Mode of Action

Pharmacokinetics

Special Populations

1. THROMBOEMBOLIC DISORDERS AND OTHER VASCULAR PROBLEMS

2. ESTIMATES OF MORTALITY FROM CONTRACEPTIVE USE

Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral-contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception.

Therefore, the Committee recommended that the benefits of oral-contraceptive use by healthy non-smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.

3. CARCINOMA OF THE REPRODUCTIVE ORGANS

The risk of having breast cancer diagnosed may be slightly increased among current and recent users of combination oral contraceptives. However, this excess risk appears to decrease over time after combination oral contraceptive discontinuation and by 10 years after cessation the increased risk disappears. Some studies report an increased risk with duration of use while other studies do not and no consistent relationships have been found with dose or type of steroid. Some studies have reported a small increase in risk for women who first use combination oral contraceptives at a younger age. Most studies show a similar pattern of risk with combination oral contraceptive use regardless of a woman's reproductive history or her family breast cancer history.

Breast cancers diagnosed in current or previous OC users tend to be less clinically advanced than in nonusers.

Women with known or suspected carcinoma of the breast or personal history of breast cancer should not use oral contraceptives because breast cancer is usually a hormonally-sensitive tumor.

Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

In spite of many studies of the relationship between combination oral contraceptive use and breast and cervical cancers, a cause-and-effect relationship has not been established.

4. HEPATIC NEOPLASIA

Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral-contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral-contraceptive users approaches less than one per million users.

5. RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT

6. OCULAR LESIONS

7. ORAL-CONTRACEPTIVE USE BEFORE OR DURING EARLY PREGNANCY

The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion.

It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral-contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral-contraceptive use should be discontinued if pregnancy is confirmed.

8. GALLBLADDER DISEASE

9. CARBOHYDRATE AND LIPID METABOLIC EFFECTS

A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS, 1a. and 1d.; PRECAUTIONS,3), changes in serum triglycerides and lipoprotein levels have been reported in oral-contraceptive users.

10. ELEVATED BLOOD PRESSURE

Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women with hypertension elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued (see CONTRAINDICATIONS section). For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users.

11. HEADACHE

12. BLEEDING IRREGULARITIES

Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was pre-existent.

13. ECTOPIC PREGNANCY

1. General

This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

2. Physical Examination and Follow-Up

3. Lipid Disorders

A small proportion of women will have adverse lipid changes while taking oral contraceptives. Nonhormonal contraception should be considered in women with uncontrolled dyslipidemias. Persistent hypertriglyceridemia may occur in a small population of combination oral contraceptive users. Elevations of plasma triglycerides may lead to pancreatitis and other complications.

4. Liver Function

5. Fluid Retention

6. Emotional Disorders

7. Contact Lenses

8. Gastrointestinal

9. Drug Interactions

Do not co-administer Falmina with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see WARINGS, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT)

Changes in Contraceptive Effectiveness Associated with Coadministration of Other Products:

Contraceptive effectiveness may be reduced when hormonal contraceptives are coadministered with antibiotics, anticonvulsants, and other drugs that increase the metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include rifampin, rifabutin, barbiturates, primidone, phenylbutazone, phenytoin, dexamethasone, carbamazepine, felbamate, oxcarbazepine, topiramate, griseofulvin, and modafinil. In such cases a back-up nonhormonal method of birth control should be considered.

Several cases of contraceptive failure and breakthrough bleeding have been reported in the literature with concomitant administration of antibiotics such as ampicillin and other penicillins, and tetracyclines. However, clinical pharmacology studies investigating drug interactions between combined oral contraceptives and these antibiotics have reported inconsistent results.

Several of the anti-HIV protease inhibitors have been studied with co-administration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The safety and efficacy of oral contraceptive products may be affected with coadministration of anti-HIV protease inhibitors. Healthcare providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.

Herbal products containing St. John's Wort (Hypericum perforatum) may induce hepatic enzymes (cytochrome P 450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.

