Levonorgestrel Oral-Ethinyl Estradiol

Levonorgestrel Oral/Ethinyl Estradiol is a prescription medicine used as contraception to prevent pregnancy in adults and postpubertal adolescents aged above 16 years after menarche.

Levonorgestrel Oral/Ethinyl Estradiol is available under the following different brand names: Altavera, Amethia, Amethia Lo, Amethyst, Ashlyna, Aubra, Aviane, Camrese, Camrese Lo, Chateal, Daysee, Elifemme, Enpresse, Falmina, Introvale, Jolessa, Kurvelo, Lessina 21, Lessina 28, Levonest, Levora, LoSeasonique, Lybrel, Marlissa, Microgynon, Nordette, Orsythia, Ovranette, Portia 21, Portia 28, Quasense, Quartette, Sronyx, Trivora 28, Seasonale, Seasonique, Setlakin, Lutera, Myzilra, FaLessa, FaLessa Kit, Delyla, Fayosim, Larissia, Lillow, Rivelsa, Vienva

Adult dosage

Tablet, monophasic (Aubra, Aviane, Delyla, Falmina, Falessa, Falessa Kit, Larissia, Lessina, Lutera, Orsythia, Vienva)

• Days 1-21: 0.1mg/20mcg
• Days 22-28: Inert tablets
• Days 22-28: folic acid 1 mg (Falessa Kit)

Tablet, monophasic (Altavera, Chateal, Kurvelo, Levora, Lillow, Marlissa, Nordette, Portia)

• Days 1-21: 0.15mg/30mcg
• Days 22-28: Inert tablets

Tablet, 91-day (Seasonale, Quasense, Introvale, Jolessa, Setlakin)

• Days 1-84: 0.15mg/30mcg
• Days 85-91: Inert tablets

Tablet, 91-day (Seasonique, Amethia, Ashlyna, Camrese, Daysee)

• Days 1-84: 0.15mg/30mcg
• Days 85-91: Ethinyl estradiol 10mcg

Tablet, 91-day (LoSeasonique, Amethia Lo, Camrese Lo)

• Days 1-84: 0.1mg/20mcg
• Days 85-91: Ethinyl estradiol 10mcg

Tablet, 91-day (Quartette, Fayosim, Rivelsa)

• Days 1-42: 0.15mg/20mcg
• Days 43-63: 0.15mg/25mcg
• Days 64-84: 0.15mg/30mcg
• Days 85-91: Ethinyl estradiol 10mcg

Tablet, triphasic (Elifemme, Enpresse, Levonest, Trivora 28)

• Days 1-6: 0.05mg/30mcg
• Days 7-11: 0.075mg/40mcg
• Days 12-21: 0.125mg/30mcg
• Days 22-28: Inert tablets

Tablet, continuous cycle

• 0.09mg/20mcg

Contraception

Adult dosage

Monophasic

• 1 active tablet orally daily for 21 days, then 1 inert tablet orally daily for 7 days (follow manufacturer's color-coding for sequence)
• 91-day
• 1 combination tablet daily for 84 days, then either 1 inert tablet or 1 tablet of ethinyl estradiol 10 mcg for 7 days
• First cycle begins on the first Sunday after the onset of menstruation; if menstruation begins on Sunday, the first combination tablet is taken that day, with subsequent tablets taken in the order specified on the dispenser
• Use a non-hormonal backup method of contraception (eg, condoms and spermicide) for the first 7 days of treatment
• Next and all subsequent 91-day courses of tablets are initiated without interruption on the same day of the week (Sunday), following the same schedule, with tablets taken at the same time of day on each day of active treatment

Triphasic

1. Regimens vary; see package inserts (follow manufacturer's color-coding for sequence)
2. Continuous cycle
3. 1 tablet orally daily at the same time each day, with no tablet-free interval

Missed Active Contraceptive Dose

Adult dosage

• One active tablet missed
• Take 1 tablet as soon as possible, or take 2 tablets on the following day
• Alternatively, take 1 tablet, discard missed tablet, and continue taking subsequent tablets as scheduled
• Use other forms of contraception for the next 7 days after a missed dose or until menses occur
• Two active tablets missed consecutively
• Take 2 tablets as soon as remembered and continue taking them as scheduled
• Alternatively, take 2 tablets daily for the next 2 days and continue taking as scheduled
• Missed 3rd week of cycle and patient is Sunday Starter: Take 1 pill every day until Sunday; discard rest of pack, and start a new pack that same day
• Missed 3rd week of cycle and patient is day-1 starter: Discard rest of pack, and start a new pack that same day
• Use other forms of contraception for the next 7 days after a missed dose or until menses occur
• Menses may not occur this month; if menses do not occur for 2 consecutive months, contact the healthcare provider about the possibility of pregnancy
• Three active tablets missed consecutively
• Sunday starter: Take 1 pill every day until Sunday; discard the rest of the pack, and start a new pack that same day

