Norgestimate And Ethinyl Estradiol Tablets, Usp

Norgestimate and Ethinyl Estradiol Tablets, USP

(nor-JES-ti-mate, ETH-i-nil es-tra-DYE-ol)

What is the most important information I should know about Norgestimate and Ethinyl Estradiol Tablets, USP?

Do not use Norgestimate and Ethinyl Estradiol Tablets, USP if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

What is Norgestimate and Ethinyl Estradiol Tablets, USP?

Norgestimate and Ethinyl Estradiol Tablets, USP is a birth control pill (oral contraceptive) used by women to prevent pregnancy.

How does Norgestimate and Ethinyl Estradiol Tablets, USP work for contraception?

Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.

Based on the results from the clinical study, about 3 out of 100 women may get pregnant during the first year they use Norgestimate and Ethinyl Estradiol Tablets, USP.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

Who should not take Norgestimate and Ethinyl Estradiol Tablets, USP?

Do not take Norgestimate and Ethinyl Estradiol Tablets, USP if you:

• smoke and are over 35 years of age
• had blood clots in your arms, legs, lungs, or eyes
• had a problem with your blood that makes it clot more than normal
• have certain heart valve problems or irregular heart beat that increases your risk of having blood clots
• had a stroke
• had a heart attack
• have high blood pressure that cannot be controlled by medicine
• have diabetes with kidney, eye, nerve, or blood vessel damage
• have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age
• have liver problems, including liver tumors
• take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood.
• have any unexplained vaginal bleeding
• are pregnant
• had breast cancer or any cancer that is sensitive to female hormones

If any of these conditions happen while you are taking Norgestimate and Ethinyl Estradiol Tablets, USP, stop taking Norgestimate and Ethinyl Estradiol Tablets, USP right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Norgestimate and Ethinyl Estradiol Tablets, USP.

What should I tell my healthcare provider before taking Norgestimate and Ethinyl Estradiol Tablets, USP?

Tell your healthcare provider if you:

• are pregnant or think you may be pregnant
• are depressed now or have been depressed in the past
• had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy)
• are breastfeeding or plan to breastfeed. Norgestimate and Ethinyl Estradiol Tablets, USP may decrease the amount of breast milk you make. A small amount of the hormones in Norgestimate and Ethinyl Estradiol Tablets, USP may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Norgestimate and Ethinyl Estradiol Tablets, USP may affect the way other medicines work, and other medicines may affect how well Norgestimate and Ethinyl Estradiol Tablets, USPworks.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Norgestimate and Ethinyl Estradiol Tablets, USP?

Read the Instructions for Use at the end of this Patient Information.

What are the possible serious side effects of Norgestimate and Ethinyl Estradiol Tablets, USP?

• Like pregnancy, Norgestimate and Ethinyl Estradiol Tablets, USP may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes.

Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:

• first start taking birth control pills
• restart the same or different birth control pills after not using them for a month or more

Call your healthcare provider or go to a hospital emergency room right away if you have:

Other serious side effects include:

• liver problems, including:
  • rare liver tumors
  • jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes.
• high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure.
• gallbladder problems
• changes in the sugar and fat (cholesterol and triglycerides) levels in your blood
• new or worsening headaches including migraine headaches
• irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking Norgestimate and Ethinyl Estradiol Tablets, USP .
• depression
• possible cancer in your breast and cervix
• swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema if higher is you have a history of angioedema.
• dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking Norgestimate and Ethinyl Estradiol Tablets, USP. Use sunscreen if you have to be in the sunlight.

What are the most common side effects of Norgestimate and Ethinyl Estradiol Tablets, USP?

These are not all the possible side effects of Norgestimate and Ethinyl Estradiol Tablets, USP. For more information, ask your healthcare provider or pharmacist.

You may report side effects to the FDA at 1-800-FDA-1088.

What else should I know about taking Norgestimate and Ethinyl Estradiol Tablets, USP?

• If you are scheduled for any lab tests, tell your healthcare provider you are taking Norgestimate and Ethinyl Estradiol Tablets, USP. Certain blood tests may be affected by Norgestimate and Ethinyl Estradiol Tablets, USP.
• Norgestimate and Ethinyl Estradiol Tablets, USP does not protect against HIV infection (AIDS) and other sexually transmitted infections.

How should I store Norgestimate and Ethinyl Estradiol Tablets, USP?

• Store Norgestimate and Ethinyl Estradiol Tablets, USP at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Norgestimate and Ethinyl Estradiol Tablets, USP and all medicines out of the reach of children.
• Store away from light.

General information about the safe and effective use of Norgestimate and Ethinyl Estradiol Tablets, USP.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Norgestimate and Ethinyl Estradiol Tablets, USP for a condition for which it was not prescribed. Do not give Norgestimate and Ethinyl Estradiol Tablets, USP to other people, even if they have the same symptoms that you have.

This Patient Information summarizes the most important information about Norgestimate and Ethinyl Estradiol Tablets, USP. You can ask your pharmacist or healthcare provider for information about Norgestimate and Ethinyl Estradiol Tablets, USP that is written for health professionals.

For more information, call AVKARE at 1-855-361-3993.

Does hormonal birth control pills cause cancer?

It is not known if hormonal birth control pills causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.

If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are

sensitive to hormones.

Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

What if I want to become pregnant?

You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.

What should I know about my period when taking Norgestimate and Ethinyl Estradiol Tablets, USP?

Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking Norgestimate and Ethinyl Estradiol Tablets, USP, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.

What are the ingredients in Norgestimate and Ethinyl Estradiol Tablets, USP?

Active ingredients: Each white, light blue, and blue pill contains norgestimate and ethinyl estradiol.

Inactive ingredients:

White tablet: crospovidone, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Light blue tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Blue tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.6 sunset yellow fcf aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Green tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, lecithin (soya), magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Starting Norgestimate and Ethinyl Estradiol Tablets, USP after Abortion or Miscarriage

Contraindications (4) 11/2021



Warnings and Precautions ( 5.11) 11/2021

If a woman taking norgestimate and ethinyl estradiol develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norgestimate and ethinyl estradiol if indicated.

