further Tri-Estarylla Generic Name: norgestimate and ethinyl estradiol Dosage Form: tablets Overview Side Effects Dosage Professional Interactions More Pregnancy Warnings User Reviews Support Group Q & A Pricing & Coupons WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see CONTRAINDICATIONS (4)]. Indications and Usage for Tri-Estarylla Oral Contraceptive Tri-Estarylla (norgestimate and ethinyl estradiol tablets, USP) is indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14) ] . Acne Tri-Estarylla is indicated for the treatment of moderate acne vulgaris in females at least 15 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Tri-Estarylla should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see CLINICAL STUDIES ( 14 )]. Slideshow 10 Common Symptoms That Should Never Be Ignored Tri-Estarylla Dosage and Administration How to Start Tri-Estarylla Tri-Estarylla (norgestimate and ethinyl estradiol tablets, USP), is dispensed in a blister pack [see HOW SUPPLIED/STORAGE AND HANDLING ( 16 )]. Tri-Estarylla may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration. How to Take Tri-Estarylla Table 1: Instructions for Administration of Tri- Estarylla Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important : Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: Tri-Estarylla active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 14) and blue (Day15 to Day 21). Tri-Estarylla has green inactive tablets (Day 22 to Day 28). Day 1 Start: Take first active tablet without regard to meals on the first day of menses. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. Begin each subsequent blister pack on the same day of Tri-Estarylla the week as the first cycle blister pack (i.e., on the day after taking the last inactive tablet) Sunday Start: Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of Tri- Estarylla . Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Tri- Estarylla from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to Tri- Estarylla Start Tri- Estarylla : Transdermal patch On the day when next application would have been scheduled Vaginal ring On the day when next insertion would have been scheduled Injection On the day when next injection would have been scheduled Intrauterine contraceptive On the day of removal If the IUD is not removed on first day of the patient's menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. Implant On the day of removal Starting Tri- Estarylla after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Tri-Estarylla may be started immediately. An additional method of contraception is not needed if Tri-Estarylla is started immediately. If Tri-Estarylla is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle blister pack of Tri-Estarylla . Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Tri-Estarylla , following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of Tri-Estarylla . [See CONTRAINDICATIONS (4) , WARNINGS AND PRECAUTIONS (5.1) , and FDA-Approved Patient Labeling .] Starting Tri- Estarylla after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Tri-Estarylla following the instructions in Table 1 (above) for women not currently using hormonal contraception. Tri-Estarylla is not recommended for use in lactating women [see USE IN SPECIFIC POPULATIONS (8.3) ]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Tri-Estarylla . [See CONTRAINDICATIONS (4) , WARNINGS AND PRECAUTIONS (5.1) , USE IN SPECIFIC POPULATIONS (8.1 and 8.3) , and FDA-Approved Patient Labeling ]. 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 BLISTER PACK The pill pack has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of "reminder" green pills (without hormones). 3.ALSO FIND: 1) where on the pack to start taking pills, 2) in what order to take the pills (follow the arrows) 3) The week numbers as shown in the diagram 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 blister pack. Missed Tablets Table 2: Instructions for Missed Tri-Estarylla Tablets If one active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the pack and start a new pack that same day. Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. Advice in Case of Gastrointestinal Disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling ]. Tri-Estarylla Use for Acne The timing of initiation of dosing with Tri-Estarylla for acne should follow the guidelines for use of Tri-Estarylla as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions Dosage Forms and Strengths Tri-Estarylla Tablets are available in blister cards. Each blister pack contains 28 tablets in the following order: 7 white (active) tablets are round, debossed with SZ on one side and T2 on the other side and contains 0.18 mg of norgestimate and 0.035 mg of ethinyl estradiol. 7 light blue (active) tablets are round, debossed with SZ on one side and T3 on the other side and contains 0.215 mg of norgestimate and 0.035 mg of ethinyl estradiol. 