Aygestin

Name: Aygestin

Norethindrone Side Effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using this medication and call your doctor at once if you have any of these serious side effects:

  • sudden numbness or weakness, especially on one side of the body;
  • sudden headache, confusion, pain behind the eyes, problems with vision, speech, or balance;
  • pain or swelling in one or both legs;
  • migraine headache;
  • swelling in your hands or feet, rapid weight gain;
  • symptoms of depression (sleep problems, weakness, mood changes);
  • severe pelvic pain;
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling; or
  • nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • mild nausea, vomiting, bloating, stomach cramps;
  • breast pain, swelling, or tenderness;
  • dizziness;
  • freckles or darkening of facial skin;
  • increased acne or hair growth;
  • changes in weight;
  • vaginal itching or discharge;
  • skin itching or rash;
  • changes in your menstrual periods, decreased sex drive; or
  • mild headache.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Norethindrone Interactions

Do not smoke while using norethindrone, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by norethindrone.

Norethindrone will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Some drugs can make norethindrone less effective, which may result in pregnancy. Before using norethindrone, tell your doctor if you are using any of the following drugs:

  • griseofulvin (Fulvicin, Grisactin);
  • rifampin (Rifadin, Rifater, Rifamate, Rimactane);
  • St. John's wort;
  • ketoconazole (Nizoral) or itraconazole (Sporanox);
  • a barbiturate such as amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), secobarbital (Seconal), or phenobarbital (Luminal, Solfoton); or
  • HIV medicines such as amprenavir (Agenerase), atazanavir (Reyataz), tipranavir (Aptivus), indinavir (Crixivan), saquinavir (Invirase), lopinavir/ritonavir (Kaletra), fosamprenavir (Lexiva), ritonavir (Norvir), or nelfinavir (Viracept).

There may be other drugs that can interact with norethindrone. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Indications

AYGESTIN (norethindrone acetate tablets USP) 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. AYGESTIN (norethindrone acetate tablets USP) is not intended, recommended or approved to be used with concomitant estrogen therapy in postmenopaus al women for endometrial protection.

Side effects

See WARNINGS and PRECAUTIONS.

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 the cervical squamo-columnar junction and cervical secretions
  • Cholestatic jaundice
  • Rash (allergic) with and without pruritus
  • Melasma or chloasma
  • Clinical depression
  • Acne
  • Breast enlargement/tenderness
  • Headache/migraine
  • Urticaria
  • Abnormalities of liver tests (i.e., AST, ALT, Bilirubin)
  • Decreased HDL cholesterol and increased LDL/HDL ratio
  • 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)

Clinical pharmacology

Norethindrone acetate induces secretory changes in an estrogen-primed endometrium. On a weight basis, it is twice as potent as norethindrone.

Pharmacokinetics

Absorption

Norethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate is rapidly absorbed from AYGESTIN tablets, with maximum plasma concentration of norethindrone generally occurring at about 2 hours post-dose. The pharmacokinetic parameters of norethindrone following single oral administration of AYGESTIN in 29 healthy female volunteers are summarized in Table 1.

Table 1: Pharmacokinetic Parameters after a Single Dose of AYGESTIN® in Healthy Women

  AYGESTIN®
(n = 29)
Arithmetic Mean ± SD
Norethindrone (NET)
AUC (0-inf)(ng/ml*h) 166.90 ± 56.28
Cmax (ng/ml) 26.19 ± 6.19
tmax (h) 1.83 ± 0.58
t½ (h) 8.51 ± 2.19
AUC = area under the curve,
Cmax = maximum plasma concentration,
tmax = time at maximum plasma concentration,
t½ = half-life,
SD = standard deviation

Figure 1: Mean Plasma Concentration Profile after a Single Dose of 5 mg Administered to 29 Healthy Female Volunteers under Fasting Conditions

Effect Of Food

The effect of food administration on the pharmacokinetics of AYGESTIN has not been studied.

Distribution

Norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is about 4 L/kg.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.

Excretion

Plasma clearance value for norethindrone is approximately 0.4 L/hr/kg. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following a single dose administration of AYGESTIN is approximately 9 hours.

Special Populations

Geriatrics

The effect of age on the pharmacokinetics of norethindrone after AYGESTIN administration has not been evaluated.

Race

The effect of race on the disposition of norethindrone after AYGESTIN administration has not been evaluated.

Renal Insufficiency

The effect of renal disease on the disposition of norethindrone after AYGESTIN administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma norethindrone concentration was unchanged compared to concentrations in premenopausal women with normal renal function.

Hepatic Insufficiency

The effect of hepatic disease on the disposition of norethindrone after AYGESTIN administration has not been evaluated. However, AYGESTIN is contraindicated in markedly impaired liver function or liver disease.

Drug Interactions

No pharmacokinetic drug interaction studies investigating any drug-drug interactions with AYGESTIN have been conducted.

Side Effects of Aygestin

Serious side effects have been reported with Aygestin. See the “Aygestin Precautions” section.

Common side effects of Aygestin include the following:

  • Headache
  • Breast pain
  • Irregular vaginal bleeding or spotting
  • Stomach/abdominal cramps/bloating
  • Nausea and vomiting
  • Hair loss

Other side effects include

  • High blood pressure
  • Liver problems
  • High blood sugar
  • Fluid retention
  • Enlargements of benign tumors of the uterus (“fibroids”)
  • Vaginal yeast infections
  • Mental depression

This is not a complete list of Aygestin side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

Missing a pill increases your risk of becoming pregnant. If you are more than 3 hours late in taking your dose, use back-up birth control such as condoms or a spermicide for at least the next 48 hours.

If you miss a period for two months in a row, call your doctor because you might be pregnant.