Consider discontinuation of norgestimate and ethinyl estradiol in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking norgestimate and ethinyl estradiol.

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.

Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.

Norgestimate and Ethinyl Estradiol Tablets, USP is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-, oxime,(17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol).

• Each active white tablet contains 0.18 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each active light blue tablet contains 0.215 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each active blue tablet contains 0.25 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.6 sunset yellow fcf aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each green placebo tablet contains only inert ingredients, as follows: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, lecithin (soya), magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Carefully observe women with a history of depression and discontinue norgestimate and ethinyl estradiol if depression recurs to a serious degree.

A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.

Norgestimate and Ethinyl Estradiol Tablets, USP are available in a blister card:

Each blister card (28 tablets) contains in the following order:

• 7 white, round, coated tablets imprinted "SZ" on one side and "T5" on the other side contains 0.18 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 light blue, round, coated tablets imprinted "SZ" on one side and "T6" on the other side contains 0.215 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 blue, round, coated tablets imprinted "SZ" on one side and "T7" on the other side contains 0.25 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 green, round, coated tablets imprinted "SZ" on one side and "J1" on the other side contains inert ingredients.

NDC 42291-565-28, one box containing 1 individual unit carton.

NDC 42291-565-84, one box containing 3 individual unit cartons.

Safety and efficacy of norgestimate and ethinyl estradiol have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Norgestimate and ethinyl estradiol has not been studied in postmenopausal women and is not indicated in this population.

Table 2: Instructions for Missed Norgestimate and Ethinyl Estradiol Tablets, USP Tablets

In an active controlled clinical trial lasting 12 months, 1,673 women, 18 to 45 years old completed 11,003 cycles of norgestimate and ethinyl estradiol use and a total of 20 pregnancies were reported in norgestimate and ethinyl estradiol users. The racial demographic of those treated with norgestimate and ethinyl estradiol was: Caucasian (86%), African-American (6%), Asian (2%), and Other (6%). There were no exclusions on the basis of weight; the weight range for women treated was 90 to 240 lbs, with a mean weight of about 142 lbs. The pregnancy rate in women aged 18 to 35 years was approximately 2.6 pregnancies per 100 woman-years of use.

Estarylla™ is contraindicated in females who are known to have or develop the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
• Smoke, if over age 35 [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1) ]
• Have deep vein thrombosis or pulmonary embolism, now or in the past [see WARNINGS AND PRECAUTIONS (5.1)]
• Have inherited or acquired hypercoagulopathies [see WARNINGS AND PRECAUTIONS (5.1)]
• Have cerebrovascular disease [see WARNINGS AND PRECAUTIONS (5.1)]
• Have coronary artery disease [see WARNINGS AND PRECAUTIONS (5.1)]
• Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS AND PRECAUTIONS (5.1)]
• Have uncontrolled hypertension [see WARNINGS AND PRECAUTIONS (5.4) ]
• Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS (5.6) ]
• Have headaches with focal neurological symptoms or migraine headaches with aura [see WARNINGS AND PRECAUTIONS (5.7) ]
  • Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS (5.7) ]
• Liver tumors, benign or malignant, or liver disease [see WARNINGS AND PRECAUTIONS (5.2)]
• Undiagnosed abnormal uterine bleeding [see WARNINGS AND PRECAUTIONS (5.8) ]
• Pregnancy, because there is no reason to use COCs during pregnancy [see WARNINGS AND PRECAUTIONS (5.9) and USE IN SPECIFIC POPULATIONS (8.1)]
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see WARNINGS AND PRECAUTIONS (5.11) ]
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS AND PRECAUTIONS (5.3)]

The following serious adverse reactions with the use of COCs are discussed elsewhere in labeling:

• Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]
• Vascular events [see WARNINGS AND PRECAUTIONS (5.1)]
• Liver disease [see WARNINGS AND PRECAUTIONS (5.2)]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

No drug-drug interaction studies were conducted with norgestimate and ethinyl estradiol.

Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

The pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in women with renal impairment.

Norgestimate and Ethinyl Estradiol Tablets, USP

(nor-JES-ti-mate, ETH-i-nil es-tra-DYE-ol)

Important Information about taking Norgestimate and Ethinyl Estradiol Tablets, USP

• Take 1 pill every day at the same time. Take the pills in the order directed on your pill dispenser.
• Do not skip your pills, even if you do not have sex often. If you miss pills (including starting the pack late) you could get pregnant. The more pills you miss, the more likely you are to get pregnant.
• If you have trouble remembering to take Norgestimate and Ethinyl Estradiol Tablets, USP talk to your healthcare provider. When you first start taking Norgestimate and Ethinyl Estradiol Tablets, USP, spotting or light bleeding in between your periods may occur. Contact your healthcare provider if this does not go away after a few months.
• You may feel sick to your stomach (nauseous), especially during the first few months of taking Norgestimate and Ethinyl Estradiol Tablets, USP. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If your nausea does not go away, call your healthcare provider.
• Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. On the days you take 2 pills to make up for missed pills (see What should I do if I miss any Norgestimate and Ethinyl Estradiol Tablets, USP pills? below), you could also feel a little sick to your stomach.
• It is not uncommon to miss a period. However, if you miss a period and have not takenNorgestimate and Ethinyl Estradiol Tablets, USP according to directions, or miss 2 periods in a row, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking Norgestimate and Ethinyl Estradiol Tablets, USP.
• If you have vomiting or diarrhea within 3 to 4 hours of taking your pill, take another pill of the same color from your extra pill dispenser. If you do not have an extra pill dispenser, take the next pill in your pill dispenser. Continue taking all your remaining pills in order. Start the first pill of your next pill dispenser the day after finishing your current pill dispenser. This will be 1 day earlier than originally scheduled. Continue on your new schedule.
• If you have vomiting or diarrhea for more than 1 day, your birth control pills may not work as well. Use an additional birth control method, like condoms and a spermicide, until you check with your healthcare provider.
• Stop taking Norgestimate and Ethinyl Estradiol Tablets, USP at least 4 weeks before you have major surgery and do not restart after the surgery without asking your healthcare provider. Be sure to use other forms of contraception (like condoms and spermicide) during this time period.

