PIRMELLA 1/35 (norethindrone 1 mg ethinyl estradiol 0.035 mg) Dailymed

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. 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.

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. TABLE  2 :  ANNUAL  NUMBER  OF  BIRTH - RELATED  OR  METHOD - RELATED  DEATHS  ASSOCIATED  WITH  CONTROL  OF  FERTILITY  PER  100 , 000  NONSTERILE  WOMEN ,  BY  FERTILITY  CONTROL  METHOD  ACCORDING  TO  AGE Method  of  control  and  outcome 15  to  19 20  to  24 25  to  29 30  to  34 35  to  39 40  to  44 No fertility-control methodsDeaths are birth-related 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smokerDeaths are method-related 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker 2.2 3.4 6.6 13.5 51.1 117.2 IUD 0.8 0.8 1.0 1.0 1.4 1.4 Condom 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/ spermicide 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence 2.5 1.6 1.6 1.7 2.9 3.6

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. Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs. Discontinue Pirmella prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see CONTRAINDICATIONS ). Pirmella can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen. 6. 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. 7. 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. 8. 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. 9. 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. 10. 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  11. 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. 12. 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. 13. Ectopic Pregnancy Ectopic as well as intrauterine pregnancy may occur in contraceptive failures.

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.

Distributed by: Lupin Pharmaceuticals, Inc. Baltimore, Maryland 21202 United States Manufactured by: Lupin Limited Pithampur (M.P.) - 454 775 INDIA Revised: November 2017                                                                               ID#: 253414 Pirmella™ 7/7/7 Tablets (norethindrone and ethinyl estradiol tablets USP) 0.5 mg/0.035 mg, 0.75 mg/0.035 mg and 1 mg/0.035 mg and Pirmella™ 1/35 Tablets (norethindrone and ethinyl estradiol tablets USP) 1 mg/0.035 mg Rx Only 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 without missing any pills, have a failure rate of approximately 1% per year. The typical failure rate is approximately 5% 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 fatal or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you: smoke have high blood pressure, diabetes, high cholesterol have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors. 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. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.

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 IMPORTANT  POINTS  TO  REMEMBER 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 1-3 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. 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. The pill pack has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of green "reminder" pills (without hormones). Pirmella 7/7/7 : There are 7 white "active" pills, 7 light peach "active" pills, 7 peach "active" pills and 7 green "reminder" pills. Pirmella 1/35: There are 21 peach "active" pills and 7 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. WHEN  TO  START  THE  FIRST  PACK  OF  PILLS You have a choice of which day to start taking your first pack of pills. Pirmella 7/7/7 and Pirmella 1/35 are available in wallet 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: Pirmella 7/7/7 : 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. Pirmella 1/35: Take the first peach "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: Pirmella 7/7/7 : Take the first white "active" pill of the first pack during the first 24 hours of your period. Pirmella 1/35: Take the first peach "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. 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 green "reminder" pill. Do not wait any days between packs. WHAT  TO  DO  IF  YOU  MISS  PILLS Pirmella 7/7/7 : If you MISS 1 white, light peach, or peach "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 peach "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 peach "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 peach, or peach "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. Pirmella 1/35 : If you MISS 1 peach "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 peach "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 peach "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 peach "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. A  REMINDER If you forget any of the 7 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. 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 “ACTIVE” PILL EACH DAY until you can reach your healthcare professional.

INSTRUCTIONS FOR USING YOUR WALLET Please Read Me! □   Sunday Start or □   Day 1 Start There are two ways to start taking birth control pills: Sunday Start or Day 1 Start. Your healthcare provider will tell you which to use. Save these instructions. 1   If this is the first time you are taking birth control pills, or if you have not taken birth control pills for 10 days or more, your first step is to wait until the first day you get your menstrual period. Then, follow these instructions for either Sunday Start or Day 1 Start. 2   When you get your period:    ▪   You will use a Sunday Start if your doctor told you to take your first pill on a Sunday. Take pill "1" on the Sunday after your period starts. If your period starts on a Sunday, take pill "1" that day.    ▪   You will use a Day 1 Start if your doctor told you to take pill "1" on the first day of your period. 3   Set the day:    ▪   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 wallet (Refer figure below). 4. Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the strip. 5. Swallow the pill. You will take one pill each day. If you use a Sunday Start and you are taking the pill for the FIRST TIME, YOU MUST USE A BACK-UP METHOD OF BIRTH CONTROL FOR THE FIRST 7 DAYS. If you use a Day 1 Start, you are protected from becoming pregnant as soon as you take your first pill. 6. Wait 24 hours to take your next pill. Continue to take one pill each day until all the pills have been taken. 7. Take your pill at the same time every day. It is important to take the correct pill each day and not miss any pills. To help you remember, take your pill at the same time as another daily activity, like turning off your alarm clock or brushing your teeth. 8. When your wallet is empty. You will start a new wallet on the day after pill "28." 9. THE FIRST PILL IN EVERY WALLET WILL ALWAYS BE TAKEN ON THE SAME DAY OF THE WEEK, NO MATTER WHEN YOUR NEXT PERIOD STARTS.

