Zarah Dailymed

Effects of Other Drugs on Combined Hormonal Contraceptives 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. 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) on plasma concentrations of synthetic steroids. 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. A reduction in contraceptive effectiveness and an increased incidence of menstrual irregularities has been suggested with phenylbutazone. Effects of Drospirenone on Other Drugs Metabolic InteractionsMetabolism of DRSP and potential effects of DRSP on hepatic cytochrome P450 (CYP) enzymes have been investigated in in vitro and in vivo studies (see Metabolism). In in vitro studies DRSP did not affect turnover of model substrates of CYP1A2 and CYP2D6, but had an inhibitory influence on the turnover of model substrates of CYP1A1, CYP2C9, CYP2C19 and CYP3A4 with CYP2C19 being the most sensitive enzyme. The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. In the study with 24 postmenopausal women [including 12 women with homozygous (wild type) CYP2C19 genotype and 12 women with heterozygous CYP2C19 genotype] the daily oral administration of 3 mg DRSP for 14 days did not affect the oral clearance of omeprazole (40 mg, single oral dose). Based on the available results of in vivo and in vitro studies it can be concluded that, at clinical dose level, DRSP shows little propensity to interact to a significant extent with cytochrome P450 enzymes. Interactions with Drugs that Have the Potential to Increase Serum PotassiumThere is a potential for an increase in serum potassium in women taking drospirenone and ethinyl estradiol with other drugs (see BOLDED WARNING ). Of note, occasional or chronic use of NSAID medication was not restricted in any of the drospirenone and ethinyl estradiol clinical trials.A drug-drug interaction study of DRSP 3 mg/estradiol (E2) 1 mg versus placebo was performed in 24 mildly hypertensive postmenopausal women taking enalapril maleate 10 mg twice daily. Potassium levels were obtained every other day for a total of 2 weeks in all subjects. Mean serum potassium levels in the DRSP/E2 treatment group relative to baseline were 0.22 mEq/L higher than those in the placebo group. Serum potassium concentrations also were measured at multiple timepoints over 24 hours at baseline and on Day 14. On Day 14, the ratios for serum potassium Cmax and AUC in the DRSP/E2 group to those in the placebo group were 0.955 (90% CI: 0.914, 0.999) and 1.010 (90% CI: 0.944, 1.080), respectively. No patient in either treatment group developed hyperkalemia (serum potassium concentrations > 5.5 mEq/L). Effects of Combined Hormonal Contraceptives on Other Drugs Combined oral contraceptives containing 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. In addition, oral contraceptives may induce the conjugation of other compounds. Decreased plasma concentrations of acetaminophen and increased clearance on temazepam, salicylic acid, morphine, and clofibric acid have been noted when these drugs were administered with oral contraceptives.

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 and corticoids; however, free or biologically active levels remain unchanged. e. Triglycerides may be increased. 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 and Sections. Estrogens and progestins should not be used during pregnancy. Fourteen pregnancies that occurred with drospirenone and ethinyl estradiol exposure (none with more than a single cycle of exposure) have been identified. One infant was born with esophageal atresia. A causal association with drospirenone and ethinyl estradiol is unknown.

Pregnancy category X. See CONTRAINDICATIONS and WARNINGS Sections. Estrogens and progestins should not be used during pregnancy. Fourteen pregnancies that occurred with drospirenone and ethinyl estradiol exposure 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 drospirenone and ethinyl estradiol is unknown. 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 drospirenone and ethinyl estradiol 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.

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. ZARAH is different from other birth control pills because they contain the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take ZARAH if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether ZARAH is right for you, and during the first month that you take drospirenone and ethinyl estradiol tablets, you should have a blood test to check your potassium level. NSAIDs (ibuprofen [Motrin®*, Advil®*], naprosyn [Aleve®* and others] when taken long-term and daily for treatment of arthritis or other problems) Potassium-sparing diuretics (spironolactone and others) Potassium supplementation ACE inhibitors (Capoten®*, Vasotec®*, Zestril®* and others) Angiotensin-II receptor antagonists (Cozaar®*, Diovan®*, Avapro®*, and others) Heparin Oral contraceptives, also known as "birth control pills" or "the pill", are taken to prevent pregnancy, and when taken correctly, have a failure rate of less than 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 5% per year when women who miss pills are included. However, forgetting to take pills considerably increases the chances of pregnancy. For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you: smoke have high blood pressure, diabetes, high cholesterol have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice, or malignant or benign liver tumors. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding.  Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke.   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: 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. 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. 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. 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 provides some important non-contraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your healthcare 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 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. It does 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. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1 to 3 PACKS OF PILLS. If you 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 doctor or clinic. 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 OR DIARRHEA, or IF YOU TAKE SOME 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 doctor or clinic. 6.  IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic 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 clinic. BEFORE YOU START TAKING YOUR PILLS DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. LOOK AT YOUR PILL PACK-IT HAS 28 PILLS:The ZARAH pill pack has 21 blue "active" pills (with hormones) to be taken for three weeks, followed by 7 peach “reminder” pills (without hormones) to be taken for one week. 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 as shown in the diagram below * For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS below. 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 doctor or clinic which is the best day for you. On the first day of your period (see DAY 1 START and SUNDAY START below), peel the day label from the sticker sheet which has the corresponding start day of your period printed on the left; apply the day label in the designated location on the buler card. Take your pill daily in the order indicated by the arrows on the buler card. Pick a time of day which will be easy to remember and take your pill at the same time every day.