Increase in Plasma Levels Associated with Co-Administered Drugs:

Co-administration of atorvastatin and certain oral contraceptives containing ethinyl estradiol increases AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen increase the bioavailability of ethinyl estradiol since these drugs act as competitive inhibitors for sulfation of ethinyl estradiol in the gastrointestinal wall, a known pathway of elimination for ethinyl estradiol. CYP 3A4 inhibitors such as indinavir, itraconazole, ketoconazole, fluconazole, and troleandomycin may increase plasma hormone levels. Troleandomycin may also increase the risk of intrahepatic cholestasis during coadministration with combination oral contraceptives.

Changes in Plasma Levels of Co-Administered Drugs:

Combination hormonal contraceptives containing some synthetic estrogens (eg, ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporin, prednisolone and other corticosteroids, and theophylline have been reported with concomitant administration of oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine, and clofibric acid, due to induction of conjugation (particularly glucuronidation), have been noted when these drugs were administered with oral contraceptives.

The prescribing information of concomitant medications should be consulted to identify potential interactions.

10. INTERACTIONS WITH LABORATORY TESTS

a. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.

b. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered.

c. Other binding proteins may be elevated in serum i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulins (SHBG) leading to increased levels of total circulating corticosteroids and sex steroids respectively. Free or biologically active hormone concentrations are unchanged.

d. Triglycerides may be increased and levels of various other lipids and lipoproteins may be affected.

e. Glucose tolerance may be decreased.

f. Serum folate levels may be depressed by oral-contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives.

11. CARCINOGENESIS

12. PREGNANCY

13. NURSING MOTHERS

14. PEDIATRIC USE

15. GERIATRIC USE

16. INFORMATION FOR THE PATIENT

During The First Cycle Of Use

After the first cycle of use

Switching from another hormonal method of contraception

If spotting or breakthrough bleeding occurs

Risk of pregnancy if tablets are missed

The risk of pregnancy increases with each active (orange) tablet missed. For additional patient instructions regarding missed tablets, see the WHAT TO DO IF YOU MISS PILLSsection in the DETAILED PATIENT LABELINGbelow.

Use after pregnancy, abortion or miscarriage

FALMINA may be initiated immediately after a first trimester abortion or miscarriage. If the patient starts FALMINA immediately, back-up contraception is not needed.

BRIEF SUMMARY PATIENT PACKAGE INSERT

Oral contraceptives, also known as "birth-control pills" or "the pill", are taken to prevent pregnancy, and when taken correctly, have a failure rate of less than 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3% per year when women who miss pills are included. For most women oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take pills considerably increases the chances of pregnancy.

For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you:

• smoke.
• have high blood pressure, diabetes, high cholesterol, or a tendency to form blood clots.
• have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice, malignant or benign liver tumors, or major surgery with prolonged immobilization.
• have headaches with neurological symptoms.

You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.

Although cardiovascular disease risks may be increased with oral-contraceptive use after age 40 in healthy, nonsmoking women, there are also greater potential health risks associated with pregnancy in older women.

The serious side effects of the pill occur very infrequently, especially if you are in good health and do not smoke. However, you should know that the following medical conditions have been associated with or made worse by the pill:

1. Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack and angina pectoris) or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences.

2. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.

3. High blood pressure, although blood pressure usually returns to normal when the pill is stopped.

The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your health-care provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics, herbal preparations containing St. John's Wort (Hypericum perforatum), and HIV/AIDS drugs may decrease oral-contraceptive effectiveness.

Various studies give conflicting reports on the relationship between breast cancer and oral contraceptive use.

Oral contraceptive use may slightly increase your chance of having breast cancer diagnosed, particularly if you started using hormonal contraceptives at a younger age.

After you stop using hormonal contraceptives, the chances of having breast cancer diagnosed begin to go down and disappear 10 years after stopping use of the pill. It is not known whether this slightly increased risk of having breast cancer diagnosed is caused by the pill. It may be that women taking the pill were examined more often, so that breast cancer was more likely to be detected.

You should have regular breast examinations by a health-care provider and examine your own breasts monthly. Tell your health-care provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormonesensitive tumor.

Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives.

Taking the pill provides some important noncontraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus.

Be sure to discuss any medical condition you may have with your health-care provider. Your health-care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health-care provider believes that it is appropriate to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information leaflet gives you further information which you should read and discuss with your health-care provider.

