AMETHIA tablets are indicated for use by women to prevent pregnancy.

Take one tablet by mouth at the same time every day. The dosage of AMETHIA tablets is one white tablet containing levonorgestrel and ethinyl estradiol daily for 84 consecutive days, followed by one light blue ethinyl estradiol tablet for 7 days. To achieve maximum contraceptive effectiveness, AMETHIA tablets must be taken exactly as directed and at intervals not exceeding 24 hours.

Instruct the patient to begin taking AMETHIA tablets on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first white tablet is taken that day. One white tablet should be taken daily for 84 consecutive days, followed by one light blue tablet for 7 consecutive days. A non-hormonal back-up method of contraception (such as condoms or spermicide) should be used until a white tablet has been taken daily for 7 consecutive days. A scheduled period should occur during the 7 days that the light blue tablets are taken.

Begin the next and all subsequent 91-day cycles without interruption on the same day of the week (Sunday) on which the patient began her first dose of AMETHIA tablets, following the same schedule: 84 days taking a white tablet followed by 7 days taking a blue tablet. If the patient does not immediately start her next pill pack, she should protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a white tablet daily for 7 consecutive days.

If unscheduled spotting or bleeding occurs, instruct the patient to continue on the same regimen. If the bleeding is persistent or prolonged, advise the patient to consult her healthcare provider.

For patient instructions regarding missed pills, see FDA-Approved Patient Labeling.

For postpartum women who are not breastfeeding, start AMETHIA tablets no earlier than four to six weeks postpartum due to increased risk of thromboembolism. If the patient starts on AMETHIA tablets postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken a white tablet for 7 consecutive days.

AMETHIA tablets are available in Extended-Cycle Tablet Dispensers, each containing a 13-week supply of tablets: 84 white tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol, and 7 light blue tablets each containing 0.01 mg of ethinyl estradiol. The white tablets are round, flat face beveled edge, unscored tablets with WATSONon one side and 268on the other side. The light blue tablets are round, flat face beveled edge, unscored tablets with WATSONon one side and 270on the other side.

AMETHIA tablets are 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:
  1. ­Smoke, if over age 35 [see Boxed Warningand Warnings and Precautions (5.1)] .
  2. ­Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1)] .
  3. ­Have cerebrovascular disease [see Warnings and Precautions (5.1)].
  4. ­Have coronary artery disease [see Warnings and Precautions (5.1)] .
  5. ­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)] .
  6. ­ Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1)] .
  7. ­ Have uncontrolled hypertension [see Warnings and Precautions (5.5)] .
  8. ­Have diabetes with vascular disease [see Warnings and Precautions (5.7)] .
  9. ­Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions (5.8)] .
• Undiagnosed abnormal genital bleeding [see Warnings and Precautions (5.9)] .
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.2)] .
• Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.3)and Use in Specific Populations (8.6)] .
• Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions (5.10)and Use in Specific Populations (8.1)] .
• 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 (5.4)].

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

• Serious cardiovascular events and smoking [see Boxed Warningand Warnings and Precautions (5.1)]
• Vascular events [see Warnings and Precautions (5.1)]
• Liver disease [see Warnings and Precautions (5.3)]

Adverse reactions commonly reported by COC users are:

• Irregular uterine bleeding
• Nausea
• Breast tenderness
• Headache

6.2 Postmarketing Experience

Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90–1.12 (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.

Figure 2: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives

RR = relative risk; OR = odds ratio; HR = hazard ratio. "ever COC" are females with current or past COC use; "never COC use" are females that never used COCs.

The following adverse reactions have been identified during post-approval use of levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disorders: abdominal distension, vomiting

General disorders and administration site conditions: chest pain, fatigue, malaise, edema peripheral, pain

Immune system disorders: hypersensitivity reaction

Investigations:blood pressure increased

Musculoskeletal and connective tissue disorders: muscle spasms, pain in extremity

Nervous system disorders: dizziness, loss of consciousness

Psychiatric disorders: insomnia

Reproductive and breast disorders: dysmenorrhea

Respiratory, thoracic and mediastinal disorders:pulmonary embolism, pulmonary thrombosis

Skin and subcutaneous tissue disorders: alopecia

Vascular disorders: thrombosis

No drug-drug interaction studies were conducted with AMETHIA tablets.