Day-1 starter: Discard the rest of the pack, and start a new pack that same day

• Use other forms of contraception for the next 7 days after a missed dose or until menses occur
• Menses may not occur this month; if menses do not occur for 2 consecutive months, contact the healthcare provider about the possibility of pregnancy

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Levonorgestrel Oral/Ethinyl Estradiol include:

• nausea,
• vomiting (especially when they first start taking the medicine),
• breast tenderness,
• breakthrough bleeding,
• acne,
• darkening of facial skin,
• weight gain, and
• problem with contact lenses.

Serious side effects of Levonorgestrel Oral/Ethinyl Estradiol include:

• sudden numbness or weakness (especially on one side of the body),
• severe headache,
• slurred speech,
• balance problems,
• sudden vision loss,
• stabbing chest pain,
• feeling short of breath,
• coughing up blood,
• swelling or redness in an arm or leg,
• chest pain or pressure,
• pain spreading to your jaw or shoulder,
• nausea,
• sweating,
• loss of appetite,
• upper stomach pain,
• tiredness,
• fever, dark urine,
• clay-colored stools,
• yellowing of the skin or eyes (jaundice),
• blurred vision,
• pounding in the neck or ears,
• swelling in the hands, ankles, or feet,
• changes in the pattern or severity of migraine headaches,
• breast lump,
• sleep problems,
• weakness,
• tired feeling, and
• mood changes.

Rare side effects of Levonorgestrel Oral/Ethinyl Estradiol include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result 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.

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.

• Levonorgestrel Oral/Ethinyl Estradiol has severe interactions with the following drugs:
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • tranexamic acid oral
• Levonorgestrel Oral/Ethinyl Estradiol has serious interactions with at least 80 other drugs.
• Levonorgestrel Oral/Ethinyl Estradiol has moderate interactions with at least 174 other drugs.
• Levonorgestrel Oral/Ethinyl Estradiol has minor interactions with the following drugs:
  • amitriptyline
  • amoxapine
  • antipyrine
  • asenapine
  • clarithromycin
  • clomipramine
  • desipramine
  • dosulepin
  • doxepin
  • duloxetine
  • enasidenib
  • eplerenone
  • levoketoconazole

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 health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Documented hypersensitivity
• Breast cancer or another estrogen- or progestin-sensitive cancer, now or in the past
• Arterial thromboembolic disease (stroke, myocardial infarction [MI]), thrombophlebitis, deep vein thrombosis or pulmonary embolism (DVT)/PE, thrombogenic valvular disease
• Estrogen-dependent neoplasia
• Liver tumors, benign or malignant, or liver disease
• Undiagnosed abnormal vaginal bleeding
• Uncontrolled hypertension or hypertension with vascular disease
• Diabetes mellitus and over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of more than 20 years duration
• Inherited or acquired hypercoagulopathies, smokers aged above 35 years (Natazia)
• Renal insufficiency, hepatic dysfunction, adrenal insufficiency
• Headaches with focal neurological symptoms or have migraine headaches with aura
• Women above 35 with any migraine headaches
• Smoking more than 15 cigarettes/day at an age above 35 years
• Major surgery with prolonged immobilization
• Cerebrovascular or coronary artery disease (current or history)
• Thrombogenic rhythm disorders
• Hereditary or acquired thrombophilias
• Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
• Undiagnosed abnormal vagina/uterine bleeding
• Cholestatic jaundice of pregnancy or jaundice with prior pill use
• Receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel Oral/Ethinyl Estradiol?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Levonorgestrel Oral/Ethinyl Estradiol?”

