2.1 Testing Prior to and During Mifepristone 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 [see Contraindications (4), Warnings and Precautions (5.2), Use in Specific Populations (8.1, 8.3)].

2.2 Adult Dosage

The recommended starting dose is 300 mg orally once daily. Mifepristone tablets must be given as a single daily dose. Mifepristone tablets should always be taken with a meal. Patients should swallow the tablet whole. Do not split, crush, or chew tablets.

Dosing and titration

The daily dose of mifepristone tablets may be increased in 300 mg increments. The dose of mifepristone tablets may be increased to a maximum of 1,200 mg once daily but should not exceed 20 mg/kg per day. Increases in dose should not occur more frequently than once every 2 to 4 weeks. Decisions about dose increases should be based on a clinical assessment of tolerability and degree of improvement in Cushing’s syndrome manifestations. Changes in glucose control, anti-diabetic medication requirements, insulin levels, and psychiatric symptoms may provide an early assessment of response (within 6 weeks) and may help guide early dose titration. Improvements in cushingoid appearance, acne, hirsutism, striae, and body weight occur over a longer period of time and, along with measures of glucose control, may be used to determine dose changes beyond the first 2 months of therapy. Careful and gradual titration of mifepristone tablets accompanied by monitoring for recognized adverse reactions [see Warnings and Precautions (5.1) and (5.2)] may reduce the risk of severe adverse reactions. Dose reduction or even dose discontinuation may be needed in some clinical situations. If mifepristone tablets treatment is interrupted, it should be reinitiated at the lowest dose (300 mg). If treatment was interrupted because of adverse reactions, the titration should aim for a dose lower than the one that resulted in treatment interruption.

2.3 Dosing in Renal Impairment

No change in initial dose of mifepristone tablets is required in renal impairment. The maximum dose should be limited to 600 mg [see Renal Impairment (8.6) and Clinical Pharmacology (12.3)].

2.4 Dosing in Hepatic Impairment

No change in the initial dose of mifepristone tablets is required in mild to moderate hepatic impairment. The maximum dose should be limited to 600 mg. Mifepristone tablets should not be used in severe hepatic impairment [see Hepatic Impairment (8.7) and Clinical Pharmacology (12.3)].

2.5 Concomitant Administration with CYP3A Inhibitors

Ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir and fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole, saquinavir, telithromycin, or voriconazole may increase exposure to mifepristone. Mifepristone tablets should be used in combination with strong CYP3A inhibitors only when necessary [see Warnings and Precautions (5.6), Drug Interactions (7.2)].

Administration of mifepristone tablets to patients already being treated with strong CYP3A inhibitors:

• Start at a dose of 300 mg. If clinically indicated, titrate to a maximum of 900 mg.

Administration of strong CYP3A inhibitors to patients already being treated with mifepristone tablets:

• Adjust the dose of mifepristone tablets according to Table 1.

5.1 Adrenal Insufficiency

Patients receiving mifepristone may experience adrenal insufficiency. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism in patients receiving mifepristone. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, including weakness, nausea, increased fatigue, hypotension, and hypoglycemia. If adrenal insufficiency is suspected, discontinue treatment with mifepristone immediately and administer glucocorticoids without delay. High doses of supplemental glucocorticoids may be needed to overcome the glucocorticoid receptor blockade produced by mifepristone. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).

Treatment with mifepristone at a lower dose can be resumed after resolution of adrenal insufficiency. Patients should also be evaluated for precipitating causes of hypoadrenalism (infection, trauma, etc.).

5.2 Hypokalemia

In a study of patients with Cushing’s syndrome, hypokalemia was observed in 44% of subjects during treatment with mifepristone. Hypokalemia should be corrected prior to initiating mifepristone. During mifepristone administration, serum potassium should be measured 1 to 2 weeks after starting or increasing the dose of mifepristone and periodically thereafter. Hypokalemia can occur at any time during mifepristone treatment. Mifepristone-induced hypokalemia should be treated with intravenous or oral potassium supplementation based on event severity. If hypokalemia persists in spite of potassium supplementation, consider adding mineralocorticoid antagonists.