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

AMETHIA tablets are an extended-cycle oral contraceptive consisting of 84 white tablets each containing 0.15 mg of levonorgestrel, a synthetic progestogen and 0.03 mg of ethinyl estradiol, and 7 light blue tablets containing 0.01 mg of ethinyl estradiol.

The structural formulas for the active components are:

Levonorgestrel is chemically 18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (17α)-, (-)-.

Ethinyl Estradiol is 19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17α)-.

Each white tablet contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, povidone, croscarmellose sodium and magnesium stearate.

Each light blue tablet contains the following inactive ingredients: vitamin E, anhydrous lactose, povidone, FD&C Blue #1, colloidal silicon dioxide, corn starch and stearic acid.

In a 12-month, multicenter, randomized, open-label clinical trial, 1,006 women aged 18-40 were studied to assess the safety and efficacy of levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets, completing the equivalent of 8,681 28-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (80%), African-American (11%), Hispanic (5%), Asian (2%), and Other (2%). There were no exclusions for body mass index (BMI) or weight. The weight range of those women treated was 91 to 360 lbs., with a mean weight of 156 lbs. Among the women in the trial, 63% were current or recent hormonal contraceptive users, 26% were prior users (who had used hormonal contraceptives in the past but not in the 6 months prior to enrollment), and 11% were new starts. Of treated women, 14.8% were lost to follow-up, 16.3% discontinued due to an adverse event, and 12.9% discontinued by withdrawing their consent.

The pregnancy rate (Pearl Index [PI]) in women aged 18-35 years was 1.34 pregnancies per 100 women-years of use (95% confidence interval 0.54-2.75), based on 7 pregnancies that occurred after the onset of treatment and within 14 days after the last combination pill. Cycles in which conception did not occur, but which included the use of backup contraception, were not included in the calculation of the PI. The PI includes patients who did not take the drug correctly.

Distributed by:
Mayne Pharma
Greenville, NC 27834

Manufactured by:
Patheon, Inc.
2100 Syntex Court
Mississauga, Ontario L5N 7K9 Canada

FDA-Approved Patient Labeling
Guide for Using
AMETHIA Levonorgestrel/Ethinyl Estradiol Tablets and Ethinyl Estradiol Tablets,
0.15 mg/0.03 mg and 0.01 mg
Revised August 2022
Rx only

Birth control pills help to lower the chances of becoming pregnant. They do not protect against HIV infection (AIDS) and other sexually transmitted diseases.

What Are AMETHIA Tablets?

Levonorgestrel/Ethinyl Estradiol tablets and Ethinyl Estradiol tablets are a birth control pill. They contain two female hormones, an estrogen called ethinyl estradiol, and a progestin called levonorgestrel.

How Well Do AMETHIA Tablets Work?

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

Based on the results of a single clinical study lasting 12 months, 1 to 3 women, out of 100 women, may get pregnant during the first year they use AMETHIA tablets.

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.

How Do I Take AMETHIA Tablets?

1. Take one pill every day at the same time. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant.
2. Many women have spotting or light bleeding, or may feel sick to their stomach during the first few months of taking AMETHIA tablets. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your healthcare provider.
3. 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, you could also feel a little sick to your stomach.
4. If you have trouble remembering to take AMETHIA tablets, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control.

Beforeyou start taking AMETHIA Tablets

1. Decide what time of day you want to take your pill. It is important to take it at about the same time every day.
2. Look at your Extended-Cycle Tablet Dispenser. Your Tablet Dispenser consists of 3 trays with cards that hold 91 individually sealed pills (a 13-week or 91-day cycle). The 91 pills consist of 84 white and 7 light blue pills. Trays 1 and 2 each contain 28 white pills (4 rows of 7 pills). Tray 3 contains 35 pills consisting of 28 white pills (4 rows of 7 pills) and 7 light blue pills (1 row of 7 pills).

   

3. Also find:
   • Where on the first tray in the pack to start taking pills (upper left corner at the Start Here arrow) and
   • In what order to take the pills (follow the weeks and arrow).
4. Be sure you have ready at all times another kind of birth control (such as condoms or spermicides), to use as a backup in case you miss pills.