Before you start taking Norgestimate and Ethinyl Estradiol Tablets, USP:

• Decide what time of day you want to take your pill. It is important to take it at the same time every day and in the order as directed on your pill dispenser.
• Have backup contraception (condoms and spermicide) available and if possible, an extra full pack of pills as needed.

When should I start taking Norgestimate and Ethinyl Estradiol Tablets, USP?

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you have not used a hormonal birth control method before:

• There are 2 ways to start taking your birth control pills. You can either start on a Sunday (Sunday Start) or on the first day (Day 1) of your natural menstrual period (Day 1 Start). Your healthcare provider should tell you when to start taking your birth control pill.
• If you use the Sunday Start, use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days that you take Norgestimate and Ethinyl Estradiol Tablets, USP. You do not need back-up contraception if you use the Day 1 Start.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from another birth control pill:

• Start your new Norgestimate and Ethinyl Estradiol Tablets, USP pack on the same day that you would start the next pack of your previous birth control method.
• Do not continue taking the pills from your previous birth control pack.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and previously used a vaginal ring or transdermal patch:

• Start using Norgestimate and Ethinyl Estradiol Tablets, USP on the day you would have reapplied the next ring or patch.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from a progestin-only method such as an implant or injection:

• Start taking v on the day of removal of your implant or on the day when you would have had your next injection.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from an intrauterine device or system (IUD or IUS):

• Start taking Norgestimate and Ethinyl Estradiol Tablets, USP on the day of removal of your IUD or IUS.
• You do not need back-up contraception if your IUD or IUS is removed on the first day (Day 1) of your period. If your IUD or IUS is removed on any other day, use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days that you take Norgestimate and Ethinyl Estradiol Tablets, USP.

Keep a calendar to track your period:

If this is the first time you are taking birth control pills, read, "When should I start taking Norgestimate and Ethinyl Estradiol Tablets, USP?" above. Follow these instructions for either a Sunday Start or a Day 1 Start.

Sunday Start:

You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.

• Take pill 1 on the Sunday after your period starts.
• If your period starts on a Sunday, take pill "1" that day and refer to Day 1 Start instructions below.
• Take 1 pill every day in the order on the pill dispenser at the same time each day for 28 days.
• After taking the last pill on Day 28 from the pill dispenser, start taking the first pill from a new pack, on the same day of the week as the first pack (Sunday). Take the first pill in the new pack whether or not you are having your period.
• Use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days of the first cycle that you take Norgestimate and Ethinyl Estradiol Tablets, USP.

Day 1 Start:

You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.

• Take 1 pill every day in the order of the blister pack, at the same time each day, for 28 days.
• After taking the last pill on Day 28 from the pill blister pack, start taking the first pill from a new pack, on the same day of the week as the first pack. Take the first pill in the new pack whether or not you are having your period.

Norgestimate and Ethinyl Estradiol Tablets, USP comes in blister pack. Read the instructions below for using your blister pack.

Each new blister pack has 28 pills

• 7 white pills with hormone, for Days 1 to 7
• 7 light blue pills with hormone, for Days 8 to 14
• 7 blue pills with hormones, for Days 15 to 21
• 7 green pills (without hormones), for Days 22 to 28.

BEFORE YOU START TAKING YOUR PILLS

• DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.
  
  
  
  It is important to take it at about the same time every day.
• The 28-pill pack has 21 white, light blue, and blue "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of green "reminder" pills (without hormones).
• 3. ALSO FIND:
• 1) where on the pack to start taking pills,
• 2) in what order to take the pills (follow the arrows),
• 3) The week numbers as shown in the diagram below.

4) BE SURE YOU HAVE READY AT ALL TIMES:



ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicide) to use as a back-up method in case you miss pills.



AN EXTRA, FULL PILL PACK.

What should I do if I miss any Norgestimate and Ethinyl Estradiol Tablets, USP pills?

If you miss 1 pill in Weeks 1, 2, or 3, follow these steps:

• Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.
• Then continue taking 1 pill every day until you finish the pack.
• You do not need to use a back-up birth control method if you have sex.

If you miss 2 pills in Week 1 or Week 2 of your pack, follow these steps:

• Take the 2 missed pills as soon as possible and the next 2 pills the next day.
• Then continue to take 1 pill every day until you finish the pack.
• Use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after missing your pills.

If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:

• If you are a Day 1 Starter:
  • Throw out the rest of the pill pack and start a new pack that same day.
  • You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
  • You could become pregnant if you have sex during the first 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.
• If you are a Sunday Starter:
  • Keep taking 1 pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of pills that same day.
  • Use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

The brands listed are the registered trademark of their respective owners and are not trademarks of Xiromed, LLC.

Manufactured by Laboratorios Leon Farma S.A., Spain

for Xiromed, LLC. Florham Park, NJ 07932

Product of Spain

Rev. January 2018

PI-120-00

No specific pharmacodynamic studies were conducted with norgestimate and ethinyl estradiol.

Norgestimate and Ethinyl Estradiol Tablets, USP are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14)].

The pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.2). ]

Norgestimate and Ethinyl Estradiol Tablets, USP is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. ( 1.1)

• Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
• Protect from light.
• Keep out of the reach of children.

Norgestimate and ethinyl estradiol is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see CONTRAINDICATIONS (4)] . For women with well-controlled hypertension, monitor blood pressure and stop norgestimate and ethinyl estradiol if blood pressure rises significantly.

An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin.

Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis.

COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

Breast Cancer

Estarylla™ is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally

sensitive [see Contraindications (4)].

Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast

cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However,

some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see Postmarketing Experience (6.2)].

Cervical Cancer

A causal relationship between the use of CHCs and the development of cervical cancer and intraepithelial neoplasia has

not been clearly established. In observational studies it suggests that COCs are associated with an increase in the risk of cervical

cancer or intraepithelial neoplasia. There is controversy about the extent to which these findings are due to differences in sexual

behavior and other factors.