5.3 Vaginal Bleeding and Endometrial Changes

Being an antagonist of the progesterone receptor, mifepristone promotes unopposed endometrial proliferation that may result in endometrium thickening, cystic dilatation of endometrial glands, and vaginal bleeding. Mifepristone should be used with caution in women who have hemorrhagic disorders or are receiving concurrent anticoagulant therapy. Women who experience vaginal bleeding during mifepristone treatment should be referred to a gynecologist for further evaluation.

5.4 QT Interval Prolongation

Mifepristone and its metabolites block IKr. Mifepristone prolongs the QTc interval in a dose-related manner. There is little or no experience with high exposure, concomitant dosing with other QT- prolonging drugs, or potassium channel variants resulting in a long QT interval [see Warnings & Precautions (5.6)]. To minimize risk, the lowest effective dose should always be used.

5.5 Exacerbation/Deterioration of Conditions Treated with Corticosteroids

Use of mifepristone in patients who receive corticosteroids for other conditions (e.g., autoimmune disorders) may lead to exacerbation or deterioration of such conditions, as mifepristone antagonizes the desired effects of glucocorticoid in these clinical settings. For medical conditions in which chronic corticosteroid therapy is lifesaving (e.g., immunosuppression in organ transplantation), mifepristone is contraindicated [see Contraindications (4.3)].

5.6 Use of Strong CYP3A Inhibitors

Mifepristone should be used with caution in patients taking ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole, saquinavir, telithromycin, or voriconazole, as these could increase the concentration of mifepristone in the blood. The benefit of concomitant use of these agents should be carefully weighed against the potential risks. Mifepristone should be used in combination with strong CYP3A inhibitors only when necessary, and in such cases the dose should be limited to 900 mg per day [see Warnings & Precautions (5.4), Drug Interactions (7.2), and Clinical Pharmacology (12.3)].

5.7 Pneumocystis jiroveci Infection

Patients with endogenous Cushing’s syndrome are at risk for opportunistic infections such as Pneumocystis jiroveci pneumonia during mifepristone treatment. Patients may present with respiratory distress shortly after initiation of mifepristone. Appropriate diagnostic tests should be undertaken and treatment for Pneumocystis jiroveci should be considered.

5.8 Potential Effects of Hypercortisolemia

Mifepristone does not reduce serum cortisol levels. Elevated cortisol levels may activate mineralocorticoid receptors which are also expressed in cardiac tissues. Caution should be used in patients with underlying heart conditions including heart failure and coronary vascular disease.

5.9 Risk of Allergic Reactions due to Tartrazine

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice.

Safety data on the use of mifepristone are available from 50 patients with Cushing’s syndrome enrolled in an uncontrolled, open-label, multi-center trial (Study 400). Forty-three patients had Cushing’s disease and all except one had previously undergone pituitary surgery. Four patients had ectopic ACTH secretion, and three had adrenal carcinoma. Patients were treated for up to 24 weeks. A dose of 300 mg per day was administered for the initial 14 days; thereafter, the dose could be escalated in increments of 300 mg per day based on assessments of tolerability and clinical response. Doses were escalated up to 900 mg per day for patients <60 kg, or 1,200 mg per day for patients >60 kg.

The most frequently reported adverse reactions (reported in ≥20% of patients, regardless of relationship to mifepristone) were nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, and endometrial hypertrophy. Drug-related adverse events resulted in dose interruption or reduction in study drug in 40% of patients.

The adverse reactions that occurred in ≥10% of the Cushing’s syndrome patients receiving mifepristone, regardless of relationship to mifepristone, are shown in Table 2.

6.2 Postmarketing Experience

The following adverse reaction has been identified during post approval use of mifepristone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

-   Angioedema

7.1 Drugs Metabolized by CYP3A

Because mifepristone is an inhibitor of CYP3A, concurrent use of mifepristone with a drug whose metabolism is largely or solely mediated by CYP3A is likely to result in increased plasma concentrations of the drug. Discontinuation or dose reduction of such medications may be necessary with mifepristone coadministration.

