COMBINED ORAL CONTRACEPTIVES

Cyclafem™ 7/7/7 (norethindrone and ethinyl estradiol tablets USP) is a combined oral contraceptive containing the progestational compound norethindrone and the estrogenic compound ethinyl estradiol.

Each white tablet contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include hypromellose 2910 6cP, lactose monohydrate, magnesium stearate, polyethylene glycol 400, polyethylene glycol 8000 and pregelatinized starch. Each light-pink tablet contains 0.75 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C red #40 aluminum lake, hypromellose 2910 6cP, lactose monohydrate, magnesium stearate, polyethylene glycol 400, polyethylene glycol 8000, and pregelatinized starch. Each pink tablet contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include FD&C red #40 aluminum lake, hypromellose 2910 6cP, lactose monohydrate, magnesium stearate, polyethylene glycol 400, polyethylene glycol 8000, and pregelatinized starch. Each light-green tablet contains only inert ingredients, as follows: FD&C blue #2, hypromellose 2910 6cP, iron oxide yellow, lactose monohydrate, magnesium stearate, polyethylene glycol 400, polyethylene glycol 8000 and pregelatinized starch.

The chemical name for norethindrone is 17-Hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one, and for ethinyl estradiol is 19-Nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. Their structural formulas are as follows:

Combined Oral Contraceptives

Combined oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes.

Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks.

The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined.

Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral con­traceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from refs. 2 and 3 with the author's permission). For further information, the reader is referred to a text on epidemiological methods.

1. Thromboembolic Disorders and Other Vascular Problems

a. Myocardial Infarction

An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six.4-10 The risk is very low under the age of 30.

Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases.11 Mortality rates associated with circulatory disease have been shown to increase substantially in smokers, especially in those 35 years of age and older, and in nonsmokers over the age of 40 among women who use oral contraceptives. (See Figure 1).

FIGURE 1: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMAN-YEARS BY AGE, SMOKING STATUS AND ORAL CONTRACEPTIVE USE

Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity.13 In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism.14-18 Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors.

2. Estimates of Mortality From Contraceptive Use

One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 2). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke, and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of an increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's.35 Current clinical recommendation involves the use of lower estrogen dose formulations and a careful consideration of risk factors. In 1989, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the use of oral contraceptives in women 40 years of age and over. 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 also 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. The Committee recommended that the benefits of low-dose 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 an oral contraceptive which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and individual patient needs.

Adapted from H.W. Ory, ref. #35.

3. Carcinoma of the Reproductive Organs and Breasts

Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives. The risk of having breast cancer diagnosed may be slightly increased among current and recent users of COCs. However, this excess risk appears to decrease over time after COC 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 found a small increase in risk for women who first use COCs before age 20. Most studies show a similar pattern of risk with COC 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 who currently have or have had 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 in some populations of women.45-48 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 oral contraceptive use and breast and cervical cancers, a cause-and-effect relationship has not been established.

4. Hepatic Neoplasia

Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose.49 Rupture of benign, hepatic adenomas may cause death through intra-abdominal hemorrhage.50,51

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. Ocular Lesions

There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately.

6. Oral Contraceptive Use Before or During Early Pregnancy

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy.56,57 The majority of recent studies also do not indicate a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned,55,56,58,59 when taken inadvertently 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. 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.

7. Gallbladder Disease

Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens.60,61 More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal.62-64 The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens.

8. Carbohydrate and Lipid Metabolic Effects

Oral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users.17 This effect has been shown to be directly related to estrogen dose.65 Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents.17,66 However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose.67 Because of these demonstrated effects, prediabetic and diabetic women in particular should be carefully monitored while taking oral contraceptives.

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

9. Elevated Blood Pressure

Women with significant hypertension should not be started on hormonal contraception.92 An increase in blood pressure has been reported in women taking oral contraceptives68 and this increase is more likely in older oral contraceptive users69 and with extended duration of use.61 Data from the Royal College of General Practitioners12 and subsequent randomized trials have shown that the incidence of hypertension increases with increasing progestational activity.

