Jolessa (Page 2 of 8)

2.3 Missed Tablets

Table 2: Instructions for Missed JOLESSA Tablets

If one active tablet (pink) is missed in Days 1 through 84	Take the tablet as soon as possible. Take the next tablet at the regular time and continue taking one tablet a day until the 91-day course is finished.
If two consecutive active tablets (pink) are missed in Days 1 through 84	Take 2 tablets on the day remembered and 2 tablets the next day. Then continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception (such as condoms or spermicide) should be used as back-up if the patient has sex within 7 days after missing 2 tablets.
If three or more consecutive active tablets (pink) are missed in Days 1 through 84	Do not take the missed tablets. Continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception (such as condoms or spermicide) must be used as back-up if the patient has sex within 7 days after missing 3 tablets.

2.4 Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3-4 hours after taking a pink tablet, handle this as a missed tablet [see FDA-approved patient labeling].

3 DOSAGE FORMS AND STRENGTHS

JOLESSA (levonorgestrel and ethinyl estradiol tablets) are available as round, film-coated, biconvex, unscored tablets with a debossed stylized b on one side, packaged in Extended-Cycle Tablet Dispensers, each containing a 13-week supply of tablets in the following order:

• 84 pink tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol; debossed with 992 on the other side
• 7 white inert tablets debossed with 208 on the other side.

4 CONTRAINDICATIONS

Do not prescribe JOLESSA to women who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  • Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions (5.1) ].
  • Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ].
  • Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ].
  • Have cerebrovascular disease [see Warnings and Precautions (5.1) ].
  • Have coronary artery disease [see Warnings and Precautions (5.1) ].
  • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions (5.1) ].
  • Have uncontrolled hypertension [see Warnings and Precautions ( 5.4) ].
  • 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) and Use in Specific Populations (8.6)].
• Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.8) ].
• Pregnancy, because there is no reason to use COCs during pregnancy [see Warnings and Precautions ( 5.9) and Use in Specific Populations (8.1) ].
• Breast cancer or other estrogen- or progestin-sensitive cancer, now or in the past [see Warnings and
• Precautions ( 5.11) ].
• 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)].

5 WARNINGS AND PRECAUTIONS

5.1 Thrombotic Disorders and Other Vascular Problems

• Stop JOLESSA if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
• Stop JOLESSA if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
• If feasible, stop JOLESSA 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 JOLESSA 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 JOLESSA provides women with more hormonal exposure on a yearly basis than conventional monthly COCs containing the same strength synthetic estrogens and progestins (an additional 9 weeks of exposure per year). In the clinical trial, one case of pulmonary embolism was reported. Postmarketing adverse reactions of VTE have been reported in women who used JOLESSA.
• 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. Stroke has been reported in women associated with the use of JOLESSA. 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.

5.2 Liver Disease

Impaired Liver Function

Do not use JOLESSA in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of the 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 JOLESSA if jaundice develops.

Liver Tumors

JOLESSA 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 attributable risk of liver cancers in COC users is less than one case per million users.