Mifepristone increased the exposure to simvastatin and simvastatin acid significantly in healthy subjects. Concomitant use of simvastatin or lovastatin is contraindicated because of the increased risk of myopathy and rhabdomyolysis [see Contraindications (4.2), Clinical Pharmacology 12.3].

The exposure of other substrates of CYP3A with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus, may be increased by concomitant administration with mifepristone. Therefore, the concomitant use of such CYP3A substrates with mifepristone is contraindicated [see Contraindications (4.2)].

Other drugs with similar high first pass metabolism in which CYP3A is the primary route of metabolism should be used with extreme caution if coadministered with mifepristone. The lowest possible dose and/or a decreased frequency of dosing must be used with therapeutic drug monitoring when possible. Use of alternative drugs without these metabolic characteristics is advised when possible with concomitant mifepristone.

If drugs that undergo low first pass metabolism by CYP3A or drugs in which CYP3A is not the major metabolic route are coadministered with mifepristone, use the lowest dose of concomitant medication necessary, with appropriate monitoring and follow-up [see Clinical Pharmacology (12.3)].

7.2 CYP3A Inhibitors

Medications that inhibit CYP3A could increase plasma mifepristone concentrations and dose reduction of mifepristone may be required.

Ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir and fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole, saquinavir, telithromycin, or voriconazole may increase exposure to mifepristone. Caution should be used when strong CYP3A inhibitors are prescribed in combination with mifepristone. The benefit of concomitant use of these agents should be carefully weighed against the potential risks. The dose of mifepristone should be limited to 900 mg, and strong inhibitors of CYP3A should be used only when necessary [see Dosage and Administration (2.4), Warnings & Precautions (5.6), and Clinical Pharmacology (12.3)].

7.3 CYP3A Inducers

No medications that induce CYP3A have been studied when coadministered with mifepristone. Avoid coadministration of mifepristone and CYP3A inducers such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John’s wort.

7.4 Drugs Metabolized by CYP2C8/2C9

Because mifepristone is an inhibitor of CYP2C8/2C9, concurrent use of mifepristone with a drug whose metabolism is largely or solely mediated by CYP2C8/2C9 is likely to result in increased plasma concentrations of the drug.

Mifepristone significantly increased exposure of fluvastatin, a typical CYP2C8/2C9 substrate, in healthy subjects. When given concomitantly with mifepristone, drugs that are substrates of CYP2C8/2C9 (including non-steroidal anti-inflammatory drugs, warfarin, and repaglinide) should be used at the smallest recommended doses, and patients should be closely monitored for adverse effects [see Clinical Pharmacology (12.3)].

7.5 Drugs Metabolized by CYP2B6

Mifepristone is an inhibitor of CYP2B6 and may cause significant increases in exposure of drugs that are metabolized by CYP2B6 such as bupropion and efavirenz. Since no study has been conducted to evaluate the effect of mifepristone on substrates of CYP2B6, the concomitant use of bupropion and efavirenz should be undertaken with caution [see Clinical Pharmacology (12.3)].

7.6 Use of Hormonal Contraceptives

Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used [See Use In Specific Populations (8.3)].

8.1 Pregnancy

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.

8.2 Lactation

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.

8.3 Females and Males of Reproductive Potential

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)]

8.4 Pediatric Use

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

8.5 Geriatric Use

Clinical studies with mifepristone did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger people.

8.6 Renal Impairment

The maximum dose should not exceed 600 mg per day in renally impaired patients [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

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)].

12.1 Mechanism of Action

Mifepristone is a selective antagonist of the progesterone receptor at low doses and blocks the glucocorticoid receptor (GR-II) at higher doses. Mifepristone has high affinity for the GR-II receptor but little affinity for the GR-I (MR, mineralocorticoid) receptor. In addition, mifepristone appears to have little or no affinity for estrogen, muscarinic, histaminic, or monoamine receptors.

