Label: SETLAKIN- levonorgestrel and ethinyl estradiol kit

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated November 23, 2018

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use SetlakinTM safely and effectively. See full prescribing information for SetlakinTM.
    SETLAKIN (levonorgestrel and ethinyl estradiol tablets) for oral use
    Initial U.S. Approval:1982

    WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

    See full prescribing information for complete boxed warning.

    • SETLAKINTMis contraindicated in women over 35 years old who smoke. (4).
    • Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. (4)

    RECENT MAJOR CHANGES

    Contraindications (4)                                 08/2017

    Warnings and Precautions (5.3)      08/2017

    INDICATIONS AND USAGE

    SETLAKINTM is an estrogen/progestin COC indicated for use by women to prevent pregnancy. (1)

    DOSAGE AND ADMINISTRATION

    • Take one tablet daily by mouth at the same time every day for 91 days. (2.1)
    • Take tablets in the order directed on the Extended-Cycle Tablet Dispenser (2.2)

    DOSAGE FORMS AND STRENGTHS

    SETLAKINTM consists of 84 round, pink tablets containing 0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol, and 7 round, white inert tablets. (3)

    CONTRAINDICATIONS

    ● A high risk of arterial or venous thrombotic diseases (4)

    ● Liver tumors or liver disease (4)

    ● Undiagnosed abnormal uterine bleeding (4)

    ● Pregnancy (4)

    ● Breast cancer or other estrogen- or progestin-sensitive cancer (4)

    ● Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (4)

    WARNINGS AND PRECAUTIONS

    ● Thrombotic disorders and other vascular problems: Stop SETLAKINTM if a thrombotic event occurs. Stop at least 4 weeks before and through 2 weeks after major surgery. Start no earlier than 4 weeks after delivery, in women who are not breastfeeding. (5.1)

    ● Liver disease: Discontinue SETLAKINTM if jaundice occurs. (5.2)

    ● High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop SETLAKINTM if blood pressure rises significantly. (5.4)

    ● Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking SETLAKINTM. Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. (5.6)

    ● Headache: Evaluate significant change in headaches and discontinue SETLAKINTM if indicated. (5.7)

    ● Bleeding irregularities and amenorrhea: Evaluate irregular bleeding or amenorrhea. (5.8)

    ADVERSE REACTIONS

    The most common adverse reactions (  2%) reported during clinical trials were headache, menorrhagia, nausea, dysmenorrhea, acne, migraine, breast tenderness, weight increased, and depression. (6.1)

    To report SUSPECTED ADVERSE REACTIONS, contact Northstar Rx LLC.Toll-Free at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    DRUG INTERACTIONS

    Drugs or herbal products that induce certain enzymes (for example CYP3A4) may decrease the effectiveness of COCs or increase breakthrough bleeding. Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs. (7.1)

    USE IN SPECIFIC POPULATIONS

    ● Nursing Mothers: Advise use of another contraceptive method. SETLAKINTM can decrease milk production. (8.3)

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 10/2017

  • Table of Contents

    FULL PRESCRIBING INFORMATION: CONTENTS*

    WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS

    1 INDICATIONS AND USAGE

    2 DOSAGE AND ADMINISTRATION

    2.1 How to Start SETLAKINTM

    2.2 How to Take SETLAKINTM

    2.3 Missed Tablets

    2.4 Advice in Case of Gastrointestinal Disturbances

    3 DOSAGE FORMS AND STRENGTHS

    4 CONTRAINDICATIONS

    5 WARNINGS AND PRECAUTIONS

    5.1 Thrombotic Disorders and Other Vascular Problems

    5.2 Liver Disease

    5.3 Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

    5.4 High Blood Pressure

    5.5 Gallbladder Disease

    5.6 Carbohydrate and Lipid Metabolic Effects

    5.7 Headache

    5.8 Bleeding Irregularities and Amenorrhea

    5.9 COC Use Before or During Early Pregnancy

    5.10 Depression

    5.11 Carcinoma of the Breast and Cervix

    5.12 Effect on Binding Globulins

    5.13 Monitoring

    5.14 Hereditary Angioedema

    5.15 Chloasma

    6 ADVERSE REACTIONS

    6.1 Clinical Trial Experience

    6.2 Postmarketing Experience

    7 DRUG INTERACTIONS

    7.1 Effects of Other Drugs on Combined Oral Contraceptives

    7.2 Effects of Combined Oral Contraceptives on Other Drugs

    7.3 Concomitant Use with Hepatitis C Vaccine (HCV) Combination Therapy – Liver Enzyme Elevatio

    7.4 Interactions with Laboratory Tests

    8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    8.3 Nursing Mothers

    8.4 Pediatric Use

    8.5 Geriatric Use

    8.6 Hepatic Impairment

    8.7 Renal Impairment

    10 OVERDOSAGE

    11 DESCRIPTION

    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    12.2 Pharmacodynamics

    12.3 Pharmacokinetics

    13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    14 CLINICAL STUDIES

    16 HOW SUPPLIED/STORAGE AND HANDLING

    16.1 How Supplied

    16.2 Storage Conditions

    17 PATIENT COUNSELING INFORMATION

    *
    Sections or subsections omitted from the full prescribing information are not listed.
  • BOXED WARNING (What is this?)

