FEMCON FE- norethindrone and ethinyl estradiol, and ferrous fumarate
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use FEMCON® Fe safely and effectively. See full prescribing information for FEMCON Fe.
FEMCON Fe (norethindrone and ethinyl estradiol tablets and ferrous fumarate tablets) for oral use
Initial U.S. Approval: 1975
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS
See Full Prescribing Information for complete boxed warning.
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
FEMCON Fe consists of 28 tablets in the following order (3):
WARNINGS AND PRECAUTIONS
The most common adverse reactions were: irregular uterine bleeding, nausea, breast tenderness, and headache. (6)
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see Contraindications (4)].
FEMCON Fe is indicated for use by females of reproductive potential to prevent pregnancy.
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.
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 CHCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)
Consider the possibility of ovulation and conception prior to initiation of this product.
|Day 1 Start:
|Switching to FEMCON Fe from another hormonal contraceptive||Start on the same day that a new pack of the previous hormonal contraceptive would have started.|
|Switching from another contraceptive method to FEMCON Fe||Start FEMCON Fe:|
|Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.|
Starting FEMCON Fe after Abortion or Miscarriage
Starting FEMCON Fe after Childbirth
||Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.|
||Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.|
||Day 1 start: Throw out the rest of the pack and start a new pack that same day.
Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day.
Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.
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].
FEMCON Fe (norethindrone and ethinyl estradiol tablets and ferrous fumarate tablets) is available in blister cards.
Each blister card contains 28 tablets in the following order:
Do not prescribe FEMCON Fe to women who are known to have the following conditions:
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.
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.
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.
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.
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.
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).
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.
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)].
Carefully observe women with a history of depression and discontinue FEMCON Fe if depression recurs to a serious degree.
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.
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.
In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:
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:
Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs:
Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.
Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.
Substances increasing the plasma concentrations of COCs:
Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors, such as itraconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations.
Human immunodeficiency virus (HIV)/Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:
Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).
COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs [see Warnings and Precautions (5.12)].
Do not co-administer FEMCON Fe with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.3)].
There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.
Do not use COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.
Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
Safety and efficacy of FEMCON Fe have been established in women of reproductive age. Efficacy is expected to be the same in post-pubertal adolescents under the age of 18 years as for users 18 years and older. Use of this product before menarche is not indicated.
FEMCON Fe has not been studied in postmenopausal women and is not indicated in this population.
The pharmacokinetics of FEMCON Fe has not been studied in women with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. 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 [see Contraindications (4) and Warnings and Precautions (5.2)].
There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
FEMCON Fe is a combinational contraceptive containing the progestational compound norethindrone and the estrogenic compound ethinyl estradiol. The packaging includes 21 white tablets composed of norethindrone and ethinyl estradiol followed by 7 brown ferrous fumarate (placebo) tablets. The chemical name for norethindrone is 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one and for ethinyl estradiol the chemical name is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The structural formulas are:
The active white FEMCON Fe tablets contain 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, and the following inactive ingredients: dibasic calcium phosphate, lactose, magnesium stearate, maltodextrin, povidone, sodium starch glycolate, spearmint flavor and sucralose.
The brown tablets contain ferrous fumarate, microcrystalline cellulose, magnesium stereate, povidone, sodium starch glycolate, and compressible sugar. The ferrous fumarate tablets do not serve any therapeutic purpose.
COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.
Ethinyl estradiol and norethindrone are rapidly absorbed with maximum plasma concentrations occurring within 2 hours after FEMCON Fe administration (see Table 1). Norethindrone appears to be completely absorbed following oral administration; however, it is subject to first-pass metabolism resulting in an absolute bioavailability of approximately 65 percent. Large intersubject variability is reflected in a 3- to 5-fold variation in norethindrone bioavailability. Ethinyl estradiol bioavailability is approximately 43 percent due to small-intestinal and hepatic first-pass metabolism.
|Norethindrone/Ethinyl Estradiol||tmax (h)||Cmax (pg/mL)||AUC0-∞ (pg•h/mL)||t1/2 (h)|
|Norethindrone 0.4 mg||1.24 ± 0.40a
||4210.6 ± 1628.8a||18034.9 ± 7852.9b||8.6 ± 3.7b|
|Ethinyl Estradiol 35 mcg||1.44 ± 0.33b ||131.4 ± 34.2b||1065.8 ± 276.2b ||17.1 ± 4.4b
an = 26
bn = 25
Cmax = maximum plasma concentration; tmax = time to reach Cmax; AUC = area under the curve; t1/2 = elimination half- life.
Single-dose administration of FEMCON Fe tablets with food decreased the maximum norethindrone and ethinyl estradiol concentration by 53 percent and 47 percent, respectively; the extent of norethindrone and ethinyl estradiol absorption (AUC values) was not affected by food administration.
Norethindrone is 36 percent bound to sex hormone-binding globulin (SHBG) and 61 percent bound to albumin. Ethinyl estradiol is not bound to SHBG but is highly (98.5 percent) bound to albumin. Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg.
Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation; less than 5 percent of a norethindrone dose is excreted unchanged; greater than 50 percent and 20-40 percent of a dose is excreted in urine and feces, respectively. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.
Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol, and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy-ethinyl estradiol, which is formed by the CYP3A4 isoform of cytochrome P450.
Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg). Ethinyl estradiol and norethindrone are excreted in both urine and feces, primarily as metabolites. Ethinyl estradiol is excreted in urine and feces as glucuronides and sulfates, and about 28-43 percent undergoes enterohepatic circulation. The mean terminal elimination half-lives of norethindrone and ethinyl estradiol following single dose administration of FEMCON Fe are approximately 9 hours and 17 hours, respectively.
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.
FEMCON Fe (norethindrone and ethinyl estradiol tablets and ferrous fumarate tablets) is available in cartons of five blister cards (dispensers):
Each blister card contains 28 tablets in the following order:
Counsel patients about the following information:
FEMCON Fe [fĕ’m kon FE]
(norethindrone and ethinyl estradiol tablets and
ferrous fumarate tablets)
What is the most important information I should know about FEMCON Fe?
Do not use FEMCON Fe if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects (heart and blood vessel problems) from birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.
What is FEMCON Fe?
FEMCON Fe is a birth control pill (oral contraceptive) used by women to prevent pregnancy.
How does FEMCON Fe work for contraception?
Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.
Based on the results of one clinical study of a 28-day regimen of norethindrone 0.4 mg/ethinyl estradiol 35 mcg tablets, about 1 to 2 out of 100 women may get pregnant during the first year they use FEMCON Fe.
The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.
Who should not take FEMCON Fe?
Do not take FEMCON Fe if you:
If any of these conditions happen while you are taking FEMCON Fe, stop taking FEMCON Fe right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking FEMCON Fe.
What should I tell my healthcare provider before taking FEMCON Fe?
Tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.
FEMCON Fe may affect the way other medicines work, and other medicines may affect how well FEMCON Fe works.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How do I take FEMCON Fe?
Read the Instructions for Use at the end of this Patient Information.
What are the possible serious side effects of FEMCON Fe?
Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:
Call your healthcare provider or go to a hospital emergency room right away if you have:
|• leg pain that will not go away||• weakness or numbness in your arm or leg
|• sudden severe shortness of breath||• trouble speaking
|• sudden change in vision or blindness|
|• chest pain|
|• a sudden, severe headache unlike |
your usual headaches
Other serious side effects include:
What are the most common side effects of FEMCON Fe?
The most common side effects of FEMCON Fe include:
These are not all the possible side effects of FEMCON Fe. For more information, ask your healthcare provider or pharmacist.
You may report side effects to the FDA at 1-800-FDA-1088.
What else should I know about taking FEMCON Fe?
How should I store FEMCON Fe?
General information about the safe and effective use of FEMCON Fe.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use FEMCON Fe for a condition for which it was not prescribed. Do not give FEMCON Fe to other people.
This Patient Information summarizes the most important information about FEMCON Fe. You can ask your pharmacist or healthcare provider for information about FEMCON Fe that is written for health professionals.
For more information, call Allergan at 1-800-678-1605.
Do birth control pills cause cancer?
Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones.
Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.
What if I want to become pregnant?
You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.
What should I know about my period when taking FEMCON Fe?
Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking FEMCON Fe, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.
What are the ingredients in FEMCON Fe?
White pills: norethindrone and ethinyl estradiol
Brown pills: ferrous fumarate
White pills: dibasic calcium phosphate, lactose, magnesium stearate, maltodextrin, povidone, sodium starch glycolate, spearmint flavor and sucralose
Brown pills: microcrystalline cellulose, magnesium stereate, povidone, sodium starch glycolate, and compressible sugar
Instructions For Use
FEMCON Fe [fĕ’m kon FE]
(norethindrone and ethinyl estradiol tablets and
ferrous fumarate tablets)
Important Information about taking FEMCON Fe
Before you start taking FEMCON Fe:
When should I start taking FEMCON Fe?
If you start taking FEMCON Fe and you have not used a hormonal birth control method before:
If you start taking FEMCON Fe and you are switching from another birth control pill:
If you start taking FEMCON Fe and previously used a vaginal ring or transdermal patch:
If you start taking FEMCON Fe and you are switching from a progestin-only method such as an implant or injection:
If you start taking FEMCON Fe and you are switching from an intrauterine device or system (IUD or IUS):
Keep a calendar to track your period:
If this is the first time you are taking birth control pills, read, “When should I start taking FEMCON Fe?” above. Follow these instructions for either a Sunday Start or a Day 1 Start
You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.
Day 1 Start:
You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.
Instructions for using your pill pack:
Look at your FEMCON Fe pill pack. See Figure A.
The FEMCON Fe pill pack has:
Remove the white pill by pressing the pill through the foil in the bottom of the pill pack. See Figure B. Continue taking the white pills for 21 days.
On the first day of Week 4 start taking the brown pills. Take the brown pill for 7 days. Your period should start during this time.
When you have taken all of the brown pills in your pill pack, get a new pill pack and start taking the white pills.
● For a Day 1 start:
Begin your next pill pack on the same day of the week as your first cycle pill pack.
● For a Sunday Start:
Begin your next pill pack on Sunday.
What should I do if I miss any FEMCON FE pills?
If you miss 1 pill in Weeks 1, 2, or 3, follow these steps:
If you miss 2 pills in Week 1 or Week 2 of your pack, follow these steps:
If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:
If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.
This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.
Allergan USA, Inc.
Irvine, CA 92612
© 2017 Allergan. All rights reserved.
Femcon® Fe is a registered trademark of Allergan Pharmaceuticals International Limited
norethindrone and ethinyl estradiol, and ferrous fumarate kit
|Labeler - Allergan, Inc. (144796497)|