Simpesse (levonorgestrel 0.15 mg ethinyl estradiol 0.03 mg) Dailymed

Begin Simpesse on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, take the first white tablet that day. For each 91-day course, take in the following order: 1.  Start the first white tablet on the first Sunday after onset of menstruation. Then take one white tablet daily for 84 consecutive days. Use a non-hormonal back-up method of contraception (such as condoms and spermicide) until a white tablet has been taken daily for 7 consecutive days. 2. Then take one light blue tablet for 7 consecutive days. Bleeding should occur during the 7 days that the light blue tablets are taken. Begin the next and all subsequent 91-day cycles without interruption on the same day of the week (Sunday) on which the patient began her first dose of Simpesse, following the same schedule: 84 days taking a white tablet followed by 7 days taking a light blue tablet. If the patient does not immediately start her next pill pack, instruct her to protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a white tablet daily for 7 consecutive days. Switching to Simpesse from another oral hormonal contraceptive or from another contraceptive method (transdermal patch, vaginal ring, injection, intrauterine contraceptive, implant) Start on the Sunday after the patient’s next period starts. Use additional non-hormonal contraceptive (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days. Starting Simpesse after Abortion or Miscarriage First-trimester Simpesse may be started on the Sunday after an abortion or miscarriage. The patient must use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days. Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Simpesse following the instructions for women not currently using hormonal contraception. Use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days [see Contraindications (4) and Warnings and Precautions (5.1)]. Starting Simpesse after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Simpesse following the instructions for women not currently using hormonal contraception. Use additional non-hormonal contraception (such as condoms and spermicide) until the patient has taken a white tablet for 7 consecutive days [see Contraindications (4) and Warnings and Precautions (5.1)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Simpesse [see Warnings and Precautions (5.1), Use in Specific Populations (8.1)].

Stop Simpesse if an arterial or deep venous thrombotic/thrombembolic event occurs. Stop Simpesse if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately. Discontinue Simpesse during prolonged immobilization. If feasible, stop Simpesse at least 4 weeks before and through 2 weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism. Start Simpesse no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. Before starting Simpesse evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Simpesse is contraindicated in women with a high risk of arterial or venous/thromboembolic diseases [see Contraindications (4)].   Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity. Simpesse is contraindicated in women over 35 years of age who smoke [see Contraindications (4)]. Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs [see Contraindications (4)]. While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.   The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.   Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE. Use of Simpesse provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs, including Simpesse, may also worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Females with a history of pregnancy-related cholestasis may be at an increased risk for COC-related cholestasis.

Women using Simpesse may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first 3 months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If unscheduled bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy. When prescribing Simpesse, the occurrence of fewer planned menses (4 per year instead of 13 per year) should be weighed against the occurrence of increased unscheduled bleeding and/or spotting. The primary clinical trial (PSE-301) that evaluated the efficacy of Simpesse also assessed unscheduled bleeding. The participants in the 12-month clinical trial  (N=1,006) completed the equivalent of 8,681 28-day cycles of exposure and were composed primarily of women who had used oral contraceptives previously (89%) as opposed to new users (11%). A total of 82 (8.2%) of the women discontinued Simpesse, at least in part, due to bleeding or spotting. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 1 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 2 presents the number of days with unscheduled spotting in treatment cycles 1 and 4. 

