DailyMed Label: Tri-VyLibra Lo

DailyMed Label: Tri-VyLibra

2024

DailyMed Prescription

Tri-VyLibra

Norgestimate and Ethinyl Estradiol

Afaxys Pharma, LLC

NDC: 50102-233

NDC: 50102-233

NDC: 50102-233

NDC: 50102-233

Tri-VyLibra 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 0.180 mg of norgestimate USP and 0.035 mg of ethinyl estradiol USP. Inactive ingredients include croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Each active light blue tablet contains 0.215 mg of norgestimate USP and 0.035 mg of ethinyl estradiol USP. Inactive ingredients include croscarmellose sodium, FD&C #2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Each active dark blue tablet contains 0.250 mg of norgestimate USP and 0.035 mg of ethinyl estradiol USP. Inactive ingredients include croscarmellose sodium, FD&C #2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Each green tablet contains only inert ingredients, as follows: anhydrous lactose, FD&C Blue No. 2 aluminum lake, ferric oxide yellow, magnesium stearate, microcrystalline cellulose, and povidone. Chemical Structure

Tri-VyLibra is combination of norgestimate, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy. ( 1.1 )  Tri-VyLibra 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-VyLibra should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control. ( 1.2 ) Tri-VyLibra tablets are indicated for use by females of reproductive potential to prevent pregnancy [see Clinical Studies (14) ] . Tri-VyLibra 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-VyLibra should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control [see Clinical Studies (14) ] .

Take one tablet daily by mouth at the same time every day. ( 2.1 ) Take tablets in the order directed on the blister pack. ( 2.1 ) Do not skip or delay tablet intake. ( 2.1 ) Take one tablet by mouth at the same time each day with or without food. Table 1 provides the recommended dosage and administration instructions for Tri-VyLibra. Table 1: Instructions for Administration of Tri-VyLibra 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-VyLibra active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 14) and dark blue (Day 15 to Day 21).   Tri-VyLibra 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 pack on the same day of the week as the first cycle 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-VyLibra. 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-VyLibra 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-VyLibra Start Tri-VyLibra:   ●    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 Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting Tri-VyLibra after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Tri-VyLibra may be started immediately. An additional method of contraception is not needed if Tri-VyLibra is started immediately. If Tri-VyLibra 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 pack of Tri-VyLibra. 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-VyLibra, 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-VyLibra [see  Contraindications (4)  and Warnings and Precautions (5.1) ]. Starting Tri-VyLibra after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Tri-VyLibra following the instructions in Table 1 for women not currently using hormonal contraception. Tri-VyLibra is not recommended for use in lactating women [see Use in Specific Populations (8.2)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Tri-VyLibra [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , and 8.2) ]. Contraceptive failure may occur when active tablets are missed. Table 2 describes instructions for Tri-VyLibra dosing and use of additional non-hormonal contraception (such as condoms) when active tablets are missed. Table 2:  Instructions for Missed Tri-VyLibra 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. 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. The timing of initiation of dosing with Tri-VyLibra  for acne should follow the guidelines for use of Tri-VyLibra  as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section ( 2.1 ) for instructions.

Tri-VyLibra tablets are available in blister packs. Each blister pack contains 28 tablets in the following order: 7 white, round, biconvex, coated tablets, debossed with “S” on one side and “19” on other side of the tablet contains 0.180 mg norgestimate and 0.035 mg ethinyl estradiol 7 light blue, round, biconvex, coated tablets, debossed with “S” on one side and “21” on other side of the tablet contains 0.215 mg norgestimate and 0.035 mg ethinyl estradiol 7 dark blue, round, biconvex, coated tablets, debossed with “S” on one side and “22” on other side of the tablet contains 0.250 mg norgestimate and 0.035 mg ethinyl estradiol 7 green, round, mottled biconvex, uncoated tablets (non-hormonal placebo) debossed with “S” on one side and “24” on other side of the tablet contains inert ingredients Tri-VyLibra consists of 28 round, biconvex tablets in the following order ( 3 ): 7 white, coated tablets each containing 0.180 mg norgestimate and 0.035 mg ethinyl estradiol 7 light blue, coated tablets each containing 0.215 mg norgestimate and 0.035 mg ethinyl estradiol 7 dark blue, coated tablets each containing 0.250 mg norgestimate and 0.035 mg ethinyl estradiol 7 green, uncoated tablets (inert)

