Tri-lo- Estarylla

Tri-Lo-Estarylla 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
  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)].

  WARNING: CIGARETTE SMOKING and SERIOUS CARDIOVASCULAR EVENTS

  See full prescribing information for complete boxed warning.

  • •
    Norgestimate and ethinyl estradiol is contraindicated in women over 35 years old who smoke. (
    4
    )
  • •
    Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use.
  and
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.
  ]
• •Have deep vein thrombosis or pulmonary embolism, now or in the past [see
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.

  ]
• •Have inherited or acquired hypercoagulopathies [see
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.

  ]
• •Have cerebrovascular disease [see
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.

  ]
• •Have coronary artery disease [see
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.

  ]
• •Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see
  5.1 Thromboembolic Disorders and Other Vascular Problems

  • •Stop norgestimate and ethinyl estradiol if an arterial thrombotic event or venous thrombotic (VTE) event occurs.
  • •Stop norgestimate and ethinyl estradiol 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 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 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.

  ]
• •Have uncontrolled hypertension [see
  5.5 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.
  ]
• •Have diabetes mellitus with vascular disease [see
  5.7 Headache

  If a woman taking norgestimate and ethinyl estradiol develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norgestimate and ethinyl estradiol if indicated.

  Consider discontinuation of norgestimate and ethinyl estradiol in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).
  ]
• •Have headaches with focal neurological symptoms or migraine headaches with aura [see
  5.8 Bleeding Irregularities and Amenorrhea

  Unscheduled Bleeding and Spotting

  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 the clinical trial of norgestimate and ethinyl estradiol, the frequency and duration of unscheduled bleeding and/or spotting was assessed in 1,673 women (11,015 evaluable cycles). A total of 3 (0.2%) women discontinued norgestimate and ethinyl estradiol, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 7 to 17% of women using norgestimate and ethinyl estradiol experienced unscheduled bleeding per cycle in the first year. The percent of women who experienced unscheduled bleeding tended to decrease over time.

  Amenorrhea and Oligomenorrhea

  Amenorrhea and Oligomenorrhea

  Women who use norgestimate and ethinyl estradiol 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.
  ]
  • ▪Women over age 35 with any migraine headaches [see
    5.8 Bleeding Irregularities and Amenorrhea

    Unscheduled Bleeding and Spotting

    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 the clinical trial of norgestimate and ethinyl estradiol, the frequency and duration of unscheduled bleeding and/or spotting was assessed in 1,673 women (11,015 evaluable cycles). A total of 3 (0.2%) women discontinued norgestimate and ethinyl estradiol, at least in part, due to bleeding or spotting. Based on data from the clinical trials, 7 to 17% of women using norgestimate and ethinyl estradiol experienced unscheduled bleeding per cycle in the first year. The percent of women who experienced unscheduled bleeding tended to decrease over time.

    Amenorrhea and Oligomenorrhea

    Amenorrhea and Oligomenorrhea

    Women who use norgestimate and ethinyl estradiol 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.
    ]
• •Liver tumors, benign or malignant, or liver disease [see
  5.2 Liver Disease

  Impaired Liver Function

  Impaired Liver Function

  Do not use norgestimate and ethinyl estradiol 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 if jaundice develops.

  Liver Tumors

  Liver Tumors

  Norgestimate and ethinyl estradiol 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.

  ]
• •Undiagnosed abnormal uterine bleeding [see
  5.9 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 norgestimate and ethinyl estradiol 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)].
  ]
• •Pregnancy, because there is no reason to use COCs during pregnancy [see
  5.10 Depression

  Carefully observe women with a history of depression and discontinue norgestimate and ethinyl estradiol if depression recurs to a serious degree.
  and
  8.1 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.

  ]
• •Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see
  5.12 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.
  ]
• •Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see
  5.4 High Blood Pressure

  Norgestimate and ethinyl estradiol 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 norgestimate and ethinyl estradiol 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.

  ]