Levonorgestrel and Ethinyl estradiol
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]
Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
Overview
Levonorgestrel and Ethinyl estradiol is a contraceptive agent that is FDA approved for the {{{indicationType}}} of contraception. Common adverse reactions include acne, increased weight,nausea, vomiting, headache, migraine, anxiety, depression, mood swings, panic attack, break-through bleeding, breast tenderness, dysmenorrhea.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
There is limited information regarding Levonorgestrel and Ethinyl estradiol FDA-Labeled Indications and Dosage (Adult) in the drug label.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Levonorgestrel and Ethinyl estradiol in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Levonorgestrel and Ethinyl estradiol in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Levonorgestrel and Ethinyl estradiol FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Levonorgestrel and Ethinyl estradiol in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Levonorgestrel and Ethinyl estradiol in pediatric patients.
Contraindications
Combination oral contraceptives should not be used in women with any of the following conditions:
- Thrombophlebitis or thromboembolic disorders
- A history of deep-vein thrombophlebitis or thromboembolic disorders
- Cerebrovascular or coronary artery disease (current or past history)
- Valvular heart disease with thrombogenic complications
- Thrombogenic rhythm disorders
- Hereditary or acquired thrombophilias
- Major surgery with prolonged immobilization
- Diabetes with vascular involvement
- Headaches with focal neurological symptoms
- Uncontrolled hypertension
- Known or suspected carcinoma of the breast or personal history of breast cancer
- Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia
- Undiagnosed abnormal genital bleeding
- Cholestatic jaundice of pregnancy or jaundice with prior pill use
- Hepatic adenomas or carcinomas, or active liver disease
- Known or suspected pregnancy
- Hypersensitivity to any of the components of Aviane
Warnings
The use of oral contraceptives is associated with increased risks of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as certain inherited or acquired thrombophilias, hypertension, hyperlipidemias, obesity, diabetes, and surgery or trauma with increased risk of thrombosis (see CONTRAINDICATIONS).
Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.
The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher doses of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower doses of both estrogens and progestogens remains to be determined.
- Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiological methods.
Thromboembolic Disorders and Other Vascular Problems
a. Myocardial Infarction
- An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary-artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30.
- Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarction in women in their mid-thirties or older with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure II) among women who use oral contraceptives.
- Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.
b. Venous Thrombosis and Thromboembolism
- An increased risk of venous thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep-vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The approximate incidence of deep-vein thrombosis and pulmonary embolism in users of low dose (< 50 mcg ethinyl estradiol) combination oral contraceptives is up to 4 per 10,000 woman-years compared to 0.5 to 3 per 10,000 woman-years for nonusers. However, the incidence is less than that associated with pregnancy (6 per 10,000 woman-years). The excess risk is highest during the first year a woman ever uses a combined oral contraceptive. Venous thromboembolism may be fatal. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and gradually disappears after pill use is stopped.
- A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four weeks after delivery in women who elect not to breastfeed or after a midtrimester pregnancy termination.
c. Cerebrovascular Diseases
- Oral contraceptives have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (> 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes.
- In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Oral contraceptives also increase the risk for stroke in women with other underlying risk factors such as certain inherited or acquired thrombophilias. Women with migraine (particularly migraine/headaches with focal neurological symptoms, see CONTRAINDICATIONS) who take combination oral contraceptives may be at an increased risk of stroke.
d. Dose-Related Risk of Vascular Disease from Oral Contraceptives
- 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. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogen used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive.
- Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing the lowest estrogen content which is judged appropriate for the individual patient.
e. Persistence of Risk of Vascular Disease
- There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40 to 49 years who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups.
- In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 mcg or higher of estrogens.
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Levonorgestrel and Ethinyl estradiol Clinical Trials Experience in the drug label.
Postmarketing Experience
There is limited information regarding Levonorgestrel and Ethinyl estradiol Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Levonorgestrel and Ethinyl estradiol Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Levonorgestrel and Ethinyl estradiol in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Levonorgestrel and Ethinyl estradiol in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Levonorgestrel and Ethinyl estradiol during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in geriatric settings.
Gender
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol with respect to specific gender populations.
Race
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Levonorgestrel and Ethinyl estradiol in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Levonorgestrel and Ethinyl estradiol in patients who are immunocompromised.
Administration and Monitoring
Administration
- To achieve maximum contraceptive effectiveness, Aviane® (levonorgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of Aviane - 28 is one orange tablet daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days, according to the prescribed schedule. It is recommended that Aviane - 28 tablets be taken at the same time each day.
