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 contraceptive products which contain 50 mcg of estrogen, should not be used unless medically indicated.

Oral contraceptives are highly effective. Table I lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception.¹ 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 I: 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 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
Withdrawal	19	4
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
Condom⁸
Female (Reality)	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 T 380A	0.8	0.6	78
LNg 20	0.1	0.1	81
Depo-Provera	0.3	0.3	70
Norplant and Norplant-2	0.05	0.05	88
Female sterilization	0.5	0.5	100
Male sterilization	0.15	0.10	100
Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.⁹
Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.¹⁰
Source: Trussell J. Contraceptive Efficacy Table from Hatcher R.A., Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, in 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 Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral (1 dose is 2 white pills), Alesse (1 dose is 5 pink pills), Nordette or Levlen (1 dose is 2 light-orange pills), Lo/Ovral (1 dose is 4 white pills), Triphasil or Tri-Levlen (1 dose is 4 yellow pills). 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 six months of age.

Dosage and Administration

To achieve maximum contraceptive effectiveness, oral contraceptives must be taken exactly as directed and at intervals not exceeding 24 hours.

For a DAY 1 START, count the first day of menstrual flow as Day 1 and the first light yellow tablet is then taken on Day 1. For a SUNDAY START when menstrual flow begins on or before Sunday, the first light yellow tablet is taken on that day. With either a DAY 1 START or SUNDAY START, 1 light yellow tablet is taken for 7 days, then 1 white tablet for 9 days, then 1 light yellow tablet for 5 days, then 1 peach tablet (inert) for 7 days, whether bleeding has stopped or not. With either a DAY 1 START or SUNDAY START 1 tablet is taken each day at the same time for 28 days. After all 28 tablets are taken, whether bleeding has stopped or not, the same dosage schedule is repeated beginning on the following day.

INSTRUCTIONS TO PATIENTS

To achieve maximum contraceptive effectiveness, the oral contraceptive pill must be taken exactly as directed and at intervals not exceeding 24 hours.
Important: Women should be instructed to use an additional method of protection until after the first 7 days of administration in the initial cycle.
Due to the normally increased risk of thromboembolism occurring postpartum, women should be instructed not to initiate treatment with oral contraceptives earlier than 4 weeks after a full-term delivery. If pregnancy is terminated in the first 12 weeks, the patient should be instructed to start oral contraceptives immediately or within 7 days. If pregnancy is terminated after 12 weeks, the patient should be instructed to start oral contraceptives after 2 weeks.^{33, 77}
If spotting or breakthrough bleeding should occur, the patient should continue the medication according to the schedule. Should spotting or breakthrough bleeding persist, the patient should notify her physician.
If the patient misses 1 pill, she should be instructed to take it as soon as she remembers and then take the next pill at the regular time. The patient should be advised that missing a pill can cause spotting or light bleeding and that she may be a little sick to her stomach on the days she takes the missed pill with her regularly scheduled pill. If the patient has missed more than one pill, see DETAILED PATIENT LABELING, HOW TO TAKE THE PILL, WHAT TO DO IF YOU MISS PILLS .
Use of oral contraceptives in the event of a missed menstrual period:
If the patient has not adhered to the prescribed dosage regimen, the possibility of pregnancy should be considered after the first missed period and oral contraceptives should be withheld until pregnancy has been ruled out.
If the patient has adhered to the prescribed regimen and misses 2 consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen.

Contraindications

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

Thrombophlebitis or thromboembolic disorders
A past history of deep vein thrombophlebitis or thromboembolic disorders
Cerebral vascular or coronary artery disease
Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive
Undiagnosed abnormal genital bleeding
Cholestatic jaundice of pregnancy or jaundice with prior pill use
Hepatic adenomas, carcinomas or benign liver tumors
Known or suspected pregnancy
Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to 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 to 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 to 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 to 10 years of COC use.

Figure 1. Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives

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 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, carcinomas 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, secretion
Change in weight (increase or decrease)
Change in cervical erosion and secretion
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:

Pre-menstrual 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

figure 1

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.⁷⁶

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation

Do not coadminister Aranelle^® with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

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.

Description

Aranelle^® 28-Day Regimen (norethindrone and ethinyl estradiol tablets USP) provides a continuous oral contraceptive regimen of 7 light yellow tablets, 9 white tablets, 5 more light yellow tablets, and then 7 peach tablets. Each light yellow tablet contains norethindrone, USP 0.5 mg and ethinyl estradiol, USP 0.035 mg, each white tablet contains norethindrone, USP 1 mg and ethinyl estradiol, USP 0.035 mg, and each peach tablet contains inert ingredients.

Norethindrone, USP is a potent progestational agent with the chemical name 17-Hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one. Ethinyl estradiol, USP is an estrogen with the chemical name 19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. Their structural formulae follow.

Norethindrone, USP

Ethinyl Estradiol, USP

The light yellow tablet contains the following inactive ingredients, D&C yellow no. 10 aluminum lake, lactose monohydrate, magnesium stearate, and pregelatinized starch.

The white tablet contains the following inactive ingredients, lactose monohydrate, magnesium stearate, and pregelatinized starch.

The inactive peach tablets contain the following inactive ingredients, anhydrous lactose, FD&C yellow no. 6 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.

Norethindrone Chemical Structure Ethinyl Estradiol Chemical Structure

Clinical Pharmacology

Combination oral contraceptives act by suppression of gonadotrophins. 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 may reduce the likelihood of implantation).

How Supplied / Storage and Handling

Aranelle^® - 28-Day Regimen (norethindrone and ethinyl estradiol tablets USP 0.5/0.035 mg and 1/0.035 mg) – Each blister card contains 12 light yellow, round, flat-faced, beveled-edge, unscored tablets, debossed with stylized b on one side and 341 on the other side each containing 0.5 mg norethindrone and 0.035 mg ethinyl estradiol; 9 white, round, flat-faced, beveled-edge, unscored tablets, debossed with stylized b on one side and 342 on the other side each containing 1 mg norethindrone and 0.035 mg ethinyl estradiol; and 7 peach, round, flat-faced, beveled-edge, unscored placebo tablets, debossed with stylized b on one side and 343 on the other side. The first row contains 7 light yellow tablets; the second row contains 7 white tablets; the third row contains 2 white and 5 light yellow tablets and the fourth row contains 7 peach inert tablets.

Available in a box of 3 blister cards (NDC: 0555-9066-67).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Keep this and all medications out of the reach of children.

Patient Counseling Information

See PATIENT LABELING printed below.

Professional Information — Aranelle B 341