DailyMed Label: Cyred EQ

DailyMed Label: Cyred EQ

2023

DailyMed Prescription

Cyred EQ

Desogestrel and Ethinyl Estradiol

RPK Pharmaceuticals, Inc.

NDC: 53002-2722

NDC: 53002-2722

NDC: 53002-2722

Cyred EQ ®  tablets provide an oral contraceptive regimen of 21 white to off-white round tablets each containing 0.15 mg desogestrel (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol) and 0.03 mg ethinyl estradiol USP (19-nor-17 alpha-pregna-1,3,5 (10)-trien-20-yne-3,17,diol). Inactive ingredients include colloidal silicon dioxide, lactose monohydrate, potato starch, povidone, stearic acid, and vitamin E. Each green tablet contains the following inactive ingredients: anhydrous lactose, croscarmellose sodium, FD&C Blue No.2 Aluminum Lake, ferric oxide yellow, magnesium stearate, microcrystalline cellulose, and povidone. Cyred EQ meets USP Dissolution Test 2. Chemical Structure

Cyred EQ ® tablets are indicated for the prevention of pregnancy in women who elect to use oral contraceptives as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combined oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and the Norplant System depends upon the reliability with which they are used. Correct and consistent use of these methods can result in lower failure rates. In a clinical trial with Cyred EQ ® , 1,195 subjects completed 11,656 cycles and a total of 10 pregnancies were reported. This represents an overall user-efficacy (typical user-efficacy) pregnancy rate of 1.12 per 100 women-years. This rate includes patients who did not take the drug correctly. Table 1: PERCENTAGE OF WOMEN EXPERIENCING AN UNINTENDED PREGNANCY DURING THE FIRST YEAR OF TYPICAL USE AND THE FIRST YEAR OF PERFECT USE OF CONTRACEPTION AND THE PERCENTAGE CONTINUING USE AT THE END OF THE FIRST YEAR. UNITED STATES.    % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year * Method (1) Typical Use † (2) Perfect Use ‡ (3)   (4) Chance # 85 85   Spermicides Þ 26 6 40 Periodic abstinence 25   63  Calendar   9    Ovulation Method   3    Sympto-Thermal ß   2    Post-Ovulation   1   Withdrawal 19 4   Cap à        Parous Women 40 26 42  Nulliparous Women 20 9 56 Sponge        Parous Women 40 20 42  Nulliparous Women 20 9 56 Diaphragm à 20 6 56 Condom è        Female (Reality ® ) 21 5 56  Male 14 3 61 Pill 5   71  Progestin Only   0.5    Combined   0.1   IUD        Progesterone T 2 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 ® and Norplant-2 ® 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.1 100 Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces the risk of pregnancy by at least 75%. § Lactation Amenorrhea Method: LAM is a highly effective, temporary method of contraception. ¶ Source: Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowel D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York, NY; Irvington Publishers, 1998. *   Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. † 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. ‡  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 other reason. §  The treatment schedule is one dose within 72 hours after unprotected intercourse, and a second dose 12 hours after the first dose. The FDA 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 4 yellow pills). ¶ However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency of duration of breastfeeds is reduced, bottle feeds are introduced, or the baby reaches 6 months of age. # 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 percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. Þ Foams, creams, gels, vaginal suppositories, and vaginal film. ß Cervical mucus (ovulation) method supplemented by calendar in the pre-ovulatory and basal body temperature in the post-ovulatory phases. à With spermicidal cream or jelly. è Without spermicides. Cyred EQ ® has not been studied for and is not indicated for use in emergency contraception.