Cautions

• Before starting therapy evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy; therapy is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases
• Use caution in patients with a family history of breast cancer, DVT/PE, or both; current or previous depression, endometriosis, diabetes mellitus, hypertension, bone mineral density changes, renal or hepatic impairment, bone metabolic disease, systemic lupus erythematosus (SLE); conditions exacerbated by fluid retention (eg, migraine, asthma, epilepsy)
• The risk of VTE is highest during the first year of use of a COCs and when restarting oral contraception after a break of 4 weeks or longer; the risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued; the use of COCs increases the risk of arterial thromboses that result in strokes and myocardial infarctions, especially in women with other risk factors for these events; COCs have been shown to increase both relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes); risk increases with age, particularly in women over 35 years of age who smoke
• Discontinue therapy if an arterial thrombotic event or venous thromboembolic (VTE) event occurs; if feasible, stop therapy at least 4 weeks before and through 2 weeks after major surgery or other surgeries are known to have an elevated risk of VTE as well as during and following prolonged immobilization; initiate therapy no earlier than 4 weeks after delivery in women who are not breastfeeding; risk of postpartum VTE decreases after third postpartum week, whereas the risk of ovulation increases after third postpartum week
• 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
• Discontinue 4 weeks before major surgery or prolonged immobilization
• Discontinue drug before starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir; therapy can be restarted approximately 2 weeks following completion of treatment with the hepatitis C combination drug regimen
• Use of warfarin or other oral anticoagulants (increase in anticoagulant dose may be warranted)
• The estrogen component of COCs may raise 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
• Some studies link oral contraceptive use with increased risk of breast cancer, whereas others do not; risk depends on conditions where naturally high hormone levels persist for long periods, including early-onset menstruation (age below 12 years), late-onset menopause (age above 55 years), first child after age 30 years, nulliparity
• Increased risk of cervical cancer with oral contraceptive use, however, human papillomavirus (HPV) remains the primary risk factor for this cancer
• 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
• Long-term (more than 5 years) use of oral contraceptives may be associated with increased risk
• Increased risk of liver cancer with oral contraceptive use; risk increases with duration of use
• CDC guidelines recommend waiting more than 3 weeks after vaginal birth or more than 6 weeks after cesarean section to decrease the risk of VTE before initiating combined hormonal contraceptives; women with additional risk factors for VTE (besides postpartum status) should not use combined hormonal contraceptives
• Scheduled withdrawal bleeding does not occur with therapy; the absence of withdrawal bleeding cannot be used as a sign of an unexpected pregnancy and as such, unexpected pregnancy may be difficult to recognize; if pregnancy is suspected, a pregnancy test should be performed
• Benign hepatic adenomas are associated with oral contraceptive use; rupture of rare, benign, hepatic adenomas may cause death through intraabdominal hemorrhage
• Retinal thrombosis associated with the use of oral contraceptives that may lead to partial or complete loss of vision reported; oral contraceptives should be discontinued if there is an unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions; appropriate diagnostic and therapeutic measures should be undertaken immediately
• Increased risk of myocardial infarction attributed to oral contraceptive use; risk is primarily in smokers or women with other underlying risk factors for coronary-artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes
• An increased risk of venous thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established; the excess risk is highest during the first year a woman ever uses a combined oral contraceptive
• 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 radiation while receiving therapy
• Oral contraceptives have been shown to increase both relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (above 35 years), hypertensive women who also smoke
• Not for use in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of the liver; acute or chronic disturbances of liver function may necessitate discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded; discontinue therapy if jaundice develops
• Women with migraine (particularly migraine/ headaches with focal neurological symptoms such as aura) who take combination oral contraceptives may be at increased risk of stroke
• A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease
• A decline in serum high-density lipoproteins (HDL) has been reported with many progestational agents; a decline in serum high-density lipoproteins has been associated with an increased incidence of ischemic heart disease; women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives; some progestogens may elevate LDL levels and may render control of hyperlipidemias more difficult; non-hormonal contraception should be considered in women with uncontrolled dyslipidemias; persistent hypertriglyceridemia may occur; elevations of plasma triglycerides may lead to pancreatitis and other complications
• Diarrhea and/or vomiting may reduce hormone absorption resulting in decreased serum concentrations
• An increase in blood pressure is reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use; women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception; if women with hypertension elect to use oral contraceptives, they should be monitored closely and if the significant elevation of blood pressure occurs, oral contraceptives should be discontinued
• Onset or exacerbation of migraine or development of headache with a new pattern that is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause
• The convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled breakthrough bleeding and spotting
• Ectopic as well as intrauterine pregnancy may occur in contraceptive failures
• Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care
• For women with well-controlled hypertension, monitor blood pressure and stop treatment if blood pressure rises significantly
• Studies suggest a small increased relative risk of developing gallbladder disease among COC users; use of COCs may worsen existing gallbladder disease; a history of COC-related cholestasis predicts an increased risk with subsequent COC use; women with a history of pregnancy-related cholestasis may be at increased risk for COC related cholestasis
• If a woman receiving therapy develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue therapy if indicated; consider discontinuation in case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event)
• 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
• Women receiving therapy may experience amenorrhea, absence of withdrawal bleeding, even if they are not pregnant; 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 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

Pregnancy and Lactation

• There is little or no increased risk of birth defects in women who inadvertently use combination oral contraceptives 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 combination oral contraceptives before conception or during early pregnancy
• Not to be administered to induce withdrawal bleeding as a test for pregnancy; not for use during pregnancy to treat threatened or habitual abortion
• Lactation
  • Advise the nursing mother to use other forms of contraception, when possible until she has weaned her child; combination oral contraceptives 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