LEVONORGESTREL AND ETHINYL ESTRADIOL tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

LEVONORGESTREL (UNII: 5W7SIA7YZW) (LEVONORGESTREL - UNII:5W7SIA7YZW), ETHINYL ESTRADIOL (UNII: 423D2T571U) (ETHINYL ESTRADIOL - UNII:423D2T571U)

Available from:

Glenmark Pharmaceuticals Inc., USA

INN (International Name):

LEVONORGESTREL

Composition:

LEVONORGESTREL 90 ug

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Levonorgestrel and ethinyl estradiol tablets 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 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. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year3 Method (1) Typical Use1  (2) Perfect Use2  (3) (4) Chance4 85 85 Spermicides5 26 6 40 Periodic abstinence 25 63    Calendar 9    Ovulation Method 3    Sympto-Thermal6 2    Post-Ovulation 1 Cap7    Parous Women 40 26 42    Nulliparous Women 20 9 56 Sponge    Parous Women 40 20 42    Nulliparous Women 20 9 56 Diaphragm7 20 6 56 Withdrawal 19 4 Condom8    Female (RealityTM ) 21 5 56    Male 14 3 61 Pill 5 71    Progestin only 0.5    Combined 0.1 IUD    Progesterone T 2 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 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. The efficacy and safety of levonorgestrel and ethinyl estradiol were studied in 2 one-year clinical trials of subjects age 18 to 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 levonorgestrel and ethinyl estradiol 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-year life table pregnancy rate was 1.59 (95% CI: 0.95 to 2.67). In a second supportive study conducted in Europe (315-EU), 641 subjects were randomized to levonorgestrel and ethinyl estradiol (n=323) or the cyclic comparator of 0.1 mg levonorgestrel and 0.02 mg 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 levonorgestrel and ethinyl estradiol pill packs and 2,886 cyclic comparator pill packs. There was one pregnancy in the levonorgestrel and ethinyl estradiol group that occurred within 14 days following the last dose. There were three pregnancies in the cyclic comparator group. 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 levonorgestrel and ethinyl estradiol, the convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled bleeding and spotting (see WARNINGS, 11 ). Levonorgestrel and ethinyl estradiol tablets are contraindicated in females who are known to have or develop the following conditions : Thrombophlebitis or thromboembolic disorders 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 such as aura Uncontrolled hypertension Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive 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. 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) .

Product summary:

Levonorgestrel and ethinyl estradiol tablets, USP (0.09 mg levonorgestrel, USP and 0.02 mg ethinyl estradiol, USP) are brownish peach to light brown, round, biconvex, film-coated tablets debossed with ‘E8’ on one side and are available as follows: Store at 20o C to 25o C (68°F to 77o F); excursions permitted to 15ºC to 30o C (59ºF to 86o F) [See USP controlled room temperature]. References available upon request. Manufactured by: Glenmark Pharmaceuticals Limited Colvale-Bardez, Goa 403513, India Manufactured for: Glenmark Pharmaceuticals Inc., USA Mahwah, NJ 07430 Questions? 1 [phone] www.glenmarkpharma-us.com May 2022

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

LEVONORGESTREL AND ETHINYL ESTRADIOL- LEVONORGESTREL AND ETHINYL
ESTRADIOL TABLET
GLENMARK PHARMACEUTICALS INC., USA
----------
LEVONORGESTREL AND ETHINYL ESTRADIOL TABLETS, USP
0.09 MG/0.02 MG
RX ONLY
PATIENTS SHOULD BE COUNSELED THAT ORAL CONTRACEPTIVES DO NOT PROTECT
AGAINST
TRANSMISSION OF HIV (AIDS) AND OTHER SEXUALLY TRANSMITTED DISEASES
(STDS)
SUCH AS CHLAMYDIA, GENITAL HERPES, GENITAL WARTS, GONORRHEA, HEPATITIS
B, AND
SYPHILIS.
DESCRIPTION
Twenty-eight (28) brownish peach to light brown tablets each
containing 0.09 mg of
levonorgestrel, USP (18, 19-Dinorpregn-4-en-20-yn-3-one,
13-ethyl-17-hydroxy-, (17α)-
(-) (-)-13-Ethyl –hydroxy-18, 19 dinor-17α-pregn-4-en-20-yn-3-one,
and 0.02 mg of
ethinyl estradiol, USP,
19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The inactive
ingredients present are lactose monohydrate, magnesium stearate,
microcrystalline
cellulose, povidone, polacrilin potassium, talc, hypromellose,
titanium dioxide,
polyethylene glycol, iron oxide red and iron oxide yellow.
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).
PHARMACOKINETICS
ABSORPTION
No specific investigation of the absolute bioavailability of
levonorgestrel and ethinyl
estradiol in humans has been conducted. However, literature indicates
that
levonorgestrel is rapidly and completely absorbed after oral
administration (bioavailability
about 100%) and is not subject to first-pass metabolism. Ethinyl
estradiol is rapidly and
almost completely absorbed from the gastrointestinal tract but, due to
first-pass
metabolism in gut mucosa and liver, the bioavailability of ethinyl
estradiol is between 38%
and 48%.
A summary of the single dose and multiple dose levonorgestrel and
ethinyl estradiol
pharmacokinetic param