    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)].

  • 1 INDICATIONS AND USAGE

    SETLAKINTM (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 How to Start SETLAKINTM

    SETLAKINTM is dispensed in an Extended-Cycle Tablet Dispenser [see How Supplied/Storage and Handling (16)]. SETLAKINTM should be started on a Sunday (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

    Instruct patients to take SETLAKINTM once a day by mouth at the same time every day for 91 days. To achieve maximum contraceptive effectiveness, SETLAKINTM should be taken exactly as directed and at intervals not exceeding 24 hours. For patient instructions regarding missed pills, see FDA-approved patient labeling.

    2.2 How to Take SETLAKINTM

    Table 1: Instructions for Administration of SETLAKINTM
    Starting COCs in women not currently using hormonal contraception (Sunday Start)

    Important:
    Consider the possibility of ovulation and conception prior to initiation of this product.

    Tablet Color:
    SETLAKINTM active tablets are pink (Day 1 to Day 84).
    SETLAKINTM inactive tablets are white (Day 85 to Day 91).
    Sunday Start:
    For each 91-day coursetake in the following order:
    Take the first pink tablet (0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol) on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, take the tablet on that day. Due to the potential risk of becoming pregnantuse additional non-hormonal contraception (such as condoms or spermicidefor the first days of treatment.
    Take subsequent pink tablets once daily at the same time each day for a total of 84 days.
    Take one white tablet (inert) daily for the following 7 days and at the same time of day that active tablets were taken. A scheduled period should occur during the 7 days that the white tablets are taken.
    Begin the next and all subsequent 91-day courses of SETLAKINTM without interruption on the same day of the week (i.e., Sunday) on which the patient began her first dose. Follow the same schedule as the initial 91-day course: a pink tablet once a day for 84 days, and a white tablet once a day for 7 days. If the patient does not immediately start her next pill pack, instruct her to protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a pink tablet daily for 7 consecutive days.
    Switching to SETLAKINTM from another oral contraceptive
    Start on the same day that a new pack of the previous oral contraceptive would have started.
    Switching from another contraceptive method to SETLAKINTM
    Start SETLAKINTM:
    Transdermal patch
    On the day when the next application would have been scheduled.
    Vaginal ring
    On the day when the next insertion would have been scheduled.
    Injection
    On the day when the next injection would have been scheduled.
    Intrauterine contraceptive (IUD)
    On the day of removal.
    If the IUD is not removed on first day of the patient’s menstrual cycle, additional non- hormonal contraception (such as condoms or spermicide) is needed for the first seven days of the first 91-day course.
    Implant
    On the day of removal.
    Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-approved patient labeling.

    Starting SETLAKINTM after Abortion or Miscarriage

    First-trimester

    ●   After a first-trimester abortion or miscarriage, SETLAKINTM may be started immediately. An additional method of contraception is not needed if SETLAKINTM is started immediately.

    ●   If SETLAKINTM is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of her first 91-day course of SETLAKINTM.

    Second-trimester

    ●   Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start SETLAKINTM following the instructions in Table 1 for Sunday start. Use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient's first 91-day course of SETLAKINTM [see Contraindications (4), Warnings and Precautions (5.1), and FDA-approved Patient Labeling].

    Starting SETLAKINTM after Childbirth

    ●   Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with SETLAKINTM following the instructions in Table 1 for women not currently using hormonal contraception.

    ●   SETLAKINTM is not recommended for use in lactating women [see Use in Specific Populations (8.3) and FDA-Approved Patient Labeling].

    ●   If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of SETLAKINTM [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-approved Patient Labeling].

    Tablet Dispenser Instructions:

    ●   The Tablet Dispenser consists of 3 blister strips that hold 91 individually sealed pills (a 13-week, or 91-day, cycle). The 91 pills consist of 84 pink pills (active pills with hormones) and 7 white pills (inactive pills without hormone).

    ●   Blister strip 1 (weeks 1 to 4) and blister strip 2 (weeks 5 to 8) each contain 28 pink pills (4 rows of 7 pills). See Figure A.

    image-01

    ●   Blister strip 3 (weeks 9 to 13) contains 35 pills consisting of 28 pink pills (4 rows of 7 pills) and 7 white pills (1 row of 7 pills). See Figure B.

    image-02
    • Advise the patient to remove the first pill in the upper left corner by pushing down on the pill. The pill will come out through a hole in the back of the Tablet Dispenser.
    • Advise the patient to wait 24 hours to take the next pill, and continue to take one pill each day until all the pills have been taken.
    • Advise the patient, after taking the last white pill, to start taking the first pink pill from a new Tablet Dispenser the very next day, regardless of when their period started.

    2.3 Missed Tablets

    Table 2:Instructions for Missed SETLAKINTM 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 spermicideshould be used as back-up if the patient has sex within days after missing 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 spermicidemust be used as back-up if the patient has sex within days after missing 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

    SETLAKINTM (levonorgestrel and ethinyl estradiol tablets) are available as round, coated, biconvex, unscored tablets, 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; with a debossed "S1" on one side

    ● 7 white inert tablets debossed with "P" on one side and "N" on the other side.

