Femcon Fe

• Actavis Pharma, Inc.

For all patients taking Femcon Fe:

• If you have an allergy to ethinyl estradiol, 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 have had any of these health problems: Blood clots, blood clotting problem, breast cancer, bulging blood vessel (aneurysm), chest pain caused by angina, high blood sugar (diabetes) that affects blood flow, diseased arteries in the brain, disease of a heart valve with problems, heart attack, heart disease, high blood pressure, liver disease, liver tumor, stroke, tumor where estrogen makes it grow, or very bad headache or migraine.
• If you have had any of these health problems: Endometrial cancer, cancer of the cervix or vagina, or vaginal bleeding where the cause is not known.
• If you have surgery and need bedrest.
• If you are pregnant or may be pregnant. Do not take Femcon Fe if you are pregnant.
• If you are breast-feeding or plan to breast-feed.
• If you turned yellow during pregnancy or with estrogen-based or hormone contraceptive use.

Children:

• If your child has not had her first period.

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 Femcon Fe with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use Femcon Fe (ethinyl estradiol and norethindrone chewable tabs & ferrous fumarate tabs) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Take this medicine at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.
• Do not skip doses, even if you do not have sex very often.
• If you throw up or have diarrhea, Femcon Fe may not work as well to prevent pregnancy. Use an extra form of birth control, like condoms, until you check with your doctor.
• If you miss 2 periods in a row, take a pregnancy test before starting a new cycle.
• Chew well before swallowing.
• Some brands may be swallowed whole. Check with your pharmacist to see if your brand may be swallowed whole.
• Some brands need to be taken with a full glass of water. Some brands need to be taken without water. Check with your pharmacist to see if you need to take your drug with water.

What do I do if I miss a dose?

• If a dose is missed, check the package insert or call the doctor to find out what to do. If using this medicine to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Protect from light.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

2.1       How to Start Femcon FE

Femcon FE is dispensed in a blister card [see How Supplied/Storage and Handling (16)]. Femcon FE may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

2.2       How to Take Femcon FE

Femcon FE (white active tablets and brown placebo tablets) may be swallowed whole or chewed and swallowed. If the tablet is chewed, the patient should drink a full glass (8 ounces) of liquid immediately after swallowing.

Starting Femcon FE after Abortion or Miscarriage

First-trimester

• After a first-trimester abortion or miscarriage, Femcon FE may be started immediately. An additional method of contraception is not needed if Femcon FE is started within 5 days after termination of the pregnancy.
  
• If Femcon FE is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of Femcon FE.

Second-trimester

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Femcon FE, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of Femcon FE. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]

Starting Femcon FE after Childbirth

• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Femcon FE following the instructions in Table 1 for women not currently using hormonal contraception.
  
• If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Femcon FE. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].

2.3       Missed Tablets

2.4       Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

Do not prescribe Femcon FE to women who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  ▪ Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1)]
  ▪ Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1)]
  ▪ Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)]
  ▪ Have cerebrovascular disease [see Warnings and Precautions (5.1)]
  ▪ Have coronary artery disease [see Warnings and Precautions (5.1)]
  ▪ Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1)]
  ▪ Have uncontrolled hypertension [see Warnings and Precautions (5.4)]
  ▪ Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.6)]
  ▪ Have headaches with focal neurological symptoms or have migraine headaches with aura [see Warnings and Precautions (5.7)]
        ▪ Women over age 35 with any migraine headaches [see Warnings and Precautions (5.7)]
  
• Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2)]
  
• Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8)]
  
• Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1)].
  
• Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see Warnings and Precautions (5.11)]
  
• Hypersensitivity to any of the components.

 ● Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.3)]

5.1       Thrombotic Disorders and Other Vascular Problems

• Stop Femcon FE if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
  
• Stop Femcon FE if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
  
• If feasible, stop Femcon FE at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during the following prolonged immobilization.
  
• Start Femcon FE no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
  
• The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued.
    
  Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). The risk increases with age, particularly in women over 35 years of age who smoke.
  
• Use COCs with caution in women with cardiovascular disease risk factors.

