Rx only

Norethindrone Tablets, USP

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

DESCRIPTION

Norethindrone Tablets, USP

Each tablet contains 0.35 mg norethindrone. Inactive ingredients include corn starch, D&C Yellow No. 10, ethyl cellulose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate and talc.

Meets USP Dissolution Test 2

CLINICAL PHARMACOLOGY

INDICATIONS AND USAGE

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.

Table 1: 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.

Adapted from Hatcher et al, 1998, Ref. #1.
Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.*
Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception.†
Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998.
* 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. ‡ Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. § 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. # 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. Þ Foams, creams, gels, vaginal suppositories, and vaginal film. ß Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. à With spermicidal cream or jelly. è Without spermicides.
	% of Women Experiencing an Unintended Pregnancy within the First Year of Use		% of Women Continuing Use at One Year‡
Method (1)	Typical Use§ (2)	Perfect Use¶ (3)	(4)
Chance#	85	85
SpermicidesÞ	26	6	40
Periodic abstinence	25		63
Calendar		9
Ovulation Method		3
Sympto-Thermalß		2
Post-Ovulation		1
Capà
Parous Women	40	26	42
Nulliparous Women	20	9	56
Sponge
Parous Women	40	20	42
Nulliparous Women	20	9	56
Diaphragmà	20	6	56
Withdrawal	19	4
Condomè
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 T380A	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	0.1	100

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

CONTRAINDICATIONS

Progestin-only oral contraceptives (POPs) 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 increases the risk of serious cardiovascular disease. Women who use oral contraceptives should be 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 (COCs). The healthcare professional is referred to the prescribing information of combined oral contraceptives for a discussion of those risks. The relationship between progestin-only oral contraceptives and these risks is not fully defined. The healthcare professional should remain alert to the earliest manifestation of symptoms of any serious disease and discontinue oral contraceptive therapy when appropriate.

PRECAUTIONS

ADVERSE REACTIONS

Adverse reactions reported with the use of POPs include:

• 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.

The following adverse reactions were also reported in clinical trials or during post-marketing experience: Gastrointestinal Disorders: vomiting, abdominal pain; General Disorders and Administration Site Conditions: fatigue, edema; Psychiatric Disorders: depression, nervousness; Musculoskeletal and Connective Tissue Disorders: pain in extremity; Reproductive System and Breast Disorders: genital discharge; breast pain, menstruation delayed, suppressed lactation, vaginal hemorrhage, menorrhagia, withdrawal bleed when product is stopped; Immune System Disorders: anaphylactic/anaphylactoid reaction, hypersensitivity; Hepatobiliary Disorders: hepatitis, jaundice cholestatic; Skin and Subcutaneous Tissue Disorders: alopecia, rash, rash pruritic.

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 Detailed Patient Labeling for detailed instruction.

HOW SUPPLIED

Norethindrone tablets USP, 0.35 mg are available in a blister pack containing 28 yellow, round, flat faced, beveled edge tablets, debossed 220 on one side and other side plain.

Package (NDC-50102-100-10) containing one blister pack of 28 tablets.

Carton (NDC-50102-100-03) containing 3 Packages

each containing one blister pack of 28 tablets.

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.

REFERENCE

1. McCann M, and Potter L. Progestin-Only Oral Contraceptives: A Comprehensive Review. Contraception, 50:60 (Suppl. 1), December 1994.
2. Van Giersbergen PLM, Halabi A, Dingemanse J. Pharmacokinetic interaction between bosentan and the oral contraceptives norethisterone and ethinyl estradiol. Int J Clin Pharmacol Ther 2006;44(3): 113-118.
3. Truitt ST, Fraser A, Gallo ME, Lopez LM, Grimes DA and Schulz KF. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation (Review). The Cochrane Collaboration. 2007, Issue 3.
4. Halderman, LD and Nelson AL. Impact of early postpartum administration of progestin-only hormonal contraceptives compared with nonhormonal contraceptives on short-term breast-feeding patterns. Am J Obstet Gynecol.; 186 (6): 1250-1258.
5. Ostrea EM, Mantaring III JB, Silvestre MA. Drugs that affect the fetus and newborn infant via the placenta or breast milk. Pediatr Clin N Am; 51(2004): 539-579.
6. Cooke ID, Back DJ, Shroff NE: Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diactetate administration. Contraception 1985; 31:611-21.
7. 2008 USPC Official:12/1/08-4/30/09, USP Monographs: Norethindrone Tablets (page 1 of 5).

DETAILED PATIENT LABELING

Norethindrone Tablets, USP

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

DESCRIPTION

Norethindrone Tablets, USP

Each tablet contains 0.35 mg norethindrone. Inactive ingredients include corn starch, D&C Yellow No. 10, ethyl cellulose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate and talc.

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.

Table 2: 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.

