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Pharmacologic class: Synthetic steroid
Therapeutic class: Antiprogestational agent, abortifacient
Pregnancy risk category NR
FDA Box Warning
• Rare cases of serious and sometimes fatal infections and bleeding have followed spontaneous, surgical, and medical abortions, including after mifepristone use. Before starting drug, inform patient of risk of these serious events and discuss medication guide and patient agreement. Ensure that patient knows whom to call and what to do, including going to emergency department (ED) if none of provided contacts are reachable; if she experiences sustained fever, severe abdominal pain, prolonged heavy bleeding, or syncope; or if she has abdominal pain or discomfort or general malaise (including weakness, nausea, vomiting, or diarrhea) more than 24 hours after taking drug.
• Patients with serious bacterial infections and sepsis may present without fever, bacteremia, or significant pelvic examination findings after abortion. Rare deaths have occurred in patients without fever, with or without abdominal pain, but with leukocytosis with marked left shift, tachycardia, hemoconcentration, and general malaise. Maintain high index of suspicion to rule out serious infection and sepsis.
• Advise patient to take medication guide with her if she visits ED or another health care provider who didn't prescribe drug, so provider will be aware that patient is undergoing medical abortion.
• Be aware that pregnancy must be excluded before initiation of treatment with Korlym. Patients must avoid pregnancy during treatment and for 1 month after therapy ends by using a nonhormonal, medically acceptable method of contraception; if patient has had a surgical sterilization, no additional contraception is needed. Pregnancy must also be excluded if treatment is interrupted for more than 14 days in females of childbearing potential.
Antagonizes progesterone receptor sites, inhibiting activity of endogenous and exogenous progesterone and stimulating uterine contractions, which causes fetus to separate from placental wall
Tablets: 200 mg, 300 mg
Indications and dosages
➣ Termination of intrauterine pregnancy through day 49 of pregnancy
Adults: On day 1, mifepristone 600 mg P.O. as a single dose. On day 3, misoprostol 400 mcg P.O. (unless abortion has been confirmed).
➣ Hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing's syndrome who have type 2 diabetes or glucose intolerance and have failed surgery or aren't candidates for surgery
Adults: Initially, 300 mg P.O. daily; increase based on clinical response and tolerability in 300-mg increments to a maximum of 1,200 mg daily. Don't exceed 20 mg/kg/day.
• Renal impairment (Korlym)
• Mild to moderate hepatic impairment (Korlym)
• Concurrent use of strong P450 CYP3A inhibitors (Korlym)
• Hypersensitivity to drug, misoprostol, or other prostaglandins
• Confirmed or suspected ectopic pregnancy or adnexal mass
• Chronic adrenal failure
• Bleeding disorders
• Concurrent anticoagulant therapy or long-term corticosteroid therapy
• Presence of intrauterine device (IUD)
• Inherited porphyrias
• Concomitant treatment with systemic corticosteroids for serious medical conditions or illnesses (Korlym)
• Concurrent use of simvastatin or lovastatin and CYP3A substrates with narrow therapeutic range (Korlym)
• History of unexplained vaginal bleeding or endometrial hyperplasia with atypia or endometrial carcinoma (Korlym)
• Pregnancy (Korlym)
Use cautiously in:
• cardiovascular, respiratory, renal, or hepatic disorders; hypertension; type 1 diabetes mellitus; anemia; jaundice; seizure disorder; cervicitis; infected endocervical lesions; acute vaginitis; uterine scarring
• hypokalemia, underlying heart conditions including heart failure and coronary vascular disease (Korlym)
• hemorrhagic disorders or concurrent use of anticoagulants (Korlym)
• concurrent use of QT interval-prolonging drugs, patients with potassium channel variants resulting in long QT interval (avoid Korlym use)
• concurrent use of drugs metabolized by CYP2B6 and moderate CYP3A inhibitors (Korlym)
• concurrent use of CYP3A inducers (such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John's wort) or hormonal contraceptives (avoid use)
• concurrent use of strong CYP3A inhibitors (use Korlym with extreme caution and only when necessary; limit dosage to 300 mg)
• concurrent use of drugs metabolized by CYP2C8/2C9 (use lowest dose of CYP2C8/2C9 substrates when used with Korlym)
• breastfeeding patients (Korlym)
• children (Korlym; safety and efficacy not established).
• Before giving dose for termination of pregnancy, make sure patient doesn't have an IUD in place.
• Correct hypokalemia before starting Korlym.