  • 4 CONTRAINDICATIONS

    Do not prescribe SETLAKINTM 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 (5.4)].
    • 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 SETLAKINTMif an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
    • Stop SETLAKINTMif there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
    • If feasible, stop SETLAKINTMat 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 SETLAKINTMno 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 SETLAKINTMprovides 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 SETLAKINTM.
    • 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 SETLAKINTM. 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 SETLAKINTM 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 SETLAKINTM if jaundice develops.

    Liver Tumors

    SETLAKINTM 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.

    5.3 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 COCs. Discontinue SETLAKINTM prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4)]. SETLAKINTM can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.

    5.4 High Blood Pressure

    SETLAKINTM 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 SETLAKINTM 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 incidence of hypertension increases with increasing concentration of progestin.

    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.

    5.6 Carbohydrate and Lipid Metabolic Effects

    Carefully monitor prediabetic and diabetic women who are taking SETLAKINTM. COCs may decrease glucose tolerance.

    Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs.

    Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs.

    5.7 Headache

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

    Consider discontinuation of SETLAKINTM in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) [see Contraindications (4)].

    5.8 Bleeding Irregularities and Amenorrhea

    Bleeding and/or spotting that occurs at any time while taking the first 84 tablets of each extended-cycle regimen is considered "unscheduled" bleeding/spotting. Bleeding that occurs during the time a woman takes the seven white inert tablets is considered "scheduled" bleeding.

    Unscheduled and Scheduled Bleeding and Spotting

    Unscheduled (breakthrough) bleeding and spotting sometimes occur in patients on COCs, especially during the first 3 months of use. If unscheduled bleeding persists or occurs after previously regular cycles on Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg, 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 COC.

    Before prescribing Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg, advise the woman to weigh the convenience of fewer scheduled menses (4 per year instead of 13 per year) against the inconvenience of increased unscheduled bleeding and/or spotting.

    The clinical trial of the efficacy of Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg (91-day cycles) in preventing pregnancy also assessed scheduled and unscheduled bleeding. The participants in the study were composed primarily of women who had used oral contraceptives previously as opposed to new users. Women with a history of breakthrough bleeding/spotting    10 consecutive days on oral contraceptives were excluded from the study. More Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg subjects, compared to subjects on the comparator 28-day cycle regimen, discontinued prematurely for unacceptable bleeding (7.7% [Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg] vs. 1.8% [28-day cycle regimen]).

    Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 3 below presents the number of days with unscheduled bleeding and/or spotting for each respective 91-day cycle.

    Table 3:Number of Unscheduled Bleeding and/or Spotting Days per 91-day Cycle
    Cycle (N)
    Days of Unscheduled Bleeding and/or Spotting per 84-Day Interval
    Median Days Per Subject-
    Month

    Mean
    Q1
    Median
    Q3

    1 (446)
    15.1
    3.0
    12
    23.0
    3.0
    2 (368)
    11.6
    2.0
    6
    17.5
    1.5
    3 (309)
    10.6
    1.0
    6
    15.0
    1.5
    4 (282)
    8.8
    1.0
    4
    14.0
    1.0
    Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled bleeding/spotting Median: 50% of women had ≤ this number of days of unscheduled bleeding/spotting Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding/spotting

    Table 4 shows the percentages of women with    7 days and    20 days of unscheduled spotting and/or bleeding in the SETLAKINTM and the 28-day cycle treatment groups.

    Table 4:Percentage of Subjects with Unscheduled Bleeding and/or Spotting
    Days of unscheduled bleeding and/or spotting
    Percentage of Subjects a
    SETLAKINTM
    Cycle 1 (N=385)
    Cycle 4 (N=261)
     7 days
    65%
    42%
     20 days
    35%
    15%
    28-day regimen
    Cycles 1-4 (N=194)
    Cycles 10-13 (N=158)
     7 days
    38%
    39%
     20 days
    6%
    4%
    aBased on spotting and/or bleeding on days 1-84 of a 91 day cycle in the SETLAKINTM subjects and days 1-21 of a 28  day cycle over 4 cycles in the 28-day dosing regimen.

    Total days of bleeding and/or spotting (scheduled plus unscheduled) were similar over one year of treatment for SETLAKINTM subjects and subjects on the 28-day cycle regimen.

    Amenorrhea and Oligomenorrhea

    Women who are not pregnant and use SETLAKINTM may experience amenorrhea. Based on data from the clinical trial, amenorrhea occurred in approximately 0.8% of women during Cycle 1, 1.2% of women during Cycle 2, 3.7% of women during Cycle 3, and 3.4% of women during Cycle 4. Because women using SETLAKINTM will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period.

    Some women may experience amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent.

    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 SETLAKINTM use if pregnancy is confirmed.

    Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations (8.1)].

    5.10 Depression

    Depression associated with the use of SETLAKINTM has been reported. Carefully observe women with a history of depression and discontinue SETLAKINTM if severe depression recurs.

    5.11 Carcinoma of the Breast and Cervix

    SETLAKINTM is contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see Contraindications (4)].

    There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings.

    Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

    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.

    5.13 Monitoring

    A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care.

    5.14 Hereditary Angioedema

    In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

    5.15 Chloasma

    Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to develop chloasma should avoid prolonged exposure to the sun or ultraviolet radiation while taking SETLAKINTM.