HOW TO TAKE FALMINA

IMPORTANT POINTS TO REMEMBER

BEFORE YOU START TAKING FALMINA:

1. BE SURE TO READ THESE DIRECTIONS:

Before you start taking FALMINA.

And

Anytime you are not sure what to do.

2. THE RIGHT WAY TO TAKE THE PILL IS TO 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. See "WHAT TO DO IF YOU MISS PILLS" below.

3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS.

If you feel sick to your stomach, do not stop taking FALMINA. The problem will usually go away. If it doesn't go away, check with your health-care provider.

4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills.

On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach.

5. IF YOU HAVE VOMITING (within 4 hours after you take your pill), you should follow the instructions for WHAT TO DO IF YOU MISS PILLS. IF YOU HAVE DIARRHEA or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well.

Use a back-up nonhormonal method (such as condoms or spermicide) until you check with your health-care provider.

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your health-care provider about how to make pill-taking easier or about using another method of birth control.

7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your health-care provider.

BEFORE YOU START TAKING YOUR PILLS

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 PILL PACK TO SEE IF IT HAS 28 PILLS: The 28-pill pack has 21 "active" orange pills (with hormones) to take for 3 weeks, followed by 1 week of reminder white 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), and

3) the week numbers as shown in the picture below.

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

AN EXTRA, FULL PILL PACK.

WHEN TO START THE FIRST PACK OF PILLS

You have a choice of which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember.

DAY 1 START:

1. Pick the day label strip that starts with the first day of your period. Place this day label strip over the area that has the days of the week (starting with Sunday) pre-printed on the tablet dispenser.

Note: if the first day of your period is a Sunday, you can skip step #1.

3. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.

SUNDAY START:

1. Take the first "active" orange pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.

2. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms or foam are good back-up methods of birth control.

WHAT TO DO DURING THE MONTH

1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.

Do not skip pills even if you are spotting or bleeding between monthly periods 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 PACK OR SWITCH YOUR BRAND OF PILLS: Start the next pack on the day after your last "reminder" pill. Do not wait any days between packs.

IF YOU SWITCH FROM ANOTHER BRAND OR COMBINATION PILLS

If your previous brand had 21 pills: Wait 7 days to start taking FALMINA. You will probably have your period during that week. Be sure that no more than 7 days pass between the 21-day pack and taking the first orange FALMINA pill ("active" with hormone).

If your previous brand had 28 pills: Start taking the first orange FALMINA pill ("active" with hormone) on the day after your last reminder pill. Do not wait any days between packs.

WHAT TO DO IF YOU MISS PILLS

If you MISS 1 orange "active" 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 "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:

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 MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms or foam) as a back-up for those 7 days.

If you MISS 2 orange "active" pills in a row in THE 3rd WEEK:

1. If you are a Day 1 Starter:

THROW OUT the rest of the pill pack and start a new pack that same day.

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.

2. 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 doctor or clinic because you might be pregnant.

3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms, or foam) as a back-up for those 7 days.

If you MISS 3 OR MORE orange "active" pills in a row (during the first 3 weeks):

1. If you are a Day 1 Starter:

THROW OUT the rest of the pill pack and start a new pack that same day.

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.

2. 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 doctor or clinic because you might be pregnant.

3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms, or foam) as a back-up for those 7 days.

If you forget any of the 7 white "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method if you start your next pack on time.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED

Use a BACK-UP METHOD anytime you have sex.

KEEP TAKING ONE PILL EACH DAY until you can reach your doctor or clinic.

BIRTH CONTROL AFTER STOPPING THE PILL

If you do not wish to become pregnant after stopping the pill, speak to your health-care provider about another method of birth control.

DETAILED PATIENT LABELING

INTRODUCTION

EFFECTIVENESS OF ORAL CONTRACEPTIVES

• History of heart attack or stroke.
• Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes.
• A history of blood clots in the deep veins of your legs.
• Chest pain (angina pectoris).
• Known or suspected breast cancer or cancer of the lining of the uterus, cervix or vagina, or certain hormonally-sensitive cancers.
• Unexplained vaginal bleeding (until a diagnosis is reached by your health-care provider).
• Liver tumor (benign or cancerous) or active liver disease.
• Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill.
• Known or suspected pregnancy.
• A need for surgery with prolonged bedrest.
• Heart valve or heart rhythm disorders that may be associated with formation of blood clots.
• Diabetes affecting your circulation.
• Headaches with neurological symptoms.
• Uncontrolled high blood pressure.
• Allergy or hypersensitivity to any of the components of FALMINA (levonorgestrel and ethinyl estradiol tablets).