Women with a history of hypertension or hypertension-related diseases, or renal disease70 should be encouraged to use another method of contraception. If these women elect to use oral contraceptives, they should be monitored closely and if a clinically significant persistent elevation of blood pressure (BP) occurs (≥ 160 mm Hg systolic or ≥ 100 mm Hg diastolic) and cannot be adequately controlled, oral contraceptives should be discontinued. In general, women who develop hypertension during hormonal contraceptive therapy should be switched to a non-hormonal contraceptive. If other contraceptive methods are not suitable, hormonal contraceptive therapy may continue combined with antihypertensive therapy. Regular monitoring of BP throughout hormonal contraceptive therapy is recommended.96 For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension between former and never users.68–71

10. Headache

The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause.

11. Bleeding Irregularities

Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out.

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

12. Ectopic Pregnancy

Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.

1. General

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

2. Physical Examination and Follow-Up

It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care.

3. Lipid Disorders

Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult.

4. Liver Function

If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function.

5. Fluid Retention

Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.

6. Emotional Disorders

Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.

7. Contact Lenses

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

8. Drug Interactions

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

Effects of Other Drugs on Combined Hormonal Contraceptives

Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs:

Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of COCs:

Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations.

Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:

Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).

Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.

Effects of Combined Hormonal Contraceptives on Other Drugs

COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.

Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs.

9. Interactions With Laboratory Tests

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives:

1. Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability.
2. 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.
3. Other binding proteins may be elevated in serum.
4. Sex-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged.
5. Triglycerides may be increased and levels of various other lipids and lipoproteins may be affected.
6. Glucose tolerance may be decreased.
7. 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.

10. Carcinogenesis

See WARNINGS.

11. Pregnancy

12. Nursing Mothers

Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, combined oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use combined oral contraceptives but to use other forms of contraception until she has completely weaned her child.

13. Pediatric Use

Safety and efficacy of norethindrone and ethinyl estradiol tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated.

14. Geriatric Use

This product has not been studied in women over 65 years of age and is not indicated in this population.

Sunday Start

When taking Cyclafem™ 7/7/7 tablets, the first "active" tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first "active" tablet should be taken that day. Take one active tablet daily for 21 days followed by one light-green "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception such as a condom or spermicide should be used until after the first 7 consecutive days of administration.

If the patient misses one (1) "active" tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) "active" tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) "active" tablets in the third week or misses three (3) or more "active" tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the DETAILED PATIENT LABELING ("HOW TO TAKE THE PILL" section).

Day 1 Start

The dosage of Cyclafem™ 7/7/7 tablets, for the initial cycle of therapy, is one "active" tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1" followed by one light-green "reminder" tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day.

If the patient misses one (1) "active" tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) "active" tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) "active" tablets in the third week or misses three (3) or more "active" tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the DETAILED PATIENT LABELING ("HOW TO TAKE THE PILL" section).

The use of Cyclafem™ 7/7/7 tablets, for contraception may be initiated 4 weeks postpartum in women who elect not to breast feed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease; see also PRECAUTIONS for "Nursing Mothers"). The possibility of ovulation and conception prior to initiation of medication should be considered.

(See Discussion of Dose-Related Risk of Vascular Disease From Oral Contraceptives.)

ADDITIONAL INSTRUCTIONS

Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease.

Use of oral contraceptives in the event of a missed menstrual period:

1. 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 and oral contraceptive use should be discontinued if pregnancy is confirmed.
2. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use.

The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. 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 or 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. 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, some studies report an increased risk of developing liver cancer. However, liver cancers are rare.

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 healthcare professional if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, bosentan, as well as some seizure medicines and herbal preparations containing St. John's wort (Hypericum perforatum) may decrease oral contraceptive effectiveness.

Oral contraceptives may interact with lamotrigine (LAMICTAL®), a seizure medicine used for epilepsy. This may increase the risk of seizures so your healthcare professional may need to adjust the dose of lamotrigine.