  • 6 ADVERSE REACTIONS

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

    ● Serious cardiovascular events and stroke [see Boxed Warning and Warnings and Precautions (5.1)]

    ● Vascular events [see Warnings and Precautions (5.1)]

    ● Liver disease [see Warnings and Precautions (5.2)]

    Adverse reactions commonly reported by COC users are:

    ● Irregular uterine bleeding

    ● Nausea

    ● Breast tenderness

    ● Headache

    6.1 Clinical Trial Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

    The clinical trial that evaluated the safety and efficacy of Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18-40, of whom 456 took at least one dose of Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg (345.14 woman-years of exposure) [see Clinical Studies (14)].

    Adverse Reactions Leading to Study Discontinuation: 14.9% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (   1% of women) leading to discontinuation in the Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg group were menorrhagia (5.7%), mood swings (1.9%), weight/appetite increase (1.5%), and acne (1.3%).

    Common Adverse Reactions (   2% of women): headache (20.6%), menorrhagia (11.6%), nausea (7.5%), dysmenorrhea (5.7%), acne (4.6%), migraine (4.4%), breast tenderness (3.5%), weight increased (3.1%), and depression (2.1%).

    Serious Adverse Reactions:  pulmonary embolus, cholecystitis.

    6.2 Postmarketing Experience

    The following adverse reactions have been identified during post-approval use of SETLAKINTM. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    Gastrointestinal disorders: abdominal distension, vomiting

    General disorders and administration site conditions: chest pain, fatigue, malaise, edema peripheral, pain Immune system disorder: hypersensitivity reactions, including itching, rash, and angioedema Investigations: blood pressure increased

    Musculoskeletal and connective tissue disorders: muscle spasms, pain in extremity

    Nervous system disorders: dizziness, loss of consciousness

    Psychiatric disorders: insomnia

    Reproductive and breast disorders: dysmenorrhea

    Skin and subcutaneous tissue disorders: alopecia

    Vascular disorders: thrombosis, pulmonary embolism, pulmonary thrombosis

  • 7 DRUG INTERACTIONS

    Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

    7.1 Effects of Other Drugs on Combined Oral Contraceptives

    Substances decreasing the plasma concentrations of COCs and potentially diminishing the efficacy of COCs:

    Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort.

    Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

    Colesevelam: Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart.

    Substances increasing the plasma concentrations of COCs:

    Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations.

    Human immunodeficiency virus (HIV)/ Hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:

    Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors(decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).

    7.2 Effects of Combined Oral Contraceptives on Other Drugs

    COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations.

    COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.

    Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs [see Warnings and Precautions (5.11)].

    7.3 Concomitant Use with Hepatitis C Vaccine (HCV) Combination Therapy – Liver Enzyme Elevatio

    Do not co-administer SETLAKINTM with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.3)].

    7.4 Interactions with Laboratory Tests

    The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

  • 8 USE IN SPECIFIC POPULATIONS

    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.

    8.3 Nursing Mothers

    Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

    8.4 Pediatric Use

    Safety and efficacy of SETLAKINTM have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of SETLAKINTM before menarche is not indicated.

    8.5 Geriatric Use

    SETLAKINTM has not been studied in postmenopausal women and is not indicated in this population.

    8.6 Hepatic Impairment

    The pharmacokinetics of SETLAKINTM have not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded [see Contraindications (4) and Warnings and Precautions (5.2)].

    8.7 Renal Impairment

    The pharmacokinetics of SETLAKINTM have not been studied in women with renal impairment.

  • 10 OVERDOSAGE

    There have been no reports of serious ill effects from overdose of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

  • 11 DESCRIPTION

    SETLAKINTM (levonorgestrel and ethinyl estradiol tablets) is an extended-cycle combination oral contraceptive consisting of 84 pink active tablets each containing 0.15 mg of levonorgestrel, a synthetic progestin and 0.03 mg of ethinyl estradiol, an estrogen , and 7 white inert tablets (without hormones).

    The structural formulas for the active components are:

    image-03

    Levonorgestrel is chemically 18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (17  )-, (-)-.

    image-04

    Ethinyl Estradiol is 19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17  )-.

    ●    Each pink active tablet contains the following inactive ingredients: polyvinyl alcohol,titanium dioxide,talc, macrogol/polyethylene glycol 3350 NF, lecithin (soya), FD&C Red #40 Aluminum Lake, FD&C Blue #2 Aluminum Lake, and FD&C Yellow #6 Aluminum Lake,lactose, magnesium stearate, pregelatinized corn starch and microcrystalline cellulose

    ●    Each white inert tablet contains the following inactive ingredients: titanium dioxide,polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol 8000, lactose,magnesium stearate and pregelatinized corn starch.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

    12.2 Pharmacodynamics

    No specific pharmacodynamic studies were conducted with SETLAKINTM.

    12.3 Pharmacokinetics

    Absorption

    No specific investigation of the absolute bioavailability of SETLAKINTM in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability nearly 100%) and is not subject to first-pass metabolism. EE is rapidly and almost completely absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, the bioavailability of EE is approximately 43%.

