Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate

Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate is a combination medication used as contraception to prevent pregnancy.

• Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate is available under the following different brand names: Loestrin 24 Fe, Loestrin Fe 1.5/30, Loestrin Fe 1/20, Lo Loestrin Fe, Lomedia 24 Fe, Lo Minastrin Fe, Estrostep Fe, Gildess Fe 1.5/30, Gildess Fe 1/20, Junel Fe 1.5/30, Junel Fe 1/20, Junel Fe 24, Microgestin Fe 1.5/30, Microgestin Fe 1/20, Minastrin 24 FE, Tilia Fe, TriLegest Fe, Blisovi 24 Fe, Blisovi Fe 1.5/30, Blisovi Fe 1/20, Taytulla, Larin 24 FE, Larin FE 1/20, Larin FE 1.5/30, Melodetta 24 FE, Mibelas 24 FE, Tarina 24 FE, Tarina FE 1/20, Merzee.

Common side effects of Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate include:

• nausea
• vomiting
• abdominal cramps and bloating
• spotting
• changes in menstrual flow
• skin discoloration
• breast tenderness or enlargement
• nipple discharge
• changes in weight
• rash
• depression
• vaginal discharge
• vaginal yeast infection
• temporary infertility after discontinuation of treatment
• swelling
• freckles or dark patches of skin on the face
• migraine
• and problems with contact lenses

Serious side effects of Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• sudden numbness or weakness (especially on the side of the body)
• sudden severe headache
• slurred speech
• problems with vision or balance
• sudden vision loss
• stabbing chest pain
• feeling short of breath
• coughing up blood
• pain or warmth in one or both legs
• chest pain or pressure
• pain spreading to the jaw or shoulder
• nausea
• sweating
• loss of appetite
• upper stomach pain
• tiredness
• dark urine
• clay-colored stools
• yellowing of the skin or eyes (jaundice)
• severe headache
• blurred vision
• pounding in the neck or ears
• swelling in the hands, ankles, or feet
• change in the pattern or severity of migraine headaches
• breast lump
• sleep problems
• weakness
• tired feeling, and
• mood changes

Rare side effects of Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet, monophasic 24-day

• 1mg/20mcg (24 tablets) plus 75mg ferrous fumarate (4 tablets) (Larin 24 Fe, Loestrin 24 Fe, Lomedia 24 Fe, Junel Fe 24, Blisovi 24 Fe, Melodetta 24 Fe, Mibelas 24 Fe Tarina 24 Fe)

Soft gel capsule, monophasic 24-day

• 1mg/20mcg (24 capsule) plus 75mg ferrous fumarate (4 capsule) (Merzee, Minastrin 24 Fe, Taytulla)

Tablet, monophasic 21-day

• 1.5mg/30mcg (21 tablets) plus 75mg ferrous fumarate (7 tablets) (Blisovi Fe 1.5/30, Larin Fe 1.5/30, Loestrin Fe 1.5/30, Junel Fe 1.5/30, Microgestin Fe 1.5/30)
• 1mg/20mcg (21 tablets) plus 75mg ferrous fumarate (7 tablets) (Blisovi Fe 1/20, Larin Fe 1/20, Loestrin Fe 1/20, Junel Fe 1/20, Microgestin Fe 1/20, Tarina Fe 1/20)

Tablet, multiphasic (Lo Loestrin Fe, Lo Minastrin Fe)

• 1mg/10mcg (24 tablets) ethinyl estradiol 10mcg only (2 tablets)
• Plus, ferrous fumarate 75mg (2 tablets)

Tablet, triphasic (Estrostep Fe, Tilia Fe, TriLegest Fe)

• 1mg/20mcg (5 tablets)
• 1mg/30mcg (7 tablets)
• 1mg/35mcg (9 tablets)
• Plus, 75mg ferrous fumarate (7 tablets)

Oral contraception

Adult dosage

• Monophasic
  • 21 days: 1 active tablet orally once a day for 21 days, then 1 Fe tablet orally once a day on Days 22-28
  • 24 days: 1 active tablet/capsule orally once a day for 24 days, then 1 Fe tablet/capsule orally once a day on Days 25-28
• Tablet, multiphasic
  • 1mg/10 mcg (Days 1-24)
  • ethinyl estradiol alone 10 mcg (Days 25-26)
  • Plus, ferrous fumarate 75 mg (Days 27-28)
• Tablet, triphasic
  • 1 mg/20 mcg (Days 1-5)
  • 1 mg/30 mcg (Days 6-12)
  • 1 mg/35 mcg (Days 13-21)
  • Plus 75 mg ferrous fumarate (Days 22-28)
• Initiating after-pregnancy
  • Increased risk for venous thromboembolism (VTE) following delivery with combined hormonal contraceptives; risk declines rapidly after 21 days, but does not return to normal until 42 days after delivery
  • CDC guidelines recommend waiting for 3-6 weeks in postpartum women without additional VTE risks (MMWR July 7, 2011)
  • Initiating after vaginal birth: Wait at least 3 weeks
  • Initiating after caesarean section birth: Wait at least 6 weeks
  • Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, 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, health care provider, or pharmacist first.

• Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate has severe interactions with the following drugs:
  • fezolinetant
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • tranexamic acid oral
• Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate has serious interactions with at least 82 other drugs
• Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate has moderate interactions with at least 180 other drugs
• Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate has minor interactions with at least 42 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Liver tumors or liver disease
• Undiagnosed abnormal uterine bleeding
• Breast cancer or other estrogen-or progestin-sensitive cancer
• Pregnancy
• Receiving hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
• Cholestatic jaundice of pregnancy or jaundice with prior pill use
• Women who currently have the following:
  • High risk of arterial or venous thrombotic diseases
  • Smoke, if over age 35
  • Have cerebrovascular disease
  • Have coronary artery disease
  • Have current or history of deep vein thrombosis (DVT) or pulmonary embolism (PE)
  • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart
  • Have inherited or acquired hypercoagulopathies
  • Have uncontrolled hypertension (HTN) or HTN with vascular disease
  • Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches
  • Have diabetes mellitus (DM) and are over age 35, DM with HTN or with vascular disease or end-organ damage, or DM of more than 20 years duration

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Norethindrone Acetate-Ethinyl Estradiol-Ferrous Fumarate?”

Cautions

• Acitretin inhibits the contraceptive efficacy of norethindrone preparations
• Family history of breast cancer and or DVT/PE, current/history of depression, endometriosis, DM, HTN, bone mineral density changes, renal/hepatic impairment, bone metabolic disease, systemic lupus erythematosus; conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)
• Discontinue if the following develop jaundice, visual problems (may cause contact lens intolerance), any signs of VTE, migraine with unusual severity, significant blood pressure increase, severe depression, increased risk of thromboembolic complications after surgery
• 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
• Patients on warfarin, oral anticoagulants (increase in anticoagulant dose may be warranted)
• Increased risk of cervical cancer with oral contraceptive pill (OCP) use, however human papilloma virus (HPV) remains as main risk factor for this cancer; evidence suggests long-term use of OCPs, 5 or more years, may be associated with increased risk
• Increased risk of liver cancer with OCP use; risk increases with longer duration of OCP use
• Steroid hormones may be poorly metabolized in patients with hepatic impairment; acute or chronic disturbances of liver function may necessitate discontinuation of combination oral contraceptive until markers of liver function return to normal and causation by combination oral contraceptive has been excluded
• CDC guidelines recommend waiting at least 3 weeks following vaginal birth or 6 weeks after cesarean section to decrease the risk for venous thromboembolism before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum) should not use combined hormonal contraceptives (MMWR July 7, 2011)
• Monitor prediabetic and diabetic women taking ethinyl estradiol/ norethindrone; consider alternative contraceptive methods for women with uncontrolled dyslipidemia
• Evaluate significant change in headaches and discontinue therapy if indicated
• Evaluate irregular bleeding or amenorrhea
• If used in women with well-controlled hypertension, monitor blood pressure and stop therapy if blood pressure rises significantly
• Discontinue hormonal therapy before starting therapy with a combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; may restart approximately 2 weeks following completion of treatment with a combination drug regimen
• In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema
• Chloasma may occur with therapy, especially in women with a history of chloasma gravidarum; advise women with a history of chloasma to avoid exposure to the sun or ultraviolet radiation while taking the drug
• Breast cancer
  • Epidemiology studies have not found a consistent association between the use of combined oral contraceptives (COCs) and breast cancer risk; studies do not show an association between every (current or past) use of COCs and the risk of breast cancer
  • Some studies report a small increase in the risk of breast cancer among current or recent users(below 6 months since last use) and current users with longer duration of COC use
  • A woman's risk depends on conditions where naturally high hormone levels persist for long periods including early-onset menstruation before age 12, late-onset menopause, after age 55, first child after age 30, nulliparity
• Drug interaction overview
  • Significant changes (increase or decrease) in plasma concentrations of estrogen and progestin were noted in some cases of co-administration with HIV/HCV protease inhibitors (decrease [neg, nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [eg, indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [eg, boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [eg, nevirapine] or increase [eg, etravirine])
  • Not for coadministration with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for alanine transaminase elevations
  • Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol concentrations, possibly by inhibition of conjugation; a reduction in contraceptive effectiveness and increased incidence of breakthrough bleeding suggested with phenylbutazone
  • COCs containing ethinyl estradiol may inhibit the metabolism of other compounds (eg, 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
  • A significant decrease in plasma concentration of lamotrigine was 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 serum concentration of thyroid-binding globulin increases with the use of COCs

Pregnancy and Lactation

• There is no use for contraception in pregnancy; therefore, the drug should be discontinued during pregnancy
• Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives before pregnancy; studies also do not suggest a teratogenic effect, particularly insofar as cardiac anomalies and limb reduction defects are concerned when taken inadvertently during early pregnancy
• Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy; oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion
• It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use; if the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of first missed period; oral contraceptive use should be discontinued if pregnancy is confirmed
• Lactation
  • Small amounts of oral contraceptive steroids were identified in the milk of nursing mothers, and a few adverse effects on children were reported, including jaundice and breast enlargement; in addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk
  • If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child