• Thromboembolic Disorders and Other Vascular Problems: Stop norgestimate and ethinyl estradiol if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. ( 5.1)
• Liver disease: Discontinue norgestimate and ethinyl estradiol if jaundice occurs. ( 5.2)
• High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop norgestimate and ethinyl estradiol if blood pressure rises significantly. ( 5.4)
• Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norgestimate and ethinyl estradiol. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.6)
• Headache: Evaluate significant change in headaches and discontinue norgestimate and ethinyl estradiol if indicated. ( 5.7)
• Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea. ( 5.8)

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

• Take one tablet daily by mouth at the same time every day. ( 2.2)
• Take tablets in the order directed on the blister pack. ( 2.2)
• Do not skip or delay tablet intake. ( 2.2)

Norgestimate and Ethinyl Estradiol Tablets, USP tablets are available in a blister card. Each blister card contains 28 tablets in the following order:

• 7 white, round, coated tablets imprinted "SZ" on one side and "T5" on the other side contains 0.18 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 light blue, round, coated tablets imprinted "SZ" on one side and "T6" on the other side contains 0.215 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 blue, round, coated tablets imprinted "SZ" on one side and "T7" on the other side contains 0.25 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 green, round, coated tablets imprinted "SZ" on one side and "J1" on the other side contains inert ingredients.

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 - 1.12 (Figure 2).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of

COCs (Figure 2). 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 - 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 8-10 years of COC use.

For your reference, below are the studies reviewed by FDA to inform the breast cancer risk:

References:

1. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med.

2002;346(26):2025-2032.

2. Dumeaux V, Fournier A, Lund E, Clavel-Chapelon F. Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women. Cancer Causes Control. 2005;16(5):537-544.

3. Dorjgochoo T, Shu XO, Li HL, et al. Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a

large prospective study, from 1996 to 2006. Int J Cancer. 2009;124(10):2442- 2449.

4. Hunter DJ, Colditz GA, Hankinson SE, et al. Oral contraceptive use and breast cancer: a prospective study of young women.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2010;19(10):2496-2502.

5. Vessey M, Yeates D. Oral contraceptive use and cancer. Final report from the Oxford-Family Planning Association contraceptive

study. Contraception. 2013; 88(6): 678-683.

6. Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med. 2017;377(23):2228-2239

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of norgestimate and ethinyl estradiol was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of norgestimate and ethinyl estradiol for contraception. This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus. Subjects were followed for up to 13 28-day cycles.

Nursing mothers: Not recommended; can decrease milk production. ( 8.3)

The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

See FDA-approved patient labeling (Patient Information and Instruction for Use).

Counsel patients about the following information:

• Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see Boxed Warning].
• Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see WARNINGS AND PRECAUTIONS (5.1) ].
• Norgestimate and Ethinyl Estradiol Tablets, USP does not protect against HIV infection (AIDS) and other sexually transmitted infections.
• Norgestimate and Ethinyl Estradiol Tablets, USP is not to be used during pregnancy; if pregnancy occurs during use of Norgestimate and Ethinyl Estradiol Tablets, USP instruct the patient to stop further use [see WARNINGS AND PRECAUTIONS (5.9) ].
• Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see DOSAGE AND ADMINISTRATION (2.2)] .
• Use a back-up or alternative method of contraception when enzyme inducers are used with Norgestimate and Ethinyl Estradiol Tablets, USP [see DRUG INTERACTIONS (7.1)].
• COCs may reduce breast milk production, this is less likely to occur if breastfeeding is well established [see USE IN SPECIFIC POPULATIONS (8.3)].
• Women who start COCs postpartum; and who have not yet had a period, should use an additional method of contraception until they have taken a white tablet for 7 consecutive days [see DOSAGE AND ADMINISTRATION (2.2)].
• Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see WARNINGS AND PRECAUTIONS (5.8) ].

Manufactured For:

AvKARE

Pulaski, TN 38478

Rev. 04/2020

The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

Carefully monitor prediabetic and diabetic women who take norgestimate and ethinyl estradiol. COCs may decrease glucose tolerance.

Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue norgestimate and ethinyl estradiol use if pregnancy is confirmed.

Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see USE IN SPECIFIC POPULATIONS (8.1)].

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

• Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
• Stop norgestimate and ethinyl estradiol if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see ADVERSE REACTIONS (6.2)].
• If feasible, stop norgestimate and ethinyl estradiol at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization.
• Start norgestimate and ethinyl estradiol no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
• The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued.
• Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke.
• Use COCs with caution in women with cardiovascular disease risk factors.

[See WARNINGS AND PRECAUTIONS (5.2, 5.11) and USE IN SPECIFIC POPULATIONS (8.1) .]

• COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations.
• COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
  
  Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs.

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see CONTRAINDICATIONS (4)].

• Table 1: Instructions for Administration of Norgestimate and Ethinyl Estradiol Tablets, USP

Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.

Norgestimate and Ethinyl Estradiol Tablets, USP is dispensed in a blister pack [see HOW SUPPLIED/STORAGE AND HANDLING (16) ]. Norgestimate and Ethinyl Estradiol Tablets, USP may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as COCs. Discontinue norgestimate and ethinyl estradiol prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see CONTRAINDICATIONS (4) ]. Norgestimate and ethinyl estradiol can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

Do not co-administer norgestimate and ethinyl estradiol with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see WARNINGS AND PRECAUTIONS (5.3)]

Starting Norgestimate and Ethinyl Estradiol Tablets, USP after Abortion or Miscarriage

Contraindications (4) 11/2021



Warnings and Precautions ( 5.11) 11/2021

If a woman taking norgestimate and ethinyl estradiol develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norgestimate and ethinyl estradiol if indicated.

Consider discontinuation of norgestimate and ethinyl estradiol in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking norgestimate and ethinyl estradiol.

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.

Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion.

Norgestimate and Ethinyl Estradiol Tablets, USP is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-, oxime,(17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol).