Precautions While Using Aygestin

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly and does not cause unwanted effects. These visits will usually be every 6 to 12 months, but some doctors require them more often. Pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.

Although you are using this medicine to prevent pregnancy, you should know that using this medicine while you are pregnant could harm the unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

Vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough bleeding when heavier.

  • If this should occur, continue with your regular dosing schedule.
  • The bleeding usually stops within 1 week. Check with your doctor if the bleeding continues for more than 1 week.
  • If bleeding continues after you have been taking hormonal contraceptives on schedule and for more than 3 months, check with your doctor.

Check with your doctor right away if you miss a menstrual period. Missed periods may occur if you skip one or more tablets and have not taken your pills exactly as directed. If you miss two periods in a row, talk to your doctor. You might need a pregnancy test.

If you suspect that you may be pregnant, stop using this medicine immediately and check with your doctor.

Check with your doctor before refilling an old prescription, especially after a pregnancy. You will need another physical examination and your doctor may change your prescription.

Call your doctor right away if you have sudden or severe lower abdominal or stomach pain. These may be symptoms of an ectopic pregnancy or an ovarian cyst.

Do not use this medicine if you smoke cigarettes. If you smoke while using birth control pills, you increase your risk of having a heart attack, stroke, or blood clot. Your risk is even higher if you have diabetes, high blood pressure, high cholesterol, or if you are overweight. Talk with your doctor about ways to stop smoking. Keep your diabetes under control. Ask your doctor about diet and exercise to control your weight and blood cholesterol level.

Check with your doctor immediately if you have trouble wearing contact lenses or if blurred vision, difficulty with reading, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Aygestin Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Frequent and irregular bleeding
  • menstrual changes
Incidence not known
  • Abdominal or stomach pain
  • blindness
  • blue-yellow color blindness
  • blurred vision
  • breast pain
  • changes in menstrual period
  • changes in vision
  • chills
  • clay-colored stools
  • confusion
  • cough
  • dark urine
  • decreased vision
  • diarrhea
  • difficulty with swallowing
  • discouragement
  • dizziness
  • double vision
  • eye pain
  • fast heartbeat
  • feeling sad or empty
  • fever
  • general tiredness and weakness
  • headache
  • heavy non-menstrual vaginal bleeding
  • hives, itching, or rash
  • irritability
  • lack of appetite
  • light-colored stools
  • light vaginal bleeding between regular menstrual periods
  • loss of interest or pleasure
  • migraine headache
  • nausea and vomiting
  • numbness of the hands
  • pain, redness, or swelling in the arm or leg
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • swelling
  • tightness in the chest
  • trouble concentrating
  • trouble sleeping
  • unpleasant breath odor
  • unusual tiredness or weakness
  • upper right abdominal or stomach pain
  • vomiting of blood
  • yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Breast tenderness
  • increased hair growth, especially on the face
  • pimples
  • weight gain
Incidence not known
  • Brown, blotchy spots on exposed skin
  • enlarged breasts
  • hair loss or thinning of the hair
  • mood swings
  • nervousness
  • weight changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What do I need to tell my doctor BEFORE I take Aygestin?

  • If you have an allergy to norethindrone or any other part of this medicine.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are pregnant or may be pregnant. Do not take Aygestin if you are pregnant.
  • If you have had any of these health problems: Bleeding disorder; blood clots or risk of having a blood clot; breast cancer; liver disease; liver tumors; recent heart attack; or recent stroke.
  • If you have had any of these health problems: Cancer of the uterus, ovary, cervix, or vagina; or vaginal bleeding where the cause is not known.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Aygestin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How is Aygestin Supplied

Aygestin® (norethindrone acetate tablets USP) is available as:

5 mg:

White, oval, flat-faced, beveled edge, tablet scored on one side. Debossed with 5 Aygestin on the unscored side and stylized b / 424 on the scored side. Available in bottles of 50 tablets (NDC 51285-424-10).

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

TEVA WOMEN’S HEALTH, INC.

Subsidiary of TEVA PHARMACEUTICALS USA, INC.
North Wales, PA 19454

Rev. A 10/2015

For the Consumer

Applies to norethindrone: oral tablet

Along with its needed effects, norethindrone (the active ingredient contained in Aygestin) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking norethindrone:

More common
  • Frequent and irregular bleeding
  • menstrual changes
Incidence not known
  • Abdominal or stomach pain
  • blindness
  • blue-yellow color blindness
  • blurred vision
  • breast pain
  • changes in menstrual period
  • changes in vision
  • chills
  • clay-colored stools
  • confusion
  • cough
  • dark urine
  • decreased vision
  • diarrhea
  • difficulty with swallowing
  • discouragement
  • dizziness
  • double vision
  • eye pain
  • fast heartbeat
  • feeling sad or empty
  • fever
  • general tiredness and weakness
  • headache
  • heavy non-menstrual vaginal bleeding
  • hives, itching, or rash
  • irritability
  • lack of appetite
  • light-colored stools
  • light vaginal bleeding between regular menstrual periods
  • loss of interest or pleasure
  • migraine headache
  • nausea and vomiting
  • numbness of the hands
  • pain, redness, or swelling in the arm or leg
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • swelling
  • tightness in the chest
  • trouble concentrating
  • trouble sleeping
  • unpleasant breath odor
  • unusual tiredness or weakness
  • upper right abdominal or stomach pain
  • vomiting of blood
  • yellow eyes and skin

Some side effects of norethindrone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Breast tenderness
  • increased hair growth, especially on the face
  • pimples
  • weight gain
Incidence not known
  • Brown, blotchy spots on exposed skin
  • enlarged breasts
  • hair loss or thinning of the hair
  • mood swings
  • nervousness
  • weight changes

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