Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate

Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate is a combined hormonal contraceptive (CHC) indicated for use by women of reproductive potential to prevent pregnancy.

• Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate is available under the following different brand names: Balcoltra

Common side effects of Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate include:

• headache
• abnormal menstrual bleeding
• menstrual cramping
• nausea
• abdominal pain
• breast pain
• mood changes
• acne
• depression
• missed menstrual periods
• vaginal yeast infection

Serious side effects of Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate include:

• heart attack: chest pain, stomach discomfort, sweating, nausea, dizziness
• stroke: sudden numbness or weakness in the arm, leg, or face, confusion, trouble seeing, headache, difficulty walking
• deep vein thrombosis [DVT] (blood clot in the leg): leg cramp, swelling, pain, muscle tightness
• pulmonary embolism [PE] (blood clot in the lung): cough, chest pain, trouble breathing, racing heart
• liver problems: yellowing of the skin or the whites of the eyes, tiredness, stomach pain

Rare side effects of Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate 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 and pediatric dosage

Tablet, monophasic

• 0.1 mg/0.02 mcg (21 tablets) plus 36.5 mg ferrous bisglycinate (7 tablets)

Oral contraception

Adult dosage

• Follow the manufacturer's color coding for the sequence
• Active tablet orally once a day for 21 days, then 1 Fe tablet orally once a day on days 22-28
• Take tablets in the order directed on the blister pack

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, healthcare provider, or pharmacist first.

• Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate has severe interactions with the following drug:
  • ombitasvir/paritaprevir/ritonavir and dasabuvir
• Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate has serious interactions with the following drugs:
  • atazanavir
  • belzutifan
  • calaspargase pegol
  • darunavir
  • elagolix
  • encorafenib
  • indinavir
  • isavuconazonium sulfate
  • lopinavir
  • mavacamten
  • mobocertinib
  • nelfinavir
  • nevirapine
  • omaveloxolone
  • pexidartinib
  • pretomanid
  • repotrectinib
  • ritonavir
  • saquinavir
  • tipranavir
• Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate has moderate interactions with at least 123 other drugs
• Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate has minor interactions with the following drug:
  • enasidenib

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, benign or malignant, or liver disease (acute viral hepatitis or severe, decompensated, cirrhosis of the liver)
• Undiagnosed abnormal uterine bleeding
• Pregnancy (no reason to use CHCs during pregnancy)
• History or current breast cancer or other estrogen- or progestin-sensitive cancer
• Hypersensitivity
• Coadministration with ombitasvir/paritaprevir/ritonavir, with or without dasabuvir
• High risk for arterial or venous thrombotic disease
• Smoking, if older than 35 years
• History or current DVT and PE
• Inherited or acquired hypercoagulopathies
• Cerebrovascular disease
• Coronary artery disease
• Thrombogenic valvular or thrombogenic rhythm diseases of the heart (eg, subacute bacterial endocarditis with valvular disease, atrial fibrillation)
• Uncontrolled hypertension
• Diabetes mellitus with vascular disease
• Headaches with focal neurological symptoms or migraine headaches with aura
• Women older than 35 years with any migraine headaches

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate?”

Cautions

• Risk of postpartum venous thromboembolism (VTE) decreases after the third postpartum week, whereas the risk for ovulation increases after the third postpartum week; start contraceptive therapy no earlier than 4 weeks after delivery in women who are not breastfeeding
• Acute or chronic disturbances of liver function may necessitate the discontinuation of CHC use until liver function resolves to normal and CHC causation has been excluded
• Hepatic adenomas are associated with CHCs use; studies have reported an increased risk of developing hepatocellular carcinoma in long-term (above 8 years) combined oral contraceptive users
• Studies report a small increased relative risk of developing gallbladder disease among CHC users; use of CHCs may worsen existing gallbladder disease; history of CHC-related cholestasis predicts an increased risk with subsequent CHC use; women with a history of pregnancy-related cholestasis may be at an increased risk for CHC-related cholestasis
• CHCs may decrease glucose tolerance; carefully monitor in prediabetes and diabetes
• Consider alternative contraception for women with uncontrolled dyslipidemia
• A small proportion of women will have adverse lipid changes while on CHCs; women with hypertriglyceridemia, or a family history thereof, may be at an increased risk for pancreatitis when using CHCs
• If new headaches that are recurrent, persistent, or severe develop in women taking the drug, evaluate the cause and discontinue therapy if indicated
• This product contains FD&C yellow no. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible people
• Carefully observe women with a history of depression, and discontinue therapy if depression recurs to a serious degree
• In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema
• 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 light
• Bleeding irregularities and amenorrhea
  • Unscheduled (breakthrough or intracyclic) bleeding and spotting may occur, especially during the first 3 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
  • 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 a day later than she should have), consider the possibility of pregnancy at the time of 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
  • In a clinical trial, 2.6% of the evaluable cycles were amenorrheic; women may experience amenorrhea or oligomenorrhea after discontinuation of CHCs, especially when such a condition was preexistent
• Thrombotic disorders and other vascular problems
  • Use of CHCs also increases the risk for arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events
  • CHCs increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes)
  • If feasible, discontinue CHC at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk for VTE, as well as during the following prolonged immobilization
  • An increase in blood pressure has been reported in women taking CHCs, and this increase is more likely in older women with extended duration of use; incidence of hypertension increases with increasing concentrations of progestin; monitor blood pressure periodically; stop therapy in women with well-controlled hypertension if blood pressure rises significantly
• Drug interactions overview
  • During clinical trials with the hepatitis C combination drug regimen containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, incidences of elevated ALT above 5x ULN, including some cases above 20x ULN, were significantly more frequent in women using ethinyl estradiol (EE)–containing medications, such as CHCs
  • Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease plasma concentrations of CHCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding
  • Coadministration of atorvastatin or rosuvastatin and certain CHCs 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 (eg, itraconazole, voriconazole, fluconazole, grapefruit juice, ketoconazole), which may increase plasma hormone concentrations
  • Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of coadministration with HIV/hepatitis C virus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors. CHCs containing EE may inhibit the metabolism of other compounds (eg, cyclosporine, prednisolone, theophylline, tizanidine, voriconazole) and increase their plasma concentrations
  • CHCs reduce plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam, and lamotrigine; a significant decrease in plasma concentration of lamotrigine has been shown, likely owing to induction of lamotrigine glucuronidation
  • The estrogen component of CHCs may increase the serum concentrations of thyroxine-binding globulin, sex hormone–binding globulin, and cortisol-binding globulin; a dose of replacement thyroid hormone or cortisol therapy may need to be increased

Pregnancy and Lactation

• Contraindicated in pregnancy because there is no reason to use CHCs in pregnancy
• Epidemiologic studies and meta-analyses have not found an increased risk for genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy
• Lactation
  • CHCs and/or metabolites are present in human milk and breastfed infants
  • CHCs, including Levonorgestrel-Ethinylestradiol-Ferrous Bisglycinate, can reduce milk production in breastfeeding women; reduction can occur at any time but is less likely to occur once breastfeeding
  • Advise nursing women to use other methods of contraception until they discontinue breastfeeding