Tri-VyLibra is contraindicated in females who are known to have or develop 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 hyper coagulopathies [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 (5.4) ] Have diabetes mellitus with vascular disease [see Warnings and Precautions (5.6) ] Have headaches with focal neurological symptoms or migraine headaches with aura [see Warnings and Precautions (5.7) ] Women   over   age   35   with   any   migraine   headaches    [see   Warnings   and Precautions (5.7) ] Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.2) ] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.8) ] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.10) ] Use of  Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see Warnings and Precautions (5.3) ] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Breast cancer ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

Thromboembolic Disorders and Other Vascular Problems: Stop norgestimate and ethinyl estradiol tablets if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. ( 5.1 ) Liver disease: Discontinue norgestimate and ethinyl estradiol tablets if jaundice occurs. ( 5.2 ) High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop norgestimate and ethinyl estradiol tablets if blood pressure rises significantly. ( 5.4 ) Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norgestimate and ethinyl estradiol tablets. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.6 ) Headache: Evaluate significant change in headaches and discontinue norgestimate and ethinyl estradiol tablets if indicated. ( 5.7 ) Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea. ( 5.8 ) Stop norgestimate and ethinyl estradiol tablets if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets 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. Impaired Liver Function Norgestimate and ethinyl estradiol tablets are contraindicated 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 norgestimate and ethinyl estradiol tablets if jaundice develops. Liver Tumors Norgestimate and ethinyl estradiol tablets are 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. During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as COCs. Discontinue norgestimate and ethinyl estradiol tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4) ] . Norgestimate and ethinyl estradiol tablets can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen. Norgestimate and ethinyl estradiol tablets are 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 norgestimate and ethinyl estradiol tablets 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. 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. Carefully monitor prediabetic and diabetic women who take norgestimate and ethinyl estradiol tablets. 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. If a woman taking norgestimate and ethinyl estradiol tablets develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norgestimate and ethinyl estradiol tablets if indicated. Consider discontinuation of norgestimate and ethinyl estradiol tablets in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event). 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 norgestimate and ethinyl estradiol tablets, the frequency and duration of breakthrough bleeding and/or spotting was assessed in 4,826 patients (35,546 evaluable cycles). A total of 231 (4.8%) women discontinued norgestimate and ethinyl estradiol tablets, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 13 to 38% of women using norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol tablets 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. Carefully observe women with a history of depression and discontinue norgestimate and ethinyl estradiol tablets if depression recurs to a serious degree. Breast Cancer Norgestimate and ethinyl estradiol tablets are contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4) ] . Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see Postmarketing Experience (6.2) ] . Cervical Cancer 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. 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. 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. In  women  with  hereditary  angioedema,  exogenous  estrogens  may  induce  or  exacerbate symptoms of angioedema. 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 norgestimate and ethinyl estradiol tablets.

The  following serious  adverse  reactions  with  the  use  of  COCs  are  discussed  elsewhere  in labeling:

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-VyLibra. Drugs or herbal products that induce certain enzymes including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. ( 7.1 ) 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, non-nucleoside reverse transcriptase inhibitors , and HIV/AIDS medications containing strong inhibitors or inducers of CYP3A 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]) or with HIV/AIDS medications containing strong inhibitors (e.g., cobicistat and ritonavir) or inducers of CYP3A. 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. The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. Do not co-administer Tri-VyLibra with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.3) ].

Lactating women: Not recommended; can decrease milk production. ( 8.2 ) Risk Summary There is no use for contraception in pregnancy, therefore, norgestimate and ethinyl estradiol tablets should be discontinued during 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 CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. Risk Summary Contraceptive hormones and/or metabolites are present in human milk. CHCs can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. When possible, advise the nursing female to use other forms of contraception until she discontinues breast-feeding. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for norgestimate and ethinyl estradiol tablets and any potential adverse effects on the breast-fed child from norgestimate and ethinyl estradiol tablets or from the underlying maternal condition. Safety and efficacy of norgestimate and ethinyl estradiol tablets 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 norgestimate and ethinyl estradiol 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. Norgestimate and ethinyl estradiol tablets have not been studied in postmenopausal women and is not indicated in this population. The pharmacokinetics of norgestimate and ethinyl estradiol tablets have 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) ] . The pharmacokinetics of norgestimate and ethinyl estradiol tablets have not been studied in women with renal impairment.