12.2 Pharmacodynamics

Because mifepristone acts at the receptor level to block the effects of cortisol, its antagonistic actions affect the hypothalamic-pituitary-adrenal (HPA) axis in such a way as to further increase circulating cortisol levels while, at the same time, blocking their effects.

Mifepristone and the three active metabolites have greater affinity for the glucocorticoid receptor [100% (mifepristone), 61% (metabolite 1), 48% (metabolite 2), and 45% (metabolite 3)] than either dexamethasone (23%) or cortisol (9%).

12.3 Pharmacokinetics

Absorption
Following oral administration, time to peak plasma concentrations of mifepristone occurred between 1 and 2 hours following single dose, and between 1 and 4 hours following multiple doses of 600 mg of mifepristone in healthy volunteers. Mean plasma concentrations of three active metabolites of mifepristone peak between 2 and 8 hours after multiple doses of 600 mg/day, and the combined concentrations of the metabolites exceed that of the parent mifepristone. Exposure to mifepristone is substantially less than dose proportional. Time to steady state is within 2 weeks, and the mean (SD) half-life of the parent mifepristone was 85 (61) hours following multiple doses of 600 mg/day of mifepristone.

Studies evaluating the effects of food on the pharmacokinetics of mifepristone demonstrate a significant increase in plasma levels of mifepristone when dosed with food. To achieve consistent plasma drug concentrations, patients should be instructed to always take their medication with meals.

Distribution
Mifepristone is highly bound to alpha-1-acid glycoprotein (AAG) and approaches saturation at doses of 100 mg (2.5 µM) or more. Mifepristone and its metabolites also bind to albumin and are distributed to other tissues, including the central nervous system (CNS). As determined in vitro by equilibrium dialysis, binding of mifepristone and its three active metabolites to human plasma proteins was concentration-dependent. Binding was approximately 99.2% for mifepristone, and ranged from 96.1% to 98.9% for the three active metabolites at clinically relevant concentrations.

Metabolism
Cytochrome P450 3A4 (CYP3A4) has been shown to be involved in mifepristone metabolism in human liver microsomes. Two of the known active metabolites are the product of demethylation (one monodemethylated and one di-demethylated), while a third active metabolite results from hydroxylation (monohydroxylated).

Elimination and Excretion
Excretion is primarily (approximately 90%) via the fecal route.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Mifepristone was evaluated for carcinogenicity potential in rats and mice. Rats were dosed for up to two years at doses of 5 mg/kg, 25 mg/kg, and 125 mg/kg of mifepristone. The high dose was the maximum tolerated dose, but exposure at all doses was below exposure at the maximum clinical dose based on AUC comparison. Female rats had a statistically significant increase in follicular cell adenomas/carcinomas and liver adenomas. It is plausible that these tumors are due to drug-induced enzyme metabolism, a mechanism not considered clinically relevant, but studies confirming this mechanism were not conducted with mifepristone. Mice were also tested for up to 2 years at mifepristone doses up to the maximum tolerated dose of 125 mg/kg, which provided exposure below the maximum clinical dose based on AUC. No drug-related tumors were seen in mice.

Mifepristone was not genotoxic in a battery of bacterial, yeast, and mammalian in vitro assays, and an in vivo micronucleus study in mice.

The pharmacological activity of mifepristone disrupts the estrus cycle of adult rats at a dose of 0.3 mg/kg (less than human exposure at the maximum clinical dose, based on body surface area). However, following withdrawal of treatment and subsequent resumption of the estrus cycle, there was no effect on reproductive function when mated.

A single subcutaneous dose of mifepristone (up to 100 mg/kg) to rats on the first day after birth did not adversely affect future reproductive function in males or females, although the onset of puberty was slightly premature in dosed females. Repeated doses of mifepristone (1 mg every other day) to neonatal rats resulted in potentially adverse fertility effects, including oviduct and ovary malformations in females, delayed male puberty, deficient male sexual behavior, reduced testicular size, and lowered ejaculation frequency.

