GIANVI (drospirenone 3 mg ethinyl estradiol 0.02 mg) Dailymed

In the primary contraceptive efficacy study of drospirenone and ethinyl estradiol tablets (3 mg DRSP/0.02 mg EE) of up to 1 year duration, 1,027 subjects were enrolled and completed 11,480 28-day cycles of use. The age range was 17 to 36 years. The racial demographic was: 87.8% Caucasian, 4.6% Hispanic, 4.3% Black, 1.2% Asian, and 2.1% other. Women with a BMI greater than 35 were excluded from the trial. The pregnancy rate (Pearl Index) was 1.41 per 100 woman-years of use based on 12 pregnancies that occurred after the onset of treatment and within 14 days after the last dose of drospirenone and ethinyl estradiol tablets in women 35 years of age or younger during cycles in which no other form of contraception was used.

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 V). 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 below that associated with childbirth.

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 V). 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 below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's - but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors uled in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, women of all ages who take oral contraceptives should take the lowest possible dose formulation that is effective. TABLE V: 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 Adapted from H.W. Ory, Family Planning Perspectives, 15:57-63, 1983. Method of Control and Outcome 15 to 19 years 20 to 24 years 25 to 29 years 30 to 34 years 35 to 39 years 40 to 44 years No fertility control methodsDeaths are birth-related 7 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 1 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

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, when taken inadvertently during early pregnancy.

Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb-reduction defects are concerned, 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. (See CONTRAINDICATIONS) 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 dosing 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.

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.

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 pre-existent.

Rifampin: Metabolism of ethinyl estradiol and some progestins (e.g., norethindrone) is increased by rifampin. A reduction in contraceptive effectiveness and an increase in menstrual irregularities have been associated with concomitant use of rifampin. Minocycline: Minocycline-related changes in estradiol, progesterone, FSH and LH plasma levels, breakthrough bleeding, or contraceptive failure cannot be ruled out. Anticonvulsants: Anticonvulsants such as phenobarbital, phenytoin, and carbamazepine have been shown to increase the metabolism of ethinyl estradiol and/or some progestins, which could result in a reduction of contraceptive effectiveness. Antibiotics: Pregnancy while taking combined hormonal contraceptives has been reported when the combined hormonal contraceptives were administered with antimicrobials such as ampicillin, tetracycline, and griseofulvin. However, clinical pharmacokinetic studies have not demonstrated any consistent effects of antibiotics (other than rifampin-see above) on plasma concentrations of synthetic steroids. See also separate discussion on minocycline (above). Atorvastatin: Coadministration of atorvastatin and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol by approximately 30% and 20%,  respectively. St. John’s Wort: Herbal products containing St. John’s Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of oral contraceptives and emergency contraceptive pills. This may also result in breakthrough bleeding. Other: Ascorbic acid and acetaminophen may increase plasma concentrations of some synthetic estrogens, possibly by inhibition of conjugation.

Certain endocrine- and liver-function tests and blood components may be affected by oral contraceptives: Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. 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. Other binding proteins may be elevated in serum. Sex-hormone-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged. Triglycerides may be increased. Glucose tolerance may be decreased. 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.



Estrogens and progestins should not be used during pregnancy. Fourteen pregnancies that occurred during exposure with 3 mg DRSP/0.03 mg EE tablets (none with more than a single cycle of exposure) have been identified. One infant was born with esophageal atresia. A causal association with the 3 mg DRSP/0.03 mg EE tablet is unknown.

Estrogens and progestins should not be used during pregnancy. Fourteen pregnancies that occurred during exposure with 3 mg DRSP/0.03 mg EE tablets in utero (none with more than a single cycle of exposure) have been identified. One infant was born with esophageal atresia. A causal association with the 3 mg DRSP/0.03 mg EE tablet is unknown. Twelve pregnancies that occurred with drospirenone and ethinyl estradiol tablets exposure in utero (none with more than a single cycle of exposure) have been identified. There were no known cases of congenital anomalies. A teratology study in pregnant rats given drospirenone orally at doses of 5, 15 and 45 mg/kg/day, 6 to 50 times the human exposure based on AUC of drospirenone, resulted in an increased number of fetuses with delayed ossification of bones of the feet in the two higher doses. A similar study in rabbits dosed orally with 1, 30 and 100 mg/kg/day drospirenone, 2 to 27 times the human exposure, resulted in an increase in fetal loss and retardation of fetal development (delayed ossification of small bones, multiple fusions of ribs) at the high dose only. When drospirenone was administered with ethinyl estradiol (100:1) during late pregnancy (the period of genital development) at doses of 5, 15 and 45 mg/kg, there was a dose dependent increase in feminization of male rat fetuses. In a study in 36 cynomolgous monkeys, no teratogenic or feminization effects were observed with orally administered drospirenone and ethinyl estradiol (100:1) at doses up to 10 mg/kg/day drospirenone, 30 times the human exposure.