• Give for termination of pregnancy only in health care facility under supervision of health care provider qualified to assess pregnancy stage and rule out ectopic pregnancy.
• Administer with fluids, but not with grapefruit juice.
• When giving for termination of pregnancy, confirm pregnancy termination 14 days after initial dose.
CNS: dizziness, fainting, headache, weakness, fatigue, insomnia, asthenia, anxiety, syncope, rigors
CV: hypertension, QT-interval prolongation (Korlym)
GI: nausea, vomiting, diarrhea, abdominal cramping, dyspepsia
GU: vaginitis, leukorrhea, uterine cramping, pelvic pain; endometrial hypertrophy, cystic dilatation of endometrial glands, vaginal bleeding (Korlym); uterine hemorrhage
Metabolic: hypokalemia, adrenal insufficiency (Korlym)
Musculoskeletal: leg pain, back pain, arthralgia
Skin: rash (Korlym)
Other: viral infections; fever, decreased appetite, peripheral edema, opportunistic infections (Korlym)
Drug-drug. CYP2C8/2C9 substrates: increased plasma concentrations of these drugs
CYP3A inducers (such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin): decreased mifepristone concentrations
CYP3A substrates with narrow therapeutic range (such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus): increased exposure of these drugs and effects
Drugs metabolized by CYP2B6 (bupropion, efavirenz): significantly increased exposure of these drugs
Drugs metabolized by CYP3A (lovastatin, simvastatin): increased risk of myopathy and rhabdomyolysis
Glucocorticoids: antagonized glucocorticoid effect
Moderate CYP3A inhibitors (such as amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, imatinib, verapamil), strong CYP3A inhibitors (such as amprenavir, boceprevir, clarithromycin, conivaptan, fosamprenavir, indinavir, itraconazole, lopinavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole): increased plasma mifepristone concentration
Oral contraceptives: decreased oral contraceptive effectiveness
Drug-diagnostic tests. Hematocrit, hemoglobin: decreased values
Potassium: decreased level
Red blood cells: decreased count
Drug-food. Grapefruit juice: increased mifepristone blood level and effects
Drug-herbs. St. John's wort: decreased mifepristone blood level and effects
• Assess vital signs, breath sounds, and bowel sounds.
• Monitor uterine contractions and type and amount of vaginal bleeding.
• Evaluate CBC.
• Monitor serum potassium level 1 to 2 weeks after starting or increasing Korlym dosage and periodically thereafter.
☞ Closely monitor patient taking Korlym for signs and symptoms of adrenal insufficiency, including weakness, nausea, increased fatigue, hypotension, and hypoglycemia. If adrenal insufficiency is suspected, discontinue drug immediately and administer glucocorticoids without delay. May resume Korlym at a lower dosage after resolution of adrenal insufficiency.
• Be aware that patients with endogenous Cushing's syndrome are at risk for opportunistic infections such as Pneumocystis jiroveci pneumonia while taking Korlym. Monitor patient for respiratory distress shortly after Korlym initiation. Initiate appropriate diagnostic tests and treat P. jiroveci as indicated.
When used for termination of pregnancy:
• After administration, tell patient she will need to return in 48 hours for a prostaglandin drug or to verify pregnancy termination.
• Tell patient she will have contractions for 3 or more hours after receiving drug and that vaginal bleeding may last 9 to 16 days.
☞ Instruct patient to contact prescriber if she has persistent or extremely heavy vaginal bleeding, extreme fatigue, or orthostatic hypotension.
Caution patient that vaginal bleeding does not prove that complete abortion has occurred. Tell her she will need follow-up appointment 2 weeks later to verify pregnancy termination.
• Inform patient that she is at risk for pregnancy right after abortion is complete. Encourage appropriate contraceptive decision.
When used for hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome:
☞ Instruct patient to recognize and report signs and symptoms of hypokalemia, respiratory infections, and adrenal insufficiency.
• Advise patient not to take drug with grapefruit juice and not to use herbal products without consulting prescriber.
When used for either indication:
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.
mifepristone/mif·e·pris·tone/ (mĭf″ĕ-pris´tōn) RU-486; an antiprogestin used with misoprostol or other prostaglandin to terminate pregnancy in the first trimester.
mifepristoneAn antiprogestin used with misoprostol, a PGE1 analogue, as a morning-after contraceptive for early pregnancy termination.
mifepristoneRU 486 Obstetrics An antiprogestin used as a morning-after contraceptive, with misoprostol, a PGE1 analogue, for early pregnancy termination. Cf Late abortion.