Velivet (desogestrel 0.1 mg ethinyl estradiol 0.025 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 IV). 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.

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 IV). 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 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 (35). However, current clinical practice involves the use of lower estrogen 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 (100,101), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are 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. Therefore, 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 the lowest possible dose formulation that is effective and meets the individual patient needs. TABLE IV: ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NON-STERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 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 Adapted from H.W. Ory, ref. #35.  

Extensive epidemiologic studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (55–57). Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned (55,56,58,59), when oral contraceptives are taken inadvertently during early pregnancy.

Extensive epidemiologic studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (55–57). Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned (55,56,58,59), when oral contraceptives are 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 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. If bleeding persists or recurs, non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy 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. If bleeding persists or recurs, non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy 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.

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

Changes in contraceptive effectiveness associated with co-administration of other drugs: a. Anti-infective agents and anticonvulsants Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with some antibiotics, anticonvulsants, and other drugs that increase metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include barbiturates, rifampin, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate, and griseofulvin. Since desogestrel is mainly metabolized by the cytochrome P450 2C9 enzyme (CYP 2C9) to form etonogestrel, the active progestin, there is a possibility of interaction with CYP 2C9 substrates or inhibitors (such as ibuprofen, piroxicam, naproxen, phenytoin, fluconazole, diclofenac, tolbutamide, glipizide, celecoxib, sulfamethoxazole, isoniazid, torsemide, irbesartan, losartan, and valsartan). The clinical relevance of these interactions is unknown. b. Anti-HIV protease inhibitors Several of the anti-HIV protease inhibitors have been studied with co-administration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the plasma levels of the estrogen and progestin have been noted in some cases. The efficacy and safety of these oral contraceptive products may be affected with co-administration of anti-HIV protease inhibitors. Healthcare providers should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information. c. Herbal products 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 contraceptive steroids. This may also result in breakthrough bleeding. Increase in plasma hormone levels associated with co-administered drugs: Co-administration of atorvastatin and certain ethinyl estradiol containing oral contraceptives increased AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. Changes in plasma levels of co-administered drugs: Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporine, prednisolone, and theophylline have been reported with concomitant administration of oral contraceptives. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine and clofibric acid have been noted when these drugs were administered with oral contraceptives. No formal drug-drug interaction studies were conducted with Velivet™.

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: a. Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. b. Increased thyroid binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered. c. Other binding proteins may be elevated in serum. d. Sex hormone-binding globulins are increased and result in elevated levels of total circulating sex steroids; however, free or biologically active levels either decrease or remain unchanged. e. Triglycerides may be increased, and levels of various other lipids and lipoproteins may be affected. f. Glucose tolerance may be decreased. g. 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.

Pregnancy Category X (see CONTRAINDICATIONS and WARNINGS sections).

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, combination 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.

Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding or spotting 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 young and in good health. However, you should know that the following medical conditions have been associated with or made worse by the pill: Blood clots in the legs (thrombophlebitis) or lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), and blockage of blood vessels in the heart (heart attack or angina pectoris) or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes, and subsequent serious medical consequences. Women with migraine headaches also may be at increased risk of stroke when taking the pill. 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. High blood pressure, although blood pressure usually returns to normal when the pill is stopped. The symptoms associated with these serious side effects are discussed in the detailed leaflet (DETAILED PATIENT PACKAGE INSERT) 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 herbal preparations containing St. John’s Wort (hypericum perforatum) may decrease oral contraceptive effectiveness. Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This very small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. 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 hormonal contraceptives because breast cancer is usually 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. Taking the pill provides some important non-contraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your doctor or healthcare provider. Your doctor or healthcare provider will take a medical and family history and may examine you before prescribing oral contraceptives. The physical examination may be delayed to another time if you request it and your doctor or healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information leaflet gives you further information which you should read and discuss with your doctor or healthcare provider. 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:

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 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 doesn't go away, check with your doctor or 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 2 pills to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics or the herbal supplement St. John's Wort, your pills may not work as well. Use a back-up method (such as condoms, spermicides, or diaphragm) until you check with your doctor or healthcare provider. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or 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 doctor or healthcare provider.