When to Start AMETHIA Tablets

1. Take the first white pill on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the first white pill that same day.
2. Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first white pill until the next Sunday (first 7 days). If you have been using a different hormonal method of birth control (such as a different pill, the "patch," or the "vaginal ring"), you need to use another method of birth control (such as condoms or spermicides) each time you have sex after stopping your old method of birth control until you have taken levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets for 7 days.

How to Take AMETHIA Tablets

1. Take one pill at the same time every day until you have taken the last pill in the tablet dispenser.
   • Do not skip pills even if you are experiencing spotting or bleeding or feel sick to your stomach (nausea).
   • Do not skip pills even if you do not have sex very often.
2. When you finish a tablet dispenser
   • After taking the last light blue pill, start taking the first white pill from a new Extended-Cycle Tablet Dispenser the very next day (this should be on a Sunday) regardless of when your period started.
3. If you miss your scheduled period when you are taking the light blue pills, contact your healthcare provider because you may be pregnant. If you are pregnant, you should stop taking AMETHIA tablets.

What To Do If You Miss Pills

If you MISS 1white pill:

1. 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.
2. You do not need to use a back-up birth control method if you have sex.

If you MISS 2white pills in a row:

1. Take 2 pills on the day you remember, and 2 pills the next day.
2. Then take 1 pill a day until you finish the pack.
3. You could become pregnant if you have sex in the 7 days after you miss two pills. You MUST use another birth control method (such as condoms or spermicide) as a back-up for the 7 days after you restart your pills.

If you MISS 3 OR MOREwhite pills in a row:

1. Do not take the missed pills. Keep taking 1 pill every day as indicated on the pack until you have completed all of the remaining pills in the pack. For example: If you resume taking the pill on Thursday, take the pill under "Thursday" and do not take the missed pills. You may experience bleeding during the week following the missed pills.
2. You could become pregnant if you have sex during the days of missed pills or during the first 7 days after restarting your pills.
3. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up when you miss pills and for the first 7 days after you restart your pills. If you do not have your period when you are taking the light blue pills, call your healthcare provider because you may be pregnant.

If you MISS ANYof the 7 light blue pills:

1. Throw away the missed pills.
2. Keep taking the scheduled pills until the pack is finished.
3. You do not need a back-up method of birth control.

Finally, if you are still not sure what to do about the pills you have missed

1. Use a back-up method anytime you have sex.
2. Keep taking one pill each day until you contact your healthcare provider.

Who Should Not Take AMETHIA Tablets?

Your healthcare provider will not give you AMETHIA tablets if you have:

• Ever had breast cancer or any cancer that is sensitive to female hormones
• Liver disease, including liver tumors
• Been prescribed 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
• Ever had blood clots in your arms, legs, or lungs
• Ever had a stroke
• Ever had a heart attack
• Certain heart valve problems or heart rhythm abnormalities that can cause blood clots to form in the heart
• An inherited problem with your blood that makes it clot more than normal
• High blood pressure that medicine can't control
• Diabetes with kidney, eye, or blood vessel damage
• Certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision

Also, do not take birth control pills if you:

• Smoke and are over 35 years old
• Are pregnant

Birth control pills may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy.

What Else Should I Know About Taking AMETHIA Tablets?

Birth control pills do notprotect you against any sexually transmitted disease, including HIV, the virus that causes AIDS.

Do not skip any pills, even if you do not have sex often.

Birth control pills should not be taken during pregnancy. However, birth control pills taken by accident during pregnancy are not known to cause birth defects.

If you are breastfeeding, consider another birth control method until you are ready to stop breastfeeding. Birth control pills that contain estrogen, like AMETHIA tablets, may decrease the amount of milk you make. A small amount of the pill's hormones pass into breast milk.

Tell your healthcare provider about all medicines and herbal products that you take. Some medicines and herbal products may make birth control pills less effective, including:

• barbiturates
• bosentan
• carbamazepine
• felbamate
• griseofulvin
• oxcarbazepine
• phenytoin
• rifampin
• St. John's wort
• topiramate

Consider using another birth control method when you take medicines that may make birth control pills less effective.

