Aygestin (norethindrone acetate tablets, USP) - 5 mg oral tablets. Aygestin, (17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one acetate), a synthetic, orally active progestin, is the acetic acid ester of norethindrone. It is a white, or creamy white, crystalline powder.

Aygestin Tablets contain the following inactive ingredients: lactose, magnesium stearate, and microcrystalline cellulose.

Last updated on RxList: 3/31/2009

Aygestin is indicated for the treatment of secondary amenorrhea, endometriosis, and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer.

Therapy with Aygestin® (norethindrone acetate tablets, USP) must be adapted to the specific indications and therapeutic response of the individual patient. This dosage schedule assumes the interval between menses to be 28 days.

Secondary amenorrhea, abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology: 2.5 to 10 mg Aygestin may be given daily for 5 to 10 days during the second half of the theoretical menstrual cycle to produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen.

Progestin withdrawal bleeding usually occurs within three to seven days after discontinuing Aygestin therapy. Patients with a past history of recurrent episodes of abnormal uterine bleeding may benefit from planned menstrual cycling with Aygestin.

Endometriosis: Initial daily dosage of 5 mg Aygestin for two weeks. Dosage should be increased by 2.5 mg per day every two weeks until 15 mg per day of Aygestin is reached. Therapy may be held at this level for six to nine months or until annoying breakthrough bleeding demands temporary termination.

Aygestin® (norethindrone acetate tablets, USP) are available as:

5 mg: White, oval, flat-faced, beveled edge, biconvex tablet, scored on one side.

Debossed with 5 Aygestin on the unscored side and B /424 on the scored side. Available in bottle of:
50.............NDC 51285-424-10

Store at controlled room temperature 20º to 25ºC (68º to 77ºF); excursions permitted between 15º to 30ºC (59º to 86ºF) [See USP].

Dispense in a well-closed container.

Duramed Pharmaceuticals, Inc. A subsidiary of Barr Laboratories, Inc. Pomona, NY 10970. Revised: July 2003.

Last updated on RxList: 3/31/2009

See “WARNINGS” for further information on Retinal vascular thrombosis, Thrombotic and thromboembolism events, and Use in pregnancy. The following adverse reactions have been observed in women taking progestins:

Breakthrough bleeding.
Spotting.
Change in menstrual flow.
Amenorrhea.
Edema.
Changes in weight (decreases, increases).
Changes in cervical erosion and cervical secretions.
Cholestatic jaundice.
Rash (allergic) with and without pruritus.
Melasma or chloasma.
Mental depression.
Acne.
Breast enlargement/tenderness.
Headache/migraine.
Urticaria.
Abnormalities of liver tests (i.e., AST, ALT, Bilirubin).
Mood swings.
Nausea.
Insomnia.
Anaphylactic/anaphylactoid reactions.
Thrombotic and thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, cerebral thrombosis and embolism).
Optic neuritis (which may lead to partial or complete loss of vision).
Progestins may alter the result of pregnanediol determinations. The following laboratory results may be altered by the concomitant use of estrogens with progestins:
Hepatic function.
Coagulation tests - increase in prothrombin, factors VII, VIII, IX, and X.
Increase in PBI, BEI, and a decrease in T³ uptake.
Reduced response to metyrapone test.

The following adverse reactions have been observed in patients receiving estrogen-progestogen combination drugs:

1. Rise in blood pressure in susceptible individuals.
2. Premenstrual-like syndrome.
3. Changes in libido.
4. Changes in appetite.
5. Cystitis-like syndrome.
6. Headache.
7. Nervousness.
8. Dizziness.
9. Fatigue.
10. Backache.
11. Hirsutism.
12. Loss of scalp hair.
13. Erythema multiforme.
14. Erythema nodosum.
15. Hemorrhagic eruption.
16. Itching.

In view of these observations, patients on progestogen therapy should be carefully observed.

No information provided.

Last updated on RxList: 3/31/2009

1. Discontinue medication pending examination if there is a sudden partial or complete loss of vision or if there is sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, medication should be withdrawn. There have been reports of retinal vascular coincident with the use of progestins.
2. Because of the occasional occurrence of thrombophlebitis and pulmonary embolism in patients taking progestogens, the physician should be alert to the earliest manifestations of the disease. Care should be used when prescribing progestins to a population that may be predisposed to thrombotic disorders (e.g., past history of thrombotic events, thrombophilia, obesity, cardiovascular disease, prolonged immobilization).
3. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female fetuses. The risk of hypospadias, 5 to 8 per 1,000 male births in the general population, may be approximately doubled with exposure to these drugs. There are insufficient data to quantify the risk to exposed female fetuses, but insofar as some of these drugs induce mild virilization of the external genitalia of the female fetus, and because of the increased association of hypospadias in the male fetus, it is prudent to avoid the use of these drugs during the first trimester of pregnancy.