• Each active white tablet contains 0.18 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each active light blue tablet contains 0.215 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each active blue tablet contains 0.25 mg of norgestimate and 0.025 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.6 sunset yellow fcf aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.
• Each green placebo tablet contains only inert ingredients, as follows: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, lecithin (soya), magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Carefully observe women with a history of depression and discontinue norgestimate and ethinyl estradiol if depression recurs to a serious degree.

A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare.

Norgestimate and Ethinyl Estradiol Tablets, USP are available in a blister card:

Each blister card (28 tablets) contains in the following order:

• 7 white, round, coated tablets imprinted "SZ" on one side and "T5" on the other side contains 0.18 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 light blue, round, coated tablets imprinted "SZ" on one side and "T6" on the other side contains 0.215 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 blue, round, coated tablets imprinted "SZ" on one side and "T7" on the other side contains 0.25 mg of the progestational compound, norgestimate, together with 0.025 mg of the estrogenic compound, ethinyl estradiol.
• 7 green, round, coated tablets imprinted "SZ" on one side and "J1" on the other side contains inert ingredients.

NDC 42291-565-28, one box containing 1 individual unit carton.

NDC 42291-565-84, one box containing 3 individual unit cartons.

Safety and efficacy of norgestimate and ethinyl estradiol have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Norgestimate and ethinyl estradiol has not been studied in postmenopausal women and is not indicated in this population.

Table 2: Instructions for Missed Norgestimate and Ethinyl Estradiol Tablets, USP Tablets

In an active controlled clinical trial lasting 12 months, 1,673 women, 18 to 45 years old completed 11,003 cycles of norgestimate and ethinyl estradiol use and a total of 20 pregnancies were reported in norgestimate and ethinyl estradiol users. The racial demographic of those treated with norgestimate and ethinyl estradiol was: Caucasian (86%), African-American (6%), Asian (2%), and Other (6%). There were no exclusions on the basis of weight; the weight range for women treated was 90 to 240 lbs, with a mean weight of about 142 lbs. The pregnancy rate in women aged 18 to 35 years was approximately 2.6 pregnancies per 100 woman-years of use.

Estarylla™ is contraindicated in females who are known to have or develop the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
• Smoke, if over age 35 [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1) ]
• Have deep vein thrombosis or pulmonary embolism, now or in the past [see WARNINGS AND PRECAUTIONS (5.1)]
• Have inherited or acquired hypercoagulopathies [see WARNINGS AND PRECAUTIONS (5.1)]
• Have cerebrovascular disease [see WARNINGS AND PRECAUTIONS (5.1)]
• Have coronary artery disease [see WARNINGS AND PRECAUTIONS (5.1)]
• Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS AND PRECAUTIONS (5.1)]
• Have uncontrolled hypertension [see WARNINGS AND PRECAUTIONS (5.4) ]
• Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS (5.6) ]
• Have headaches with focal neurological symptoms or migraine headaches with aura [see WARNINGS AND PRECAUTIONS (5.7) ]
  • Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS (5.7) ]
• Liver tumors, benign or malignant, or liver disease [see WARNINGS AND PRECAUTIONS (5.2)]
• Undiagnosed abnormal uterine bleeding [see WARNINGS AND PRECAUTIONS (5.8) ]
• Pregnancy, because there is no reason to use COCs during pregnancy [see WARNINGS AND PRECAUTIONS (5.9) and USE IN SPECIFIC POPULATIONS (8.1)]
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see WARNINGS AND PRECAUTIONS (5.11) ]
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS AND PRECAUTIONS (5.3)]

The following serious adverse reactions with the use of COCs are discussed elsewhere in labeling:

• Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1)]
• Vascular events [see WARNINGS AND PRECAUTIONS (5.1)]
• Liver disease [see WARNINGS AND PRECAUTIONS (5.2)]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

No drug-drug interaction studies were conducted with norgestimate and ethinyl estradiol.

Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

Norgestimate and Ethinyl Estradiol Tablets, USP

(nor-JES-ti-mate, ETH-i-nil es-tra-DYE-ol)

What is the most important information I should know about Norgestimate and Ethinyl Estradiol Tablets, USP?

Do not use Norgestimate and Ethinyl Estradiol Tablets, USP if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

What is Norgestimate and Ethinyl Estradiol Tablets, USP?

Norgestimate and Ethinyl Estradiol Tablets, USP is a birth control pill (oral contraceptive) used by women to prevent pregnancy.

How does Norgestimate and Ethinyl Estradiol Tablets, USP work for contraception?

Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.

Based on the results from the clinical study, about 3 out of 100 women may get pregnant during the first year they use Norgestimate and Ethinyl Estradiol Tablets, USP.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

Who should not take Norgestimate and Ethinyl Estradiol Tablets, USP?

Do not take Norgestimate and Ethinyl Estradiol Tablets, USP if you:

• smoke and are over 35 years of age
• had blood clots in your arms, legs, lungs, or eyes
• had a problem with your blood that makes it clot more than normal
• have certain heart valve problems or irregular heart beat that increases your risk of having blood clots
• had a stroke
• had a heart attack
• have high blood pressure that cannot be controlled by medicine
• have diabetes with kidney, eye, nerve, or blood vessel damage
• have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age
• have liver problems, including liver tumors
• take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood.
• have any unexplained vaginal bleeding
• are pregnant
• had breast cancer or any cancer that is sensitive to female hormones

If any of these conditions happen while you are taking Norgestimate and Ethinyl Estradiol Tablets, USP, stop taking Norgestimate and Ethinyl Estradiol Tablets, USP right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Norgestimate and Ethinyl Estradiol Tablets, USP.

What should I tell my healthcare provider before taking Norgestimate and Ethinyl Estradiol Tablets, USP?

Tell your healthcare provider if you:

• are pregnant or think you may be pregnant
• are depressed now or have been depressed in the past
• had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy)
• are breastfeeding or plan to breastfeed. Norgestimate and Ethinyl Estradiol Tablets, USP may decrease the amount of breast milk you make. A small amount of the hormones in Norgestimate and Ethinyl Estradiol Tablets, USP may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Norgestimate and Ethinyl Estradiol Tablets, USP may affect the way other medicines work, and other medicines may affect how well Norgestimate and Ethinyl Estradiol Tablets, USPworks.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Norgestimate and Ethinyl Estradiol Tablets, USP?

