Jaimiess

Jaimiess 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 females 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 contraceptives (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, including Jaimiess, are contraindicated in women who are over 35 years of age and smoke.

    [See Contraindications (4)and Warnings and Precautions (5.1)].

    WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

    See full prescribing information for complete boxed warning.

    • Jaimiess is contraindicated in women over 35 years old who smoke.

    • Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.

    and

    5.1 Thromboembolic Disorders and Other Vascular Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .
  • -Have current or history of deep vein thrombosis or pulmonary embolism
    [see

    5.1 Thromboembolic Disorders and Other Vascular Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .

  • -Have cerebrovascular disease

    [see

    5.1 Thromboembolic Disorders and Other Vascular Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .

  • -Have coronary artery disease
    [see

    5.1 Thromboembolic Disorders and Other Vascular Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .
  • -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 Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .
  • -Have inherited or acquired hypercoagulopathies
    [see

    5.1 Thromboembolic Disorders and Other Vascular Conditions

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if an arterial or deep venous thrombotic/thromboembolic event occurs.

    • Stop levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.

    • Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets during prolonged immobilization. If feasible, stop levonorgestrel and ethinyl estradiol tablets 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 thromboembolism.

    • Start levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week.

    • Before starting levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with a high risk of arterial or venous/thromboembolic diseases

      [see Contraindications (4)]
      .

    Arterial Events

    COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (>35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

    Venous Events

    Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of CHCs

    [see Contraindications (4)]

    . While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years.

    The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

    Figure 1 shows the risk of developing a VTE for women who are not pregnant and do not use oral contraceptives, for women who use oral contraceptives, and for women in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 women who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these women will develop a VTE.

    Figure 1: Likelihood of Developing a VTE

    

    Use of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year).

    

    ]
    .
  • -Have uncontrolled hypertension or hypertension with vascular disease
    [see

    5.3 Hypertension

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with uncontrolled hypertension or hypertension with vascular disease

    [see Contraindications (4)]

    . For all women, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop levonorgestrel and ethinyl estradiol tablets 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 and with extended duration of use. The effect of COCs on blood pressure may vary according to the progestin in the COC.

    ]
    .

  • -Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or with vascular disease or other end-organ damage, or diabetes mellitus of > 20 years duration

    [see

    5.7 Adverse Carbohydrate and Lipid Metabolic Effects

    Hyperglycemia

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in diabetic women over age 35, or females who have diabetes with hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or females with diabetes of > 20 years duration

    [see Contraindications (4)]

    . Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets may decrease glucose tolerance. Carefully monitor prediabetic and diabetic women who are taking levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets.

    Dyslipidemia

    Consider alternative contraception for women with uncontrolled dyslipidemias. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets may cause adverse lipid changes.

    Women with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets, which may increase the risk of pancreatitis.

    ]
    .

  • -Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches

    [see

    5.8 Headache

    Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in females who have headaches with focal neurological symptoms or have migraine headaches with aura, and in women over 35 years of age who have migraine headaches with or without aura

    [see Contraindications (4)].

    If a woman taking levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if indicated. Consider discontinuation of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if there is an increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

    ]
    .

• Current diagnosis of, or history of, breast cancer, which may be hormone sensitive

  [see

  5.11 Malignant Neoplasms

  Breast Cancer

  Levonorgestrel and ethinyl estradiol tablets 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 COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings are due to differences in sexual behavior and other factors.

  ].

• Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis

  [see

  5.2 Liver Disease

  Elevated Liver Enzymes

  Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with acute viral hepatitis or severe (decompensated) cirrhosis of the liver

  [see Contraindications (4)]

  . Acute liver test abnormalities may necessitate the discontinuation of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets until the liver tests return to normal and levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets causation has been excluded. Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets if jaundice develops.

  Liver Tumors

  Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in women with benign or malignant liver tumors

  [see Contraindications (4)]

  . COCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage.

  Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. The attributable risk of liver cancers in COC users is less than one case per million users.

  and

  8.6 Hepatic Impairment

  No studies have been conducted to evaluate the effect of hepatic disease on the disposition of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets. However, steroid hormones may be poorly metabolized in patients with impaired liver function. Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets are contraindicated in females with acute hepatitis or severe decompensated cirrhosis

  [see Contraindications (4)and Warnings and Precautions (5.2)].

  ].

• Undiagnosed abnormal uterine bleeding

  [see

  5.9 Bleeding Irregularities and Amenorrhea

  Unscheduled Bleeding and Spotting

  Women using levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first 3 months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If unscheduled bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy.

  When prescribing levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets, the occurrence of fewer planned menses (4 per year instead of 13 per year) should be weighed against the occurrence of increased unscheduled bleeding and/or spotting. The primary clinical trial (PSE-301) that evaluated the efficacy of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets also assessed unscheduled bleeding. The participants in the 12-month clinical trial (N=1,006) completed the equivalent of 8,681 28-day cycles of exposure and were composed primarily of women who had used oral contraceptives previously (89%) as opposed to new users (11%). A total of 82 (8.2%) of the women discontinued levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets, at least in part, due to bleeding or spotting.

  Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 2 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 3 presents the number of days with unscheduled spotting in treatment cycles 1 and 4.

  Table 2: Total Number of Days with Unscheduled Bleeding

  Q1=Quartile 1: 25% of women had this number of days of unscheduled bleeding
  Median: 50% of women had ≤ this number of days of unscheduled bleeding
  Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding
  91-Day Treatment Cycle	Days per 84-Day Interval				Days per 28- Day Interval
  	Q1	Median	Q3	Mean	Mean
  1st	1	4	10	6.9	1.7
  4th	0	1	4	3.2	0.8

  Table 3: Total Number of Days with Unscheduled Spotting

  Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled spotting
  Median: 50% of women had ≤ this number of days of unscheduled spotting
  Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled spotting
  91-Day Treatment Cycle	Days per 84-Day Interval				Days per 28- Day Interval
  	Q1	Median	Q3	Mean	Mean
  1st	1	4	11	7.4	1.9
  4th	0	2	7	4.4	1.1

  Figure 2 shows the percentage of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets subjects participating in trial PSE-301 with ≥ 7 days or ≥ 20 days of unscheduled bleeding and/or spotting, or only unscheduled bleeding, during each 91-day treatment cycle.

  Figure 2: Percent of Women Taking Levonorgestrel and Ethinyl Estradiol Tablets and Ethinyl Estradiol Tablets Who Reported Unscheduled Bleeding and/or Spotting or only Unscheduled Bleeding

  

  If unscheduled spotting or bleeding occurs, instruct the patient to continue on the same regimen. If the bleeding is persistent or prolonged, advise the patient to consult her healthcare provider.

  

  Amenorrhea and Oligomenorrhea

  Women who use levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant.

  If scheduled bleeding does not occur, consider the possibility of pregnancy.

  After discontinuation of levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent.

  ].

• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations

  [see

  5.4 Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

  During clinical trials with the Hepatitis C combination drug regimen that contains obmitasvir/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 levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets. Discontinue levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir

  [see Contraindications (4)]

  . Levonorgestrel and ethinyl estradiol tablets and ethinyl estradiol tablets can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

  ].