Birth control pills may interact with lamotrigine, an anticonvulsant used for epilepsy. This may increase the risk of seizures, so your physician may need to adjust the dose of lamotrigine.

If you have vomiting or diarrhea, your birth control pills may not work as well. Use another birth control method, like condoms or a spermicide, until you check with your healthcare provider.

What Are The Most Serious Risks Of Taking Birth Control Pills?

Like pregnancy, birth control pills increase the risk of serious blood clots, especially in women who have other risk factors, such as smoking, obesity, or age > 35. It is possible to die from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of serious blood clots are blood clots in the:

• Legs (thrombophlebitis)
• Lungs (pulmonary embolus)
• Eyes (loss of eyesight)
• Heart (heart attack)
• Brain (stroke)

Women who take birth control pills may get:

• High blood pressure
• Gallbladder problems
• Rare cancerous or noncancerous liver tumors

All of these events are uncommon in healthy women.

Call your healthcare provider right away if you have:

• Persistent leg pain
• Sudden shortness of breath
• Sudden blindness, partial or complete
• Severe pain in your chest
• Sudden, severe headache unlike your usual headaches
• Weakness or numbness in an arm or leg, or trouble speaking
• Yellowing of the skin or eyeballs

What Are Common Side Effects Of Birth Control Pills?

The most common side effects of birth control pills are:

• Spotting or bleeding between menstrual periods
• Nausea
• Breast tenderness
• Headache

These side effects are usually mild and usually disappear with time.

Less common side effects are:

• Acne
• Less sexual desire
• Bloating or fluid retention
• Blotchy darkening of the skin, especially on the face
• High blood sugar, especially in women who already have diabetes
• High fat levels in the blood
• Depression, especially if you have had depression in the past. Call your healthcare provider immediately if you have any thoughts of harming yourself.
• Problems tolerating contact lenses
• Weight changes

This is not a complete list of possible side effects. Talk to your healthcare provider if you develop any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088.

No serious problems have been reported from a birth control pill overdose, even when accidentally taken by children.

Do Birth Control Pills Cause Cancer?

It is not known if hormonal birth control pills cause 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 Should I Know About My Period When Taking AMETHIA tablets?

When you take AMETHIA tablets, which have a 91-day extended dosing cycle, you should expect to have 4 scheduled periods per year (bleeding when you are taking the 7 light blue pills). Each period is likely to last about 3 days. However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28-day dosing cycle. During the first AMETHIA tablets 91-day treatment cycle, about 3 in 10 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking AMETHIA tablets because of this bleeding or spotting. If the spotting continues for more than 7 consecutive days or if the bleeding is heavy, call your healthcare provider.

What If I Miss My Scheduled Period When Taking AMETHIA tablets?

You should consider the possibility that you are pregnant if you miss your scheduled period (no bleeding on the days that you are taking light blue tablets). Since scheduled periods are less frequent when you are taking AMETHIA tablets, notify your healthcare provider that you have missed your period and that you are taking AMETHIA tablets. Also notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider evaluates you to determine if you are pregnant. Stop taking AMETHIA tablets if it is determined that you are pregnant.

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.

General Advice About AMETHIA tablets

Your healthcare provider prescribed AMETHIA tablets for you. Do not share AMETHIA tablets with anyone else. Keep AMETHIA tablets out of the reach of children.

If you have concerns or questions, ask your healthcare provider. You may also ask your healthcare providers for a more detailed label written for medical professionals.

Distributed by:
Mayne Pharma
Greenville, NC 27834

Manufactured by:
Patheon Inc.
2100 Syntex Court
Mississauga, Ontario L5N 7K9
Canada

Revised: August 2022

NDC 51862-047-91

Amethia™
(Levonorgestrel/Ethinyl Estradiol Tablets
and Ethinyl Estradiol Tablets,
0.15 mg/0.03 mg and 0.01 mg)

Contains 2 Extended-Cycle Tablet Dispensers, each containing 91 tablets: 84 white tablets,
each containing 0.15 mg levonorgestrel with 0.03 mg ethinyl estradiol, and 7 light blue
tablets, each containing 0.01 mg ethinyl estradiol.

Rx only

2 Extended-Cycle Tablet Dispensers, 91 Tablets Each

maynepharma