Tyblume

TYBLUME is contraindicated in females who are known to have 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 combined hormonal contraceptive (CHC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including TYBLUME (levonorgestrel and ethinyl estradiol) tablets, 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

    .

    • TYBLUME is contraindicated in women over 35 years old who smoke.
    • Cigarette smoking increases the risk of serious cardiovascular side effects from combination hormonal contraceptive (CHC) use.

    and
    
    
    

    5.1 Thromboembolic Disorders and Other Vascular Problems

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

    ]
    
    
    
  • Have current or history of deep vein thrombosis or pulmonary embolism [see
    
    
    
    5.1 Thromboembolic Disorders and Other Vascular Problems

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

    ]
    
    
    
  • Have cerebrovascular disease
    
    
    
    [see
    
    
    

    5.1 Thromboembolic Disorders and Other Vascular Problems

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

    ]
    
    
    
  • Have coronary artery disease
    
    
    
    [see
    
    
    

    5.1 Thromboembolic Disorders and Other Vascular Problems

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

    ]
    
    
    
  • 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

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

    ]
    
    
    
  • Have inherited or acquired hypercoagulopathies
    
    
    
    [see
    
    
    

    5.1 Thromboembolic Disorders and Other Vascular Problems

    Before starting TYBLUME evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. TYBLUME is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases

    [see Contraindications (4)].

    • Stop TYBLUME if an arterial or venous thrombotic/thromboembolic event occurs.
    • Stop TYBLUME if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
    • Discontinue TYBLUME during prolonged immobilization. If feasible, stop TYBLUME at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
    • Start TYBLUME no earlier than four weeks after delivery in females who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.

    Arterial Events

    CHCs 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.

    TYBLUME is contraindicated in women over 35 years of age who smoke

    [see Contraindications (4)]

    . Cigarette smoking increases the risk of serious cardiovascular events from CHC 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 CHCs 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 CHCs 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 CHC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to CHCs gradually disappears after CHC use is discontinued.

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

    *Pregnancy data based on actual duration of pregnancy in the reference studies. Based on a model assumption that pregnancy duration is nine months, the rate is 7 to 27 per 10,000 WY.

    Figure 1 Likelihood of Developing a VTE

    

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

    5.3 Hypertension

    TYBLUME is contraindicated in females with uncontrolled hypertension or hypertension with vascular disease

    [see Contraindications (4)]

    . For all females, including those with well-controlled hypertension, monitor blood pressure at routine visits and stop TYBLUME if blood pressure rises significantly.

    An increase in blood pressure has been reported in females using CHCs, and this increase is more likely in older women with extended duration of use. The effect of CHCs on blood pressure may vary according to the progestin in the CHC.

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

    5.6 Adverse Carbohydrate and Lipid Metabolic Effects

    Hyperglycemia

    TYBLUME is 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)].

    TYBLUME may decrease glucose tolerance. Carefully monitor prediabetic and diabetic females who are using TYBLUME.

    Dyslipidemia

    Consider alternative contraception for females with uncontrolled dyslipidemia. TYBLUME may cause adverse lipid changes.

    Females with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using TYBLUME, 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
    
    
    

    5.7 Headache

    TYBLUME is contraindicated in females who have headaches with focal neurological symptoms or have migraine headaches with aura, and in women over age 35 years who have migraine headaches with or without aura

    [see Contraindications (4)].

    If a woman using TYBLUME develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue TYBLUME if indicated. Consider discontinuation of TYBLUME if there is an increased frequency or severity of migraines during CHC use (which may be prodromal of a cerebrovascular event).

    ]
    
    
    
• Current or history of breast cancer or other estrogen- or progestin-sensitive cancer
• Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis
  
  
  
  [see
  
  
  

  5.2 Liver Disease

  Elevated Liver Enzymes

  TYBLUME is contraindicated in females with acute viral hepatitis or severe (decompensated) cirrhosis of the liver

  [see Contraindications (4)].

  Discontinue TYBLUME if jaundice develops. Acute liver test abnormalities may necessitate the discontinuation of CHC use until the liver tests return to normal and CHC causation has been excluded.

  Liver Tumors

  TYBLUME is contraindicated in females with benign or malignant liver tumors

  [see Contraindications (4)]

  . CHCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 CHC 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) CHC users. The attributable risk of liver cancers in CHC users is less than one case per million users.

  ]
  
  
  
• Undiagnosed abnormal uterine bleeding
  
  
  
  [see
  
  
  

  5.8 Bleeding Irregularities and Amenorrhea

  Unscheduled Bleeding and Spotting

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

  Amenorrhea and Oligomenorrhea

  Females who use TYBLUME may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant.

  If scheduled bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or two 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 perform appropriate diagnostic measures. If the patient has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy.

  After discontinuation of a CHC, 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
  
  
  

  5.14 Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

  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. COCs are contraindicated for use with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir

  [see Contraindications (4)]

  . Discontinue TYBLUME prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.

  TYBLUME can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

  ]