7 blue (active) tablets are round, debossed with SZ on one side and T4 on the other side and contains 0.25 mg of norgestimate and 0.035 mg of ethinyl estradiol. 7 green (inert) tablets are round, debossed with SZ on one side and J1 on the other side. Contraindications Do not prescribe Tri-Estarylla to women who are known to have the following conditions: A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: Smoke, if over age 35 [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1) ] Have deep vein thrombosis or pulmonary embolism, now or in the past [see WARNINGS AND PRECAUTIONS (5.1) ] Have inherited or acquired hypercoagulopathies [see WARNINGS AND PRECAUTIONS (5.1) ] Have cerebrovascular disease [see WARNINGS AND PRECAUTIONS (5.1) ] Have coronary artery disease [see WARNINGS AND PRECAUTIONS (5.1) ] Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS AND PRECAUTIONS (5.1) ] Have uncontrolled hypertension [see WARNINGS AND PRECAUTIONS (5.3) ] Have diabetes mellitus with vascular disease [see WARNINGS AND PRECAUTIONS (5.5) ] Have headaches with focal neurological symptoms or migraine headaches with aura [see WARNINGS AND PRECAUTIONS (5.6) ] 1. Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS (5.6) ] Liver tumors, benign or malignant, or liver disease [see WARNINGS AND PRECAUTIONS (5.2) ] Undiagnosed abnormal uterine bleeding [see WARNINGS AND PRECAUTIONS (5.7) ] Pregnancy, because there is no reason to use COCs during pregnancy [see WARNINGS AND PRECAUTIONS (5.8) and USE IN SPECIFIC POPULATIONS (8.1) ] Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see WARNINGS AND PRECAUTIONS (5.10) ] Warnings and Precautions Thromboembolic Disorders and Other Vascular Problems Stop Tri-Estarylla if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop Tri-Estarylla if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see ADVERSE REACTIONS (6.2) ]. If feasible, stop Tri-Estarylla at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization. Start Tri-Estarylla no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued. Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke. Use COCs with caution in women with cardiovascular disease risk factors. Liver Disease Impaired Liver Function Do not use Tri-Estarylla in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of liver [see CONTRAINDICATIONS (4) ]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue Tri-Estarylla if jaundice develops. Liver Tumors Tri-Estarylla is contraindicated in women with benign and malignant liver tumors [see CONTRAINDICATIONS (4) ] . Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) COC users. However, the risk of liver cancers in COC users is less than one case per million users. High Blood Pressure Tri-Estarylla is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see CONTRAINDICATIONS (4) ]. For women with well-controlled hypertension, monitor blood pressure and stop Tri-Estarylla if blood pressure rises significantly. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women with extended duration of use. The incidence of hypertension increases with increasing concentrations of progestin. Gallbladder Disease Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC related cholestasis. Carbohydrate and Lipid Metabolic Effects Carefully monitor prediabetic and diabetic women who take Tri-Estarylla . COCs may decrease glucose tolerance. Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs. Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Headache If a woman taking Tri-Estarylla develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Tri-Estarylla if indicated. Consider discontinuation of Tri-Estarylla in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event). Bleeding Irregularities and Amenorrhea Unscheduled Bleeding and Spotting Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different contraceptive product. In clinical trials of Tri-Estarylla , the frequency and duration of breakthrough bleeding and/or spotting was assessed in 1,647 patients (21,275 evaluable cycles) and 4,826 patients (35,546 evaluable cycles), respectively. A total of 231 (4.8%) women discontinued Tri-Estarylla at least in part, due to bleeding or spotting. Based on data from the clinical trials, 13 to 38% of women using Tri-Estarylla experienced unscheduled bleeding per cycle in the first year. The percent of women who experienced breakthrough/unscheduled bleeding tended to decrease over time. Amenorrhea and Oligomenorrhea Women who use Tri-Estarylla may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was pre-existent. If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. COC Use Before or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when oral contraceptives are taken inadvertently during early pregnancy. Discontinue Tri-Estarylla use if pregnancy is confirmed. Administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy [see USE IN SPECIFIC POPULATIONS (8.1) ]. Depression Carefully observe women with a history of depression and discontinue Tri-Estarylla if depression recurs to a serious degree. Carcinoma of Breast and Cervix Tri-Estarylla is contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see CONTRAINDICATIONS (4) ]. There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings. Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. Effect on Binding Globulins The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Monitoring A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated healthcare. Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. Chloasma Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking Tri-Estarylla . Adverse Reactions The following serious adverse reactions with the use of COCs are discussed elsewhere in labeling: Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS (5.1) ] Vascular events [see WARNINGS AND PRECAUTIONS (5.1) ] Liver disease [see WARNINGS AND PRECAUTIONS (5.2) ] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of Tri-Estarylla was evaluated in 4,826 healthy women of child-bearing potential who participated in 6 clinical trials and received at least 1 dose of Tri-Estarylla for contraception. Two trials were randomized active-controlled trials and 4 were uncontrolled open-label trials. In 3 trials, subjects were followed for up to 24 cycles; in 2 trials, subjects were followed for up to 12 cycles; and in 1 trial, subjects were followed for up to 6 cycles. Common Adverse Reactions ( 2% of subjects): The most common adverse reactions reported by at least 2% of the 4,826 women were the following in order of decreasing incidence: headache/migraine (33.6%), breast issues (including breast pain, enlargement, and discharge) (8%), vaginal infection (7.1%), abdominal/gastrointestinal pain (5.6%), mood disorders (including mood alteration and depression) (3.8%), genital discharge (3.2%), and changes in weight (including weight fluctuation, increased or decreased) (2.5%). Adverse Reactions Leading to Study Discontinuation: Over the trials, between 9 to 27% of subjects discontinued the trial due to an adverse reaction. The most common adverse reactions ( 1%) leading to discontinuation were: metrorrhagia (4.3%), nausea/vomiting (2.8%), headache/migraine (2.4%), mood disorders (including depression and mood altered) (1.1%), and weight increased (1.1%). Serious Adverse Reactions: breast cancer (1 subject), carcinoma of the cervix in situ (1 subject), hypertension (1 subject), and migraine (2 subjects). Postmarketing Experience The following additional adverse drug reactions have been reported from worldwide postmarketing experience with norgestimate/ ethinyl estradiol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections and Infestations : Urinary tract infection; Neoplasms Benign, Malignant and Unspecified (Incl. Cysts and Polyps) : Breast cancer, benign breast neoplasm, hepatic adenoma, focal nodular hyperplasia, breast cyst; Immune System Disorders : Hypersensitivity; Metabolism and Nutrition Disorders : Dyslipidemia; Psychiatric Disorders : Anxiety, insomnia; Nervous System Disorders : Syncope, convulsion, paresthesia, dizziness; Eye Disorders : Visual impairment, dry eye, contact lens intolerance; Ear and Labyrinth Disorders : Vertigo; Cardiac Disorders : Tachycardia, palpitations; Vascular Events : Deep vein thrombosis, pulmonary embolism, retinal vascular thrombosis, hot flush; Arterial Events: Arterial thromboembolism, myocardial infarction, cerebrovascular accident; Respiratory, Thoracic and Mediastinal Disorders : Dyspnea; Gastrointestinal Disorders : Pancreatitis, abdominal distension, diarrhea, constipation; Hepatobiliary Disorders : Hepatitis; Skin and Subcutaneous Tissue Disorders : Angioedema, erythema nodosum, hirsutism, night sweats, hyperhidrosis, photosensitivity reaction, urticaria, pruritus, acne; Musculoskeletal, Connective Tissue, and Bone Disorders : Muscle spasms, pain in extremity, myalgia, back pain; Reproductive System and Breast Disorders : Ovarian cyst, suppressed lactation, vulvovaginal dryness; General Disorders and Administration Site Conditions : Chest pain, asthenic conditions. Drug Interactions Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. No drug-drug interaction studies were conducted with Tri-Estarylla . Effects of Other Drugs on Combined Oral Contraceptives Substances decreasing the plasma concentrations 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 COCs 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 COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Colesevelam : Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Substances increasing the plasma concentrations of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (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]). Effects of Combined Oral 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 the serum concentration of thyroid-binding globulin increases with use of COCs. Interference with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. USE IN SPECIFIC POPULATIONS Pregnancy There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy. Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion. Nursing Mothers Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk. Pediatric Use Safety and efficacy of Tri-Estarylla have been established in women of reproductive age. Efficacy is expected to be the same for post-pubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated. There was no significant difference between Tri-Estarylla tablets and placebo in mean change in total lumbar spine (L1-L4) and total hip bone mineral density between baseline and Cycle 13 in 123 adolescent females with anorexia nervosa in a double-blind, placebo-controlled, multicenter, one-year treatment duration clinical trial for the Intent To Treat (ITT) population. Geriatric Use Tri-Estarylla has not been studied in postmenopausal women and are not indicated in this population. Hepatic Impairment The pharmacokinetics of Tri-Estarylla has not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. [See CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.2) .] Renal Impairment The pharmacokinetics of Tri-Estarylla has not been studied in women with renal impairment. Overdosage There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea. Tri-Estarylla Description Each of the following products is a combination oral contraceptive containing the progestational compound norgestimate and the estrogenic compound ethinyl estradiol. Norgestimate is designated as (18,19-Dinor-17-pregn-4-en-20-yn-3-one,17-(acetyloxy)-13-ethyl-, oxime,(17α)-(+)-) and ethinyl estradiol is designated as (19-nor-17α-pregna,1,3,5(10)-trien-20-yne-3,17-diol). Each active white tablet contains 0.18 mg norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include crospovidone, lactose anhydrous, magnesium stearate, and pregelatinized starch. Each active light blue tablet contains 0.215 mg norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD & C Blue No.2 lake, lactose anhydrous, magnesium stearate, and pregelatinized starch Each active blue tablet contains 0.25 mg norgestimate and 0.035 mg of ethinyl estradiol. Inactive ingredients include crospovidone, FD & C Blue No.2 lake, lactose anhydrous, magnesium stearate, and pregelatinized starch Each green tablet contains only inert ingredients, as follows: crospovidone, D &C Yellow No.10 aluminum Lake, FD & C Blue No.2 lake, lactose anhydrous, magnesium stearate, and pregelatinized starch Tri-Estarylla - Clinical Pharmacology Mechanism of Action Oral Contraception COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. Acne Acne is a skin condition with a multifactorial etiology, including androgen stimulation of sebum production. While the combination of ethinyl estradiol and norgestimate increases sex hormone-binding globulin (SHBG) and decreases free testosterone, the relationship between these changes and a decrease in the severity of facial acne in otherwise healthy women with this skin condition has not been established. Pharmacodynamics No specific pharmacodynamic studies were conducted with norgestimate and ethinyl estradiol. Pharmacokinetics Absorption Norgestimate (NGM) and EE are rapidly absorbed following oral administration. NGM is rapidly and completely metabolized by first pass (intestinal and/or hepatic) mechanisms to norelgestromin (NGMN) and norgestrel (NG), which are the major active metabolites of norgestimate. Peak serum concentrations of NGMN and EE are generally reached by 2 hours after administration of norgestimate/ ethinyl estradiol. Accumulation following multiple dosing of the 250 mcg NGM / 35 mcg EE dose is approximately 2-fold for NGMN and EE compared with single dose administration. The pharmacokinetics of NGMN is dose-proportional following NGM doses of 180 mcg to 250 mcg. Steady-state concentration of EE is achieved by Day 7 of each dosing cycle. Steady-state concentrations of NGMN and NG are achieved by Day 21. Non-linear accumulation (approximately 8 fold) of NG is observed as a result of high-affinity binding to SHBG, which limits its biological activity (Table 3). Table 3: Summary of NGMN, NG and EE pharmacokinetic parameters. C max = peak serum concentration, t max = time to reach peak serum concentration, AUC 0 24h = area under serum concentration vs time curve from 0 to 24 hours, t 1/2 = elimination half-life, NC = not calculated. NGMN and NG: C max = ng/mL, AUC 0 24h = h ng/mL EE: C max = pg/mL, AUC 0 24h = h pg/mL Mean (SD) Pharmacokinetic before
a likely Tri-Estarylla massacre
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