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 after using hormonal contraceptives at a younger age. After you stop using hormonal contraceptives, the chances of having breast cancer diagnosed begin to go back down. You should have regular breast examinations by a healthcare professional and examine your own breasts monthly. Tell your healthcare professional 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 hormone-sensitive 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. There is insufficient evidence to rule out the possibility that the pill may cause such cancers.

Taking the combination pill provides some important non-contraceptive 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 healthcare professional. Your healthcare professional 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 healthcare professional believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. Your pharmacist should have given you the detailed patient information labeling which gives you further information which you should read and discuss with your healthcare professional.

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.
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 healthcare professional.

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, or IF YOU TAKE SOME MEDICINES, your pills may not work as well. Use a back-up method (such as a condom or spermicide) until you check with your healthcare professional.

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare professional 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 healthcare professional.

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.
The pill pack has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of light-green "reminder" pills (without hormones). There are 7 white "active" pills, 7 light-pink "active" pills, 7 pink "active" pills and 7 light-green "reminder" pills.

3. ALSO FIND:
     1) where on the pack to start taking pills,
     2) in what order to take the pills.

4. BE SURE YOU HAVE READY AT ALL TIMES:
ANOTHER KIND OF BIRTH CONTROL (such as a condom or spermicide) to use as a back-up method in case you miss pills.

AN EXTRA, FULL PILL PACK.

You have a choice of which day to start taking your first pack of pills. Cyclafem™ 7/7/7 is available in the blister pack tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided. Decide with your healthcare professional which is the best day for you. Pick a time of day that will be easy to remember.

SUNDAY START:
Take the first white "active" 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 the same day.

Use another method of birth control such as a condom or spermicide as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days).

DAY 1 START:
Take the first white "active" pill of the first pack during the first 24 hours of your period.

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.

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 light-green "reminder" pill. Do not wait any days between packs.

If you MISS 1 white, light-pink, or pink "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 white or light-pink "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 COULD BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as a condom or spermicide) as a back-up method for those 7 days.

If you MISS 2 pink "active" pills in a row in THE 3RD WEEK:
1a. 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.

1b. If you are a Day 1 Starter:
THROW OUT the rest of the pill pack and start a new pack 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 healthcare professional because you might be pregnant.

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

If you MISS 3 OR MORE white, light-pink, or pink "active" pills in a row (during the first 3 weeks):
1a. 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.

1b. If you are a Day 1 Starter:

THROW OUT the rest of the pill pack and start a new pack 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 healthcare professional because you might be pregnant.

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

If you forget any of the 7 light-green "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.

Manufactured In Canada By:
Patheon Inc.
Ontario, Canada L5N 7K9

Manufactured For:
QUALITEST PHARMACEUTICALS USA
Huntsville, AL 35811

Some women should not use the pill. For example, you should not take the pill if you have any of the following conditions:

• A 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
• An inherited problem that makes your blood clot more than normal
• Chest pain (angina pectoris)
• Known or suspected breast cancer or cancer of the lining of the uterus, cervix or vagina
• Unexplained vaginal bleeding (until a diagnosis is reached by your healthcare professional)
• Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill
• Liver tumor (benign or cancerous)
• Known or suspected pregnancy
• Valvular heart disease with complications
• Severe hypertension
• Diabetes with vascular involvement
• Headaches with focal neurological symptoms
• If you plan to have surgery with prolonged bed rest
• Hypersensitivity to any component of this product

Tell your healthcare professional if you have ever had any of these conditions. Your healthcare professional can recommend a safer method of birth control.

OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES
Tell your healthcare professional if you have or have had:

• Breast nodules, fibrocystic disease of the breast, an abnormal breast x-ray or mammogram
• Diabetes
• Elevated cholesterol or triglycerides
• High blood pressure
• Migraine or other headaches or epilepsy
• Mental depression
• Gallbladder, liver, heart or kidney disease
• History of scanty or irregular menstrual periods

Women with any of these conditions should be checked often by their healthcare professional if they choose to use oral contraceptives.

