1. INDICATIONS AND USAGE Norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets are indicated for use by females of reproductive potential to prevent pregnancy. Norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets are progestin/estrogen COC indicated for use by females of reproductive potential to prevent pregnancy. ( 1 )
Contraindications
4. CONTRA IN DIC A TIONS Norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg is contraindicated in females who are known to have or develop 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 (5.9) ] Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1) ].
Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [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)] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 ) Breast cancer or other estrogen- or progestin-sensitive cancer ( 4 )
5. WARNINGS AND PRECAUTIONS Thrombotic Disorders and Other Vascular Problems: Stop norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if a thrombotic event occurs. Stop at least 4 weeks before through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding ( 5.1 ) Liver disease: Discontinue norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if jaundice occurs ( 5.2 ) High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if blood pressure rises significantly.( 5.3 ) Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets.
Consider an alternative contraceptive method for women with uncontrolled dyslipidemia ( 5.5 ) Headache: Evaluate significant change in headaches and discontinue norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if indicated ( 5.6 ) Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea ( 5.7 )
5.1Thrombotic Disorders and Other Vascular Problems
Stop norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
If feasible, stop norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets 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 norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets 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.
5.2Liver Disease Impaired Liver Function Do
not use norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets 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 norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if jaundice develops. Liver Tumors Norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets are 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.
5.3Risk 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.
5.4High Blood
Pres sure Norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets are 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 norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets 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.
5.5Gallbladder 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.
5.6Carbohydrate and Lipid Metabolic Effects
Carefully monitor prediabetic and diabetic women who take norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets. 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.
5.7Headache If
a woman taking norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets if indicated. Consider discontinuation of norethindrone and ethinyl estradiol tablets (chewable) 0.4 mg/0.035 mg and ferrous fumarate tablets in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).
5.8Bleeding 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 Oligo
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
7. DRUG INTERACTIONS Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 )
7.1Effects of Other Drugs on Combined Oral Contraceptives
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: 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 to 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]).
7.2Effects of Combined Oral Contraceptives on Other Drugs
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 (5.11) ].
7.3Concomitant Use with HCV Combination
Therapy – Liver Enzyme Elevation 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)].
7.4Interference with Laboratory Tests
The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
Pregnancy and breastfeeding
8.1Pregnancy
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.
Adverse reactions
6. ADVERSE REACTIONS
6.2Postmarketing Experience
Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 - 1.12 (Figure 1). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). One of these studies reported no association between breast cancer risk and COC use.
The other two studies found an increased relative risk of 1.19 - 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8-10 years of COC use. Figure 1 Risk of Breast Cancer with Combined Oral Contraceptive Use RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs.
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 most common adverse reactions were: irregular uterine bleeding, nausea, breast tenderness, and headache.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. figure-01
Composition
Active ingredients
ETHINYL ESTRADIOL 0.035MG; NORETHINDRONE 0.4MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Norethindrone and Ethinyl Estradiol and Ferrous Fumarate
Active substance
ethinyl estradiol
Drug class
Progestogens and estrogens, fixed combinations, Progestogens and estrogens, sequential preparations