14.1 Cushing’s Syndrome

An uncontrolled, open-label, 24-week, multicenter clinical study was conducted to evaluate the safety and efficacy of mifepristone in the treatment of endogenous Cushing’s syndrome. The study enrolled 50 subjects with clinical and biochemical evidence of hypercortisolemia despite prior surgical treatment and radiotherapy. The reasons for medical treatment were failed surgery, recurrence of disease, and poor medical candidate for surgery. Forty-three patients (86%) had Cushing’s disease, four patients (8%) had ectopic ACTH secretion, and three (6%) had adrenal carcinoma. Baseline characteristics included: mean age of 45 years (range 26 to 71), mean BMI of 36 kg/m2 (range 24 to 66), mean weight 100 kg (range 61 to 199), and mean waist circumference was 119 cm (range 89 to 178); 70% were female; 84% were white and 16% were black or African American. Baseline mean urinary free cortisol level was 365 mcg per 24 hr.

Patients belonged to one of two cohorts: a “diabetes” cohort (29 patients, 26 with type 2 diabetes and 3 with glucose intolerance), and a “hypertension” cohort (21 patients). Efficacy was evaluated separately in the two cohorts. Mifepristone treatment was started in all patients at a dose of 300 mg once a day. The study protocol allowed an increase in dose to 600 mg after 2 weeks, and then by additional 300 mg increments every 4 weeks to a maximum of 900 mg per day for patients <60 kg, or 1,200 mg per day for patients >60 kg, based on clinical tolerance and clinical response.

Results in the diabetes cohort
Patients in the diabetes cohort underwent standard oral glucose tolerance tests at baseline and periodically during the clinical study. Anti-diabetic medications were allowed but had to be kept stable during the trial and patients had to be on stable anti-diabetic regimens prior to enrollment. The primary efficacy analysis for the diabetes cohort was an analysis of responders. A responder was defined as a patient who had a ≥25% reduction from baseline in glucose AUC. The primary efficacy analysis was conducted in the modified intent-to-treat population (n=25) defined as all patients who received a minimum of 30 days on mifepristone. Fifteen of 25 patients (60%) were treatment responders (95% CI: 39%, 78%).

Mean HbA1c was 7.4% in the 24 patients with HbA1c values at baseline and Week 24. For these 24 patients mean reduction in HbA1c was 1.1% (95% CI -1.6, -0.7) from baseline to the end of the trial. Fourteen of 24 patients had above normal HbA1c levels at baseline, ranging between 6.7% and 10.4%; all of these patients had reductions in HbA1c by the end of the study (range -0.4 to -4.4%) and eight of 14 patients (57%) normalized HbA1c levels at trial end. Antidiabetic medications were reduced in 7 of the 15 DM subjects taking antidiabetic medication and remained constant in the others.

Results in the hypertension cohort
There were no changes in mean systolic and diastolic blood pressures at the end of the trial relative to baseline in the modified intent-to-treat population (n=21).

Signs and symptoms of Cushing’s syndrome in both cohorts
Individual patients showed varying degrees of improvement in Cushing's syndrome manifestations such as cushingoid appearance, acne, hirsutism, striae, psychiatric symptoms, and excess total body weight. Because of the variability in clinical presentation and variability of response in this open label trial, it is uncertain whether these changes could be ascribed to the effects of mifepristone.

17.1 Importance of Preventing Pregnancy

• Advise patients that mifepristone tablets will cause termination of pregnancy. Mifepristone tablets are contraindicated in pregnant patients.
• Mifepristone tablets reduce the effectiveness of hormonal contraceptives. Counsel females of reproductive potential regarding pregnancy prevention and planning with a non-hormonal contraceptive prior to use of mifepristone tablets and up to one month after the end of treatment.
• Instruct patients to contact their physician immediately if they suspect or confirm they are pregnant.

Dispense with Medication Guide available at: www.tevausa.com/medguides

Manufactured For:
Teva Pharmaceuticals
Parsippany, NJ 07054

Iss. 2/2022