DESCRIPTION

SPL UNCLASSIFIED SECTION

Revised AUGUST 20021007150102

Rx only

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

DESCRIPTION

Each light pink norethindrone tablet provides a continuous oral contraceptive regimen of 0.35 mg norethindrone daily, and has the following inactive ingredients: corn starch, FD&C red no. 40 aluminum lake, lactose monohydrate, magnesium stearate, povidone, and sodium starch glycolate.

The chemical name for norethindrone is 17-Hydroxy-19-Nor-17α-pregn-4-en-20-yn-3-one. The structural formula follows:

Norethindrone Therapeutic class=oral contraceptive

CLINICAL PHARMACOLOGY

Progestin-only oral contraceptives prevent conception by suppressing ovulation in approximately half of users, thickening the cervical mucus to inhibit sperm penetration, lowering the midcycle LH and FSH peaks, slowing the movement of the ovum through the fallopian tubes, and altering the endometrium.

Serum progestin levels peak about two hours after oral administration, followed by rapid distribution and elimination. By 24 hours after drug ingestion, serum levels are near baseline, making efficacy dependent upon rigid adherence to the dosing schedule. There are large variations in serum levels among individual users. Progestin-only administration results in lower steady-state serum progestin levels and a shorter elimination half-life than concomitant administration with estrogens.

INDICATIONS AND USAGE

Progestin-only oral contraceptives are indicated for the prevention of pregnancy.

If used perfectly, the first-year failure rate for progestin-only oral contraceptives is 0.5%. However, the typical failure rate is estimated to be closer to 5%, due to late or omitted pills. The following table lists the pregnancy rates for users of all major methods of contraception.

Percent of women experiencinga pregnancy within the first year of use
Method	Average Use	Perfect Use
No contraception	85	85
Spermicides	21	6
Periodic abstinence	20	1-9†
Withdrawal	19	4
Cervical capsGiven birthNever given birth	3618	269
Diaphragms	18	6
CondomsFemaleMale	2112	53
PillsProgestin-onlyCombined	3	0.50.1
IUDsProgesteroneCopper T 380A	20.8	1.50.6
Injectables	0.3	0.3
Implant	0.09	0.09

CONTRAINDICATIONS

Progestin-only oral contraceptives should not be used by women who currently have the following conditions:

Known or suspected pregnancy
Known or suspected carcinoma of the breast
Undiagnosed abnormal genital bleeding
Hypersensitivity to any component of this product
Benign or malignant liver tumors
Acute liver disease

WARNINGS

Cigarette smoking greatly increases the possibility of suffering heart attacks and strokes. Women who use oral contraceptives are strongly advised not to smoke.

Norethindrone Tablets do not contain estrogen and, therefore, this insert does not discuss the serious health risks that have been associated with the estrogen component of combined oral contraceptives. The healthcare provider is referred to the prescribing information of combined oral contraceptives for a discussion of those risks, including, but not limited to, an increased risk of serious cardiovascular disease in women who smoke, carcinoma of the breast and reproductive organs, hepatic neoplasia, and changes in carbohydrate and lipid metabolism. The relationship between progestin-only oral contraceptives and these risks have not been established and there are no studies definitely linking progestin-only pill (POP) use to an increased risk of heart attack or stroke.

The physician should remain alert to the earliest manifestation of symptoms of any serious disease and discontinue oral contraceptive therapy when appropriate.

The incidence of ectopic pregnancies for progestin-only oral contraceptive users is 5 per 1000 woman-years. Up to 10% of pregnancies reported in clinical studies of progestin-only oral contraceptive users are extrauterine. Although symptoms of ectopic pregnancy should be watched for, a history of ectopic pregnancy need not be considered a contraindication to use of this contraceptive method. Health providers should be alert to the possibility of an ectopic pregnancy in women who become pregnant or complain of lower abdominal pain while on progestin-only oral contraceptives.

If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally these enlarged follicles disappear spontaneously. Often they are asymptomatic; in some cases they are associated with mild abdominal pain. Rarely they may twist or rupture, requiring surgical intervention.