    Following continuous dosing with once-daily administration of SETLAKINTM tablets, plasma concentrations of levonorgestrel and EE reached steady-state within 7 days. The mean plasma pharmacokinetic parameters for SETLAKINTM under fasting conditions in normal healthy women following once-daily administration of one levonorgestrel/EE combination tablet for 10 days are summarized in Table 5.

    Table 5:Mean ±SD Pharmacokinetic Parameters Under Fasting Conditions in Healthy Women Following 10 Days Administration of One Tablet of Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg (n=44)
    Analyte
    AUC0-24
    Cmax
    Cmin
    Cavga
    Tmax
    Levonorgestrel
    54.6±16.5
    ng*hr/mL
    5.0±1.5 ng/mL
    1.6±0.5
    ng/mL
    2.3±0.7
    ng/mL
    1.4±0.7 hours
    Ethinyl estradiol
    935.5±346.9
    pg*hr/mL
    106.1±41.2
    pg/mL
    18.5±9.4
    pg/mL
    38.9±14.4
    pg/mL
    1.6±0.6
    hours
    a Cavg =AUC0-24/24

    Food Effect

    The effect of food on the rate and the extent of levonorgestrel and EE absorption following oral administration of SETLAKINTM has not been evaluated.

    Distribution

    The apparent volume of distribution of levonorgestrel and EE are reported to be approximately 1.8 L/kg and 4.3 L/kg, respectively. Levonorgestrel is about 97.5 - 99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. EE is about 95 - 97% bound to serum albumin. EE does not bind to SHBG, but induces SHBG synthesis, which leads to decreased levonorgestrel clearance.

    Following repeated daily dosing of levonorgestrel/EE oral contraceptives, levonorgestrel plasma concentrations accumulate more than predicted based on single-dose pharmacokinetics, due in part, to increased SHBG levels that are induced by EE, and a possible reduction in hepatic metabolic capacity.

    Metabolism

    Following absorption, levonorgestrel is conjugated at the 17  -OH position to form sulfate and to a lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3  ,5  -tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3  ,5  -tetrahydrolevonorgestrel and 16  -hydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users.

    First-pass metabolism of EE involves formation of EE-3-sulfate in the gut wall, followed by 2-hydroxylation of a portion of the remaining untransformed EE by hepatic cytochrome P-450 3A4 (CYP3A4). Levels of CYP3A4 vary widely among individuals and can explain the variation in rates of EE hydroxylation. Hydroxylation at the 4-, 6-, and 16- positions may also occur, although to a much lesser extent than 2-hydroxylation. The various hydroxylated metabolites are subject to further methylation and/or conjugation.

    Excretion

    About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. The terminal elimination half-life for levonorgestrel after a single dose of SETLAKINTM was about 30 hours.

    EE is excreted in the urine and feces as glucuronide and sulfate conjugates, and it undergoes enterohepatic recirculation. The terminal elimination half-life of EE after a single dose of SETLAKINTM was found to be about 15 hours.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    [see Warnings and Precautions (5.2, 5.10) and Use in Specific Populations (8.1)].

  • 14 CLINICAL STUDIES

    In a 12-month, multicenter, randomized, open-label clinical trial, 456 women aged 18-40 were studied to assess the safety and efficacy of Levonorgestrel and Ethinyl Estradiol Tablets 0.15 mg and 0.03 mg, completing 809 91-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (77%), African-American (11%), Hispanic (7%), Asian (2%), and Other (3%).

    There were no exclusions for body mass index (BMI) or weight. The weight range of those women treated was 84 to 304 pounds, with a mean weight of 157 pounds and a median weight of 147 pounds. Among the women in the trial, 63% were current or recent hormonal contraceptive users, 29% were prior users (who had used hormonal contraceptives in the past but not in the 6 months prior to enrollment), and 8% were new starts.

    The pregnancy rate (Pearl Index [PI]) in the 397 women aged 18-35 years was 1.98 pregnancies per 100 women-years of use (95% CI: 0.54 to 5.03), based on 4 pregnancies that occurred after the onset of treatment

    and within 14 days after the last combination pill. Cycles in which conception did not occur, but which included the use of back-up contraception, were not included in the calculation of the PI.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    16.1 How Supplied

    SETLAKINTM tablets (Levonorgestrel and Ethinyl Estradiol Tablets, USP) 0.15 mg/0.03 mg are available as an Extended-Cycle Tablet Dispenser (NDC 16714-366-01) with each dispenser containing a 13-week (91 tablet) supply of tablets: 84 pink tablets, each pink tablet containing 0.15 mg levonorgestrel and 0.03 mg ethinyl estradiol, and 7 white inert tablets. The Extended-Cycle Tablet Dispenser is available in the two configurations shown below. The active pink tablets are round, coated, biconvex, unscored tablets with a debossed "S1" on one side.The inert tablets are white, round, coated, biconvex, unscored tablets debossed with "P" on one side and "N" on the other side.

    SETLAKINTM is available in the following configuations:

    Carton of 1 x 91 tablet extended-cycle dispenser NDC 16714-366-02

    Carton of 3 x 91 tablet extended-cycle dispensers NDC 16714-366-03

    16.2 Storage Conditions

    Store at 20° to 25° C (68° to 77° F), [See USP Controlled Room Temperature].

    References available upon request.

