Levonorgestrel And Ethinyl Estradiol - Levonorgestrel And Ethinyl Estradiol prescribing information
Cigarette smoking increases the risk of serious cardiovascular side effects from oral-contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.
INDICATIONS AND USAGE
Levonorgestrel and ethinyl estradiol tablets USP, 0.1 mg and 0.02 mg are indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.
Oral contraceptives are highly effective. Table II lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and Norplant ® System, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
Emergency Contraceptive Pills: The FDA has concluded that certain combined oral contraceptives containing ethinyl estradiol and norgestrel or levonorgestrel are safe and effective for use as postcoital emergency contraception. Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%. 9 | |||
Lactation Amenorrhea Method: LAM is a highly effective, temporary method of contraception.10 | |||
Source: Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowel D, Guest F. Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers; 1998. | |||
| Header$% of Women Experiencing an | % of Women Continuing | ||
| Unintended Pregnancy within the | Use at One Year Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. | ||
| First Year of Use | |||
| Method | Typical Use Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. | Perfect Use Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. | |
| (1) | (2) | (3) | (4) |
| Chance The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. | 85 | 85 | |
| Spermicides Foams, creams, gels, vaginal suppositories, and vaginal film. | 26 | 6 | 40 |
| Periodic abstinence | 25 | 63 | |
| Calendar | 9 | ||
| Ovulation Method | 3 | ||
| Sympto-Thermal Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. | 2 | ||
| Post-Ovulation | 1 | ||
| Cap With spermicidal cream or jelly. | |||
| Parous Women | 40 | 26 | 42 |
| Nulliparous Women | 20 | 9 | 56 |
| Sponge | |||
| Parous Women | 40 | 20 | 42 |
| Nulliparous Women | 20 | 9 | 56 |
| Diaphragm | 20 | 6 | 56 |
| Withdrawal | 19 | 4 | |
| Condom Without spermicides. | |||
| Female (Reality) | 21 | 5 | 56 |
| Male | 14 | 3 | 61 |
| Pill | 5 | 71 | |
| Progestin only | 0.5 | ||
| Combined | 0.1 | ||
| IUD | |||
| Progesterone T | 2.0 | 1.5 | 81 |
| Copper T380A | 0.8 | 0.6 | 78 |
| LNg 20 | 0.1 | 0.1 | 81 |
| Depo-Provera ® | 0.3 | 0.3 | 70 |
| Levonorgestrel Implants (Norplant ® ) | 0.05 | 0.05 | 88 |
| Female Sterilization | 0.5 | 0.5 | 100 |
In a clinical trial with levonorgestrel and ethinyl estradiol tablets, 1,477 subjects had 7,720 cycles of use and a total of 5 pregnancies were reported. This represents an overall pregnancy rate of 0.84 per 100 woman-years. This rate includes patients who did not take the drug correctly. One or more pills were missed during 1,479 (18.8%) of the 7,870 cycles; thus all tablets were taken during 6,391 (81.2%) of the 7,870 cycles. Of the total 7,870 cycles, a total of 150 cycles were excluded from the calculation of the Pearl index due to the use of backup contraception and/or missing 3 or more consecutive pills.
DOSAGE AND ADMINISTRATION
To achieve maximum contraceptive effectiveness, levonorgestrel and ethinyl estradiol tablets must be taken exactly as directed and at intervals not exceeding 24 hours.
The dosage of levonorgestrel and ethinyl estradiol tablets is one white tablet daily for 21 consecutive days, followed by one orange inert tablet daily for 7 consecutive days, according to the prescribed schedule.
It is recommended that levonorgestrel and ethinyl estradiol tablets be taken at the same time each day.
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 levonorgestrel and ethinyl estradiol tablets 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 levonorgestrel and ethinyl estradiol tablets on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (white) is taken that day. One white tablet should be taken daily for 21 consecutive days, followed by one orange inert tablet daily for seven consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of white tablets and may not have finished before the next pack is started. During the first cycle, contraceptive reliance should not be placed on levonorgestrel and ethinyl estradiol tablets until a white tablet has been taken daily for 7 consecutive days, and a nonhormonal back-up 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 levonorgestrel and ethinyl estradiol tablets during the first 24 hours of her period (day one of her menstrual cycle). One white tablet should be taken daily for 21 consecutive days, followed by one orange inert tablet daily for seven consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of white tablets may not have finished before the next pack is started. If medication is begun on day one of the menstrual cycle, no back-up contraception is necessary. If levonorgestrel and ethinyl estradiol tablets are started later than day one of the first menstrual cycle or postpartum, contraceptive reliance should not be placed on levonorgestrel and ethinyl estradiol tablets until after the first 7 consecutive days of administration, and a nonhormonal back-up 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 orange tablet. She should follow the same dosing schedule: 21 days on white tablets followed by 7 days on orange tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a nonhormonal back-up method of birth control until she has taken a white 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 levonorgestrel and ethinyl estradiol tablets. 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 levonorgestrel and ethinyl estradiol tablets 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 levonorgestrel and ethinyl estradiol tablets the next day. If switching from an implant or injection, the patient should start levonorgestrel and ethinyl estradiol tablets 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 back-up 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 white tablets are missed, the possibility of ovulation increases with each successive day that scheduled white tablets are missed. Although the occurrence of pregnancy is unlikely if levonorgestrel and ethinyl estradiol tablets are 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 (white) 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
Levonorgestrel and ethinyl estradiol tablets 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 non-hormonal back-up method for the first 7 days of tablet taking.