To achieve maximum contraceptive effectiveness, Cyred EQ ®   must be taken exactly as directed and at intervals not exceeding 24 hours. Cyred EQ ® is available in the blister pack which is preset for a Sunday Start. Day 1 Start is also provided. The dosage of Cyred EQ ® for the initial cycle of therapy is one white to off-white “active” tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1". Tablets are taken without interruption as follows: One white to off-white “active” tablet daily for 21 days, then one green “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a white to off-white “active” tablet is taken the next day. The use of Cyred EQ ® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also  PRECAUTIONS: Nursing Mothers .) If the patient starts on Cyred EQ ® postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white to off-white “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) white to off-white “active” tablet in Weeks 1, 2, or 3, the white to off-white “active” tablet should be taken as soon as she remembers. If the patient misses two (2) white to off-white “active” tablets in Week 1 or Week 2, the patient should take two (2) white to off-white “active” tablets the day she remembers and two (2) white to off-white “active” tablets the next day; and then continue taking one (1) white to off-white “active” tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) white to off-white “active” tablets in the third week or misses three (3) or more white to off-white “active” tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. When taking Cyred EQ ® , the first white to off-white “active” tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first white to off-white “active” tablet is taken on that day. If switching directly from another oral contraceptive, the first white to off-white “active” tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One white to off-white “active” tablet daily for 21 days, then one green “reminder” tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a white to off-white “active” tablet is taken the next day (Sunday). When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. The use of Cyred EQ ® for contraception may be initiated 4 weeks postpartum. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See  CONTRAINDICATIONS   and WARNINGS concerning thromboembolic disease. See also  PRECAUTIONS: Nursing Mothers .) If the patient starts on Cyred EQ ® postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a white to off-white “active” tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) white to off-white active tablet in Weeks 1, 2, or 3, the white to off-white “active” tablet should be taken as soon as she remembers. If the patient misses two (2) white to off-white “active” tablets in Week 1 or Week 2, the patient should take two (2) white to off-white “active” tablets the day she remembers and two (2) white to off-white “active” tablets the next day; and then continue taking one (1) white to off-white “active” tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) white to off-white “active” tablets in the third week or misses three (3) or more white to off-white “active” tablets in a row, the patient should continue taking one white to off-white “active” tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease. Use of oral contraceptives in the event of a missed menstrual period: 1.  If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. 2.  If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.

Cyred EQ ® is contraindicated in females who are known to have or develop the following conditions: Thrombophlebitis or thromboembolic disorders A past history of deep vein thrombophlebitis or thromboembolic disorders Known thrombophilic conditions Cerebral vascular or coronary artery disease (current or history) Valvular heart disease with complications Persistent blood pressure values of ≥ 160 mm Hg systolic or ≥ 100 mg Hg diastolic 102   Diabetes with vascular involvement Headaches with focal neurological symptoms Major surgery with prolonged immobilization Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Acute or chronic hepatocellular disease with abnormal liver function Hepatic adenomas or carcinomas Known or suspected pregnancy Hypersensitivity to any component of this product Are receiving Hepatitis C drug combinations containing ombitasivir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see section 5 in  WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ).

Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. If jaundice develops in any woman receiving oral contraceptives, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation: Do not co-administer Cyred EQ ® with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs. 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. See WARNINGS . Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS . 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. Safety and efficacy of Cyred EQ ® tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated. This product has not been studied in women over 65 years of age and is not indicated in this population. See Patient Labeling printed below.

An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see

Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects of Other Drugs on Combined Hormonal Contraceptives Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs: Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of CHCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John’s wort. Interactions between hormonal contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with CHCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Substances increasing the plasma concentrations of COCs: Co-administration of atorvastatin or rosuvastatin and certain COCs containing EE increase AUC values for EE by approximately 20 to 25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir]) /HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation: Do not co-administer Cyred EQ ® with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see section 5 in WARNINGS, Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment ). Colesevelam: Colesevelam, a bile acid sequestrant, given together with a combination oral hormonal contraceptive, has been shown to significantly decrease the AUC of EE. A drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Effects of Combined Hormonal Contraceptives on Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid-binding globulin increases with use of COCs.

Cyred EQ ® (Desogestrel and Ethinyl Estradiol Tablets USP 0.15 mg/0.03 mg)  is available in a carton of  3 pouches, each containing 28 tablets: 21 active tablets: White to off-white, round, biconvex, beveled-edge tablets, debossed with “S” on one side and “25” on other side. 7 inert tablets: Green, round, mottled, biconvex, beveled-edge tablets, debossed with “S” on one side and “7” on other side.             1 Pouch of 28 tablets                                      NDC 50102-254-21             Carton of 3 Pouches                                       NDC 50102-254-23 STORAGE Store at 20º to 25°C (68° to 77º F) [see USP Controlled Room Temperature].