    KEEP OUT OF THE REACH OF CHILDREN

    Rx only

  • 17 PATIENT COUNSELING INFORMATION

    See FDA-approved patient labeling (Patient Information and Instructions for Use). Counsel patients on the following information:

    ● Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see Boxed Warning].

    ● Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see Warnings and Precautions (5.1)].

    ● SETLAKINTM does not protect against HIV-infection (AIDS) and other sexually transmitted infections.

    ● SETLAKINTM is not to be used during pregnancy; if pregnancy occurs during use of SETLAKINTM, instruct the patient to stop further use [see Warnings and Precautions (5.9)].

    ● Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see Dosage and Administration (2.3)].

    ● Use a back-up or alternative method of contraception when enzyme inducers are used with SETLAKINTM [see Drug Interactions (7.1)].

    ● COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations (8.3)].

    ● Women who start on COCs postpartum, and who have not yet had a period, should use an additional method of contraception until they have taken a pink tablet for 7 consecutive days [see Dosage and Administration (2.2)].

    ● Amenorrhea may occur. Because women using SETLAKINTM will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period [see Warnings and Precautions (5.8)].

    image-05
  • SPL UNCLASSIFIED SECTION

    Patient Information SETLAKINTM[set-LAA-kin]

    (levonorgestrel and ethinyl estradiol tablets)

    What is the most important information I should know about SETLAKINTM?

    Do not use SETLAKINTM if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

    What is SETLAKINTM?

    SETLAKINTM is a birth control pill (oral contraceptive) used by women to prevent pregnancy.

    How does SETLAKINTM work for contraception?

    Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.

    Based on the results of clinical studies, about 1 to 5 out of 100 women may get pregnant during the first year they use SETLAKINTM.

    The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

    image-06

    Who should not take SETLAKINTM? Do not take SETLAKINTM if you:

           ● smoke and are over 35 years of age

           ● had blood clots in your arms, legs, lungs, or eyes

           ● had a problem with your blood that makes it clot more than normal

           ● have certain heart valve problems or irregular heart beat

           ● had a stroke

           ● had a heart attack

           ● have high blood pressure that cannot be controlled by medicine

           ● have diabetes with kidney, eye, nerve, or blood vessel damage

           ● have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age

           ● have liver problems, including liver tumors

    ● take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme             "alanine aminotransferase" (ALT) in the blood.

           ● have any unexplained vaginal bleeding

           ● are pregnant

           ● had breast cancer or any cancer that is sensitive to female hormones

    If any of these conditions happen while you are taking SETLAKINTM, stop taking SETLAKINTM right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking SETLAKINTM.

    What should I tell my healthcare provider before taking SETLAKINTM?

    Tell your healthcare provider if you:

           ● are pregnant or think you may be pregnant

           ● are depressed now or have been depressed in the past

           ● had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy)

           ● are breastfeeding or plan to breastfeed. SETLAKINTM may decrease the amount of breast milk you make. A small amount of the hormones in SETLAKINTM may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding.

    Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

    SETLAKINTM may affect the way other medicines work, and other medicines may affect how well SETLAKINTM works.

    Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

    How should I take SETLAKINTM?

    Read the Instructions for Use at the end of this Patient Information.

    What are the possible serious side effects of SETLAKINTM?

    Like pregnancy, SETLAKINTM may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes.

    Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:

    o  first start taking birth control pills

    o  restart the same or different birth control pills after not using them for a month or more

    Call your healthcare provider or go to a hospital emergency room right away if you have:

    o  leg pain that will not go away       

    o chest pain

    o a sudden, severe headache unlike your usual headaches

    o  sudden severe shortness of breath

    o  sudden change in vision or blindness       

    o weakness or numbness in your arm or leg

    o  trouble speaking

    Other serious side effects include:

    ●  liver problems, including:

    o  rare liver tumors

    o  jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes.

           ● high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure.

           ● gallbladder problems

           ● changes in the sugar and fat (cholesterol and triglycerides) levels in your blood

           ● new or worsening headaches including migraine headaches

           ● irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking SETLAKINTM.

           ● depression

           ● possible cancer in your breast and cervix

           ● swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema is higher is you have a history of angioedema.

           ● dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking SETLAKINTM. Use sunscreen if you have to be in the sunlight.

    What are the most common side effects of SETLAKINTM?

    ●  headache (migraine)    

    ●  acne

    ●  heavier or longer periods, pain with period    

    ●  breast tenderness

    ●  nausea                             

    ●  increase in weight

    These are not all the possible side effects of SETLAKINTM. For more information, ask your healthcare provider or pharmacist.

    You may report side effects to the FDA at 1-800-FDA-1088.

    What else should I know about taking SETLAKINTM?

    ●  If you are scheduled for any lab tests, tell your healthcare provider you are taking SETLAKINTM. Certain blood tests may be affected by SETLAKINTM.

    ●  SETLAKINTM does not protect against HIV infection (AIDS) and other sexually transmitted infections.

    How should I store SETLAKINTM?

    ●   Store SETLAKINTM at room temperature between 68°F to 77°F (20°C to 25°C).

    General information about the safe and effective use of SETLAKINTM.

    Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use SETLAKINTM for a condition for which it was not prescribed. Do not give SETLAKINTM to other people, even if they have the same symptoms that you have.

