Amethia Lo

• It is used to prevent pregnancy.
• It may be given to you for other reasons. Talk with the doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Take Amethia Lo at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.
• Do not skip doses, even if you do not have sex very often.
• If you throw up or have diarrhea, this medicine may not work as well to prevent pregnancy. Use an extra form of birth control, like condoms, until you check with your doctor.
• If your monthly cycle is 28 days and you miss 2 periods in a row, take a pregnancy test before starting a new dosing cycle.
• If you have a cycle longer than 91 days and you miss one period, take a pregnancy test before starting a new dosing cycle.

What do I do if I miss a dose?

• If a dose is missed, check the package insert or call the doctor to find out what to do. If using Amethia Lo to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Amethia Lo (ethinyl estradiol and levonorgestrel) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Amethia Lo. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Vascular Events

Stop COCs if an arterial or deep venous thrombotic event occurs. Although use of COCs increases the risk of venous thromboembolism, pregnancy increases the risk of venous thromboembolism as much or more than the use of COCs. The risk of venous thromboembolism in women using COCs is 3 to 9 per 10,000 woman-years. 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.

Use of Amethia Lo provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year.)

If feasible, stop COCs at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism.

Start COCs no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

Stop COCs if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.

Carcinoma of the Breast and Cervix

Women who currently have or have had breast cancer should not use COCs because breast cancer may be hormonally sensitive.

There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.

Some studies suggest that COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings are due to differences in sexual behavior and other factors.

Liver Disease

Discontinue COCs if jaundice develops. Steroid hormones may be poorly metabolized in patients with impaired liver function.

Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. However, the attributable risk of liver cancers in COC users is less than one case per million users.

Oral contraceptive-related cholestasis may occur in women with a history of pregnancy-related cholestasis. Women with a history of COC-related cholestasis may have the condition recur with subsequent COC use.

High Blood Pressure

For women with well-controlled hypertension, monitor blood pressure and stop COCs if blood pressure rises significantly. Women with uncontrolled hypertension or hypertension with vascular disease should not use COCs.

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

Gallbladder Disease

Studies suggest a small increased relative risk of developing gallbladder disease among COC users.

Carbohydrate and Lipid Metabolic Effects

Carefully monitor prediabetic and diabetic women who are taking COCs. COCs may decrease glucose tolerance in a dose-related fashion.

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

Headache

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

Bleeding Irregularities

Unscheduled (breakthrough) bleeding and spotting sometimes occur in patients on COCs, especially during the first 3 months of use. If bleeding persists, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different COC product.

When prescribing Amethia Lo, the convenience of fewer planned menses (4 per year instead of 13 per year) should be weighed against the inconvenience of increased unscheduled bleeding and/or spotting. The clinical trial that evaluated the efficacy of Amethia Lo also assessed unscheduled bleeding. The participants in this 12-month clinical trial (N=2,185) completed the equivalent of over 20,000 28-day cycles of exposure and were composed primarily of women who had used OCs previously (89%), as opposed to new users (11%). A total of 209 subjects (9.6%) discontinued Amethia Lo, at least in part, due to bleeding and/or spotting.

Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 2-3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 1 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 2 presents the number of days with unscheduled spotting in treatment cycles 1 and 4.

Table 1: Total Number of Days with Unscheduled Bleeding

91-Day Treatment Cycle	Days per 84-Day Interval				Days per 28-Day Interval
	Q1	Median	Q3	Mean	Mean
1st	0	5	11	7.5	2.5
4th	0	0	5	3.5	1.2

 Q1=Quartile 1: 25% of women had this number of days of unscheduled bleeding

Median: 50% of women had ≤ this number of days of unscheduled bleeding

Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding

Table 2: Total Number of Days with Unscheduled Spotting

91-Day Treatment Cycle	Days per 84-Day Interval				Days per 28-Day Interval
	Q1	Median	Q3	Mean	Mean
1st	3	10	19	14.0	4.7
4th	0	3	10	6.5	2.2

 Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled spotting

Median: 50% of women had ≤ this number of days of unscheduled spotting

Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled spotting

Figure 1 shows the percentage of Amethia Lo subjects participating in the primary clinical trial with ≥ 7 days or ≥ 20 days of unscheduled bleeding and/or spotting, or just unscheduled bleeding, during each 91-day treatment cycle.

Figure 1. Percent of Women Taking Amethia Lo who Reported Unscheduled Bleeding and/or Spotting (Based on Daily Diaries)

Amenorrhea sometimes occurs in women who are using COCs. Pregnancy should be ruled out in the event of amenorrhea. Some women may encounter amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent.

Interference with Laboratory Tests

The use of COCs may change the results of some laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid binding globulin increase with use of COCs.

Monitoring

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.