Irregular menstrual patterns are common among women using progestin-only oral contraceptives. If genital bleeding is suggestive of infection, malignancy or other abnormal conditions, such nonpharmacologic causes should be ruled out. If prolonged amenorrhea occurs, the possibility of pregnancy should be evaluated.

Some epidemiologic studies of oral contraceptive users have reported an increased relative risk of developing breast cancer, particularly at a younger age and apparently related to duration of use. These studies have predominantly involved combined oral contraceptives and there is insufficient data to determine whether the use of POPs similarly increases the risk. Women with breast cancer should not use oral contraceptives because the role of female hormones in breast cancer has not been fully determined.

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. There is insufficient data to determine whether the use of POPs increases the risk of developing cervical intraepithelial neoplasia.

Benign hepatic adenomas are associated with combined oral contraceptive use, although the incidence of benign tumors is rare in the United States. Rupture of benign, hepatic adenomas may cause death through intraabdominal hemorrhage

Studies from Britain and the U.S. have shown an increased risk of developing hepatocellular carcinoma in combined oral contraceptive users. However, these cancers are rare. There is insufficient data to determine whether POPs increase the risk of developing hepatic neoplasia.

PRECAUTIONS

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

It is considered good medical practice for sexually active women using oral contraceptives to have annual history and physical examinations. The physical examination may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician.

Some users may experience slight deterioration in glucose tolerance, with increases in plasma insulin but women with diabetes mellitus who use progestin-only oral contraceptives do not generally experience changes in their insulin requirements. Nonetheless, prediabetic and diabetic women in particular should be carefully monitored while taking POPs.

Lipid metabolism is occasionally affected in that HDL, HDL2, and apolipoprotein A-I and A-II may be decreased; hepatic lipase may be increased. There is no effect on total cholesterol, HDL3, LDL, or VLDL.

The effectiveness of progestin-only pills is reduced by hepatic enzyme-inducing drugs such as the anticonvulsants phenytoin, carbamazepine, and barbiturates, and the anti-tuberculosis drug rifampin. No significant interaction has been found with broad-spectrum antibiotics.

The following endocrine tests may be affected by progestin-only oral contraceptive use

See WARNINGS section.

Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted have not demonstrated significant adverse effects. It is nonetheless prudent to rule out suspected pregnancy before initiating any hormonal contraceptive use.

No adverse effects have been found on breastfeeding performance or on the health, growth or development of the infant. Small amounts of progestin pass into the breast milk, resulting in steroid levels in infant plasma of 1-6% of the levels of maternal plasma.

The limited available data indicate a rapid return of normal ovulation and fertility following discontinuation of progestin-only oral contraceptives.

The onset or exacerbation of migraine or the development of severe headache with focal neurological symptoms which is recurrent or persistent requires discontinuation of progestin-only contraceptives and evaluation of the cause.

Safety and efficacy of norethindrone have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

Sex hormone-binding globulin (SHBG) concentrations may be decreased.
Thyroxine concentrations may be decreased, due to a decrease in thyroid binding globulin (TBG).

INFORMATION FOR THE PATIENT

The following points should be discussed with prospective users before prescribing progestin-only oral contraceptives:

See PATIENT LABELING for detailed information.
Counseling Issues:

ADVERSE REACTIONS

Menstrual irregularity is the most frequently reported side effect.
Frequent and irregular bleeding are common, while long duration of bleeding episodes and amenorrhea are less likely.
Headache, breast tenderness, nausea, and dizziness are increased among progestin-only oral contraceptive users in some studies.
Androgenic side effects such as acne, hirsutism, and weight gain occur rarely.

OVERDOSAGE

There have been no reports of serious ill effects from overdosage, including ingestion by children.

DOSAGE AND ADMINISTRATION

To achieve maximum contraceptive effectiveness, Norethindrone Tablets must be taken exactly as directed. One tablet is taken every day, at the same time. Administration is continuous, with no interruption between pill packs. See PATIENT LABELING for detailed instructions.