Combined oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus, which increase the difficulty of sperm entry into the uterus, and changes in the endometrium which reduce the likelihood of implantation. Receptor binding studies, as well as studies in animals, have shown that 3-keto-desogestrel, the biologically active metabolite of desogestrel, combines high progestational activity with minimal intrinsic androgenicity. 91,92 The relevance of this latter finding in humans is unknown. Desogestrel is rapidly and almost completely absorbed and converted into 3-keto-desogestrel, its biologically active metabolite. Following oral administration, the relative bioavailability of desogestrel, as measured by serum levels of 3-keto-desogestrel, is approximately 84%. In the third cycle of use after a single dose of Cyred EQ ® , maximum concentrations of 3-keto-desogestrel of 2,805 ± 1,203 pg/mL (mean ± SD) are reached at 1.4 ± 0.8 hours. The area under the curve (AUC 0-∞ ) is 33,858 ± 11,043 pg/mL⋅hr after a single dose. At steady state, attained from at least day 19 onwards, maximum concentrations of 5,840 ± 1,667 pg/mL are reached at 1.4 ± 0.9 hours. The minimum plasma levels of 3-keto-desogestrel at steady state are 1,400 ± 560 pg/mL. The AUC 0-24 at steady state is 52,299 ± 17,878 pg/mL⋅hr. The mean AUC 0-∞ for 3-keto-desogestrel at single dose is significantly lower than the mean AUC 0-24 at steady state. This indicates that the kinetics of 3-keto-desogestrel are non-linear due to an increase in binding of 3-keto-desogestrel to sex hormone-binding globulin in the cycle, attributed to increased sex hormone-binding globulin levels which are induced by the daily administration of ethinyl estradiol. Sex hormone-binding globulin levels increased significantly in the third treatment cycle from day 1 (150 ± 64 nmol/L) to day 21 (230 ± 59 nmol/L). The elimination half-life for 3-keto-desogestrel is approximately 38 ± 20 hours at steady state. In addition to 3-keto-desogestrel, other phase I metabolites are 3α-OH-desogestrel, 3β-OH-desogestrel, and 3α-OH-5α-H-desogestrel. These other metabolites are not known to have any pharmacologic effects, and are further converted in part by conjugation (phase II metabolism) into polar metabolites, mainly sulfates and glucuronides. Ethinyl estradiol is rapidly and almost completely absorbed. In the third cycle of use after a single dose of Cyred EQ ® , the relative bioavailability is approximately 83%. In the third cycle of use after a single dose of Cyred EQ ® , maximum concentrations of ethinyl estradiol of 95 ± 34 pg/mL are reached at 1.5 ± 0.8 hours. The AUC 0-∞ is 1,471 ± 268 pg/mL⋅hr after a single dose. At steady state, attained from at least day 19 onwards, maximum ethinyl estradiol concentrations of 141 ± 48 pg/mL are reached at about 1.4 ± 0.7 hours. The minimum serum levels of ethinyl estradiol at steady state are 24 ± 8.3 pg/mL. The AUC 0-24 at steady state is 1,117 ± 302 pg/mL⋅hr. The mean AUC 0-∞ for ethinyl estradiol following a single dose during treatment cycle 3 does not significantly differ from the mean AUC 0-24 at steady state. This finding indicates linear kinetics for ethinyl estradiol. The elimination half-life is 26 ± 6.8 hours at steady state. Ethinyl estradiol is subject to a significant degree of presystemic conjugation (phase II metabolism). Ethinyl estradiol escaping gut wall conjugation undergoes phase I metabolism and hepatic conjugation (phase II metabolism). Major phase I metabolites are 2-OH-ethinyl estradiol and 2-methoxy-ethinyl estradiol. Sulfate and glucuronide conjugates of both ethinyl estradiol and phase I metabolites, which are excreted in bile, can undergo enterohepatic circulation.

