at: www.tevausa.com/medguides
Mifepristone (mifʺ e pris′ tone) Tablets
What is the most important information I should know about
mifepristone tablets?
Mifepristone tablets can cause serious side effects, including:
•
Loss of a pregnancy. Women who can become pregnant must:
•
have a negative pregnancy test before starting mifepristone tablets
•
have a negative pregnancy test before restarting mifepristone tablets
if you stop taking it for more than 14 days
•
use a non-hormonal form of birth control while taking mifepristone
tablets and for 1 month after stopping mifepristone tablets.
Talk to your doctor about how to prevent pregnancy. Tell your doctor
right away if you think you may be pregnant.
What are mifepristone tablets?
Mifepristone tablets are a prescription medicine used to treat high
blood sugar (hyperglycemia) caused by high cortisol levels in the
blood
(hypercortisolism) in adults with endogenous Cushing’s syndrome who
have type 2 diabetes mellitus or glucose intolerance and have failed
surgery or
cannot have surgery.
Mifepristone tablets are not for people who have type 2 diabetes
mellitus not caused by Cushing’s syndrome.
It is not known if mifepristone tablets are safe and effective in
children.
Do not take mifepristone tablets if you:
•
are pregnant. See “What is the most important information I should
know about mifepristone tablets?”
•
are taking:
•
simvastatin (Zocor®, Vytorin®, Simcor®)
•
lovastatin (Mevacor®, Altoprev®, Advicor®)
•
cyclosporine (Gengraf®, Neoral®, Restasis®, Sandimmune®)
•
dihydroergotamine (Migranal®)
•
ergotamine (Ergomar®, Migergot®)
•
fentanyl (Abstral®, Actiq®, Duragesic®, Fentora®, Lazanda®,
Onsolis®, Sublimaze Preservative Free®, Subsys®)
•
pimozide (Orap®)
•
quinidine (Nuedexta®)
•
sirolimus (Rapamune®, Torisel®)
•
tacrolimus (Prograf®, Protopic®)
•
must take corticosteroid medicines for other serious medical

Summary of Product characteristics

MIFEPRISTONE- MIFEPRISTONE TABLET, FILM COATED
ACTAVIS PHARMA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
MIFEPRISTONE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
MIFEPRISTONE TABLETS.
MIFEPRISTONE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2000
WARNING: TERMINATION OF PREGNANCY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
MIFEPRISTONE HAS POTENT ANTIPROGESTATIONAL EFFECTS AND WILL RESULT IN
THE TERMINATION
OF PREGNANCY. PREGNANCY MUST THEREFORE BE EXCLUDED BEFORE THE
INITIATION OF TREATMENT
WITH MIFEPRISTONE, OR IF TREATMENT IS INTERRUPTED FOR MORE THAN 14
DAYS IN FEMALES OF
REPRODUCTIVE POTENTIAL.
INDICATIONS AND USAGE
Mifepristone is a cortisol receptor blocker indicated to control
hyperglycemia secondary to
hypercortisolism in adult patients with endogenous Cushing's syndrome
who have type 2 diabetes mellitus
or glucose intolerance and have failed surgery or are not candidates
for surgery (1).
IMPORTANT LIMITATIONS OF USE: Do not use for the treatment of type 2
diabetes mellitus unrelated to
endogenous Cushing’s syndrome.
DOSAGE AND ADMINISTRATION
Obtain a negative pregnancy test in females of reproductive potential
prior to initiating treatment with
mifepristone tablets or if treatment is interrupted for more than 14
days (2.1).
Administer once daily orally with a meal (2.2).
The recommended starting dose is 300 mg once daily (2.2).
Based on clinical response and tolerability, the dose may be increased
in 300 mg increments to a
maximum of 1,200 mg once daily. Do not exceed 20 mg/kg per day (2.2).
Renal impairment: do not exceed 600 mg once daily (2.3).
Mild-to-moderate hepatic impairment: do not exceed 600 mg once daily.
Do not use in severe hepatic
impairment (2.4).
Concomitant administration with strong CYP3A inhibitors: Do not exceed
900 mg once daily (2.5).
DOSAGE FORMS AND STRENGTHS
Tablets: 300 mg (3).
CONTRAINDICATIONS
Pregnancy (4, 8.1).
Patients taking drugs metabolized by CYP3