Read the Instructions for Use at the end of this Patient Information.

What are the possible serious side effects of Norgestimate and Ethinyl Estradiol Tablets, USP?

• Like pregnancy, Norgestimate and Ethinyl Estradiol Tablets, USP may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes.

Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:

• first start taking birth control pills
• restart the same or different birth control pills after not using them for a month or more

Call your healthcare provider or go to a hospital emergency room right away if you have:

Other serious side effects include:

• liver problems, including:
  • rare liver tumors
  • jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes.
• high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure.
• gallbladder problems
• changes in the sugar and fat (cholesterol and triglycerides) levels in your blood
• new or worsening headaches including migraine headaches
• irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking Norgestimate and Ethinyl Estradiol Tablets, USP .
• depression
• possible cancer in your breast and cervix
• swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema if higher is you have a history of angioedema.
• dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking Norgestimate and Ethinyl Estradiol Tablets, USP. Use sunscreen if you have to be in the sunlight.

What are the most common side effects of Norgestimate and Ethinyl Estradiol Tablets, USP?

These are not all the possible side effects of Norgestimate and Ethinyl Estradiol Tablets, USP. For more information, ask your healthcare provider or pharmacist.

You may report side effects to the FDA at 1-800-FDA-1088.

What else should I know about taking Norgestimate and Ethinyl Estradiol Tablets, USP?

• If you are scheduled for any lab tests, tell your healthcare provider you are taking Norgestimate and Ethinyl Estradiol Tablets, USP. Certain blood tests may be affected by Norgestimate and Ethinyl Estradiol Tablets, USP.
• Norgestimate and Ethinyl Estradiol Tablets, USP does not protect against HIV infection (AIDS) and other sexually transmitted infections.

How should I store Norgestimate and Ethinyl Estradiol Tablets, USP?

• Store Norgestimate and Ethinyl Estradiol Tablets, USP at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Norgestimate and Ethinyl Estradiol Tablets, USP and all medicines out of the reach of children.
• Store away from light.

General information about the safe and effective use of Norgestimate and Ethinyl Estradiol Tablets, USP.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Norgestimate and Ethinyl Estradiol Tablets, USP for a condition for which it was not prescribed. Do not give Norgestimate and Ethinyl Estradiol Tablets, USP to other people, even if they have the same symptoms that you have.

This Patient Information summarizes the most important information about Norgestimate and Ethinyl Estradiol Tablets, USP. You can ask your pharmacist or healthcare provider for information about Norgestimate and Ethinyl Estradiol Tablets, USP that is written for health professionals.

For more information, call AVKARE at 1-855-361-3993.

Does hormonal birth control pills cause cancer?

It is not known if hormonal birth control pills causes breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use.

If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are

sensitive to hormones.

Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

What if I want to become pregnant?

You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.

What should I know about my period when taking Norgestimate and Ethinyl Estradiol Tablets, USP?

Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking Norgestimate and Ethinyl Estradiol Tablets, USP, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.

What are the ingredients in Norgestimate and Ethinyl Estradiol Tablets, USP?

Active ingredients: Each white, light blue, and blue pill contains norgestimate and ethinyl estradiol.

Inactive ingredients:

White tablet: crospovidone, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Light blue tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Blue tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Blue No.1 brilliant blue aluminum lake, FD&C Yellow No.6 sunset yellow fcf aluminum lake, lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

Green tablet: crospovidone, FD&C Blue No.2 indigo carmine aluminum lake, FD&C Yellow No.5 tartrazine aluminum lake, lactose anhydrous, lecithin (soya), magnesium stearate, polyethylene glycol, polyvinyl alcohol, pregelatinised starch, talc, and titanium dioxide.

The pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in women with renal impairment.

Norgestimate and Ethinyl Estradiol Tablets, USP

(nor-JES-ti-mate, ETH-i-nil es-tra-DYE-ol)

Important Information about taking Norgestimate and Ethinyl Estradiol Tablets, USP

• Take 1 pill every day at the same time. Take the pills in the order directed on your pill dispenser.
• Do not skip your pills, even if you do not have sex often. If you miss pills (including starting the pack late) you could get pregnant. The more pills you miss, the more likely you are to get pregnant.
• If you have trouble remembering to take Norgestimate and Ethinyl Estradiol Tablets, USP talk to your healthcare provider. When you first start taking Norgestimate and Ethinyl Estradiol Tablets, USP, spotting or light bleeding in between your periods may occur. Contact your healthcare provider if this does not go away after a few months.
• You may feel sick to your stomach (nauseous), especially during the first few months of taking Norgestimate and Ethinyl Estradiol Tablets, USP. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If your nausea does not go away, call your healthcare provider.
• Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. On the days you take 2 pills to make up for missed pills (see What should I do if I miss any Norgestimate and Ethinyl Estradiol Tablets, USP pills? below), you could also feel a little sick to your stomach.
• It is not uncommon to miss a period. However, if you miss a period and have not takenNorgestimate and Ethinyl Estradiol Tablets, USP according to directions, or miss 2 periods in a row, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking Norgestimate and Ethinyl Estradiol Tablets, USP.
• If you have vomiting or diarrhea within 3 to 4 hours of taking your pill, take another pill of the same color from your extra pill dispenser. If you do not have an extra pill dispenser, take the next pill in your pill dispenser. Continue taking all your remaining pills in order. Start the first pill of your next pill dispenser the day after finishing your current pill dispenser. This will be 1 day earlier than originally scheduled. Continue on your new schedule.
• If you have vomiting or diarrhea for more than 1 day, your birth control pills may not work as well. Use an additional birth control method, like condoms and a spermicide, until you check with your healthcare provider.
• Stop taking Norgestimate and Ethinyl Estradiol Tablets, USP at least 4 weeks before you have major surgery and do not restart after the surgery without asking your healthcare provider. Be sure to use other forms of contraception (like condoms and spermicide) during this time period.