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, 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 oral contraceptives but to use other forms of contraception until she has completely weaned her child.

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, 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 oral contraceptives but to use other forms of contraception until she has completely weaned her child. After oral administration of 3 mg DRSP/0.03 mg EE tablets about 0.02% of the drospirenone dose was excreted into the breast milk of postpartum women within 24 hours. This results in a maximal daily dose of about 3 mcg drospirenone in an infant.

During the first cycle of Gianvi tablet use, the patient should be instructed to take one pink Gianvi tablet daily, beginning on the first Sunday after the onset of her menstrual period. She should take one pink Gianvi tablet daily for 24 consecutive days, followed by one white inert tablet daily on menstrual cycle days 25 through 28. It is recommended that Gianvi tablets be taken at the same time each day, preferably after the evening meal or at bedtime. Gianvi tablets can be taken without regard to meals. Gianvi tablets should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. The possibility of ovulation and conception prior to initiation of medication should be considered. The patient should begin her next and all subsequent 28-day regimens of Gianvi tablets on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her pink tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Gianvi tablets is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a pink Gianvi tablet daily for seven consecutive days. When switching from another oral contraceptive, Gianvi tablets should be started on the same day that a new pack of the previous oral contraceptive would have been started. Withdrawal bleeding usually occurs within 3 days following the last pink tablet. If spotting or breakthrough bleeding occurs while taking Gianvi, the patient should be instructed to continue taking her Gianvi tablets as instructed and by the regimen described above. She should be instructed that this type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient should be advised to consult her physician. Although the occurrence of pregnancy is low if Gianvi tablets are taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), the possibility of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed. The risk of pregnancy increases with each active pink tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the DETAILED PATIENT LABELING, which follows. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking pink tablets again on the proper day. In the nonlactating mother, Gianvi tablets may be initiated 4 to 6 weeks postpartum, for contraception. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS concerning thromboembolic disease.)