Also, be sure to inform your healthcare professional if you smoke or are on any medications.

RISKS OF TAKING ORAL CONTRACEPTIVES
1. Risk of Developing Blood Clots
Blood clots and blockage of blood vessels are one of 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.

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 healthcare professional 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. It is advisable to wait for at least four weeks after delivery if you are not breast feeding or four weeks after a second trimester abortion. If you are breast feeding, you should wait until you have weaned your child before using the pill (see also the section on Breast Feeding in GENERAL PRECAUTIONS).

The risk of circulatory disease in oral contraceptive users may be higher in users of high-dose pills and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44, it is estimated that about 1 in 2,000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among nonusers in the same age group, about 1 in 20,000 would be hospitalized each year. For oral contraceptive users in general, it has been estimated that in women between the ages of 15 and 34 the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for nonusers the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2,500 per year for oral contraceptive users and about 1 in 10,000 per year for nonusers.

2. Heart Attacks and Strokes
Oral contraceptives may increase the tendency to develop strokes (stoppage 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.

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.

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, some studies report an increased risk of developing liver cancer. However, liver cancers are rare.

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 after using hormonal contraceptives at a younger age. After you stop using hormonal contraceptives, the chances of having breast cancer diagnosed begin to go back down. You should have regular breast examinations by a healthcare professional and examine your own breasts monthly. Tell your healthcare professional 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 hormone-sensitive 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. There is insufficient evidence to rule out the possibility that the pill may cause such cancers.

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.

In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7 to 26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group, although over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group.

The suggestion that women over 40 who do not smoke should not take oral contraceptives is based on information from older, higher-dose pills. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of low-dose oral contraceptive use by healthy, non-smoking women over 40 years of age may outweigh the possible risks.

WARNING SIGNALS
If any of these adverse effects occur while you are taking oral contraceptives, call your healthcare professional 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 healthcare professional 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)

SIDE EFFECTS OF ORAL CONTRACEPTIVES
1. Vaginal Bleeding
Irregular vaginal bleeding or spotting may occur while you are taking the pills. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular 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 healthcare professional.

2. Contact Lenses
If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your healthcare professional.

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 healthcare professional.

4. Melasma
A spotty darkening of the skin is possible, particularly of the face, which may persist.

5. Other Side Effects
Other side effects may include nausea, vomiting and diarrhea, muscle cramps, change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, vaginal infections, pancreatitis, skin sensitivity to the sun or ultraviolet and allergic reactions.

If any of these side effects bother you, call your healthcare professional.

GENERAL PRECAUTIONS
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 healthcare professional before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, you may be pregnant. If you missed two consecutive menstrual periods, you may be pregnant. Check with your healthcare professional immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of contraception.

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 findings have not been seen in more recent studies. Nevertheless, oral contraceptives should not be used during pregnancy. You should check with your healthcare professional about risks to your unborn child of any medication taken during pregnancy.

2. While Breast Feeding
If you are breast feeding, consult your healthcare professional 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, combined oral contraceptives may decrease the amount and quality of your milk. If possible, do not use combined 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 combined oral contraceptives only after you have weaned your child completely.

3. Laboratory Tests
If you are scheduled for any laboratory tests, tell your healthcare professional you are taking birth control pills. Certain blood tests may be affected by birth control pills.

4. Drug Interactions

Tell your healthcare provider about all medicines and herbal products that you take.

Some medicines and herbal products may make hormonal birth control less effective, including, but not limited to:

• certain seizure medicines (carbamazepine, felbamate, oxcarbazepine, phenytoin, rufinamide, and topiramate)
• aprepitant
• barbiturates
• bosentan
• colesevelam
• griseofulvin
• certain combinations of HIV medicines (nelfinavir, ritonavir, ritonavirboosted protease inhibitors)
• certain non nucleoside reverse transcriptase inhibitors (nevirapine)
• rifampin and rifabutin
• St. John's wort

Use another birth control method (such as a condom and spermicide or diaphragm and spermicide) when you take medicines that may make Cyclafem™ 7/7/7 (norethindrone and ethinyl estradiol tablets USP) less effective.

