1. Mode of Action

Norethindrone 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.

2. Pharmacokinetics

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.

1. Indications

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

2. Efficacy

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. Table 1 lists the pregnancy rates for users of all major methods of contraception.

Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception.

1. Ectopic Pregnancy

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. Healthcare professionals 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.

2. Delayed Follicular Atresia/Ovarian Cysts

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.

3. Irregular Genital Bleeding

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.

4. Carcinoma of the Breast and Reproductive Organs

Some epidemiological 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.

A meta-analysis of 54 studies found a small increase in the frequency of having breast cancer diagnosed for women who were currently using combined oral contraceptives or had used them within the past ten years.

This increase in the frequency of breast cancer diagnosis, within ten years of stopping use, was generally accounted for by cancers localized to the breast. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of use.

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.

5. Hepatic 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 intra-abdominal hemorrhage.

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

1. General

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

2. Physical Examination and Follow up

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 healthcare professional.

3. Carbohydrate and Lipid Metabolism

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 usually no effect on total cholesterol, HDL3, LDL, or VLDL.

4. Drug Interactions

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

Herbal products containing St. John’s Wort (Hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

Concurrent use of bosentan and norethindrone containing products may result in decreased concentrations of these contraceptive hormones thereby increasing the risk of unintended pregnancy and unscheduled bleeding.

5. Interactions with Laboratory Tests

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

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Sex hormone-binding globulin (SHBG) concentrations may be decreased.

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

6. Carcinogenesis

See WARNINGS.

7. Pregnancy

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.

8. Nursing Mothers

In general, no adverse effects have been found on breastfeeding performance or on the health, growth, or development of the infant. However, isolated post-marketing cases of decreased milk production have been reported. Small amounts of progestins pass into the breast milk of nursing mothers, resulting in detectable steroid levels in infant plasma.

9. Pediatric Use

Safety and efficacy of norethindrone tablets 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.

10. Fertility Following Discontinuation

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

11. Headache

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

INFORMATION FOR THE PATIENT

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See “Detailed Patient Labeling” for detailed information.

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Counseling issues

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

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The necessity of taking pills at the same time every day, including throughout all bleeding episodes.

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The need to use a backup method such as a condom and spermicide for the next 48 hours whenever a progestin-only oral contraceptive is taken 3 or more hours late.

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The potential side effects of progestin-only oral contraceptives, particularly menstrual irregularities.

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The need to inform the healthcare professional of prolonged episodes of bleeding, amenorrhea or severe abdominal pain.

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The importance of using a barrier method in addition to progestin-only oral contraceptives if a woman is at risk of contracting or transmitting STDs/HIV.

DESCRIPTION

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 healthcare professional.

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 POP 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” POP users (including women who are late taking pills or miss pills) gets pregnant in the first year of use. Table 2 will help you compare the efficacy of different methods.

Norethindrone tablets have not been studied for and are not indicated for use in emergency contraception.

HOW DO POPs WORK?

POPs can prevent pregnancy in different ways including:

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They make the cervical mucus at the entrance to the womb (the uterus) too thick for the sperm to get through to the egg

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They prevent ovulation (release of the egg from the ovary) in about half of the cycles

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They also affect other hormones, the fallopian tubes and the lining of the uterus

YOU SHOULD NOT TAKE POPs

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If there is any chance you may be pregnant.

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If you have breast cancer

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If you have bleeding between your periods that has not been diagnosed

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If you are taking certain drugs for epilepsy (seizures) or for TB, or medicine for pulmonary hypertension or certain herbal products. (See "Using POPs with Other Medicines" below)

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If you are hypersensitive, or allergic, to any component of this product.

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If you have liver tumors, either benign or cancerous

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If you have acute liver disease

RISKS OF TAKING POPs

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

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

USING POPs WITH OTHER MEDICINES

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

These medicines can make POPs less effective:

Medicines for seizures such as:

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Phenytoin (Dilantin®)

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Carbamazepine (Tegretol®)

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Phenobarbital

Medicine for TB:

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Rifampin (Rifampicin)

Medicine for pulmonary hypertension such as:

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Bosentan (Tracleer®)

Herbal products such as:

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St. John’s Wort

Before you begin taking any new medicines be sure your healthcare professional knows you are taking a progestin-only birth control pill.

HOW TO TAKE POPs

STARTING POPs

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It’s best to take your first POP on the first day of your menstrual period.

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If you decide to take your first POP on another day, use a backup method (such as a condom and/or a spermicide) every time you have sex during the next 48 hours.

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If you have had a miscarriage or an abortion, you can start POPs the next day.

IF YOU ARE LATE OR MISS TAKING YOUR POPs

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If you are more than 3 hours late or you miss one or more POPs:

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TAKE a missed pill as soon as you remember that you missed it,

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THEN go back to taking POPs at your regular time,

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BUT be sure to use a backup method (such as a condom and/or a spermicide) every time you have sex for the next 48 hours.

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If you are not sure what to do about the pills you have missed, keep taking POPs and use a backup method until you can talk to your healthcare professional.

IF YOU ARE BREASTFEEDING

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If you are fully breastfeeding (not giving your baby any food or formula), you may start your pills 6 weeks after delivery.

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If you are partially breastfeeding (giving your baby some food or formula), you should start taking pills by 3 weeks after delivery.

IF YOU ARE SWITCHING PILLS

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If you are switching from the combined pills to POPs, take the first POP the day after you finish the last active combined pill. Do not take any of the 7 inactive pills from the combined pill pack. You should know that many women have irregular periods after switching to POPs, but this is normal and to be expected.

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If you are switching from POPs to the combined pills, take the first active combined pill on the first day of your period, even if your POPs pack is not finished.

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If you switch to another brand of POPs, start the new brand anytime.

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If you are breastfeeding, you can switch to another method of birth control at any time, except do not switch to the combined pills until you stop breastfeeding or at least until 6 months after delivery.

PREGNANCY WHILE ON THE PILL

If you think you are pregnant, contact your healthcare professional. 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:

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If your period is late and you took one or more pills late or missed taking them and had sex without a backup method.

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Anytime it has been more than 45 days since the beginning of your last period.

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 breast milk or the health of your nursing baby. However, isolated cases of decreased milk production have been reported.

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.

OTHER QUESTIONS OR CONCERNS

If you have any questions or concerns, check with your healthcare professional. You can also ask for the more detailed “Professional Labeling” written for doctors and other healthcare professionals.

HOW TO STORE YOUR POPs

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

Keep out of reach of children.

Manufactured by:

Glenmark Pharmaceuticals Limited

Colvale-Bardez, Goa 403 513, India

Manufactured for:

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 0743

Relabeled by:

Proficient Rx LP

Thousand Oaks, CA 91320

Questions? 1 (888)721-7115

www.glenmarkpharma.com/usa

February 2015