You should not take the pills if you 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.

OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES

Tell your health-care provider if you or any family member has ever had:

• Breast nodules, fibrocystic disease of the breast, an abnormal breast X-ray or mammogram.
• Diabetes.
• Elevated cholesterol or triglycerides.
• High blood pressure.
• A tendency to form blood clots.
• Migraine or other headaches or epilepsy.
• Depression.
• Gallbladder, liver, heart, or kidney disease.
• History of scanty or irregular menstrual periods.

Although cardiovascular disease risks may be increased with oral contraceptive use in healthy, non-smoking women over 40 (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women.

RISKS OF TAKING ORAL CONTRACEPTIVES

1. Risks of developing blood clots

Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision.

Users of combination oral contraceptives have a higher risk of developing blood clots compared to non-users. This risk is highest during the first year of combination oral-contraceptive use.

If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness or injury, or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your health-care provider about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby or after a midtrimester pregnancy termination. It is advisable to wait for at least four weeks after delivery if you are not breast-feeding. If you are breast-feeding, you should wait until you have weaned your child before using the pill. (See also the section While breast-feedingin GENERAL PRECAUTIONS.)

The risk of blood clots is greater in users of combination oral contraceptives compared to nonusers. This risk may be higher in users of high-dose pills (those containing 50 mcg or more of estrogen) and may also be greater with longer use. In addition, some of these increased risks may continue for a number of years after stopping combination oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of combination oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages.

The excess risk of blood clots is highest during the first year a woman ever uses a combined oral contraceptive. This increased risk is lower than blood clots associated with pregnancy. The use of combination oral contraceptives also increases the risk of other clotting disorders, including heart attack and stroke. Blood clots in veins cause death in 1% to 2% of cases. The risk of clotting is further increased in women with other conditions. Examples include: smoking, high blood pressure, abnormal lipid levels, certain inherited or acquired clotting disorders, obesity, surgery or injury, recent delivery or second trimester abortion, prolonged inactivity or bedrest. If possible, combination oral contraceptives should be stopped before surgery and during prolonged inactivity or bedrest.

Cigarette smoking increases the risk of serious cardiovascular events. This risk increases with age and amount of smoking and is quite pronounced in women over 35. Women who use combination oral contraceptives should be strongly advised not to smoke. If you smoke you should talk to your health care professional before taking combination oral contraceptives.

2. Heart attacks and strokes

Oral contraceptives may increase the tendency to develop strokes or transient ischemic attacks (blockage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or serious disability.

Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease.

Women with migraine (especially migraine/headache with neurological symptoms) who take oral contraceptives also may be at higher risk of stroke and must not use combination oral contraceptives (see section WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES).

3. Gallbladder disease

Oral-contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens. Oral contraceptives may worsen existing gallbladder disease or accelerate the development of gallbladder disease in women previously without symptoms.

4. Liver tumors

In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible but not definite association has been found with the pill and liver cancers in two studies in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer.

5. Cancer of the reproductive organs and breasts

Various studies give conflicting reports on the relationship between breast cancer and oral contraceptive use.

Oral contraceptive use may slightly increase your chance of having breast cancer diagnosed, particularly if you started using hormonal contraceptives at a younger age.

After you stop using hormonal contraceptives, the chances of having breast cancer diagnosed begin to go down and disappear 10 years after stopping use of the pill. It is not known whether this slightly increased risk of having breast cancer diagnosed is caused by the pill. It may be that women taking the pill were examined more often, so that breast cancer was more likely to be detected.

You should have regular breast examinations by a health-care provider and examine your own breasts monthly. Tell your health-care provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormonesensitive tumor.

Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives.

6. Lipid Metabolism and Pancreatitis

There have been reports of increases of blood cholesterol and triglycerides in users of combination oral contraceptives. Increases in triglycerides have led to inflammation of the pancreas (pancreatitis) in some cases.