    This Patient Information summarizes the most important information about SETLAKINTM. You can ask your pharmacist or healthcare provider for information about SETLAKINTM that is written for health professionals.

    For more information, call 1-800-206-7821.

    Do birth control pills cause cancer?

    Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones.

    Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

    What if I want to become pregnant?

    You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.

    What should I know about my period when taking SETLAKINTM?

    When you take SETLAKINTM, which has a 91-day extended dosing cycle, you should have 4 scheduled periods a year (bleeding when you are taking the 7 white pills). However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28-day dosing cycle. During the first SETLAKINTM 91-day treatment cycle, about 1 in 3 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking SETLAKINTM because of this bleeding or spotting. If the spotting continues for more than 7 days in a row or if the bleeding is heavy, call your healthcare provider.

    What are the ingredients in SETLAKINTM?

    Active ingredients: Each pink pill contains levonorgestrel and ethinyl estradiol.

    Inactive ingredients:

    Pink pills: polyvinyl alcohol,titanium dioxide,talc, macrogol/polyethylene glycol 3350 NF, lecithin (soya), FD&C Red #40 Aluminum Lake, FD&C Blue #2 Aluminum Lake, and FD&C Yellow #6 Aluminum Lake,lactose, magnesium stearate, pregelatinized corn starch and microcrystalline cellulose

    White pills: titanium dioxide,polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol 8000, lactose,magnesium stearate and pregelatinized corn starch.

  • SPL UNCLASSIFIED SECTION

    Instructions For Use SETLAKINTM[set-LAA-kin]

    (levonorgestrel and ethinyl estradiol tablets)

    Important Information about taking SETLAKINTM

           ● Take 1 pill every day at the same time. Take the pills in the order directed on your pill dispenser.

           ● Do not skip your pills, even if you do not have sex often. If you miss pills (including starting the pack late) you could get pregnant. The more pills you miss, the more likely you are to get pregnant.

           ● If you have trouble remembering to take SETLAKINTM, talk to your healthcare provider.

           ● When you first start taking SETLAKINTM, spotting or light bleeding in between your periods may occur. Contact your healthcare provider if this does not go away after a few months.

           ● You may feel sick to your stomach (nauseous), especially during the first few months of taking SETLAKINTM. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If your nausea does not go away, call your healthcare provider.

           ● Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. On the days you take 2 pills to make up for missed pills (see What should I do if I miss any SETLAKINTM pills? below), you could also feel a little sick to your stomach.

           ● It is not uncommon to miss a period. However, if you miss a period and have not taken SETLAKINTM according to directions, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking SETLAKINTM.

           ● If you have vomiting or diarrhea within 3-4 hours of taking a pink pill, take another pink pill as soon as possible. Continue taking one pill a day until the 91-day course is finished.

           ● If you have vomiting or diarrhea for more than 1 day, your birth control pills may not work as well. Use an additional birth control method, like condoms or spermicide, until you check with your healthcare provider.

           ● Stop taking SETLAKINTM at least 4 weeks before you have major surgery and do not restart after the surgery without asking your healthcare provider. Be sure to use other forms of contraception (like condoms or spermicide) during this time period.

    Before you start taking SETLAKINTM:

    ● Decide what time of day you want to take your pill. It is important to take it at about the same time every day.

    ● Look at your Extended-Cycle Tablet Dispenser. Your Tablet Dispenser consists of blister strips that hold 91 individually sealed pills (a 13-week or 91-day      cycle). The 91 pills consist of 84 pink pills (active pills with hormones) and 7 white pills (inactive pills without hormone). Blister strip 1 (weeks 1 to 4) and blister strip 2 (weeks 5 to 8) each contain 28 pink pills (4 rows of 7 pills). Blister strip 3 (weeks 9 to 13) contains 35 pills consisting of 28 pink pills (4 rows of 7 pills) and 7 white pills (1 row of 7 pills).

    image-07

           ● Also find:

    o Where on the first blister strip in the pack to start taking pills (upper left corner at the start arrow) and

    o In what order to take the pills (follow the order of weeks and arrow)

           ● Be sure you have ready at all times another kind of birth control (such as condoms or spermicides), to use as a back-up in case you miss pills.

    When should I start taking SETLAKINTM?

    If you start taking SETLAKINTM and you have not used a hormonal birth control method before:

           ● Take the first pink pill on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the first pink pill that same day.

           ● Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first pink pill until the next Sunday (first 7 days).

    If you start taking SETLAKINTM and you are switching from another birth control pill:

    ●  Start your new SETLAKINTM pack on the same day that you would start the next pack of your previous birth control method.

    ●  Do not continue taking the pills from your previous birth control pack.

    If you start taking SETLAKINTM and previously used a vaginal ring:

    ●  Start using SETLAKINTM on the day you would have reapplied the next ring.

    If you start taking SETLAKINTM and previously used a transdermal patch:

    ●  Start using SETLAKINTM on the day you would have started a new cycle (first patch application).

    If you start taking SETLAKINTM and you are switching from a progestin-only method such as an implant or injection:

    ●  Start taking SETLAKINTM on the day of removal of your implant, or on the day when you would have had your next injection.

