GILDESS 1.5/30- norethindrone acetate and ethinyl estradiol tablet, film coated
NORETHINDRONE ACETATE (1.5 mg) AND ETHINYL ESTRADIOL (0.03 mg) TABLETS, USP
(Each light green tablet contains 1.5 mg norethindrone acetate and 0.03 mg ethinyl estradiol.)
Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.
Norethindrone acetate and ethinyl estradiol tablets, USP are progestogen-estrogen combinations.
Norethindrone acetate and ethinyl estradiol tablets, USP provide a continuous dosage regimen consisting of 21 oral contraceptive tablets.
Each light green tablet contains norethindrone acetate (17 alpha-ethinyl-19-nortestosterone acetate), 1.5 mg; ethinyl estradiol (17 alpha-ethinyl-1,3,5(10)-estratriene-3, 17 beta-diol), 0.03 mg. Also contains colloidal silicon dioxide, compressible sugar, croscarmellose sodium, D&C Yellow #10 aluminum lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol 400, polyethylene glycol 8000, pregelatinized starch, sodium lauryl sulfate and Vitamin E.
The structural formulas are as follows:This is an image of the structural formula for norethindrone acetate.This is an image of the structural formula for ethinyl estradiol.
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).
The pharmacokinetics of norethindrone acetate and ethinyl estradiol tablets have not been characterized; however, the following pharmacokinetic information regarding norethindrone acetate and ethinyl estradiol is taken from the literature.
Norethindrone acetate appears to be completely and rapidly deacetylated to norethindrone after oral administration, since the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone (1). Norethindrone acetate and ethinyl estradiol are subject to first-pass metabolism after oral dosing, resulting in an absolute bioavailability of approximately 64% for norethindrone and 43% for ethinyl estradiol (1 to 3).
Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg (1 to 3). Plasma protein binding of both steroids is extensive (> 95%); norethindrone binds to both albumin and sex hormone binding globulin, whereas ethinyl estradiol binds only to albumin (4).
Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites (5). A small amount of norethindrone acetate is metabolically converted to ethinyl estradiol. Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy ethinyl estradiol, formed by the CYP3A4 isoform of cytochrome P450. Part of the first-pass metabolism of ethinyl estradiol is believed to occur in gastrointestinal mucosa. Ethinyl estradiol may undergo enterohepatic circulation (6).
Norethindrone and ethinyl estradiol are excreted in both urine and feces, primarily as metabolites (5,6). Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg) (1 to 3).
The effect of race on the disposition of norethindrone acetate and ethinyl estradiol tablets have not been evaluated.
The effect of renal disease on the disposition of norethindrone acetate and ethinyl estradiol tablets has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function.
The effect of hepatic disease on the disposition of norethindrone acetate and ethinyl estradiol tablets has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function.
Numerous drug-drug interactions have been reported for oral contraceptives. A summary of these is found under PRECAUTIONS, Drug Interactions.
Norethindrone acetate and ethinyl estradiol tablets, USP 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 I 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, depends 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 in the First Year of Continuous Use|
|Diaphragm with spermicidal cream or jelly||6||20|
|Spermicides alone (foam, creams, gels,vaginal suppositories, and vaginal film)||6||26|
|Injection: depot medroxyprogesterone acetate||0.3||0.3|
|copper T 380A||0.6||0.8|
|Condom without spermicides|
|Cervical Cap with spermicidal cream or jelly|
|Periodic abstinence (all methods)||1 to 9||25|
Adapted from RA Hatcher et al., Reference 7.
* The authors’ best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any other reason.
** This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any other reason.
*** N/A—Data not available.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.