Adapted from Hatcher et al, 1998, Ref. #1.
Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.*
Lactational Amenorrhea Method: LAM is highly effective, temporary method of contraception.†
Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York NY: Irvington Publishers, 1998.
* 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. ‡ Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. § 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. # 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. Þ Foams, creams, gels, vaginal suppositories, and vaginal film. ß Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. à With spermicidal cream or jelly. è Without spermicides.
	% of Women Experiencing an Unintended Pregnancy within the First Year of Use		% of Women Continuing Use at One Year‡
Method (1)	Typical Use§ (2)	Perfect Use¶ (3)	(4)
Chance#	85	85
SpermicidesÞ	26	6	40
Periodic abstinence	25		63
Calendar		9
Ovulation Method		3
Sympto-Thermalß		2
Post-Ovulation		1
Capà
Parous Women	40	26	42
Nulliparous Women	20	9	56
Sponge
Parous Women	40	20	42
Nulliparous Women	20	9	56
Diaphragmà	20	6	56
Withdrawal	19	4
Condomè
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 T380A	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	0.1	100

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:

• They make the cervical mucus at the entrance to the womb (the uterus) too thick for the sperm to get through to the egg.
• They prevent ovulation (release of the egg from the ovary) in about half of the cycles.
• They also affect other hormones, the fallopian tubes and the lining of the uterus.

YOU SHOULD NOT TAKE POPs

• If there is any chance you may be pregnant.
• If you have breast cancer.
• If you have bleeding between your periods that has not been diagnosed.
• 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.)
• If you are hypersensitive, or allergic, to any component of this product.
• If you have liver tumors, either benign or cancerous.
• 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.

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 healthcare professional immediately.

Ectopic Pregnancy

An ectopic pregnancy is a pregnancy outside the womb. Because POPs protect against pregnancy, the chance of having a pregnancy outside the womb is very low. If you do get pregnant while taking POPs, you have a slightly higher chance that the pregnancy will be ectopic than do users of some other birth control methods.

Ovarian Cysts

These cysts are small sacs of fluid in the ovary. They are more common among POP users than among users of most other birth control methods. They usually disappear without treatment and rarely cause problems.

Cancer of the Reproductive Organs and Breasts

Some studies in women who use combined oral contraceptives that contain both estrogen and a progestin have reported an increase in the risk of developing breast cancer, particularly at a younger age and apparently related to duration of use. There is insufficient data to determine whether the use of POPs similarly increases this 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.

Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives and there is insufficient data to determine whether the use of POPs increases the risk of developing cancer of the cervix.

Liver Tumors

In rare cases, combined oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, some studies report an increased risk of developing liver cancer among women who use combined oral contraceptives. However, liver cancers are rare. There is insufficient data to determine whether POPs increase the risk of liver tumors.

Diabetic Women

Diabetic women taking POPs do not generally require changes in the amount of insulin they are taking. However, your healthcare professional may monitor you more closely under these conditions.

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

Irregular Bleeding:

The most common side effect of POPs is a change in menstrual bleeding. Your periods may be either early or late, and you may have some spotting between periods. Taking pills late or missing pills can result in some spotting or bleeding.

Other Side Effects:

Less common side effects include headaches, tender breasts, nausea, vomiting, dizziness, and fatigue. Depression, nervousness, leg pain, vaginal discharge, fluid retention, allergic reactions, jaundice or a yellowing of the skin or eyeballs, loss of scalp hair, rash/itchy rash, weight gain, acne and extra hair on your face and body have been reported, but are rare.

If you are concerned about any of these side effects, check with your healthcare professional.

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:

●  Phenytoin (Dilantin®)

●  Carbamazepine (Tegretol)

●  Phenobarbital

Medicine for TB:

●  Rifampin (Rifampicin)

Medicine for pulmonary hypertension such as:

●  Bosentan (Tracleer®)

Herbal products such as:

●  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

IMPORTANT POINTS TO REMEMBER

• POPs must be taken at the same time every day, so choose a time and then take the pill at that same time every day. Every time you take a pill late, and especially if you miss a pill, you are more likely to get pregnant.
• Start the next pack the day after the last pack is finished. There is no break between packs. Always have your next pack of pills ready.
• You may have some menstrual spotting between periods. Do not stop taking your pills if this happens.
• If you vomit soon after taking a pill, use a backup method (such as a condom and/or a spermicide) for 48 hours.
• If you want to stop taking POPs, you can do so at any time, but, if you remain sexually active and don't wish to become pregnant, be certain to use another birth control method.
• If you are not sure about how to take POPs, ask your healthcare professional.

STARTING POPs

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

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

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

2. THEN go back to taking POPs at your regular time,

3. 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.

•  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

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

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

• If your period is late and you took one or more pills late or missed taking them and had sex without a backup method.
• 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 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

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

Manufactured for:

Afaxys Pharma LLC

Charleston, SC 29403, USA.

Manufactured by:

Mylan Laboratories Limited

200012302-000                                                                                               

REVISED: JUNE 2017

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

This carton contains:

3 packages, each package contains one blister pack of 28 tablets

NDC 50102-100-03

Lyza®

Norethindrone Tablets,

USP 0.35 mg

Each yellow tablet contains 0.35 mg norethindrone.

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

Rx only