Unscheduled Bleeding and Spotting Women using Simpesse may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first 3 months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If unscheduled bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy. When prescribing Simpesse, the occurrence of fewer planned menses (4 per year instead of 13 per year) should be weighed against the occurrence of increased unscheduled bleeding and/or spotting. The primary clinical trial (PSE-301) that evaluated the efficacy of Simpesse also assessed unscheduled bleeding. The participants in the 12-month clinical trial  (N=1,006) completed the equivalent of 8,681 28-day cycles of exposure and were composed primarily of women who had used oral contraceptives previously (89%) as opposed to new users (11%). A total of 82 (8.2%) of the women discontinued Simpesse, at least in part, due to bleeding or spotting. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 1 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 2 presents the number of days with unscheduled spotting in treatment cycles 1 and 4.  Table 2: Total Number of Days with Unscheduled Bleeding Q1=Quartile 1: 25% of women had this number of days of unscheduled bleedingMedian: 50% of women had ≤ this number of days of unscheduled bleedingQ3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding 91-Day Treatment Cycle  Days per 84-Day Interval  Days per 28-Day Interval  Q1  Median  Q3  Mean  Mean  1st 1 4 10 6.9 1.7 4th 0 1 4 3.2 0.8 Table 3: Total Number of Days with Unscheduled Spotting Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled spottingMedian: 50% of women had ≤ this number of days of unscheduled spottingQ3=Quartile 3: 75% of women had ≤ this number of days of unscheduled spotting 91-Day Treatment Cycle     Days per 84-Day Interval   Days per 28­-Day Interval   Q1   Median   Q3   Mean   Mean   1st 1 4 11 7.4 1.9 4th 0 2 7 4.4 1.1 Figure 2 shows the percentage of Simpesse subjects participating in trial PSE-301 with ≥ 7 days or ≥ 20 days of unscheduled bleeding and/or spotting, or only unscheduled bleeding, during each 91-day treatment cycle. If unscheduled spotting or bleeding occurs, instruct the patient to continue on the same regimen. If the bleeding is persistent or prolonged, advise the patient to consult her healthcare provider. Amenorrhea and Oligomenorrhea Women who use Simpesse may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant. If scheduled bleeding does not occur, consider the possibility of pregnancy. After discontinuation of Simpesse, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent.



Risk Summary There is no use for contraception in pregnancy; therefore, Simpesse should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb- reduction defects) following exposure to COCs before conception or during early pregnancy.  In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

COCs prevent pregnancy primarily by suppressing ovulation.  