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), blockage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack and angina pectoris) or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Women with migraine headaches also may be at increased risk of stroke when taking the pill. 2. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer. 3. High blood pressure, although blood pressure usually returns to normal when the pill is stopped. 4. Cancer of the breast. 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 getting breast cancer begin to go back down. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormone-sensitive tumor. Some studies have found an increase in the incidence of cancer or precancerous lesions of the cervix in women who use the pill. However, this finding may be related to factors other than the use of the pill. The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your doctor or healthcare provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants, some antibiotics and some herbal products such as St. John’s Wort, may decrease oral contraceptive effectiveness. Taking the pill may provide 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 provider. Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is appropriate to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information booklet gives you further information, which you should read and discuss with your healthcare provider. This product (like all oral contraceptives) is intended to prevent pregnancy. Oral contraceptives do not protect against HIV infection (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. INSTRUCTIONS TO PATIENTS 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. GIANVI™ TABLETS CAN BE TAKEN WITHOUT REGARD TO MEALS. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. See “WHAT TO DO IF YOU MISS PILLS” below. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1 TO 3 PACKS OF PILLS. If you do have spotting or light bleeding or feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it does not go away, check with your healthcare provider. 4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take two pills, to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING (within 3 to 4 hours after you take your pill), you should follow the instructions for “WHAT TO DO IF YOU MISS PILLS”. IF YOU HAVE DIARRHEA, or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics and some herbal products such as St. John’s Wort, your pills may not work as well. Use a back-up method (such as condoms or spermicides) until you check with your healthcare provider. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control. 7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare provider. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take Gianvi tablets at about the same time every day. Gianvi tablets can be taken without regard to meals. 2. LOOK AT YOUR PILL PACK: – IT HAS 28 PILLS: The Gianvi tablets-pill pack has 24 pink “active” pills (with hormones) to be taken for 24 days, followed by 4 white “reminder” pills (without hormones) to be taken for four days. 3. ALSO FIND: 1) Where on the pack to start taking pills, 2) In what order to take the pills (follow the arrows) 3) The week numbers are shown on the buler card picture below 4. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicides) to use as a back-up in case you miss pills. AN EXTRA, FULL PILL PACK. WHEN TO START THE FIRST  PACK OF PILLS You have a choice for which day to start taking your first pack of pills. Decide with your healthcare provider, which is the best day for you. Pick a time of day, which will be easy to remember. DAY 1 START: 1. Take the first pink “active” pill of the first pack during the first 24 hours of your period. 2. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: 1. Take the first pink “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 that same day. 2. Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). WHEN YOU SWITCH FROM A DIFFERENT BIRTH CONTROL PILL When switching from another birth control pill, Gianvi tablets should be started on the same day that a new pack of the previous birth control pills would have been started. 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 OF PILLS: Start the next pack on the day after your last white “reminder” pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 pink “active” pill in Week 1 of your pack: 1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take two pills in one day. 2. You do not need to use a back-up birth control method if you have sex. If you MISS 2 pink “active” pills in a row in WEEK 1 or WEEK 2 of your pack: 1. Take two pills on the day you remember and two pills the next day. 2. Then take one pill a day until you finish the pack. 3. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days. If you MISS 2 pink “active” pills in a row in WEEK 3 or WEEK 4 of your pack: 1 . If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking one pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicide) as a back-up for those 7 days. 3. You may not have your period this month but this is expected. However, if you miss your period two months in a row, call your healthcare provider because you might be pregnant. If you MISS 3 OR MORE pink “active” pills in a row during ANY WEEK: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days. 3. You may not have your period this month but this is expected. However, if you miss your period two months in a row, call your healthcare provider because you might be pregnant. If you MISS ANY of the 4 white “reminder” pills in WEEK 4: THROW AWAY the pills you missed. Keep taking one pill each day until the pack is empty. You do not need a back-up method of birth control. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD (such as condoms or spermicides) anytime you have sex. KEEP TAKING ONE ACTIVE PINK PILL EACH DAY until you can contact your healthcare provider. For additional information see “Detailed Patient Labeling”

Some women should not use Gianvi tablets. For example, you should not take Gianvi tablets if you are pregnant or think you may be pregnant. You should also not use Gianvi tablets if you have had any of the following conditions:

Some women should not use Gianvi tablets. For example, you should not take Gianvi tablets if you are pregnant or think you may be pregnant. You should also not use Gianvi tablets if you have had any of the following conditions: A history of heart attack or stroke A history of blood clots in the legs (deep vein thrombosis), lungs (pulmonary embolism), or eyes (retinal thrombosis) 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 doctor) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill or other hormonal contraceptives Liver tumor (benign or cancerous) Known or suspected pregnancy Heart valve or heart rhythm disorders that may be associated with formation of blood clots Diabetes with complications of the kidneys, eyes, nerves, or blood vessels Severe high blood pressure A need for surgery with prolonged bedrest Headaches with neurological symptoms Allergy or hypersensitivity to any of the components of drospirenone and ethinyl estradiol tablets In addition, you should not use Gianvi tablets if you have any of the following conditions: Kidney Disease Liver Disease Adrenal Disease Tell your healthcare provider if you have ever had any of the above conditions (Your healthcare provider can recommend another method of birth control). If you are currently on daily, long-term treatment for a chronic condition with any of the following medications, you should consult your healthcare provider before taking Gianvi tablets: NSAIDs (ibuprofen, naprosyn and others) Potassium-sparing diuretics (spironolactone and others) Potassium supplementation ACE inhibitors (captopril, enalapril, lisinopril and others) Angiotensin-II receptor antagonists (Cozaar*, Diovan*, Avapro* and others) Heparin Aldosterone antagonists OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES Tell your healthcare provider if you have or ever had: Breast nodules, fibrocystic disease of the breast, an abnormal breast X-ray or mammogram Diabetes Elevated cholesterol or triglycerides High blood pressure A blood test indicating a higher risk of having blood clots Migraine or other headaches or epilepsy Mental depression Gallbladder, heart or kidney disease History of scanty or irregular menstrual periods Women with any of these conditions should be checked often by their healthcare provider if they choose to use oral contraceptives. Also, be sure to inform your doctor or healthcare provider if you smoke, are on any medications, recently had a baby or miscarriage, or are breast feeding. RISKS OF TAKING ORAL CONTRACEPTIVES 1. Risk of Developing Blood Clots Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives and can be fatal. In particular, a clot in the legs (deep vein thrombosis) can cause pain and swelling, and a clot that travels to the lungs can cause 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 have recently delivered a baby, you may be at risk of developing blood clots. You should consult your doctor about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby or a mid-trimester pregnancy loss or termination. It is advisable to wait for at least four to six weeks after delivery if you are not breast feeding. If you are breast feeding, you should wait until you have weaned your child before using the pill. (See also the section on Breast Feeding in GENERAL PRECAUTIONS.) 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, a possible but not definite association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer. 5. Cancer of the Reproductive Organs and Breasts Various studies give conflicting reports on the relationship between breast cancer and oral contraceptive use. Oral contraceptive use may slightly increase your chance of having breast cancer diagnosed, particularly after using hormonal contraceptives at a younger age. After you stop using hormonal contraceptives, the chances of getting breast cancer begin to go back down. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is 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. 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 Adapted from H.W. Ory, Family Planning Perspectives, 15:57-63, 1983. Method of Control and Outcome 15 to 19 years 20 to 24 years 25 to 29 years 30 to 34 years 35 to 39 years 40 to 44 years No fertility control methodsDeaths are birth-related 7 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 1 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 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, except for those women over the age of 40, when 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 high-dose pills and on less-selective use of pills than is practiced today. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, non-smoking women over 40 years of age may outweigh the possible risks. However, all women, especially older women, are cautioned to use the lowest-dose pill that is effective. WARNING SIGNALS If any of these adverse effects occur while you are taking oral contraceptives, call your doctor 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 doctor or healthcare provider to show you how to examine your breasts) Severe pain or tenderness in the stomach area (indicating a possibly ruptured liver tumor) Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression) Jaundice or a light 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 doctor or healthcare provider. 2. Contact Lenses If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your doctor or healthcare provider. 3. Fluid Retention Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your doctor or healthcare provider. 4. Melasma A spotty darkening of the skin is possible, particularly of the face. 5. Other Side Effects Other side effects may include nausea, vomiting, change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, and vaginal infections. If any of these side effects bother you, call your doctor or healthcare provider. 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 provider. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your healthcare provider immediately to determine whether you are pregnant. Stop taking oral contraceptives if pregnancy is confirmed. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives should not be used during pregnancy. You should check with your doctor about risks to your unborn child of any medication taken during pregnancy. 2. While Breast Feeding If you are breast feeding, consult your doctor 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 light yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breast feeding. You should use another method of contraception since breast feeding provides only partial protection from becoming pregnant, and this partial protection decreases significantly as you breast feed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory Tests If you are scheduled for any laboratory tests, tell your doctor you are taking birth control pills. Certain blood tests may be affected by birth control pills. 