If you MISS 1 blue "active" pill: 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. You do not need to use a back-up birth control method if you have sex. If you MISS 2 blue "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: Take two pills on the day you remember and two pills the next day. Then take one pill a day until you finish the pack. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss 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 blue "active" pills in a row in THE 3rd WEEK: 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. 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. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days. If you MISS 3 OR MORE blue "active" pills in a row (during the first 3 weeks): 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. 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. 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 or spermicides) as a back-up for those 7 days. If you forget any of the 7 peach "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 PILL EACH DAY until you can reach your doctor or clinic. For additional information see "Detailed Patient Labeling." Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. ZARAH is different from other birth control pills because they contain the progestin drospirenone. Drospirenone may increase potassium. Therefore, you should not take ZARAH if you have kidney, liver or adrenal disease because this could cause serious heart and health problems. Other drugs may also increase potassium. If you are currently on daily, long-term treatment for a chronic condition with any of the medications below, you should consult your healthcare provider about whether ZARAH is right for you, and during the first month that you take ZARAH, you should have a blood test to check your potassium level. NSAIDs (ibuprofen [Motrin®*, Advil®*], naprosyn [Aleve®* and others] when taken long-term and daily for treatment of arthritis or other problems) Potassium-sparing diuretics (spironolactone and others) Potassium supplementation ACE inhibitors (Capoten®*, Vasotec®*, Zestril®* and others) Angiotensin-II receptor antagonists (Cozaar®*, Diovan®*, Avapro®*, and others) Heparin 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 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 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 nonsurgical methods of birth control. When they are taken correctly, the chance of becoming pregnant is less than 1% (one pregnancy per 100 women per year of use) when used perfectly, without missing any pills. Typical failure rates, including women who don’t always follow the instructions exactly, are about 5% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical failure rates for other nonsurgical methods of birth control during the first year of use are as follows: Percentage of women experiencing an unintended pregnancy during the first year of typical use and first year of perfect use of contraception and the percentage continuing use at the end of the first year: United States.    % of Women Experiencing anAccidental Pregnancywithin the First Year of Use  % of WomenContinuing Useat One Year3  Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%.9  Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception.10  Source: Trussell J, Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998.  1   Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason.  2   Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any reason.  3   Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year.  4   The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether.  5   Foams, creams, gels, vaginal suppositories, and vaginal film.  6   Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases.  7   With spermicidal cream or jelly.  8   Without spermicides.  9   The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral®* (1 dose is 2 white pills), Alesse®* (1 dose is 5 pink pills), Nordette®* or Levlen®* (1 dose is 2 light-orange pills), Lo Ovral®* (1 dose is 4 white pills), Triphasil®* or Tri-Levlen®* (1 dose is 4 yellow pills).  10   However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches six months of age.  Method(1)  Typical Use1 (2)  Perfect Use2 (3)  (4)  Chance4  85  85    Spermicides5  26  6  40  Periodic abstinence  25    63       Calendar    9         Ovulation method    3    Sympto-thermal6    2    Post-ovulation    1    Withdrawal  19  4    Cap7             Parous women  40  26  42       Nulliparous women  20  9  56  Sponge             Parous women  40  20  42       Nulliparous women  20  9  56  Diaphragm7  20  6  56  Condom8             Female (Reality®*)  21  5  56       Male  14  3  61  Pill  5    71       Progestin only    0.5         Combined    0.1    IUD             Progesterone T  2.0  1.5  81       Copper T380A  0.8  0.6  78       Lng 20  0.1  0.1  81  Depo-Provera®*  0.3  0.3  70  Norplant®* andNorplant®* II  0.05  0.05  88  Female sterilization  0.5  0.5  100  Male sterilization  0.15  0.10  100

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

 Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke.   Some women should not use ZARAH. For example, you should not take ZARAH if you are pregnant or think you may be pregnant. You should also not use ZARAH if you have had any of the following conditions: A history of heart attack or stroke Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), brain (stroke) or eyes A history of blood clots in the deep veins of your legs 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 Liver tumor (benign or cancerous) Known or suspected pregnancy In addition, you should not use ZARAH 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 ZARAH: 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 OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVESTell 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 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 or are on any medications. RISKS OF TAKING ORAL CONTRACEPTIVES 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 can cause thrombophlebitis 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. It is advisable to wait for at least four weeks after delivery if you are not breastfeeding. If you are breastfeeding, you should wait until you have weaned your child before using the pill. (See also the section on breastfeeding in "GENERAL PRECAUTIONS"). 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. 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. 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. 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  Method of Control and Outcome  AGE  15 to 19  20 to 24  25 to 29  30 to 34  35 to 39  40 to 44  \1\ Deaths are birth related  \2\ Deaths are method related  Adapted from H.W. Ory, Family Planning Perspectives, 15:57 to 63, 1983.  No fertility control methods\1\  7.0  7.4  9.1  14.8  25.7  28.2  Oral contraceptives                   Nonsmoker \2\  0.3  0.5  0.9  1.9  13.8  31.6  Oral contraceptives                   Smoker \2\  2.2  3.4  6.6  13.5  51.1  117.2  lUD \2\  0.8  0.8  1  1  1.4  1.4  Condom \1\  1.1  1.6  0.7  0.2  0.3  0.4  Diaphragm/ spermicide \1\  1.9  1.2  1.2  1.3  2.2  2.8  Periodic abstinence \1\  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 25.7 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 31.6 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 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. 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. 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. MELASMA A spotty darkening of the skin is possible, particularly of the face. 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 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 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 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. While Breastfeeding If you are breastfeeding, 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 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 breastfeeding. You should use another method of contraception since breastfeeding provides only partial protection from becoming pregnant, and this partial protection decreases significantly as you breastfeed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 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. 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 (also See BOLDED TEXT AT BEGINNING ). 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.