Before you start taking Norgestimate and Ethinyl Estradiol Tablets, USP:

• Decide what time of day you want to take your pill. It is important to take it at the same time every day and in the order as directed on your pill dispenser.
• Have backup contraception (condoms and spermicide) available and if possible, an extra full pack of pills as needed.

When should I start taking Norgestimate and Ethinyl Estradiol Tablets, USP?

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you have not used a hormonal birth control method before:

• There are 2 ways to start taking your birth control pills. You can either start on a Sunday (Sunday Start) or on the first day (Day 1) of your natural menstrual period (Day 1 Start). Your healthcare provider should tell you when to start taking your birth control pill.
• If you use the Sunday Start, use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days that you take Norgestimate and Ethinyl Estradiol Tablets, USP. You do not need back-up contraception if you use the Day 1 Start.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from another birth control pill:

• Start your new Norgestimate and Ethinyl Estradiol Tablets, USP pack on the same day that you would start the next pack of your previous birth control method.
• Do not continue taking the pills from your previous birth control pack.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and previously used a vaginal ring or transdermal patch:

• Start using Norgestimate and Ethinyl Estradiol Tablets, USP on the day you would have reapplied the next ring or patch.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from a progestin-only method such as an implant or injection:

• Start taking v on the day of removal of your implant or on the day when you would have had your next injection.

If you start taking Norgestimate and Ethinyl Estradiol Tablets, USP and you are switching from an intrauterine device or system (IUD or IUS):

• Start taking Norgestimate and Ethinyl Estradiol Tablets, USP on the day of removal of your IUD or IUS.
• You do not need back-up contraception if your IUD or IUS is removed on the first day (Day 1) of your period. If your IUD or IUS is removed on any other day, use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days that you take Norgestimate and Ethinyl Estradiol Tablets, USP.

Keep a calendar to track your period:

If this is the first time you are taking birth control pills, read, "When should I start taking Norgestimate and Ethinyl Estradiol Tablets, USP?" above. Follow these instructions for either a Sunday Start or a Day 1 Start.

Sunday Start:

You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.

• Take pill 1 on the Sunday after your period starts.
• If your period starts on a Sunday, take pill "1" that day and refer to Day 1 Start instructions below.
• Take 1 pill every day in the order on the pill dispenser at the same time each day for 28 days.
• After taking the last pill on Day 28 from the pill dispenser, start taking the first pill from a new pack, on the same day of the week as the first pack (Sunday). Take the first pill in the new pack whether or not you are having your period.
• Use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days of the first cycle that you take Norgestimate and Ethinyl Estradiol Tablets, USP.

Day 1 Start:

You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.

• Take 1 pill every day in the order of the blister pack, at the same time each day, for 28 days.
• After taking the last pill on Day 28 from the pill blister pack, start taking the first pill from a new pack, on the same day of the week as the first pack. Take the first pill in the new pack whether or not you are having your period.

Norgestimate and Ethinyl Estradiol Tablets, USP comes in blister pack. Read the instructions below for using your blister pack.

Each new blister pack has 28 pills

• 7 white pills with hormone, for Days 1 to 7
• 7 light blue pills with hormone, for Days 8 to 14
• 7 blue pills with hormones, for Days 15 to 21
• 7 green pills (without hormones), for Days 22 to 28.

BEFORE YOU START TAKING YOUR PILLS

• DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.
  
  
  
  It is important to take it at about the same time every day.
• The 28-pill pack has 21 white, light blue, and blue "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of green "reminder" pills (without hormones).
• 3. ALSO FIND:
• 1) where on the pack to start taking pills,
• 2) in what order to take the pills (follow the arrows),
• 3) The week numbers as shown in the diagram below.

4) BE SURE YOU HAVE READY AT ALL TIMES:



ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicide) to use as a back-up method in case you miss pills.



AN EXTRA, FULL PILL PACK.

What should I do if I miss any Norgestimate and Ethinyl Estradiol Tablets, USP pills?

If you miss 1 pill in Weeks 1, 2, or 3, follow these steps:

• Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.
• Then continue taking 1 pill every day until you finish the pack.
• You do not need to use a back-up birth control method if you have sex.

If you miss 2 pills in Week 1 or Week 2 of your pack, follow these steps:

• Take the 2 missed pills as soon as possible and the next 2 pills the next day.
• Then continue to take 1 pill every day until you finish the pack.
• Use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after missing your pills.

If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:

• If you are a Day 1 Starter:
  • Throw out the rest of the pill pack and start a new pack that same day.
  • You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
  • You could become pregnant if you have sex during the first 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.
• If you are a Sunday Starter:
  • Keep taking 1 pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of pills that same day.
  • Use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

The brands listed are the registered trademark of their respective owners and are not trademarks of Xiromed, LLC.

Manufactured by Laboratorios Leon Farma S.A., Spain

for Xiromed, LLC. Florham Park, NJ 07932

Product of Spain

Rev. January 2018

PI-120-00

No specific pharmacodynamic studies were conducted with norgestimate and ethinyl estradiol.

Norgestimate and Ethinyl Estradiol Tablets, USP are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14)].

The pharmacokinetics of norgestimate and ethinyl estradiol has not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.2). ]

Norgestimate and Ethinyl Estradiol Tablets, USP is an estrogen/progestin COC, indicated for use by women to prevent pregnancy. ( 1.1)

• Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
• Protect from light.
• Keep out of the reach of children.

Norgestimate and ethinyl estradiol is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see CONTRAINDICATIONS (4)] . For women with well-controlled hypertension, monitor blood pressure and stop norgestimate and ethinyl estradiol if blood pressure rises significantly.

An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin.

Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis.

COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

Breast Cancer

Estarylla™ is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally

sensitive [see Contraindications (4)].

Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast

cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However,

some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see Postmarketing Experience (6.2)].