General Precautions

1. The pretreatment physical examination should include special reference to breasts and pelvic organs, as well as a Papanicolaou smear.
2. Because this drug may cause some degree of fluid retention, conditions which might be influenced by this factor, such as epilepsy, migraine, asthma, cardiac or renal dysfunctions, require careful observation.
3. In cases of breakthrough bleeding, as in all cases of irregular bleeding per vagina, nonfunctional causes should be borne in mind. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures are indicated.
4. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.
5. Any possible influence of prolonged progestogen therapy on pituitary, ovarian, adrenal, hepatic, or uterine functions awaits further study.
6. Data suggest that progestin therapy may have adverse effects on lipid and carbohydrate metabolism. The choice of progestin, its dose, and its regimen may be important in minimizing these adverse effects, but these issues will require further study before they are clarified. Women with hyperlipidemias and/or diabetes should be monitored closely during progestin therapy.
7. The age of the patient constitutes no absolute limiting factor, although treatment with progestogens may mask the onset of the climacteric.
8. The pathologist should be advised of progestogen therapy when relevant specimens are submitted.

Information for the Patient

See PATIENT INFORMATION section.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Some beagle dogs treated with medroxyprogesterone acetate developed mammary nodules. Although nodules occasionally appeared in control animals, they were intermittent in nature, whereas nodules in treated animals were larger and more numerous, and persisted. There is no general agreement as to whether the nodules are benign or malignant. Their significance with respect to humans has not been established.

Pregnancy Category X

Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. Several reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female fetuses. Hypospadias occurs in about 5 to 8 per 1, 000 male births and is about doubled with exposure to these drugs. Some progestational drugs induce mild virilization of the external genitalia of female fetuses.

Nursing Mothers

Detectable amounts of progestogens have been identified in the milk of mothers receiving them. The effect of this on the nursing infant has not been determined.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Last updated on RxList: 3/31/2009

No information provided.

Known or suspected pregnancy.
Thrombophlebitis, thromboembolic disorders, cerebral apoplexy, or a past history of these conditions.
Markedly impaired liver function or liver disease.
Known or suspected carcinoma of the breast.
Undiagnosed vaginal bleeding.
Missed abortion.
As a diagnostic test for pregnancy.
Hypersensitivity to norethindrone acetate tablets.

Last updated on RxList: 3/31/2009

Norethindrone acetate induces secretory changes in an estrogen-primed endometrium. It acts to inhibit the secretion of pituitary gonadotropins which, in turn, prevent follicular maturation and ovulation. On a weight basis, it is twice as potent as norethindrone.

Last updated on RxList: 3/31/2009

Your doctor has prescribed Aygestin (norethindrone acetate) Tablets, USP, a progestin, for you. Aygestin is similar to the progesterone hormones naturally produced by the body. Progestins are used to treat menstrual disorders and to test if the body is producing certain hormones.

WARNINGS

AYGESTIN TABLETS SHOULD NOT BE USED IN WOMEN WITH THE FOLLOWING CONDITIONS:

• Known or suspected pregnancy.
• History of blood clots in the legs, lungs, eyes, brain, or elsewhere, or a past history of these conditions.
• Liver impairment or disease.
• Known or suspected cancer of the breast.
• Undiagnosed vaginal bleeding.
• Hypersensitivity to Aygestin tablets.

The information below relates only to the risk to the unborn child associated with use of progestin during pregnancy, abnormal blood clotting, and eye abnormalities.

Risk to the Fetus

Aygestin tablets should not be used if you are pregnant. Norethindrone acetate is contraindicated during pregnancy as it may cause fetal harm when administered to pregnant women. There is an increased risk of minor birth defects in children whose mothers take this drug during the first 4 months of pregnancy. Several reports suggest an association between mothers who take these drugs in the first trimester of pregnancy and genital abnormalities in male and female babies. The risk to the male baby is the possibility of being born with a condition in which the opening of the penis is on the underside rather than the tip of the penis (hypospadias). Hypospadias occurs in about 5 to 8 per 1,000 male births and is about doubled with exposure to these drugs. There is not enough information to quantify the risk to exposed female fetuses, but enlargement of the clitoris and fusion of the labia may occur, although rarely. Therefore, avoid using the drug during the first trimester of pregnancy.

If you take Aygestin (norethindrone acetate tablets, USP) and later find you were pregnant when you took it, be sure to discuss this with your doctor as soon as possible.

Abnormal Blood Clotting

Use of progestational drugs has been associated with changes in the blood-clotting system. These changes allow the blood to clot more easily, possibly allowing clots to form in the bloodstream. If blood clots do form in your bloodstream, they can cut off the blood supply to vital organs, causing serious problems. These problems may include a stroke (by cutting off blood to part of the brain), a heart attack (by cutting off blood to part of the heart), a pulmonary embolus (by cutting off blood to part of the lungs), visual loss or blindness (by cutting off blood vessels in the eye), or other problems. Any of these condition may cause death or serious long-term disability. Call your doctor immediately if you suspect you have any of these conditions. He or she may advise you to stop using the drug.