4. Drug Interactions Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital) and phenytoin (Dilantin is one brand of this drug), phenylbutazone (Butazolidin is one brand) and possibly certain antibiotics. Herbal products containing St. John’s Wort (hypericum perforatum) may reduce the effectiveness of oral contraceptives. This may also result in breakthrough bleeding. You may need to use an additional method of contraception during any cycle in which you take drugs that can make oral contraceptives less effective (See BOLDED TEXT AT BEGINNING). 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. INSTRUCTIONS TO PATIENTS 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. GIANVI™ TABLETS CAN BE TAKEN WITHOUT REGARD TO MEALS. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. See “WHAT TO DO IF YOU MISS PILLS” below. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1 TO 3 PACKS OF PILLS. If you do have spotting or light bleeding or feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it does not go away, check with your healthcare provider. 4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take two pills, to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING (within 3 to 4 hours after you take your pill), you should follow the instructions for “WHAT TO DO IF YOU MISS PILLS”. IF YOU HAVE DIARRHEA or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics and some herbal products such as St. John’s Wort, your pills may not work as well. Use a back-up method (such as condoms or spermicides) until you check with your healthcare provider. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control. 7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare provider. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take Gianvi tablets at about the same time every day. Gianvi tablets can be taken without regard to meals. 2. LOOK AT YOUR PILL PACK: – IT HAS 28 PILLS The Gianvi tablets-pill pack has 24 pink “active” pills (with hormones) to be taken for 24 days, followed by 4 white “reminder” pills (without hormones) to be taken for four days. 3. ALSO FIND: 1) Where on the pack to start taking pills, 2) In what order to take the pills (follow the arrows) 3) The week numbers are shown on the buler card picture below 4. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicides) to use as a back-up in case you miss pills. AN EXTRA, FULL PILL PACK. WHEN TO START THE FIRST PACK OF PILLS You have a choice for which day to start taking your first pack of pills. Decide with your healthcare provider which is the best day for you. Pick a time of day, which will be easy to remember. DAY 1 START: 1. Take the first pink “active” pill of the first pack during the first 24 hours of your period. 2. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: 1. Take the first pink “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 that same day. 2. Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). WHEN YOU SWITCH FROM A DIFFERENT BIRTH CONTROL PILL When switching from another birth control pill, Gianvi tablets should be started on the same day that a new pack of the previous birth control pill would have been started. 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 OF PILLS: Start the next pack on the day after your last white “reminder” pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 pink “active” pill: 1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take two pills in one day. 2. You do not need to use a back-up birth control method if you have sex. If you MISS 2 pink “active” pills in a row in WEEK 1 OR WEEK 2 of your pack: 1. Take two pills on the day you remember and two pills the next day. 2. Then take one pill a day until you finish the pack. 3. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days. If you MISS 2 pink “active” pills in a row in WEEK 3 or WEEK 4 of your pack: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicide) as a back-up for those 7 days. 3. You may not have your period this month but this is expected. However, if you miss your period two months in a row, call your doctor or clinic because you might be pregnant. If you MISS 3 OR MORE pink “active” pills in a row during ANY WEEK: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You COULD BECOME PREGNANT if you have sex in the 7 days after you restart your pills. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days. 3. You may not have your period this month but this is expected. However, if you miss your period two months in a row, call your doctor or clinic because you might be pregnant. If you MISS ANY of the 4 white “reminder” pills in WEEK 4: THROW AWAY the pills you missed. Keep taking one 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 (such as condoms or spermicides) anytime you have sex. KEEP TAKING ONE ACTIVE PINK PILL EACH DAY until you contact your healthcare provider. PREGNANCY AFTER STOPPING THE PILL There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. OVERDOSAGE Serious ill effects have not been reported following ingestion of large doses of other oral contraceptives by young children. Overdosage of drospirenone and ethinyl estradiol tablets may cause nausea and withdrawal bleeding in females and may increase blood levels of potassium or decrease blood levels of sodium, which could be dangerous. In case of overdosage, contact your healthcare provider. OTHER INFORMATION Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is appropriate to postpone it. You should be re-examined at least once a year. Be sure to inform your healthcare provider 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 provider, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use the drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth control pills. HEALTH BENEFITS FROM ORAL CONTRACEPTIVES In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are: Menstrual cycles may become more regular. Blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur. Pain or other symptoms during menstruation may be encountered less frequently. Ovarian cysts may occur less frequently. Ectopic (tubal) pregnancy may occur less frequently. Noncancerous cysts or lumps in the breast may occur less frequently. Acute pelvic inflammatory disease may occur less frequently. Oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus. If you want more information about birth control pills, ask your doctor or pharmacist. They have a more technical leaflet called the Prescribing Information which you may wish to read. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. *Other trademarks are the properties of their respective owners. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. Manufactured By:BARR LABORATORIES, INC.Pomona, NY 10970 Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev. D 6/2010

NDC 54868-6162-0 Gianvi™ (drospirenone and ethinyl estradiol tablets) 3 mg/0.02 mg Contents: One dispenser of 28 tablets, 24 pink tablets and 4 white inert tablets. Each pink tablet (24) contains 3 mg drospirenone and 0.02 mg ethinyl estradiol. Each white tablet (4) contains inert ingredients. 28 DAY REGIMEN Rx only THIS PRODUCT (LIKE ALL ORAL CONTRACEPTIVES) IS INTENDED TO PREVENT PREGNANCY. IT DOES NOT PROTECT AGAINST HIV INFECTION (AIDS) AND OTHER SEXUALLY TRANSMITTED DISEASES. TEVA SHAPING WOMEN'S HEALTH®