    If you start taking SETLAKINTM and you are switching from an intrauterine device or system (IUD or IUS):

    ●  Start taking SETLAKINTM on the day of removal of your IUD or IUS.

    ●  You do not need back-up contraception if your IUD or IUS is removed on the first day (Day 1) of your period. If your IUD or IUS is removed on any other day, use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days that you take SETLAKINTM.

    Keep a calendar to track your period: If this is the first time you are taking birth control pills, read, "When should I start taking SETLAKINTM?" above. Follow these instructions for a Sunday Start.

    Instructions for using your SETLAKINTM Extended-Cycle Tablet Dispenser:

    Sunday Start:

    ●  Take pill 1 on the Sunday after your period starts. To remove your pill from the dispenser, press the pill through the hole in the bottom of the dispenser. See Figure C.

    image-08

    ●  If your period starts on a Sunday, take pill "1" that same day.

    ●  Take 1 pill at about the same time every day until you have taken the last pill in the tablet dispenser.

    ●  After taking the last white pill on Day 91 from the pill dispenser, start taking the first pink pill from a new Extended-Cycle Tablet Dispenser on the very next day (this should be a Sunday). Take the first pill in the new pack whether or not you are having your period.

    ●  Use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days of the first cycle that you take SETLAKINTM.

    What should I do if I miss any SETLAKINTM pills? If you miss 1 pink pill, follow these steps:

    ●  Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.

    ●  Then continue taking 1 pill every day until you finish the pack.

    ●  You do not need to use a back-up birth control method if you have sex.

    If you miss 2 pink pills in a row, follow these steps:

    ●  Take 2 pills on the day you remember and 2 pills the next day.

    ●  Then continue to take 1 pill every day until you finish the pack.

    ●  You could become pregnant if you have sex in the 7 days after you miss two pills. You must use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

    If you miss 3 or more pink pills in a row, follow these steps:

    ●  Do not take the missed pills. Keep taking 1 pill every day until you have completed all of the remaining pills in the pack. For example, if you start taking the pill on Thursday, take the pill under "Thursday" and do not take the missed pills. You may have bleeding during the week following the missed pills.

    ●  You could become pregnant if you have sex during the days of missed pills or during the first 7 days after restarting your pills. You must use a non-hormonal birth control method (such as a condom or spermicide) as a back-up when you miss pills and for the first 7 days after you restart your pills. If you do not have your period when you are taking the white pills, call your healthcare provider because you may be pregnant.

    If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.

    image-09

    This Patient Information and Instructions for Use have been approved by the

    U.S. Food and Drug Administration.

    Revised September 2017

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

    image-10
  • INGREDIENTS AND APPEARANCE
    SETLAKIN  
    levonorgestrel and ethinyl estradiol kit
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:16714-366
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:16714-366-033 in 1 CARTON08/01/2015
    11 in 1 POUCH
    11 in 1 BLISTER PACK
    Quantity of Parts
    Part #Package QuantityTotal Product Quantity
    Part 1 84 
    Part 2
    Part 1 of 2
    SETLAKIN  
    levonorgestrel and ethinyl estradiol tablet, coated
    Product Information
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    LEVONORGESTREL (UNII: 5W7SIA7YZW) (LEVONORGESTREL - UNII:5W7SIA7YZW) LEVONORGESTREL0.15 mg
    ETHINYL ESTRADIOL (UNII: 423D2T571U) (ETHINYL ESTRADIOL - UNII:423D2T571U) ETHINYL ESTRADIOL0.03 mg
    Inactive Ingredients
    Ingredient NameStrength
    POLYVINYL ALCOHOL (UNII: 532B59J990)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    TALC (UNII: 7SEV7J4R1U)  
    POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
    LECITHIN, SOYBEAN (UNII: 1DI56QDM62)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
    FD&C YELLOW NO. 6 (UNII: H77VEI93A8)  
    LACTOSE (UNII: J2B2A4N98G)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    STARCH, PREGELATINIZED CORN (UNII: O8232NY3SJ)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    Product Characteristics
    ColorPINKScoreno score
    ShapeROUNDSize5mm
    FlavorImprint Code S1
    Contains    
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA09071608/01/2015
    Part 2 of 2
    INERT  
    placebo tablet, coated
    Product Information
    Route of AdministrationORAL
    Inactive Ingredients
    Ingredient NameStrength
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    POLYDEXTROSE (UNII: VH2XOU12IE)  
    HYPROMELLOSES (UNII: 3NXW29V3WO)  
    TRICETIN (UNII: 5627PY99ZO)  
    POLYETHYLENE GLYCOL 8000 (UNII: Q662QK8M3B)  
    LACTOSE (UNII: J2B2A4N98G)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    STARCH, PREGELATINIZED CORN (UNII: O8232NY3SJ)  
    Product Characteristics
    ColorWHITEScoreno score
    ShapeROUNDSize5mm
    FlavorImprint Code P;N
    Contains    
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA09071608/01/2015
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA09071608/01/2015
    Labeler - Northstar Rx LLC (830546433)
    Registrant - Novast Laboratories, Ltd. (527695995)
    Establishment
    NameAddressID/FEIBusiness Operations
    Novast Laboratories, Ltd.527695995analysis(16714-366) , label(16714-366) , manufacture(16714-366) , pack(16714-366)