5.2       Liver Disease

Impaired Liver Function

Do not use Femcon FE in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of liver [see Contraindications (4)]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue Femcon FE if jaundice develops.

Liver Tumors

Femcon FE is contraindicated in women with benign and malignant liver tumors [see Contraindications (4)]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) COC users. However, the risk of liver cancers in COC users is less than one case per million users.

5.3       Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN),including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as COCs. Discontinue Femcon FE prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. Femcon FE can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

5.4       High Blood Pressure

Femcon FE is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see Contraindications (4)]. For women with well-controlled hypertension, monitor blood pressure and stop Femcon FE if blood pressure rises significantly.

An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin.

5.5       Gallbladder Disease

Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis.

5.6       Carbohydrate and Lipid Metabolic Effects

Carefully monitor prediabetic and diabetic women who take Femcon FE. COCs may decrease glucose tolerance.

Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

5.7       Headache

If a woman taking Femcon FE develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Femcon FE if indicated.

Consider discontinuation of Femcon FE in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

5.8       Bleeding Irregularities and Amenorrhea

Unscheduled Bleeding and Spotting

Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product.

Amenorrhea and Oligomenorrhea

Women who use Femcon FE may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was preexistent.

If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.

5.9       COC Use Before or During Early Pregnancy

Extensive epidemiologic studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue Femcon FE use if pregnancy is confirmed.

Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations (8.1)].

5.10       Depression

Carefully observe women with a history of depression and discontinue Femcon FE if depression recurs to a serious degree.

5.11       Carcinoma of the Breast and Cervix

• Femcon FE is contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].
  
• There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.
  
• Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

5.12       Effect on Binding Globulins

The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sec hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

5.13       Monitoring

A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.

5.14       Hereditary Angioedema

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

5.15       Chloasma

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking Femcon FE.

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1)]
  
• Vascular events [see Warnings and Precautions (5.1)]
  
• Liver disease [see Warnings and Precautions (5.2)]

The following adverse reactions are commonly reported by COC users. Because these reactions are voluntarily reported by from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

• Irregular uterine bleeding
  
• Nausea
  
• Breast tenderness
  
• Headache

The data presented in Section 14 are from a clinical trial conducted with norethindrone 0.4 mg/ethinyl estradiol 35 mcg tablets. Femcon FE is bioequivalent to these norethindrone acetate/ethinyl estradiol tablets.

In a multicenter open-label clinical trial, 1,970 women, 98% of whom were 16 to 39 years of age, were studied for up to 31 cycles (28 days per cycle) to assess the efficacy of norethindrone /ethinyl estradiol tablets, completing the equivalent of 20,230 cycles of exposure. The racial demographic of all enrolled women was: Caucasian (56%), African-American (14%), and Other (30%) (Hispanic, Native American, etc.). Of treated women, 10% were lost to follow-up, 11% discontinued related to cycle control and 7% discontinued due to other adverse events

The pregnancy rate (Pearl Index [PI]) in all 1,970 women was 1.48 pregnancies per 100 women-years of use (95% confidence interval 0.94 –2.22), based on 23 pregnancies that occurred after the onset of treatment of norethindrone /ethinyl estradiol tablets.

16.1       How Supplied

Femcon FE (norethindrone and ethinyl estradiol tablets and ferrous fumarate tablets) is available in cartons of five blister cards (dispensers):

NDC 0023-5970-05

Each blister card contains 28 tablets in the following order:

• 21 round, white (active) tablets imprinted with “W|C” on one side and “581” on the other and each containing 0.4 mg norethindrone and 35 mcg ethinyl estradiol.
  
• 7 brown, round (non-hormonal placebo) tablets imprinted with “PD 622” on one side and each containing 75 mg ferrous fumarate.

16.2       Storage Conditions

• Store at 20 º C - 25º C (68 º F - 77º F); excursions permitted to 15 º C - 30º C (59 º F - 86º F) [see USP Controlled Room Temperature].
  
• Protect from light.

Keep out of the reach of children.