Tri-VyLibra ® tablets are available in a blister pack. Each blister pack (28 tablets) contains in the following order: 7 white, round, biconvex, coated tablets, debossed with “S” on one side and “19” on other side of the tablet contains 0.180 mg norgestimate USP and 0.035 mg ethinyl estradiol USP 7 light blue, round, biconvex, coated tablets, debossed with “S” on one side and “21” on other side of the tablet contains 0.215 mg norgestimate USP and 0.035 mg ethinyl estradiol USP 7 dark blue, round, biconvex, coated tablets, debossed with “S” on one side and “22” on other side of the tablet contains 0.250 mg norgestimate USP and 0.035 mg ethinyl estradiol USP 7 green, round, mottled biconvex, uncoated tablets (non-hormonal Placebo), debossed with “S” on one side and “24” on other side of the tablet. The blister packs are available in the following packages: •  The blister packs are packaged in mono cartons             Carton of 1 Blister Pack                                        NDC 50102-233-11             Carton of 3 Blister packaged in mono cartons      NDC 50102-233-13 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].  Protect from light. Keep out of the reach of children.

Oral Contraception COCs lower the risk of becoming pregnant primarily by suppressing ovulation. 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. No specific pharmacodynamic studies were conducted with Tri-VyLibra. 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 Tri-VyLibra. 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 Parameters of Tri-VyLibra  During a Three Cycle Study Analyte Cycle Day C max t max (h) AUC 0-24h t 1/2 (h) NGMN 3 7 1.80 (0.46) 1.42 (0.73) 15.0 (3.88) NC     14 2.12 (0.56) 1.21 (0.26) 16.1 (4.97) NC     21 2.66 (0.47) 1.29 (0.26) 21.4 (3.46) 22.3 (6.54) NG 3 7 1.94 (0.82) 3.15 (4.05) 34.8 (16.5) NC     14 3.00 (1.04) 2.21 (2.03) 55.2 (23.5) NC     21 3.66 (1.15) 2.58 (2.97) 69.3 (23.8) 40.2 (15.4) EE 3 7 124 (39.5) 1.27 (0.26) 1130 (420) NC     14 128 (38.4) 1.32 (0.25) 1130 (324) NC     21 126 (34.7) 1.31 (0.56) 1090 (359) 15.9 (4.39) Food Effect The effect of food on the pharmacokinetics of Tri-VyLibra has not been studied. Distribution NGMN and NG are highly bound (>97%) to serum proteins. NGMN is bound to albumin and not to SHBG, while NG is bound primarily to SHBG. EE is extensively bound (>97%) to serum albumin and induces an increase in the serum concentrations of SHBG. Metabolism NGM is extensively metabolized by first-pass mechanisms in the gastrointestinal tract and/or liver. NGM’s primary active metabolite is NGMN. Subsequent hepatic metabolism of NGMN occurs and metabolites include NG, which is also active, and various hydroxylated and conjugated metabolites. Although NGMN and its metabolites inhibit a variety of P450 enzymes in human liver microsomes, under the recommended dosing regimen, the in vivo concentrations of NGMN and its metabolites, even at the peak serum levels, are relatively low compared to the inhibitory constant (K i ). EE is also metabolized to various hydroxylated products and their glucuronide and sulfate conjugates. Excretion The metabolites of NGMN and EE are eliminated by renal and fecal pathways. Following administration of 14 C-norgestimate, 47% (45 to 49%) and 37% (16 to 49%) of the administered radioactivity was eliminated in the urine and feces, respectively. Unchanged NGM was not detected in the urine. In addition to 17-deacetyl norgestimate, a number of metabolites of NGM have been identified  in  human urine following administration of radiolabeled NGM. These include 18, 19-Dinor-17-pregn-4-en-20-yn-3-one,17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5β­-17-pregnan-20-yn,3α,17β-dihydroxy-13-ethyl,(17α), various hydroxylated metabolites and conjugates of these metabolites.