DETAILED PATIENT LABELING PLEASE NOTE : This labeling is revised from time to time as important new medical information becomes available. Therefore, please review this labeling carefully. The following oral contraceptive products contain a combination of an estrogen and progestogen, the two kinds of female hormones: Pirmella 7/7/7 Each white tablet contains 0.5 mg norethindrone and 0.035 mg ethinyl estradiol. Each light peach tablet contains 0.75 mg norethindrone and 0.035 mg ethinyl estradiol. Each peach tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Each green tablet contains inert ingredients. Pirmella 1/35 Each peach tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Each green tablet contains inert ingredients. INTRODUCTION Any woman who considers using oral contraceptives (the birth control pill or the pill) should understand the benefits and risks of using this form of birth control. This patient labeling will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this labeling is not a replacement for a careful discussion between you and your healthcare professional. You should discuss the information provided in this labeling with him or her, both when you first start taking the pill and during your revisits. You should also follow your healthcare professional's advice with regard to regular check-ups while you are on the pill. EFFECTIVENESS OF ORAL CONTRACEPTIVES Oral contraceptives or "birth control pills" or "the pill" are used to prevent pregnancy and are more effective than other non-surgical methods of birth control. When they are taken correctly without missing any pills, the chance of becoming pregnant is approximately 1% (1 pregnancy per 100 women per year of use). Typical failure rates are approximately 5% per year including women who do not always take the pills exactly as directed. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical failure rates for other methods of birth control during the first year of use are as follows: Implant: <1%  Male sterilization: <1% Injection: <1%  Cervical Cap with spermicides: 20 to 40% IUD: 1 to 2% Condom alone (male): 14% Diaphragm with spermicides: 20%  Condom alone (female): 21% Spermicides alone: 26% Periodic abstinence: 25% Vaginal sponge: 20 to 40% Withdrawal: 19% Female sterilization: <1%  No methods: 85% WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES

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) 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. 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

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. ANNUAL  NUMBER  OF  BIRTH - RELATED  OR  METHOD - RELATED  DEATHS  ASSOCIATED  WITH  CONTROL  OF  FERTILITY  PER  100 , 000  NONSTERILE  WOMEN ,  BY  FERTILITY  CONTROL  METHOD  ACCORDING  TO  AGE Method  of  control  and  outcome 15  to  19 20  to  24 25  to  29 30  to  34 35  to  39 40  to  44 No fertility-control methodsDeaths are birth-related 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smokerDeaths are method-related 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker 2.2 3.4 6.6 13.5 51.1 117.2 IUD 0.8 0.8 1.0 1.0 1.4 1.4 Condom 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide  1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence 2.5 1.6 1.6 1.7 2.9 3.6

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 (7–26 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.

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 (7–26 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 breastfeeding If you are breastfeeding, 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 breastfeeding. You should use another method of contraception since breastfeeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breastfeed 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, ritonavir-boosted 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 Pirmella 7/7/7 or Pirmella 1/35 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 ul 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 IMPORTANT  POINTS  TO  REMEMBER 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 1-3 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. 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. The pill pack has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of green "reminder" pills (without hormones). Pirmella 7/7/7: There are 7 white "active" pills, 7 light peach "active" pills, 7 peach "active" pills and 7 green "reminder" pills. Pirmella 1/35: There are 21 peach "active" pills and 7 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. WHEN  TO  START  THE  FIRST  PACK  OF  PILLS

You have a choice of which day to start taking your first pack of pills. Pirmella 7/7/7 and Pirmella 1/35 are available in wallet 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: Pirmella 7/7/7 : 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. Pirmella 1/35: Take the first peach "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: Pirmella 7/7/7 : Take the first white "active" pill of the first pack during the first 24 hours of your period. Pirmella 1/35: Take the first peach "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. 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 green "reminder" pill. Do not wait any days between packs. WHAT  TO  DO  IF  YOU  MISS  PILLS Pirmella 7/7/7 : If you MISS 1 white, light peach, or peach "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 peach "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 peach "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 peach, or peach "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. Pirmella 1/35 : If you MISS 1 peach "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 peach "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 peach "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 peach "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. A  REMINDER If you forget any of the 7 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. 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 “ACTIVE” PILL EACH DAY until you can reach your healthcare professional.

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 uled 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.