ESTIMATED RISK OF DEATH FROM A BIRTH-CONTROL METHOD OR PREGNANCY

All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table.

The suggestion that women over 40 who do not smoke should not take oral contraceptives is based on information from older high-dose pills. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral-contraceptive use by healthy, nonsmoking women over 40 years of age may outweigh the possible risks. Older women, as all women, who take oral contraceptives, should take an oral contraceptive which contains the least amount of estrogen and progestogen that is compatible with the individual patient needs.

WARNING SIGNALS

If any of these adverse effects occur while you are taking oral contraceptives, call your healthcare provider immediately:

• Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung).
• Pain in the calf (indicating a possible clot in the leg).
• Crushing chest pain or heaviness in the chest (indicating a possible heart attack).
• Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke).
• Sudden partial or complete loss of vision (indicating a possible clot in the eye).
• Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your health-care provider to show you how to examine your breasts).
• Severe pain or tenderness in the stomach area (indicating a possibly ruptured liver tumor).
• Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression).
• Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems).

1. Unscheduled or breakthrough vaginal bleeding or spotting

Unscheduled vaginal bleeding or spotting may occur while you are taking the pills. Unscheduled bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Unscheduled bleeding occurs most often during the first few months of oral-contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle or lasts for more than a few days, talk to your health-care provider.

2. Contact lenses

If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your health-care provider.

3. Fluid retention

Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your health-care provider.

4. Melasma

A spotty darkening of the skin is possible, particularly of the face.

5. Other side effects

Other side effects may include nausea, breast tenderness, change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, vaginal infections, inflammation of the pancreas, and allergic reactions.

If any of these side effects bother you, call your health-care provider.

1. Missed periods and use of oral contraceptives before or during early pregnancy

There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your health-care provider before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your health-care provider immediately to determine whether you are pregnant. Stop taking oral contraceptives if you are pregnant.

There is no conclusive evidence that oral-contraceptive use is associated with an increase in birth defects, when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives should not be used during pregnancy. You should check with your health-care provider about risks to your unborn child of any medication taken during pregnancy.

If you are breast-feeding, consult your health-care provider before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breast-feeding. You should use another method of contraception since breast-feeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breast-feed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely.

3. Laboratory tests

If you are scheduled for any laboratory tests, tell your doctor you are taking birth-control pills. Certain blood tests may be affected by birth-control pills.

4. Drug interactions

Certain drugs may interact with birth-control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital) and phenytoin (Dilantin® is one brand of this drug), primidone (Mysoline®), topiramate (Topamax®), carbamazepine (Tegretol® is one brand of this drug), phenylbutazone (Butazolidin® is one brand), some drugs used for HIV or AIDS such as ritonavir (Norvir®), modafinil (Provigil®) and possibly certain antibiotics (such as ampicillin and other penicillins, and tetracyclines), and herbal products containing St. John's Wort (Hypericum perforatum). You may also need to use a nonhormonal method of contraception during any cycle in which you take drugs that can make oral contraceptives less effective.

You may be at higher risk of a specific type of liver dysfunction if you take troleandomycin and oral contraceptives at the same time.

You should inform your health-care provider about all medicines you are taking, including nonprescription products.

5. Sexually transmitted diseases

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis.

HOW TO TAKE THE PILL

BEFORE YOU START TAKING YOUR PILLS:

1. BE SURE TO READ THESE DIRECTIONS:

Before you start taking your pills.

And

Anytime you are not sure what to do.

2. THE RIGHT WAY TO TAKE THE PILL IS TO 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.

3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1 TO 3 PACKS OF PILLS.

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 doctor or clinic.

4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach.

5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well.

Use a back-up method (such as condoms or foam) until you check with your doctor or clinic.

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control.

7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic.

BEFORE YOU START TAKING YOUR PILLS

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 PILL PACK TO SEE IF IT HAS 28 PILLS: The 28-pill pack has 21 "active" orange pills (with hormones) to take for 3 weeks, followed by 1 week of reminder white 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), and

3) the week numbers as shown in the picture below.

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

AN EXTRA, FULL PILL PACK.

For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS below.

WHEN TO START THE FIRST PACK OF PILLS

Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember.