If you MISS 1 “active” [beige, orange, or pink] 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 “active” [beige or orange] 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 restart your pills. You MUST use another birth control method (such as condoms, spermicides, or diaphragm) as a back-up method for those 7 days. If you MISS 2 “active” [pink] pills in a row in WEEK 3: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or healthcare provider 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 condoms, spermicides, or diaphragm) as a back-up method for those 7 days. If you MISS 3 OR MORE “active” [beige, orange, or pink] pills in a row (during the first 3 weeks): 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex on the days when you missed pills or during the first 7 days after restarting your pills. You MUST use another birth control method (such as condoms, spermicides, or diaphragm) as a back-up method the next time you have sex and for the first 7 days after you restart your pills.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD of birth control anytime you have sex. KEEP TAKING ONE “ACTIVE” [BEIGE, ORANGE, OR PINK] PILL EACH DAY until you can reach your doctor or healthcare provider. DETAILED PATIENT PACKAGE INSERT Velivet™ (desogestrel and ethinyl estradiol, USP tablets - triphasic regimen) This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. PLEASE NOTE: This labeling is revised from time to time as important new medical information becomes available. Therefore, please review this labeling carefully. DESCRIPTION: Velivet™ (desogestrel and ethinyl estradiol, USP) Tablets are a triphasic oral contraceptive product, containing a combination of a progestin and estrogen, the two kinds of female hormones. Each beige tablet contains 0.1 mg desogestrel and 0.025 mg ethinyl estradiol; each orange tablet contains 0.125 mg desogestrel and 0.025 mg ethinyl estradiol; and each pink tablet contains 0.15 mg desogestrel and 0.025 mg ethinyl estradiol. Each white 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 leaflet 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 leaflet is not a replacement for a careful discussion between you and your doctor or healthcare provider. You should discuss the information provided in this leaflet with him or her, both when you first start taking the pill and during your revisits. You should also follow your doctor’s or healthcare provider’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, the chance of becoming pregnant is less than 1% (1 pregnancy per 100 women per year of use) when used perfectly, without missing any pills. Typical failure rates are actually 5% (5 pregnancies per 100 women per year of use). 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: No methods: 85% Spermicides alone: 26% Periodic abstinence: 25% Withdrawal: 19% Cervical Cap with spermicides: 20 to 40% Vaginal sponge: 20 to 40% Diaphragm with spermicides: 20% Condom alone (female): 21% Condom alone (male): 14% IUD: less than 1 to 2% Implants: less than 1% Injectable progestogen less than 1% Male sterilization: less than 1% Female sterilization: less than 1% WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES:  

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

Some women should not use the pill. For example, you should not take the pill if you are pregnant or think you may be pregnant. You should also not use the pill if you have any of the following conditions: A history of heart attack or stroke A history of blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes A history of blood clots in the deep veins of your legs Chest pain (angina pectoris) Severe high blood pressure Diabetes with complications of the kidneys, eyes, nerves or blood vessels Headache with neurological symptoms Known or suspected breast cancer or cancer of the lining of the uterus, cervix, or vagina (now or in the past) Unexplained vaginal bleeding (until a diagnosis is reached by your healthcare provider) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of hormonal birth control of any kind (the pill, patch, vaginal ring, injection, or implant) Liver tumor (benign or cancerous) Heart valve or heart rhythm disorders that may be associated with formation of blood clots Need for a long period of bed rest following major surgery Known or suspected pregnancy Active liver disease with abnormal liver function tests An allergy or hypersensitivity to any of the components of Velivet™ Tell your doctor or healthcare provider if you have ever had any of the above conditions. Your doctor or healthcare provider can recommend another method of birth control. OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES: Tell your doctor or healthcare provider if you have: 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 Depression Gallbladder, liver, heart, or kidney disease Scanty or irregular menstrual periods. Women with any of these conditions should be checked often by their doctor or healthcare provider if they choose to use oral contraceptives. Talk to your healthcare provider about using Velivet™ if you: Smoke Recently had a baby Recently had a miscarriage or abortion Are breast feeding Are taking any other medications RISKS OF TAKING ORAL CONTRACEPTIVES: 1. Risk of developing blood clots: Blood clots and blockage of blood vessels are one of the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the leg can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blockage of a vessel carrying blood to the lungs. The risks of these side effects may be greater with desogestrel-containing oral contraceptives such as Velivet™ (desogestrel and ethinyl estradiol, USP tablets - triphasic regimen) than with certain other low-dose pills. 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 or healthcare provider about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breast feeding. If you are breast feeding, you should wait until you have weaned your child before using the pill (see While breast feeding in GENERAL PRECAUTIONS). The risk of circulatory disease in oral contraceptive users may be higher in users of high dose pills and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of venous thromboembolic disease associated with oral contraceptives does not increase with length of use and disappears after pill use is stopped. The risk of abnormal blood clotting increases with age in both users and non-users of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44, it is estimated that about 1 in 2000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among non-users in the same age group, about 1 in 20,000 would be hospitalized each year. For oral contraceptive users in general, it has been estimated that in women between the ages of 15 and 34 the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for non-users the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2500 per year for oral contraceptive users and about 1 in 10,000 per year for non-users. 2. Heart attacks and strokes: Oral contraceptives may increase the tendency to develop strokes (blockage or rupture of blood vessels in the brain), angina pectoris (chest pain), and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or serious disability. Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease. Women with migraine (especially migraine with aura) who take oral contraceptives also may be at a higher risk of stroke. 3. Gallbladder disease: Oral contraceptive users probably have a greater risk than non-users 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: Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. 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 usually a hormone-sensitive tumor. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. There is insufficient evidence to rule out the possibility that pills may cause such cancers. 6. Lipid metabolism and inflammation of the pancreas In patients with inherited defects of lipid metabolism, there have been reports of significant elevations of plasma triglycerides during estrogen therapy. This has led to pancreatitis in some cases. ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY: All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table. ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NON-STERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 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 is 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 per 100,000 women) than the estimated risk associated with pregnancy (28 per 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 or healthcare provider immediately: Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung) Pain in the calf (indicating a possible clot in the leg) Crushing chest pain or heaviness in the chest (indicating a possible heart attack) Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke) Sudden partial or complete loss of vision (indicating a possible clot in the eye) Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your 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 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 In addition to the risks and more serious side effects discussed above (see RISKS OF TAKING ORAL CONTRACEPTIVES, ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY and WARNING SIGNALS sections), the following may also occur: 1. Irregular 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 and 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 doctor or healthcare provider before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your doctor or healthcare provider immediately to determine whether you are pregnant. Stop taking Velivet™ if you are pregnant. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor or healthcare provider. You should check with your doctor or healthcare provider about risks to your unborn child of any medication taken during pregnancy. 2. While breast feeding: If you are breast feeding, consult your doctor or healthcare provider before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breast feeding. You should use another method of contraception since breast feeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breast feed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory tests: If you are scheduled for any laboratory tests, tell your doctor or healthcare provider 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), phenytoin (Dilantin® is one brand of this drug), phenylbutazone (Butazolidin® is one brand), herbal products containing St. John’s Wort (hypericum perforatum), and possibly certain antibiotics. You may need to use additional contraception when you take drugs which can make oral contraceptives less effective. Be sure to tell your healthcare provider if you are taking or start taking any medications while taking birth control pills. 5. Sexually transmitted diseases: This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. HOW TO TAKE THE PILL:

BEFORE YOU START TAKING YOUR PILLS: 1. BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills. Anytime you are not sure what to do. 2. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you 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 doesn't go away, check with your doctor or 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 2 pills to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics or the herbal supplement St. John's Wort, your pills may not work as well. Use a back-up method (such as condoms, spermicides, or diaphragm) until you check with your doctor or healthcare provider. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or 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 doctor or healthcare provider.

If you MISS 1 “active” [beige, orange, or pink] 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 “active” [beige or orange] 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 restart your pills. You MUST use another birth control method (such as condoms, spermicides, or diaphragm) as a back-up method for those 7 days. If you MISS 2 “active” [pink] pills in a row in WEEK 3: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or healthcare provider because you might be pregnant. 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, spermicides, or diaphragm) as a back-up method for those 7 days. If you MISS 3 OR MORE “active” [beige, orange, or pink] pills in a row (during the first 3 weeks): 1.  If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex on the days when you missed pills or during the first 7 days after restarting your pills. You MUST use another birth control method (such as condoms, spermicides, or diaphragm) as a back-up method the next time you have sex and for the first 7 days after you restart your pills.

FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD of birth control anytime you have sex. KEEP TAKING ONE “ ACTIVE” [BEIGE, ORANGE, OR PINK] PILL EACH DAY until you can reach your doctor or healthcare provider. ADDITIONAL INFORMATION 1. PREGNANCY DUE TO PILL FAILURE The incidence of pill failure resulting in pregnancy is approximately one percent (i.e., one pregnancy per 100 women per year of use) if taken every day as directed, but more typical failure rates are about 5% (5 pregnancies per 100 women per year of use). If failure does occur, the risk to the fetus is minimal. 2. 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. 3. 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 doctor, healthcare provider or pharmacist. 4. OTHER INFORMATION Your doctor or healthcare provider will take a medical and family history and may examine you before prescribing an oral contraceptive. The physical examination may be delayed to another time if you request it and your doctor or the healthcare provider 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 doctor or 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 doctor or 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 combination 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. non-cancerous 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, healthcare provider, or pharmacist. They have a more technical leaflet called the Prescribing Information which you may wish to read. BARR LABORATORIES, INC. Pomona, NY 10970 Revised JUNE 2011

NDC 54868-5031-0 Velivet™ (desogestrel and ethinyl estradiol tablets - triphasic regimen) Contents: One dispenser of 28 tablets Each beige tablet contains 0.1 mg desogestrel and 0.025 mg ethinyl estradiol; each orange tablet contains 0.125 mg desogestrel and 0.025 mg ethinyl estradiol; each pink tablet contains 0.15 mg desogestrel and 0.025 mg ethinyl estradiol. Each white tablets 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 TRANSMTTED DISEASES.