HOW SUPPLIED

Camila™(norethindrone tablets, USP 0.35 mg) are packaged in cartons of six blister cards each containing 28 tablets. Each light pink, round, flat-faced, unscored tablet is debossed with stylizedb on one side and 715 on the other side. (NDC 54868-4814-0)

Store at controlled room temperature 15°-30°C (59°-86°F) [See USP].

REFERENCES

McCann M, and Potter L. Progestin-Only Oral Contraceptives: A Comprehensive Review. Contraception, 50:60 (Suppl. 1), December 1994.

DETAILED INFORMATION FOR THE PATIENT

This product (like all oral contraceptives) is used to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases.

INTRODUCTION

This leaflet is about birth control pills that contain one hormone, a progestin. Please read this leaflet before you begin to take your pills. It is meant to be used along with talking with your doctor or clinic.

Progestin-only pills are often called "POPs" or "the minipill." POPs have less progestin than the combined birth control pill (or "the pill") which contains both an estrogen and a progestin.

HOW EFFECTIVE ARE POPS?

About 1 in 200 POPs users will get pregnant in the first year if they all take POPs perfectly (that is, on time, every day). About 1 in 20 "typical" POPs users (including women who are late taking pills or miss pills) gets pregnant in the first year of use. The following table will help you compare the efficacy of different methods.

Adapted with permission.*

HOW DO POPS WORK?

YOU SHOULD NOT TAKE POPS

RISKS OF TAKING POPS

WARNING: If you have sudden or severe pain in your lower abdomen or stomach area, you may have an ectopic pregnancy or an ovarian cyst. If this happens, you should contact your doctor or clinic immediately.

SEXUALLY-TRANSMITTED DISEASES (STDS)

WARNING: POPs do not protect against getting or giving someone HIV (AIDS) or any other STD, such as chlamydia, gonorrhea, genital warts or herpes.

SIDE EFFECTS

If you are concerned about any of these side effects, check with your doctor or clinic.

USING POPS WITH OTHER MEDICINES

Before taking a POP, inform your healthcare provider of any other medication, including over-the-counter medicine, that you may be taking.

If you are taking medicines for seizures (epilepsy) or tuberculosis (TB), tell your doctor or clinic. These medicines can make POPs less effective:

Medicines for seizures:

Medicine for TB:

Before you begin taking any new medicines be sure your doctor or clinic knows you are taking birth control pills that contain a progestin.

HOW TO TAKE POPS

IMPORTANT POINTS TO REMEMBER

STARTING POPS

IF YOU ARE LATE OR MISS TAKING YOUR POPS

IF YOU ARE BREASTFEEDING

IF YOU ARE SWITCHING PILLS

PREGNANCY WHILE ON THE PILL

If you become pregnant, or think you might be, stop taking POPs and contact your physician. Even though research has shown that POPs do not cause harm to the unborn baby, it is always best not to take any drugs or medicines that you don't need when you are pregnant.

You should get a pregnancy test:

WILL POPS AFFECT YOUR ABILITY TO GET PREGNANT LATER?

If you want to become pregnant, simply stop taking POPs. POPs will not delay your ability to get pregnant.

BREASTFEEDING

If you are breastfeeding, POPs will not affect the quality or amount of your breastmilk or the health of your nursing baby.

OVERDOSE

No serious problems have been reported when many pills were taken by accident, even by a small child, so there is usually no reason to treat an overdose.

Percent of woman experiencinga pregnancy within the first year of use
Method	Average Use	Perfect Use
No contraception	85	85
Spermicides	21	6
Periodic abstinence	20	1-9†
Withdrawal	19	4
Cervical capsGiven birthNever given birth	3618	269
Diaphragms	18	6
CondomsFemaleMale	2112	53
PillsPOPSCombined	3	0.50.1
IUDsProgesteroneCopper T 380A	20.8	1.50.6
Injectables	0.3	0.3
Implant	0.09	0.09