Some medicines and grapefruit juice may increase your level of the hormone ethinyl estradiol if used together, including:

• acetaminophen
• ascorbic acid
• medicines that affect how your liver breaks down other medicines (itraconazole, ketoconazole, voriconazole, and fluconazole)
• certain HIV medicines (atazanavir, indinavir)
• atorvastatin
• rosuvastatin
• etravirine

Hormonal birth control methods may interact with lamotrigine, a seizure medicine used for epilepsy. This may increase the risk of seizures, so your healthcare provider may need to adjust the dose of lamotrigine.

Women on thyroid replacement therapy may need increased doses of thyroid hormone.

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

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.

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 healthcare professional.

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, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well. Use a back-up method (such as a condom or spermicide) until you check with your healthcare professional.

6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare professional 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 healthcare professional.

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.
The pill pack has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of light-green "reminder" pills (without hormones). There are 7 white "active" pills, 7 light-pink "active" pills, 7 pink "active" pills and 7 light-green "reminder" pills.

3. ALSO FIND:
     1) where on the pack to start taking pills,
     2) in what order to take the pills.

CHECK PICTURE OF PILL PACK AND ADDITIONAL INSTRUCTIONS FOR USING THIS PACKAGE IN THE BRIEF SUMMARY PATIENT PACKAGE INSERT.

4. BE SURE YOU HAVE READY AT ALL TIMES:
ANOTHER KIND OF BIRTH CONTROL (such as a condom or spermicide) to use as a back-up method in case you miss pills.

AN EXTRA, FULL PILL PACK.

You have a choice of which day to start taking your first pack of pills. Cyclafem™ 7/7/7 is available in the blister pack tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided. Decide with your healthcare professional which is the best day for you. Pick a time of day that will be easy to remember.

SUNDAY START:
Take the first white "active" 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 the same day.

Use another method of birth control such as a condom or spermicide as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days).

DAY 1 START:
Take the first white "active" pill of the first pack during the first 24 hours of your period.

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.

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 light-green "reminder" pill. Do not wait any days between packs.

If you MISS 1 white, light-pink, or pink "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 white or light-pink "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 COULD BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as a condom or spermicide) as a back-up method for those 7 days.

If you MISS 2 pink "active" pills in a row in THE 3RD WEEK:
1a. 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.

1b. If you are a Day 1 Starter:
THROW OUT the rest of the pill pack and start a new pack 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 healthcare professional because you might be pregnant.

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

If you MISS 3 OR MORE white, light-pink, or pink "active" pills in a row (during the first 3 weeks):
1a. 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.

1b. If you are a Day 1 Starter:
THROW OUT the rest of the pill pack and start a new pack 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 healthcare professional because you might be pregnant.

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

PREGNANCY DUE TO PILL FAILURE
Combined Oral Contraceptives
The incidence of pill failure resulting in pregnancy is approximately one percent (i.e., one pregnancy per 100 women per year) if taken every day as directed, but more typical failure rates are 5%. If failure does occur, the risk to the fetus is minimal.

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.

OVERDOSAGE
Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your healthcare professional or pharmacist.

OTHER INFORMATION
Your healthcare professional 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 healthcare professional believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be sure to inform your healthcare professional if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your healthcare professional, 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 combined 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
• 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.

If you want more information about birth control pills, ask your healthcare professional. They have a more technical leaflet called the Professional Labeling, which you may wish to read.

Manufactured In Canada By:
Patheon Inc.
Ontario, Canada L5N 7K9

Manufactured For:
QUALITEST PHARMACEUTICALS USA
Huntsville, AL 35811

Rev. 10/2013
R0