[See  Warnings and Precautions (5.2 ,  5.10) ].

In four clinical trials with norgestimate and ethinyl estradiol tablets, 4,756 women aged 15 to 41 years were studied for 24 cycles, providing a total of 45,244 cycles of exposure. The racial demographic was about 87 to 90% Caucasian, 6 to 10% African-American, with the remainder Asian (≤1%) or Other (2 to 5%). There were no exclusions on the basis of weight; the weight range for women treated was 80 to 310 lbs, with a mean weight of about 132 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years. Norgestimate and ethinyl estradiol tablets were evaluated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, six- (28 day) cycle studies. Two hundred twenty-one patients received norgestimate and ethinyl estradiol tablets and 234 patients received placebo. Mean age at enrollment for both groups was 28 years. At the end of 6 months, the mean total lesion count changed from 55 to 31 (42% reduction) in patients treated with norgestimate and ethinyl estradiol tablets and from 54 to 38 (27% reduction) in patients similarly treated with placebo. Table 4 summarizes the changes in lesion count for each type of lesion. Based on the investigator’s global assessment conducted at the final visit, patients treated with norgestimate and ethinyl estradiol tablets showed a statistically significant improvement in total lesions compared to those treated with placebo. Table 4: Acne Vulgaris Indication. Combined Results: Two Multicenter, Placebo-Controlled Trials. Observed Means at Six Months (LOCF)* and at Baseline. Intent-to-Treat Population. *LOCF: Last Observation Carried Forward   Norgestimate and Ethinyl Estradiol Tablets (N=221) Placebo (N=234) Difference in Counts between Norgestimate and Ethinyl Estradiol Tablets   and Placebo at 6 Months # of Lesions Counts % Reduction Counts % Reduction   INFLAMMATORY LESIONS             Baseline Mean 19   19       Sixth Month Mean 10 48% 13 30% 3 (95% CI: -1.2, 5.1) NON-INFLAMMATORY LESIONS             Baseline Mean 36   35       Sixth Month Mean 22 34% 25 21% 3 (95% CI: -0.2, 7.8) TOTAL LESIONS             Baseline Mean 55   54   7 (95% CI: 2.0, 11.9)    Sixth Month Mean 31 42% 38 27%

