Iclevia (levonorgestrel 0.15 mg ethinyl estradiol 0.03 mg) Dailymed

Iclevia is dispensed in an Extended-Cycle Wallet [see How Supplied/Storage and Handling (16)]. Iclevia 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. Table 1:  Instructions for Administration of Iclevia Starting Iclevia in females with no current use of hormonal contraception (Sunday Start)    Important: Consider the possibility of ovulation and conception prior to initiation of this product.   Tablet Color:   Iclevia active tablets are white (Day 1 to Day 84).   Iclevia inactive tablets are green (Day 85 to Day 91). Sunday Start: For each 91-day course, take in the following order:   Take the first white 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 pregnant, use additional non-hormonal contraception (such as condoms or spermicide) for the first 7 days of treatment.   Take subsequent white tablets once daily at the same time each day for a total of 84 days.   Take one green 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 green tablets are taken.   Begin the next and all subsequent 91-day courses of Iclevia without interruption on the same day of the week (Sunday) on which the patient began her first dose. Follow the same schedule as the initial 91-day course: a white tablet once a day for 84 days, and a green 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 white tablet daily for 7 consecutive days. Switching from another contraceptive method to Iclevia Start Iclevia: Another oral contraceptive On the day when the new pack of the previous COC would have been started   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.   Starting Iclevia   after Abortion or Miscarriage First-trimester After a first-trimester abortion or miscarriage, Iclevia may be started immediately. An additional method of contraception is not needed if Iclevia is started immediately. If Iclevia 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 Iclevia. Second-trimester Do not start Iclevia until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Iclevia 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 Iclevia [see Contraindications (4), Warnings and Precautions (5.1)]. Starting Iclevia   after Childbirth Do not start Iclevia until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Iclevia following the instructions in Table 1 for women not currently using hormonal contraception. Iclevia is not recommended for use in lactating women [see Use in Specific Populations (8.2)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Iclevia [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.2)].

Stop Iclevia if an arterial or venous thrombotic/thromboembolic event occurs. Stop Iclevia if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. Discontinue Iclevia during prolonged immobilization. If feasible, stop Iclevia at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism. Start Iclevia no earlier than 4 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. Before starting Iclevia evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Iclevia is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases [see Contraindications (4)]. Arterial Events COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity. Iclevia is contraindicated in women over 35 years of age who smoke [see Contraindications (4) ]. Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. Venous Events Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs [see Contraindications (4)]. While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman years. The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued. Figure 1 shows the risk of developing a VTE for 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. Use of Iclevia 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 Iclevia.

Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs, including Iclevia, may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Females with a history of pregnancy-related cholestasis may be at an increased risk for COC-related cholestasis.

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 green inert tablets is considered “scheduled” bleeding. Unscheduled Bleeding and Spotting Females using Iclevia may experience unscheduled (breakthrough or intracyclic) bleeding and spotting especially during the first 3 months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If unscheduled bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy. Before prescribing Iclevia, advise the woman to weigh the occurrence of fewer scheduled menses (4 per year instead of 13 per year) against the occurrence of increased unscheduled bleeding and/or spotting. The clinical trial of the efficacy of Iclevia (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 Iclevia subjects, compared to subjects on the comparator 28-day cycle regimen, discontinued prematurely for unacceptable bleeding (7.7% [Iclevia] 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 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 Cycl e (N) Day s 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 Table 4 shows the percentages of women with ≥7 days and ≥20 days of unscheduled spotting and/or bleeding in the Iclevia 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 Subjectsa a Based on spotting and/or bleeding on days 1 to 84 of a 91 day cycle in the Iclevia subjects and days 1 to 21 of a 28 day cycle over 4 cycles in the 28-day dosing regimen.   Iclevia Cycle 1 (N=385) Cycle 4 (N=261)   ≥ 7 days 65% 42%   ≥ 20 days 35% 15%   28-day regimen Cycles 1 to 4 (N=194) Cycles 10 to 13 (N=158)   ≥ 7 days 38% 39%   ≥ 20 days 6% 4% Total days of bleeding and/or spotting (scheduled plus unscheduled) were similar over one year of treatment for Iclevia subjects and subjects on the 28-day cycle regimen. Amenorrhea and Oligomenorrhea Females who use Iclevia may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant. Based on data from the clinical trial of Iclevia, amenorrhea occurred in approximately 0.8% of females during Cycle 1, 1.2% of females during Cycle 2, 3.7% of females during Cycle 3, and 3.4% of females during Cycle 4. Because females using Iclevia will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period. After discontinuation of Iclevia, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent.



Risk Summary There is no use for contraception in pregnancy; therefore, Iclevia should be discontinued during 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 COCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

COCs prevent pregnancy primarily by suppressing ovulation.

COCs prevent pregnancy primarily by suppressing ovulation.