Indications and Usage

Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception.

Oral contraceptives are highly effective. Table 1 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.

TABLE 1: LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD
% of Women Experiencing an Accidental Pregnancy in the First Year of Continuous Use
Method	Lowest
Expected*	Typical**
Reproduced with permission of the Population Council from J. Trussell, et al: Contraceptive failure in the United States: An update. Studies in Family Planning, 21(1), January-February 1990.
*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 reason other than pregnancy.
**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 reason other than pregnancy.
***Combined typical rate for both combined and progestin only.
#Combined typical rate for both medicated and nonmedicated IUD.
(No contraception)	(85)	(85)
Oral contraceptives
combined	0.1	3***
progestin only	0.5	3***
Diaphragm with spermicidal
cream or jelly	6	18
Spermicides alone (foam, creams,
jellies and vaginal suppositories)	3	21
Vaginal sponge
nulliparous	6	18
multiparous	9	28
IUD	0.8-2.0	3#
Condom without spermicides	2	12
Periodic abstinence (all methods)	1-9	20
Injectable progestogen	0.3-0.4	0.3-0.4
Implants
6 capsules	0.04	0.04
2 rods	0.03	0.03
Female sterilization	0.2	0.4
Male sterilization	0.1	0.15

Dosage and Administration

The following is a summary of the instructions given to the patient in the “HOW TO TAKE THE PILL” section of the DETAILED PATIENT LABELING.

The patient is given instructions in five (5) categories:

IMPORTANT POINTS TO REMEMBER: The patient is told (a) that she should take one pill every day at the same time, (b) many women have spotting or light bleeding or gastric distress during the first one to three cycles, (c) missing pills can also cause spotting or light bleeding, (d) she should use a back-up method for contraception if she has vomiting or diarrhea or takes some concomitant medications, and/or if she has trouble remembering the pill, (e) if she has any other questions, she should consult her physician.
BEFORE SHE STARTS TAKING HER PILLS: She should decide what time of day she wishes to take the pill, check whether her pill pack has 28 pills, and note the order in which she should take the pills (diagrammatic drawings of the pill pack are included in the patient insert).
WHEN SHE SHOULD START THE FIRST PACK: The Day-One start is listed as the first choice and the Sunday start (the Sunday after her period starts) is given as the second choice. If she uses the Sunday start she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills.
WHAT TO DO DURING THE CYCLE: The patient is advised to take one pill at the same time every day until the pack is empty. If she is on the 28-day regimen, she should start the next pack the day after the last inactive tablet and not wait any days between packs.
WHAT TO DO IF SHE MISSES A PILL OR PILLS: The patient is given instructions about what she should do if she misses one, two or more than two pills at varying times in her cycle for both the Day-One and the Sunday start. The patient is warned that she may become pregnant if she has unprotected intercourse in the seven days after missing pills. To avoid this, she must use another birth control method such as condom, foam, or sponge in these seven days.

Contraindications

Oral contraceptives should not be used in women who currently have the following conditions:

Thrombophlebitis or thromboembolic disorders
A past history of deep vein thrombophlebitis or thromboembolic disorders
Cerebrovascular or coronary artery disease
Known or suspected carcinoma of the breast
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
Known or suspected pregnancy

Adverse Reactions

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section):

Thrombophlebitis
Arterial thromboembolism
Pulmonary embolism
Myocardial infarction
Cerebral hemorrhage
Cerebral thrombosis
Hypertension
Gallbladder disease
Hepatic adenomas or benign liver tumors

There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed:

Mesenteric thrombosis
Retinal thrombosis

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related:

Nausea
Vomiting
Gastrointestinal symptoms (such as abdominal cramps and bloating)
Breakthrough bleeding
Spotting
Change in menstrual flow
Amenorrhea
Temporary infertility after discontinuation of treatment
Edema
Melasma which may persist
Breast changes: tenderness, enlargement, and secretion
Change in weight (increase or decrease)
Change in cervical ectropion and secretion
Possible diminution in lactation when given immediately postpartum
Cholestatic jaundice
Migraine
Rash (allergic)
Mental depression
Reduced tolerance to carbohydrates
Vaginal candidiasis
Change in corneal curvature (steepening)
Intolerance to contact lenses

The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted:

Premenstrual syndrome
Cataracts
Changes in appetite
Cystitis-like syndrome
Headache
Nervousness
Dizziness
Hirsutism
Loss of scalp hair
Erythema multiforme
Erythema nodosum
Hemorrhagic eruption
Vaginitis
Porphyria
Impaired renal function
Hemolytic uremic syndrome
Budd-Chiari syndrome
Acne
Changes in libido
Colitis

Drug Interactions

Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.

Overdosage

Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females.

NONCONTRACEPTIVE HEALTH BENEFITS

The following noncontraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.

Effects on menses:

Increased menstrual cycle regularity
Decreased blood loss and decreased incidence of iron deficiency anemia
Decreased incidence of dysmenorrheal

Effects related to inhibition of ovulation:

Decreased incidence of functional ovarian cysts
Decreased incidence of ectopic pregnancies

Effects from long-term use:

Decreased incidence of fibroadenomas and fibrocystic disease of the breast
Decreased incidence of acute pelvic inflammatory disease
Decreased incidence of endometrial cancer
Decreased incidence of ovarian cancer

Description

Zenchent® tablets provide a continuous regimen for oral contraception derived from 21 orange tablets composed of norethindrone and ethinyl estradiol to be followed by 7 white tablets of inert ingredients. The structural formulas are:

C₂₀H₂₆O₂Molecular Weight: 298.42 C₂₀H₂₄O₂ Molecular Weight: 296.40

The orange active tablets each contain 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, and contain the following inactive ingredients: dibasic calcium phosphate dihydrate, lactose monohydrate, sodium starch glycolate, magnesium stearate, povidone, FD&C yellow #6 aluminum lake 15-18%, D&C yellow #10 aluminum lake 15-20%

The white tablets in the 28-Day regimen contain only inert ingredients as follows: lactose anhydrous, magnesium stearate, and microcrystalline cellulose.

Norethindrone and ethinyl estradiol structural formulas

Clinical Pharmacology

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 / Storage and Handling

Zenchent® (norethindrone and ethinyl estradiol tablets USP, 28-Day) are packaged in cartons of 1 blister card. Each blister card contains 21 orange tablets impressed with WATSON on one side and 953 on the other side, and 7 white tablets impressed with WATSON on one side and P on the other side.

NDC 54868-6273-0

Store at 20º to 25ºC (68º to 77ºF). [See USP Controlled Room Temperature.]

Patient Counseling Information

See patient labeling printed below.

Professional Information — Zenchent 28 Day