Levonorgestrel and ethinyl estradiol tablets may be initiated immediately after a first trimester abortion or miscarriage. If the patient starts levonorgestrel and ethinyl estradiol tablets immediately, back-up contraception is not needed.
CONTRAINDICATIONS
Levonorgestrel and ethinyl estradiol tablets are contraindicated in females who are known to have or develop 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
Current diagnosis of, or history of, breast cancer, which may be hormonesensitive
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 levonorgestrel and ethinyl estradiol tablets.
Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see WARNINGS , RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ).
ADVERSE REACTIONS
Post Marketing 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.
An increased risk of the following serious adverse reactions (see WARNINGS section for additional information) has been associated with the use of oral contraceptives:
Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs and breasts, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.
The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related (alphabetically listed):
Acne
Amenorrhea
Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms
Breast changes: tenderness, pain, enlargement, secretion
Budd-Chiari syndrome
Cervical erosion and secretion, change in
Cholestatic jaundice
Chorea, exacerbation of
Colitis
Contact lenses, intolerance to
Corneal curvature (steepening), change in
Dizziness
Edema/fluid retention
Erythema multiforme
Erythema nodosum
Gastrointestinal symptoms (such as abdominal pain, cramps, and bloating) Hirsutism
Infertility after discontinuation of treatment, temporary
Lactation, diminution in, when given immediately postpartum
Libido, change in
Melasma/chloasma which may persist Menstrual flow, change in
Mood changes, including depression
Nausea
Nervousness
Pancreatitis
Porphyria, exacerbation of
Rash (allergic)
Scalp hair, loss of
Serum folate levels, decrease in
Spotting
Systemic lupus erythematosus, exacerbation of
Unscheduled bleeding
Vaginitis, including candidiasis
Varicose veins, aggravation of
Vomiting Weight or appetite (increase or decrease), change in
The following adverse reactions have been reported in users of oral contraceptives:
Cataracts
Cystitis-like syndrome
Dysmenorrhea
Hemolytic uremic syndrome
Hemorrhagic eruption
Optic neuritis, which may lead to partial or complete loss of vision
Premenstrual syndrome
Renal function, impaired
DESCRIPTION
Each active, white tablet (21) contains 0.1 mg of levonorgestrel, d(-)-13β- ethyl-17α-ethinyl-17β-hydroxygon-4-en-3-one, a totally synthetic progestogen, and 0.02 mg of ethinyl estradiol, 17α-ethinyl-1,3,5(10)-estratriene-3, 17β-diol. The inactive ingredients present are croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose and povidone.
Each inert, orange tablet (7) contains the following inactive ingredients: croscarmellose sodium, FD&C Yellow #6, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.
CLINICAL PHARMACOLOGY
Mode of Action
Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).
HOW SUPPLIED
Levonorgestrel and ethinyl estradiol tablets USP, 0.1 mg/0.02 mg are available in 3 blisters, each containing 28 tablets as follows.
Each blister contains 21 white to off white round bevel edged tablets each containing 0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol, debossed with "LU" on one side and "T21" on the other side and 7 orange round bevel edged inert tablets debossed with "LU" on one side and "T22" on the other side.
They are supplied as follows:
Levonorgestrel and ethinyl estradiol tablets USP, 0.1 mg/0.02 mg are available in a blister (NDC 68180-854-71) of 28 tablets, such 3 blisters are packed in a carton (NDC 68180-854-73).
Store at 25° C (77° F); excursions permitted to 15°- 30° C (59°- 86° F) [see USP Controlled Room Temperature]
Distributed by:
Lupin Pharmaceuticals, Inc.
Naples, FL 34108
United States
Manufactured by:
Lupin Limited
Pithampur (M.P.) - 454 775
INDIA
Revised: December 2024