Eye Abnormalities

Discontinue medication and call your physician immediately if you experience sudden partial or complete loss of vision, blurred vision, or sudden onset of bulging eyes, double vision, or migraine.

OTHER INFORMATION

For further information on the use, side effects and other risks associated with this product, ask your doctor. If you want more information, ask your doctor to show you the professional labeling. The professional labeling is also published in a book called the Physicians' Desk Reference, which is available in bookstores and public libraries.

Last updated on RxList: 3/31/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

NORETHINDRONE - ORAL

(nor-ETH-in-drone)

COMMON BRAND NAME(S): Aygestin

USES: This medication is used to treat women with abnormal bleeding from the uterus. It is also used to treat women who have stopped having menstrual periods for several months (amenorrhea) but who are not pregnant or going through menopause. In addition, this medication is used to treat a condition (endometriosis) in which tissue that normally lines the inside of the uterus is found outside the uterus in the abdomen/pelvic area, causing painful/irregular periods. Norethindrone is a type of female hormone (progestin). It is like the hormone progesterone that your body makes naturally. This medication works by stopping the normal growth of the uterus lining during the menstrual cycle and signaling hormone changes in the uterus to restore normal menstrual periods.

This medication must not be used to test for pregnancy.

Progestins are not effective in preventing miscarriages.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using this drug and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth as prescribed by your doctor. You may take it with food or after a meal to prevent stomach upset. Follow the dosing schedule carefully. Ask your doctor if you have any questions. The dosage is based on your medical condition and response to therapy.

For the treatment of stopped menstrual periods and abnormal bleeding from the uterus, this drug is usually taken once daily for 5-10 days during the second half of the planned menstrual cycle or as directed by your doctor. Withdrawal bleeding usually occurs within 3-7 days after you stop taking the medication.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: Nausea, vomiting, headache, dizziness, mood swings, trouble sleeping, weight gain/loss, acne, breast swelling/tenderness, change in sexual interest, unwanted hair growth, or hair loss may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these serious side effects occur: changes in vaginal bleeding (e.g., spotting, breakthrough bleeding, changes in menstrual flow, no menstrual bleeding), change in vaginal discharge, depression, swelling of the hands/feet, frequent/burning/painful urination, yellowing eyes/skin, dark patches on the skin or face (melasma).

This medication may rarely cause very serious (possibly fatal) problems from blood clots (e.g., heart attack, stroke, blood clots in the lungs or legs, blindness). Seek immediate medical attention if you experience any of the following: chest/jaw/left arm pain, weakness on one side of the body, slurred speech, sudden vision changes (e.g., blurred/double vision, loss of vision, bulging eyes), confusion, sudden severe headache, severe dizziness, fainting, trouble breathing, coughing up blood, pain/redness/swelling/weakness of the arms/legs, calf pain/swelling that is warm to the touch.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking norethindrone, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: history of blood clots, history of bleeding in the brain, liver disease, history of cancer of the breast or other female organs, vaginal bleeding of unknown cause, a loss of pregnancy with some tissue remaining in the uterus ("missed abortion"), recent stroke or heart attack (within 1 year).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: family medical history (especially breast lumps/cancer or blood clots), obesity, heart disease (e.g., past heart attacks, coronary artery disease, congestive heart failure), high blood pressure, lupus, seizures, migraine headaches, asthma, kidney problems, high blood levels of cholesterol/fats, depression, diabetes, strokes.

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Notify your doctor beforehand if you will be having surgery or will be confined to a chair/bed for a long time (e.g., a long plane flight). You may need to stop the medication for a time or take special precautions because of the increased risk for blood clots. Ask your doctor for more details.

Do not smoke. Smoking combined with this medication further increases your risk for strokes, blood clots, high blood pressure, and heart attacks.

This medication may cause blotchy, dark areas on your skin (melasma). Sunlight may worsen this effect. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen, and wear protective clothing when outdoors.

This medication must not be used during pregnancy because it may harm an unborn baby, especially during the first 4 months of pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately.

This drug passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs affecting liver enzymes that remove norethindrone from your body (such as rifampin, St. John's wort, azole antifungals including itraconazole, certain anti-seizure medicines including carbamazepine/phenobarbital/phenytoin).

This medication can affect the results of certain lab tests. Make sure laboratory personnel and all your doctors know you use this medication.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include severe nausea and vomiting.

NOTES: Do not share this medication with others.

Keep all appointments with your doctor and the laboratory. You should have regular complete physical exams including blood pressure, breast exam, pelvic exam, and screening for cervical cancer (Pap smear) as directed by your doctor. Follow your doctor's instructions for examining your own breasts, and report any lumps immediately. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.