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

• Serious cardiovascular events and smoking [see BOXED WARNING] • 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

Clinical Trial Experience

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 the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The clinical trial that evaluated the safety and efficacy of Amethia Lo was a 12-month, multicenter, non-comparative open-label study, which enrolled women aged 18-41, of whom 2,185 took at least one dose of Amethia Lo.

Adverse Reactions Leading to Study Discontinuation: 11% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions leading to discontinuation were irregular and/or heavy uterine bleeding, headache, mood changes, nausea, acne, and weight gain.

Common Treatment-Emergent Adverse Reactions (≥ 5% of women): headaches (33%); irregular and/or heavy uterine bleeding (13%), dysmenorrhea (11%), nausea and/or vomiting (11%), back pain (8%).

Amethia Lo (levonorgestrel/ethinyl estradiol and ethinyl estradiol) tablets provide an oral contraceptive regimen of 84 orange tablets each containing 0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol, followed by 7 yellow tablets each containing 0.01 mg ethinyl estradiol.

The structural formulas for the active components are:

Levonorgestrel

C21H28O2 MW: 312.4

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

Ethinyl Estradiol

C20H24O2 MW: 296.4

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

Inactive ingredients for the orange tablets include FD&C Yellow # 6 (Sunset Yellow) aluminum lake, hypromellose, lactose, magnesium stearate, microcrystalline cellulose, corn starch, titanium dioxide and triacetin.

Inactive ingredients for the yellow tablets include anhydrous lactose, FD&C Yellow # 10 aluminum lake, FD&C Yellow # 6 (Sunset Yellow) aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polacrilin potassium, polyethylene glycol, polysorbate 80 and titanium dioxide.

Carcinogenesis, Mutagenesis, Impairment of Fertility

[See WARNINGS AND PRECAUTIONS (5.2, 5.3).]

See FDA-APPROVED PATIENT LABELING (17.2)

Information for Patients

• Counsel patients that 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. • Counsel patients that this product does not protect against HIV-infection (AIDS) and other sexually transmitted diseases. • Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed. • Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. • Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established. • Counsel any patient who starts COCs postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken an orange tablet for 7 consecutive days.

FDA Approved Patient Labeling

Guide for Using Amethia Lo

WARNING TO WOMEN WHO SMOKE

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

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 IS Amethia Lo?

Amethia Lo is a birth control pill. It contains two female hormones, an estrogen called ethinyl estradiol, and a progestin called levonorgestrel.

HOW WELL DOES Amethia Lo 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, 2 to 4 women, out of 100 women, may get pregnant during the first year they use Amethia Lo.

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 Lo?

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 Lo. 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 Lo, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control.

Before you start taking Amethia Lo

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 orange and 7 yellow pills. Trays 1 and 2 each contain 28 orange pills (4 rows of 7 pills). Tray 3 contains 35 pills consisting of 28 orange pills (4 rows of 7 pills) and 7 yellow 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 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 back-up in case you miss pills.

When to Start Amethia Lo

1. Take the first orange pill on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the first orange 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 orange 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 Amethia Lo for 7 days.

How to Take Amethia Lo

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 yellow pill, start taking the first orange 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 yellow pills, contact your healthcare provider because you may be pregnant. If you are pregnant, you should stop taking Amethia Lo.

WHAT TO DO IF YOU MISS PILLS

If you MISS 1 orange 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 2 orange 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 MORE orange 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 yellow pills, call your healthcare provider because you may be pregnant.

If you MISS ANY of the 7 yellow 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 Lo?

Your healthcare provider will not give you Amethia Lo if you have:

• Ever had breast cancer or any cancer that is sensitive to female hormones • Liver disease, including liver tumors • 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 Lo?

Birth control pills do not protect 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 Lo, may decrease the amount of milk you make. A small amount of the pill's hormones pass into breast milk, but this has not caused harmful effects in breastfeeding infants.

Tell your health care 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 health care 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)

A few 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 health care 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 health care 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 health care provider if you develop any side effects that concern you.

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

DO BIRTH CONTROL PILLS CAUSE CANCER?

Birth control pills do not appear to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills 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 Lo?

When you take Amethia Lo, which has a 91-day extended dosing cycle, you should expect to have 4 scheduled periods per year (bleeding when you are taking the 7 yellow pills). Each period is likely to last about 2 to 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. This bleeding or spotting tends to decrease with time. Do not stop taking Amethia Lo 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 Lo?

You should consider the possibility that you are pregnant if you miss your scheduled period (no bleeding on the days that you are taking yellow tablets). Since scheduled periods are less frequent when you are taking Amethia Lo, notify your healthcare provider that you have missed your period and that you are taking Amethia Lo. 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 Lo 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 health care provider for a pre-pregnancy checkup before you stop taking the pill.

Rx only

Manufactured by:
TEVA WOMEN’S HEALTH, INC.
Subsidiary of TEVA PHARMACEUTICALS USA, INC.
North Wales, PA  19454

Distributed by:

Mayne Pharma

Greenville, NC 27834

Rev. A 04/2016