Cervical Cancer

A causal relationship between the use of CHCs and the development of cervical cancer and intraepithelial neoplasia has

not been clearly established. In observational studies it suggests that COCs are associated with an increase in the risk of cervical

cancer or intraepithelial neoplasia. There is controversy about the extent to which these findings are due to differences in sexual

behavior and other factors.

• Thromboembolic Disorders and Other Vascular Problems: Stop norgestimate and ethinyl estradiol if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. ( 5.1)
• Liver disease: Discontinue norgestimate and ethinyl estradiol if jaundice occurs. ( 5.2)
• High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop norgestimate and ethinyl estradiol if blood pressure rises significantly. ( 5.4)
• Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norgestimate and ethinyl estradiol. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.6)
• Headache: Evaluate significant change in headaches and discontinue norgestimate and ethinyl estradiol if indicated. ( 5.7)
• Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea. ( 5.8)

In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

• Take one tablet daily by mouth at the same time every day. ( 2.2)
• Take tablets in the order directed on the blister pack. ( 2.2)
• Do not skip or delay tablet intake. ( 2.2)

Norgestimate and Ethinyl Estradiol Tablets, USP tablets are available in a blister card. Each blister card contains 28 tablets in the following order:

• 7 white, round, coated tablets imprinted "SZ" on one side and "T5" on the other side contains 0.18 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 light blue, round, coated tablets imprinted "SZ" on one side and "T6" on the other side contains 0.215 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 blue, round, coated tablets imprinted "SZ" on one side and "T7" on the other side contains 0.25 mg norgestimate and 0.025 mg ethinyl estradiol.
• 7 green, round, coated tablets imprinted "SZ" on one side and "J1" on the other side contains inert ingredients.

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 - 1.12 (Figure 2).

Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of

COCs (Figure 2). 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 - 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 8-10 years of COC use.

For your reference, below are the studies reviewed by FDA to inform the breast cancer risk:

References:

1. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med.

2002;346(26):2025-2032.

2. Dumeaux V, Fournier A, Lund E, Clavel-Chapelon F. Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women. Cancer Causes Control. 2005;16(5):537-544.

3. Dorjgochoo T, Shu XO, Li HL, et al. Use of oral contraceptives, intrauterine devices and tubal sterilization and cancer risk in a

large prospective study, from 1996 to 2006. Int J Cancer. 2009;124(10):2442- 2449.

4. Hunter DJ, Colditz GA, Hankinson SE, et al. Oral contraceptive use and breast cancer: a prospective study of young women.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2010;19(10):2496-2502.

5. Vessey M, Yeates D. Oral contraceptive use and cancer. Final report from the Oxford-Family Planning Association contraceptive

study. Contraception. 2013; 88(6): 678-683.

6. Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med. 2017;377(23):2228-2239

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of norgestimate and ethinyl estradiol was evaluated in 1,723 subjects who participated in a randomized, partially blinded, multicenter, active-controlled clinical trial of norgestimate and ethinyl estradiol for contraception. This trial examined healthy, nonpregnant, volunteers aged 18 to 45 (nonsmoker if 35 to 45 years of age), who were sexually active with regular coitus. Subjects were followed for up to 13 28-day cycles.

Nursing mothers: Not recommended; can decrease milk production. ( 8.3)

The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

See FDA-approved patient labeling (Patient Information and Instruction for Use).

Counsel patients about the following information:

• Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see Boxed Warning].
• Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see WARNINGS AND PRECAUTIONS (5.1) ].
• Norgestimate and Ethinyl Estradiol Tablets, USP does not protect against HIV infection (AIDS) and other sexually transmitted infections.
• Norgestimate and Ethinyl Estradiol Tablets, USP is not to be used during pregnancy; if pregnancy occurs during use of Norgestimate and Ethinyl Estradiol Tablets, USP instruct the patient to stop further use [see WARNINGS AND PRECAUTIONS (5.9) ].
• Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see DOSAGE AND ADMINISTRATION (2.2)] .
• Use a back-up or alternative method of contraception when enzyme inducers are used with Norgestimate and Ethinyl Estradiol Tablets, USP [see DRUG INTERACTIONS (7.1)].
• COCs may reduce breast milk production, this is less likely to occur if breastfeeding is well established [see USE IN SPECIFIC POPULATIONS (8.3)].
• Women who start COCs postpartum; and who have not yet had a period, should use an additional method of contraception until they have taken a white tablet for 7 consecutive days [see DOSAGE AND ADMINISTRATION (2.2)].
• Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see WARNINGS AND PRECAUTIONS (5.8) ].

Manufactured For:

AvKARE

Pulaski, TN 38478

Rev. 04/2020

The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

Carefully monitor prediabetic and diabetic women who take norgestimate and ethinyl estradiol. COCs may decrease glucose tolerance.

Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.

Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue norgestimate and ethinyl estradiol use if pregnancy is confirmed.

Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see USE IN SPECIFIC POPULATIONS (8.1)].

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

• Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
• Stop norgestimate and ethinyl estradiol if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see ADVERSE REACTIONS (6.2)].
• If feasible, stop norgestimate and ethinyl estradiol at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization.
• Start norgestimate and ethinyl estradiol no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.
• The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued.
• Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke.
• Use COCs with caution in women with cardiovascular disease risk factors.

[See WARNINGS AND PRECAUTIONS (5.2, 5.11) and USE IN SPECIFIC POPULATIONS (8.1) .]

• COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations.
• COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
  
  Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs.

Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see CONTRAINDICATIONS (4)].

• Table 1: Instructions for Administration of Norgestimate and Ethinyl Estradiol Tablets, USP

Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.

Norgestimate and Ethinyl Estradiol Tablets, USP is dispensed in a blister pack [see HOW SUPPLIED/STORAGE AND HANDLING (16) ]. Norgestimate and Ethinyl Estradiol Tablets, USP may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as COCs. Discontinue norgestimate and ethinyl estradiol prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see CONTRAINDICATIONS (4) ]. Norgestimate and ethinyl estradiol can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

Do not co-administer norgestimate and ethinyl estradiol with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see WARNINGS AND PRECAUTIONS (5.3)]