DAY 1 START:

1. Pick the day label strip that starts with the first day of your period. Place this day label strip over the area that has the days of the week (starting with Sunday) pre-printed on the tablet dispenser.

Note: if the first day of your period is a Sunday, you can skip step #1.

3. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period.

SUNDAY START:

1. Take the first "active" orange pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day.

2. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms or foam are good back-up methods of birth control.

WHAT TO DO DURING THE MONTH

1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.

Do not skip pills even if you are spotting or bleeding between monthly periods 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 PACK OR SWITCH YOUR BRAND OF PILLS: Start the next pack on the day after your last "reminder" pill. Do not wait any days between packs.

IF YOU SWITCH FROM ANOTHER BRAND OR COMBINATION PILLS

If your previous brand had 21 pills: Wait 7 days to start taking FALMINA. You will probably have your period during that week. Be sure that no more than 7 days pass between the 21-day pack and taking the first orange FALMINA pill ("active" with hormone).

If your previous brand had 28 pills: Start taking the first orange FALMINA pill ("active" with hormone) on the day after your last reminder pill. Do not wait any days between packs.

WHAT TO DO IF YOU MISS PILLS

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 "active" pills in a row in WEEK 1 OR WEEK 2 of your pack:

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 MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms or foam) as a back-up for those 7 days.

If you MISS 2 orange "active" pills in a row in THE 3rd WEEK:

1. If you are a Day 1 Starter:

THROW OUT the rest of the pill pack and start a new pack that same day.

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.

2. 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 doctor or clinic because you might be pregnant.

3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms, or foam) as a back-up for those 7 days.

If you MISS 3 OR MORE orange "active" pills in a row (during the first 3 weeks):

1. If you are a Day 1 Starter:

THROW OUT the rest of the pill pack and start a new pack that same day.

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.

2. 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 doctor or clinic because you might be pregnant.

3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth-control method (such as condoms, or foam) as a back-up for those 7 days.

If you forget any of the 7 white "reminder" pills in Week 4:

THROW AWAY the pills you missed.

Keep taking 1 pill each day until the pack is empty.

You do not need a back-up method if you start your next pack on time.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED

Use a BACK-UP METHOD anytime you have sex.

KEEP TAKING ONE PILL EACH DAY until you can reach your doctor or clinic.

Pregnancy due to pill failure

The incidence of pill failure resulting in pregnancy is approximately 1 per year (1 pregnancy per100 women per year of use) if taken every day as directed, but the more typical failure rate is approximately 5% per year (5 pregnancies per 100 women per year of use) including women who do not always take the pill exactly as directed without missing any pills. If you do become pregnant, the risk to the fetus is minimal, but you should stop taking your pills and discuss the pregnancy with your health-care provider

Pregnancy after stopping the pill

There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy.

There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill.

Birth Control after stopping the pill

If you do not wish to become pregnant after stopping the pill, you should use another method of birth control immediately after stopping FALMINA. Speak to your health-care provider about another method of birth control.

Overdosage

Overdosage may cause nausea, vomiting, breast tenderness, dizziness, abdominal pain and fatigue/drowsiness. Withdrawal bleeding may occur in females. In case of overdosage, contact your health-care provider or pharmacist.

Other information

Your health-care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health-care provider believes that it is appropriate to postpone it. You should be re-examined at least once a year. Be sure to inform your health-care provider if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your health-care provider, because this is a time to determine if there are early signs of side effects of oral-contraceptive use.

Do not use the drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth-control pills.

HEALTH BENEFITS FROM ORAL CONTRACEPTIVES

In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are:

• Menstrual cycles may become more regular
• Blood flow during menstruation may be lighter, and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur
• Pain or other symptoms during menstruation may be encountered less frequently
• Ovarian cysts may occur less frequently
• Ectopic (tubal) pregnancy may occur less frequently
• Noncancerous cysts or lumps in the breast may occur less frequently
• Acute pelvic inflammatory disease may occur less frequently
• Oral-contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus

To report SUSPECTED ADVERSE REACTIONS, contact Novast Laboratories, Ltd. Toll-Free at 1-877-966-8278 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Memphis TN 38141

Toll Free 1-800-206-7821

Manufactured by: Novast Laboratories Ltd.

Nantong, China 226009

I0017 Rev.A Iss.10/2018