Cyred EQ ® (Desogestrel and Ethinyl Estradiol Tablets USP) This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Oral contraceptives, also known as "birth control pills" or "the pill," are taken to prevent pregnancy, and when taken correctly without missing any pills, have a failure rate of approximately 1% per year. The typical failure rate is approximately 5% per year when women who miss pills are included. For most women, oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take pills considerably increases the chances of pregnancy. For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be life-threatening or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you: smoke have high blood pressure, diabetes, high cholesterol have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors Although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy, non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding. Do not use Cyred EQ ® if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects (heart and blood vessel problems) from combination oral contraceptives, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you 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, headache, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use. The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill: 1.  Blood clots in the legs (thrombophlebitis) or lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), 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. 2.  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, some studies report an increased risk of developing liver cancer. However, liver cancers are rare. 3.  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 patient labeling given to you with your supply of pills. Notify your healthcare professional if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, bosentan, as well as some seizure medicines and herbal preparations containing St. John’s wort ( Hypericum perforatum ) may decrease oral contraceptive effectiveness. Oral contraceptives may interact with lamotrigine (LAMICTAL ® ), a seizure medicine used for epilepsy. This may increase the risk of seizures so your healthcare professional may need to adjust the dose of lamotrigine. There may be slight increases in the risk of breast cancer among current users of hormonal birth control pills with longer duration of use of 8 years or more. 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 the pill may cause such cancers. 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 professional. Your healthcare professional will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare professional believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information labeling gives you further information which you should read and discuss with your healthcare professional. 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: 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 feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn’t go away, check with your healthcare professional. 4.    MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills.         On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. 5.     IF YOU HAVE VOMITING OR DIARRHEA, or IF YOU TAKE SOME MEDICINES, your pills may not work as well.         Use a back-up method (such as a condom or spermicide) until you check with your healthcare professional. 6.     IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare professional about how to make pill-taking easier or about using another method of birth control. 7.     IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare professional. BEFORE YOU START TAKING YOUR PILLS 1.    DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL.         It is important to take it at about the same time every day. 2.     LOOK AT YOUR PILL PACK:         The pill pack has 21 white to off-white “active” pills (with hormones) to take for 3 weeks, followed by 1 week of green “reminder” pills (without hormones). 3.     ALSO FIND:         1)   where on the pack to start taking pills,         2)   in what order to take the pills,         3)   check picture of pill pack and additional instructions for using this package below. 4.     BE SURE YOU HAVE READY AT ALL TIMES:         ANOTHER KIND OF BIRTH CONTROL (such as a condom or spermicide) to use as a back-up method in case you miss pills.         AN EXTRA, FULL PILL PACK. ______________________________________________________________________________________ WHEN TO START THE FIRST PACK OF PILLS ______________________________________________________________________________________ You have a choice of which day to start taking your first pack of pills. Cyred EQ ® is available in the blister pack which is preset for a Sunday Start. Day 1 Start is also provided. Decide with your healthcare professional which is the best day for you. Pick a time of day that will be easy to remember. DAY 1 START: 1.       Take the first white to off-white “active” pill of the first pack during the first 24 hours of your period . 2.     You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: 1.       Take the first white to off-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. 2.      Use another method of birth control such as a condom or spermicide as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). ______________________________________________________________________________________ WHAT TO DO DURING THE MONTH ______________________________________________________________________________________ 1.     TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY.             Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea).             Do not skip pills even if you do not have sex very often. 2.     WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS:             Start the next pack on the day after your last green "reminder" pill. Do not wait any days between packs. ______________________________________________________________________________________ WHAT TO DO IF YOU MISS PILLS ______________________________________________________________________________________   If you MISS 1 white to off-white "active" pill: 1.     Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. 2.     You do not need to use a back-up birth control method if you have sex. If you MISS 2 white to off-white "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: 1.     Take 2 pills on the day you remember and 2 pills the next day. 2.     Then take 1 pill a day until you finish the pack. 3.     You COULD BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as a condom or spermicide) as a back-up method for those 7 days. If you MISS 2 white to off-white "active" pills in a row in THE 3RD WEEK : 1.      If you are a Day 1 Starter:         THROW OUT the rest of the pill pack and start a new pack that same day.          If you are a Sunday Starter :         Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2.     You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare professional because you might be pregnant. 3.     You COULD BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as a condom or spermicide) as a back-up method for those 7 days. If you MISS 3 OR MORE white to off-white "active" 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 healthcare professional because you might be pregnant. 3.     You COULD BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as a condom or spermicide) as a back-up method for those 7 days. A REMINDER: If you forget any of the 7 green "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE WHITE TO OFF-WHITE "ACTIVE" PILL EACH DAY until you can reach your healthcare professional. 1.   The blister pack comes to you set up for Sunday Start. If your healthcare professional has instructed you to start pill-taking on the first SUNDAY after your menstrual period has begun, or has instructed you to start pill-taking on the first day of your menstrual period and that day is SUNDAY, go to the directions in Number 3. 2.  If you are to start pill-taking on a day other than SUNDAY, the enclosed calendar label has been provided and will be placed over the calendar printed on the blister pack. To put label in place, identify your correct starting day, locate that day label present in the calendar label and affix that day label over the printed calendar on the blister pack. 3. The first white to off-white "active" pill you will take is indicated by START and lines up with the black Day Arrow as indicated on the blister pack. For details, see the directions in the following picture. DAY-1 STARTERS: If your period begins on a day other than Sunday, place the day label strip that starts with the first day of your period here. Push down on the first white to off-white “active” pill with your thumb or forefinger. The pill will come out through a hole in the back of the package. After you have taken all 21 white to off-white “active” pills, take one green “reminder” pill daily for 7 days. During this time your period should begin. After you have taken all the pills, start a new pack of pills even if your period is not yet over. STORAGE Store at 20º to 25°C (68° to 77º F) [see USP Controlled Room Temperature]. Figure 3

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