What is the most important information I should know about Simpesse? Do not use Simpesse if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke. What is Simpesse? Simpesse is a birth control pill (hormonal contraceptive) used by women to prevent pregnancy. It contains two female hormones, an estrogen called ethinyl estradiol, and a progestin called levonorgestrel. Simpesse does not protect against HIV infection (AIDS) and other sexually transmitted infections. How Does Simpesse Work for contraception? Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The more carefully you follow the directions, the less chance you have of getting pregnant. Based on the results of a single clinical study lasting 12 months, 1 to 3 women, out of 100 women, may get pregnant during the first year they use Simpesse. The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a ul of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. Who Should Not Take Simpesse? Do not take Simpesse if you: smoke and are over 35 years of age have or had blood clots in your arms, legs, eyes or lungs   had a stroke had a heart attack have certain heart valve problems or heart rhythm abnormalities that can cause blood clots to form in the heart have or had a problem with your blood that makes it clot more than normal have high blood pressure that cannot be controlled by medicine or have high blood pressure with blood vessel problems have diabetes and are over the age of 35; have diabetes with high blood pressure; kidney, eye, nerve, or blood vessel damage; or for more than 20 years have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over the age of 35 have or had breast cancer have liver disease, including liver tumors have unexplained vaginal bleeding 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. Birth control pills may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy. If any of these conditions happen to you while you are taking Simpesse, stop taking Simpesse right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Simpesse. What should I tell my healthcare provider before taking Simpesse? Tell your healthcare provider if you: are pregnant or think you may be pregnant are scheduled for surgery. Simpesse may increase your risk of blood clots after surgery. You should stop taking Simpesse at least 4 weeks before you have surgery and not restart Simpesse until at least 2 weeks after your surgery. are depressed now or have been depressed in the past had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy) are breastfeeding or plan to breastfeed. Simpesse may decrease the amount of breast milk you make. A small amount of the hormones in Simpesse may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding. Tell your healthcare provider if you have ever had any of the conditions uled in, “Who should not take Simpesse” above. Your healthcare provider may recommend another method of birth control. Tell your healthcare provider about all medicines and herbal products that you take. Some medicines and herbal products may make birth control pills less effective, including: barbiturates bosentan carbamazepine  felbamate  griseofulvin oxcarbazepine phenytoin rifampin St. John’s wort topiramate Use a back-up or alternative birth control method when you take medicines that may make birth control pills less effective. Birth control pills may interact with lamotrigine, an anticonvulsant used for epilepsy. This may increase the risk of seizures, so your physician may need to adjust the dose of lamotrigine. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone. Know the medicines you take. Keep a ul of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take Simpesse? Read the Instructions for Use at the end of this Patient Information. What are the most serious risks of taking birth control pills? Like pregnancy, birth control pills increase the risk of serious blood clots, especially in women who have other risk factors, such as smoking, obesity, or age over 35 years old. It is possible to die from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of serious blood clots are blood clots in the: Legs (thrombophlebitis) Lungs (pulmonary embolus) Eyes (loss of eyesight) Heart (heart attack) Brain (stroke) Women who take birth control pills may get: High blood pressure. You should see your healthcare provider to check your blood pressure regularly. Gallbladder problems Rare cancerous or noncancerous liver tumors All of these events are uncommon in healthy women. Call your healthcare provider right away if you have: Persistent leg pain Sudden shortness of breath  Sudden blindness, partial or complete  Severe pain in your chest Sudden, severe headache unlike your usual headaches Weakness or numbness in an arm or leg, or trouble speaking Yellowing of the skin or eyeballs What are common side effects of birth control pills? The most common side effects of birth control pills are: Spotting or bleeding between menstrual periods Nausea Breast tenderness Headache These side effects are usually mild and usually disappear with time. Less common side effects are: Acne Less sexual desire Bloating or fluid retention  Blotchy darkening of the skin, especially on the face  High blood sugar, especially in women who already have diabetes High fat levels in the blood Depression, especially if you have had depression in the past. Call your healthcare provider immediately if you have any thoughts of harming yourself. Problems tolerating contact lenses Weight changes This is not a complete ul of possible side effects. Talk to your healthcare provider if you develop any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088. No serious problems have been reported from a birth control pill overdose, even when accidentally taken by children. What else should I know about taking Simpesse? If you are scheduled for any lab tests, tell your healthcare provider you are taking Simpesse. Certain blood tests may be affected by Simpesse. Do not skip any pills, even if you do not have sex often. Birth control pills should not be taken during pregnancy. However, birth control pills taken by accident during pregnancy are not known to cause birth defects. You should stop Simpesse at least four weeks before you have major surgery and not restart it for at least two weeks after the surgery, due to an increased risk of blood clots. If you are breastfeeding, consider another birth control method until you are ready to stop breastfeeding. Birth control pills that contain estrogen, like Simpesse, may decrease the amount of milk you make. A small amount of the pill's hormones pass into breast milk. If you have vomiting or diarrhea, your birth control pills may not work as well. Use another birth control method, like condoms or a spermicide, until you check with your healthcare provider. How should I store Simpesse? Store Simpesse at room temperature between 68°F to 77°F (20°C to 25°C). Keep Simpesse and all medicines out of the reach of children. General information about Simpesse Medicines are sometimes prescribed for purposes other than those uled in a Patient Information leaflet. Do not use Simpesse for a condition for which it was not prescribed. Do not give Simpesse to anyone else. This Patient Information summarizes the most important information about Simpesse. If you have concerns or questions, ask your healthcare provider. You may also ask your healthcare providers for a more detailed label written for medical professionals. Do birth control pills cause cancer? It is not known if hormonal birth control pills cause breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use. If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones. Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners. What if I want to become pregnant? You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill. What should I know about my period when taking Simpesse? When you take Simpesse, which has a 91-day extended dosing cycle, you should expect to have 4 scheduled periods per year (bleeding when you are taking the 7 light blue pills). Each period is likely to last about 3 days. However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28 -day dosing cycle. During the first Simpesse 91-day treatment cycle, about 3 in 10 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking Simpesse because of this bleeding or spotting. If the spotting continues for more than 7 consecutive days or if the bleeding is heavy, call your healthcare provider. What if I miss my scheduled period when taking Simpesse? You should consider the possibility that you are pregnant if you miss your scheduled period (no bleeding on the days that you are taking light blue tablets). Since scheduled periods are less frequent when you are taking Simpesse, notify your healthcare provider that you have missed your period and that you are taking Simpesse. Also notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider evaluates you to determine if you are pregnant. Stop taking Simpesse if it is determined that you are pregnant. What are the ingredients in Simpesse? Active ingredients: White tablets: levonorgestrel and ethinyl estradiol                                                                                       Light blue tablets: ethinyl estradiol Inactive ingredients: White tablets: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone Light blue tablets: colloidal silicon dioxide, FD&C Blue No. 1, lactose monohydrate, povidone, pregelatinized starch (maize), stearic acid, and vitamin E. Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown RoadEast Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India Revised: 04/2023