INDICATIONS AND USAGE
LYBREL is indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception.
Oral contraceptives are highly effective for pregnancy prevention. Table 2 lists the typical unintended pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and implants, depend upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates.
Table 2: Percentage of Women Experiencing an Unintended Pregnancy During The First Year of Typical Use and The First Year of Perfect Use of Contraception and The Percentage Continuing Use at The End of the First Year. United States.
|% of Women Experiencing an Unintended Pregnancy within the First Year of Use ||% of Women Continuing Use at One Year 3|
|Method (1) ||Typical Use 1 (2) ||Perfect Use 2 (3) ||(4) |
|Chance 4||85 ||85 |
|Spermicides 5||26 ||6 ||40 |
|Periodic abstinence ||25 ||63 |
| Calendar ||9 |
| Ovulation Method ||3 |
| Sympto-Thermal 6||2 |
| Post-Ovulation ||1 |
| Parous Women ||40 ||26 ||42 |
| Nulliparous Women ||20 ||9 ||56 |
| Parous Women ||40 ||20 ||42 |
| Nulliparous Women ||20 ||9 ||56 |
|Diaphragm 7||20 ||6 ||56 |
|Withdrawal ||19 ||4 |
| Female (RealityTM) ||21 ||5 ||56 |
| Male ||14 ||3 ||61 |
|Pill ||5 ||71 |
| Progestin only ||0.5 |
| Combined ||0.1 |
| 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 |
|0.05 ||0.05 ||88 |
|Female Sterilization ||0.5 ||0.5 ||100 |
|Male Sterilization ||0.15 ||0.10 ||100 |
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.
- 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.
- 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.
- Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.
- 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.
- Foams, creams, gels, vaginal suppositories, and vaginal film.
- Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases.
- With spermicidal cream or jelly.
- Without spermicides.
- The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The FDA has declared the following dosage regimens of oral contraceptives to be safe and effective for emergency contraception: for tablets containing 50 mcg of ethinyl estradiol and 500 mcg of norgestrel 1 dose is 2 tablets; for tablets containing 20 mcg of ethinyl estradiol and 100 mcg of levonorgestrel 1 dose is 5 tablets; for tablets containing 30 mcg of ethinyl estradiol and 150 mcg of levonorgestrel 1 dose is 4 tablets.
- However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age.
The efficacy and safety of LYBREL were studied in 2 one-year clinical trials of subjects age 18-49. There were no exclusions for body mass index (BMI), weight, or bleeding history.
The primary efficacy and safety study (313-NA) was a one-year open-label clinical trial that treated 2,134 subjects in North America. Of these subjects 1,213 (56.8%) discontinued prematurely, including 102 (4.8%) discontinued by the Sponsor for early study closure. The mean weight of subjects in this study was 70.38 kg. The efficacy of LYBREL was assessed by the number of pregnancies that occurred after the onset of treatment and within 14 days of the last dose. Among subjects 35 years or less, there were 23 pregnancies (4 of these occurred during the interval 1 to 14 days after the last day of pill use) during 12,572 28-day pill packs of use. The resulting total Pearl Index was 2.38 (95% CI: 1.51, 3.57) and the one-year life table pregnancy rate was 2.39 (95% CI: 1.57, 3.62). Pill pack cycles during which subjects used back-up contraception or were not sexually active were not included in these calculations. Among women 35 years or less who took the pills completely as directed, there were 15 pregnancies (method failures) resulting in a Pearl Index of 1.55 (95% CI: 0.87, 2.56) and the one-yearlife table pregnancy rate was 1.59 (95% CI: 0.95-2.67).
In a second supportive study conducted in Europe (315-EU), 641 subjects were randomized to LYBREL (n=323) or the cyclic comparator of 100 mcg levonorgestrel and 20 mcg ethinyl estradiol (n=318). The mean weight of subjects in this study was 63.86 kg. The efficacy analysis among women 35 years or less included 2,756 LYBREL pill packs and 2,886 cyclic comparator pill packs. There was one pregnancy in the LYBREL group that occurred within 14 days following the last dose. There were three pregnancies in the cyclic comparator group.
Inhibition of Menses (Bleeding Profile)
The bleeding profile for subjects in Study 313-NA also was assessed. Women with a history of unscheduled bleeding and/or spotting were not excluded from the study.
In those subjects who provided complete bleeding data, the percentage of patients who were amenorrheic in a given cycle and remained amenorrheic through cycle 13 (cumulative amenorrhea rate) was determined (Figure 2).
Figure 2: Percentage of Subjects with Cumulative Amenorrhea for Each Pill Pack through Pill Pack 13
When prescribing LYBREL, the convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled bleeding and spotting (see WARNINGS, 11).
DOSAGE AND ADMINISTRATION
To achieve maximum contraceptive effectiveness, LYBREL (levonorgestrel and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. The possibility of ovulation and conception prior to initiation of medication should be considered. Women who do not wish to become pregnant after discontinuation should be advised to immediately use another method of birth control. The dosage of LYBREL is one yellow tablet daily without any tablet-free interval.
It is recommended that LYBREL tablets be taken at the same time each day.
Initiation of Therapy
Instructions for beginning LYBREL are provided in Table 4 below.
| Current contraceptive therapy || LYBREL start day || Nonhormonal back-up method of birth control needed when correctly starting LYBREL? |
|None ||Day 1 of patient's menstrual cycle (during the first 24 hours of her period) ||No |
|21-day COC regimen|
28-day COC regimen
|Day 1 of patient's withdrawal bleed, at the latest 7 days after her last active tablet ||No |
|Progestin-only pill ||Day after taking a progestin-only pill ||Yes, for the first 7 days of LYBREL tablet taking |
|Implant ||Day of implant removal ||Yes, for the first 7 days of LYBREL tablet taking |
|Injection ||Day the next injection is due ||Yes, for the first 7 days of LYBREL tablet taking |
If spotting or unscheduled bleeding occurs, 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 health care professional. The possibility of ovulation increases with each successive day that scheduled yellow tablets are missed. 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. Hormonal contraception must be discontinued if pregnancy is confirmed.
The risk of pregnancy increases with each 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.
LYBREL 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 back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, pregnancy should be excluded before the start of combined oral contraceptive use or the patient must wait for her first menstrual period.
In the case of first-trimester abortion, if the patient starts LYBREL immediately, additional contraceptive measures are not needed.
LYBREL® (90 mcg levonorgestrel and 20 mcg ethinyl estradiol) Tablets are available in a ClickCase®, NDC 0008-1117-30 containing:
28 round, yellow biconvex, film-coated tablet debossed with “W” on one side and “1117” on the other side.
Store at up to 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
United States Patent Numbers: 6,500,814; D497,803S
References available upon request.