- The dispenser should be kept in the wallet supplied to avoid possible fading of the pills. If the pills fade, patients should continue to take them as directed.
During The First Cycle Of Use
- The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should be instructed to begin taking Aviane on either the first Sunday after the onset of menstruation (Sunday Start) or on Day 1 of menstruation (Day 1 Start).
Sunday Start
- The patient is instructed to begin taking Aviane - 28 on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (orange) is taken that day. One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on Aviane - 28 until an orange tablet has been taken daily for 7 consecutive days, and a nonhormonal backup method of birth control should be used during those 7 days.
Day 1 Start
- During the first cycle of medication, the patient is instructed to begin taking Aviane - 28 during the first 24 hours of her period (day one of her menstrual cycle). One orange tablet should be taken daily for 21 consecutive days, followed by one light-green inert tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within 3 days following discontinuation of orange tablets and may not have finished before the next pack is started. If medication is begun on day one of the menstrual cycle, no backup contraception is necessary. If Aviane - 28 tablets are started later than day one of the first menstrual cycle or postpartum, contraceptive reliance should not be placed on Aviane - 28 tablets until after the first 7 consecutive days of administration, and a nonhormonal backup method of birth control should be used during those 7 days.
After the First Cycle of Use
- The patient begins her next and all subsequent courses of tablets on the day after taking her last light-green tablet. She should follow the same dosing schedule: 21 days on orange tablets followed by 7 days on light-green tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a nonhormonal backup method of birth control until she has taken an orange tablet daily for 7 consecutive days.
Switching from Another Hormonal Method of Contraception
- When the patient is switching from a 21 day regimen of tablets, she should wait 7 days after her last tablet before she starts Aviane. She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21 day regimen. When the patient is switching from a 28 day regimen of tablets, she should start her first pack of Aviane on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin Aviane the next day. If switching from an implant or injection, the patient should start Aviane on the day of implant removal or, if using an injection, the day the next injection would be due. In switching from a progestin-only pill, injection, or implant, the patient should be advised to use a nonhormonal backup method of birth control for the first 7 days of tablet taking.
If Spotting or Breakthrough Bleeding Occurs
- If spotting or breakthrough bleeding occur, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her physician.
Risk of Pregnancy if Tablets are Missed
- While there is little likelihood of ovulation occurring if only one or two orange tablets are missed, the possibility of ovulation increases with each successive day that scheduled orange tablets are missed. Although the occurrence of pregnancy is unlikely if Aviane is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.
- The risk of pregnancy increases with each active (orange) tablet missed. For additional patient instructions regarding missed tablets, see the WHAT TO DO IF YOU MISS PILLS section in the DETAILED PATIENT LABELING below.
Use After Pregnancy, Abortion or Miscarriage
- Aviane may be initiated no earlier than day 28 postpartum in the nonlactating mother or after a second trimester abortion due to the increased risk for thromboembolism (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease). The patient should be advised to use a nonhormonal backup method for the first 7 days of tablet taking.
- Aviane may be initiated immediately after a first trimester abortion or miscarriage. If the patient starts Aviane immediately, backup contraception is not needed.
Monitoring
- If women with hypertension elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued.
- Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.
- Oral contraceptives should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.
IV Compatibility
There is limited information regarding the compatibility of Levonorgestrel and Ethinyl estradiol and IV administrations.
Overdosage
- Symptoms of oral contraceptive overdosage in adults and children may include nausea, vomiting, and drowsiness/fatigue; withdrawal bleeding may occur in females. There is no specific antidote and further treatment of overdose, if necessary, is directed to the symptoms.
Pharmacology
There is limited information regarding Levonorgestrel and Ethinyl estradiol Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Levonorgestrel and Ethinyl estradiol Mechanism of Action in the drug label.
Structure
There is limited information regarding Levonorgestrel and Ethinyl estradiol Structure in the drug label.
Pharmacodynamics
There is limited information regarding Levonorgestrel and Ethinyl estradiol Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Levonorgestrel and Ethinyl estradiol Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Levonorgestrel and Ethinyl estradiol Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Levonorgestrel and Ethinyl estradiol Clinical Studies in the drug label.
How Supplied
There is limited information regarding Levonorgestrel and Ethinyl estradiol How Supplied in the drug label.
Storage
There is limited information regarding Levonorgestrel and Ethinyl estradiol Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Levonorgestrel and Ethinyl estradiol |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Levonorgestrel and Ethinyl estradiol |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Levonorgestrel and Ethinyl estradiol Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Levonorgestrel and Ethinyl estradiol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Levonorgestrel and Ethinyl estradiol Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Levonorgestrel and Ethinyl estradiol Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.