Tri-VyLibra ® (norgestimate and ethinyl estradiol tablets USP) What is the most important information I should know about Tri-VyLibra? Do not use Tri-VyLibra if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke. What is Tri-VyLibra? Tri-VyLibra is a birth control pill (oral contraceptive) used by women to prevent pregnancy. Tri-VyLibra is also used to treat moderate acne vulgaris in females 15 years of age and older, who have no known history of allergies or problems taking birth control pills, and have started their menstrual cycle (“period”). Tri-VyLibra should only be used to treat acne in women who want to take birth control pills to prevent pregnancy. How does Tri-VyLibra work for contraception? Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant. Based on the results of clinical studies, about 1 out of 100 women may get pregnant during the first year they use Tri-VyLibra. The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. Who should not take Tri-VyLibra? D o not take Tri-VyLibra if you: smoke and are over 35 years of age had blood clots in your arms, legs, lungs, or eyes had a problem with your blood that makes it clot more than normal have certain heart valve problems or irregular heart beat that increases your risk of having blood clots had a stroke had a heart attack have high blood pressure that cannot be controlled by medicine have diabetes with kidney, eye, nerve, or blood vessel damage have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age have liver problems, including liver tumors take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood. have any unexplained vaginal bleeding are pregnant had breast cancer If any of these conditions happen while you are taking Tri-VyLibra, stop taking Tri-VyLibra right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Tri-VyLibra. What should I tell my healthcare provider before taking Tri-VyLibra? Tell your healthcare provider if you: are pregnant or think you may be pregnant are depressed now or have been depressed in the past had  yellowing  of your  skin  or  eyes  (jaundice)  caused  by  pregnancy (cholestasis of pregnancy) are breastfeeding or plan to breastfeed. Tri-VyLibra may decrease the amount of breast milk you make. A small amount of the hormones in Tri-VyLibra may pass into your  breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Tri-VyLibra may affect the way other medicines work, and other medicines may affect how well Tri-VyLibra works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take Tri-VyLibra?  Read the Instructions for Use at the end of this Patient Information. What are the possible serious side effects of Tri-VyLibra? Like pregnancy, Tri-VyLibra may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes. Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you: first start taking birth control pills restart the same or different birth control pills after not using them for a month or more Call your healthcare provider or go to a hospital emergency room right away if you have: leg pain that will not go away      sudden severe shortness of breath sudden change in vision or blindness chest pain a sudden, severe headache unlike your usual headaches weakness or numbness in your arm or leg trouble speaking Other serious side effects include: liver problems, including: rare liver tumors jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes. high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure. gallbladder problems changes in the sugar and fat (cholesterol and triglycerides) levels in your blood new or worsening headaches including migraine headaches irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking Tri-VyLibra. depression possible cancer in your breast and cervix severe allergic reactions that may include swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth, tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema is higher is you have a history of angioedema. dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking Tri-VyLibra. Use sunscreen if you have to be in the sunlight. What are the most common side effects of Tri-VyLibra? headache (migraine) breast pain or tenderness, enlargement or discharge stomach pain, discomfort, and gas vaginal infections and discharge mood changes, including depression nervousness changes in weight skin rash These are not all the possible side effects of Tri-VyLibra. For more information, ask your healthcare provider or pharmacist. You may report side effects to the FDA at 1-800-FDA-1088 . What else should I know about taking Tri-VyLibra? If you are scheduled for any lab tests, tell your healthcare provider you are taking Tri-VyLibra. Certain blood tests may be affected by Tri-VyLibra. Tri-VyLibra does not protect against HIV infection (AIDS) and other sexually transmitted infections. How should I store Tri-VyLibra? Store Tri-VyLibra at room temperature between 20° to 25°C (68° to 77°F). Keep Tri-VyLibra and all medicines out of the reach of children. Store away from light. General information about the safe and effective use of Tri-VyLibra. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Tri-VyLibra for a condition for which it was not prescribed.  Do not give Tri-VyLibra to other people, even if they have the same symptoms that you have. This Patient Information summarizes the most important information about Tri-VyLibra. You can ask your pharmacist or healthcare provider for information about Tri-VyLibra that is written for health professionals . For more information, call Afaxys Pharma, LLC at 1-855-888-2467 Do birth control pills cause cancer? It is not known if hormonal birth control pills cause breast cancer. Some studies, but not all, suggest that there could be a slight increase in the risk of breast cancer among current users with longer duration of use. If you have breast cancer now, or have had it in the past, do not use hormonal birth control because some breast cancers are sensitive to hormones. Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners. What if I want to become pregnant? You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill. What should I know about my period when taking Tri-VyLibra? Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking Tri-VyLibra, especially during the first few months of use. This usually is not a serious problem.  It is important to continue taking your pills on a regular schedule to prevent a pregnancy. What are the ingredients in Tri-VyLibra? Active ingredients: Each white, light blue, and dark blue pill contains norgestimate and ethinyl estradiol. Inactive ingredients: White pills: croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Light blue pills: croscarmellose sodium, FD&C#2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Dark blue pills: croscarmellose sodium, FD&C#2/Indigo carmine aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide. Green pills: anhydrous lactose, FD&C Blue No. 2 aluminum lake, ferric oxide yellow, magnesium stearate, microcrystalline cellulose, and povidone. Figure 4

afaxys ®                                 NDC 50102-233-11 pharma Rx only Tri-VyLibra ® Norgestimate and Ethinyl Estradiol Tablets, USP 0.180 mg/0.035 mg, 0.215 mg/0.035 mg, 0.250 mg/0.035 mg Each 7 white coated tablets contain norgestimate USP 0.180 mg and ethinyl estradiol USP 0.035 mg. Each 7 light blue coated tablets contain norgestimate USP 0.215 mg and ethinyl estradiol USP 0.035 mg. Each 7 dark blue coated tablets contain norgestimate USP 0.250 mg and ethinyl estradiol USP 0.035 mg. Each 7 green tablets contain inert ingredients. This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 1 Blister Card of 28 tablets each PACKAGE LABEL-PRINCIPAL DISPLAY PANEL- Carton Label