IMPORTANT POINTS TO REMEMBER BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS:Before you start taking your pills.Anytime you are not sure what to do. 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. MMANY 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 doctor or clinic. 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. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME 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 foam spermicides) until you check with your doctor or clinic. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic. BEFORE YOU START TAKING YOUR PILLS DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.It is important to take it at about the same time every day. LOOK AT YOUR PILL PACK – IT HAS 28 PILLSThe ZARAH pill pack has 21 blue "active" pills (with hormones) to be taken for three weeks, followed by 7 peach “reminder” pills (without hormones) to be taken for one week. 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 as shown in the diagram below * For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS below. 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 doctor or clinic which is the best day for you. On the first day of your period (see DAY 1 START and SUNDAY START below), peel the day label from the sticker sheet which has the corresponding start day of your period printed on the left; apply the day label in the designated location on the buler card. Take your pill daily in the order indicated by the arrows on the buler card. Pick a time of day which will be easy to remember and take your pill at the same time every day. DAY 1 START: Take the first white "active" pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first white "active" pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. 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). WHAT TO DO DURING THE MONTH TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTYDo 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. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS: Start the next pack on the day after your last peach "reminder" pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 blue "active" pill: 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. You do not need to use a back-up birth control method if you have sex. If you MISS 2 blue "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: Take two pills on the day you remember and two pills the next day. Then take one pill a day until you finish the pack. 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 or spermicides) as a back-up for those 7 days. If you MISS 2 blue "active" pills in a row in THE 3rd WEEK: 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. 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. 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 or spermicide) as a back-up for those 7 days. If you MISS 3 OR MORE blue "active" pills in a row (during the first 3 weeks). 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. 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. 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 or spermicides) as a back-up for those 7 days. If you forget any of the 7 peach "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 PILL EACH DAY until you can reach your doctor or clinic. PREGNANCY DUE TO PILL FAILURE The incidence of pill failure resulting in pregnancy is approximately less than 1% (one pregnancy per 100 women per year or use) if taken every day as directed, but more typical failure rates are about 5%. If failure does occur with ZARAH use, the risk to the fetus is unknown. 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 ZARAH 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 CONTRACEPTIVESIn 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. *Motrin® is manufactured by McNeil Pediatrics and a registered trademark of Johnson & Johnson Corporation; Advil® is manufactured by Wyeth Consumer Healthcare and a registered trademark of Wyeth Corporation; Aleve® is manufactured by Bayer Healthcare and a registered trademark of Bayer Healthcare, LLC; Capoten® is manufactured by Par Pharmaceutical and a registered trademark of Par Pharmaceutical, Inc.; Vasotec® is manufactured by Merck Sharp & Dohme Ltd. and a registered trademark of Biovail Laboratories International SRL; Zestril® is manufactured by AstraZeneca Pharmaceuticals LP and a registered trademark of AstraZeneca UK Limited; Cozaar® is manufactured by Merck & Co., Inc. and a registered trademark of E.I. du Pont de Nemours and Company; Diovan® is manufactured by Novartis and a registered trademark of Novartis Corporation; Avapro® is manufactured by and a registered trademark of Sanofi-Aventis; Reality® is manufactured by Female Health Company and a registered trademark of Meijer, Inc.; Depo-Provera® is manufactured by and a registered trademark of Pharmacia and Upjohn; Norplant® is manufactured by and a registered trademark of Population Council; Ovral®, Alesse®, Lo Ovral® and Triphasil® are manufactured by Wyeth Pharmaceuticals, Inc. and registered trademarks of Wyeth Corporation; Nordette® is manufactured by and a registered trademark of Duramed Pharmaceuticals, Inc.; Levlen® and Tri-Levlen® are manufactured by and registered trademarks of Bayer Healthcare; Dilantin® is manufactured by and a registered trademark of Pfizer Pharmaceuticals; Butazolidin was formerly manufactured by Novartis. Manufactured By: Watson Laboratories, Inc. Corona, CA 92880  USA Distributed By: Watson Pharma, Inc. Corona, CA 92880 USA Issued:  May 2010                    193910