Norgestimate and Ethinyl Estradiol: Package Insert and Label Information

NORGESTIMATE AND ETHINYL ESTRADIOL — norgestimate and ethinyl estradiol
Lupin Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

1.1 Oral Contraceptive

Norgestimate and ethinyl estradiol tablets USP are indicated for use by females of reproductive potential to prevent pregnancy [see CLINICAL STUDIES (14)].

2 DOSAGE AND ADMINISTRATION

2.1 How to Start Norgestimate and Ethinyl Estradiol Tablets USP

Norgestimate and ethinyl estradiol tablets USP are dispensed in a blister [see HOW SUPPLIED/STORAGE AND HANDLING (16)]. Norgestimate and ethinyl estradiol tablets USP may be started using either a Day 1 start or a Sunday start (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.

2.2 How to Take Norgestimate and Ethinyl Estradiol Tablets USP

Table 1 : Instructions for Administration of Norgestimate and Ethinyl Estradiol Tablets USP
Starting COCs in women not currently using hormonal contraception ( Day 1 Start or Sunday Start ) Important : Consider the possibility of ovulation and conception prior to initiation of this product.Tablet Color : ● Norgestimate and ethinyl estradiol tablets USP active tablets are blue (Day 1 to Day 21).● Norgestimate and ethinyl estradiol tablets USP have green inactive tablets (Day 22 to Day 28).	Day 1 Start : ● Take first active tablet without regard to meals on the first day of menses.● Take subsequent active tablets once daily at the same time each day for a total of 21 days.● Take one green inactive tablet daily for 7 days and at the same time of day that active tablets were taken.● Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet)
	Sunday Start : ● Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant , use additional non – hormonal contraception ( such as condoms and spermicide ) for the first seven days of the patient’s first cycle pack of norgestimate and ethinyl estradiol tablets USP . ● Take subsequent active tablets once daily at the same time each day for a total of 21 days.● Take one green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken.● Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed.
Switching to norgestimate and ethinyl estradiol tablets USP 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 norgestimate and ethinyl estradiol tablets USP	Start norgestimate and ethinyl estradiol tablets USP :
● Transdermal patch	● On the day when next application would have been scheduled
● Vaginal ring	● On the day when next insertion would have been scheduled
● Injection	● On the day when next injection would have been scheduled
● Intrauterine contraceptive	● On the day of removal● If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack.
● 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 Norgestimate and Ethinyl Estradiol Tablets USP after Abortion or Miscarriage

First-trimester:

• After a first-trimester abortion or miscarriage, norgestimate and ethinyl estradiol tablets USP may be started immediately. An additional method of contraception is not needed if norgestimate and ethinyl estradiol tablets USP is started immediately.
• If norgestimate and ethinyl estradiol tablets USP is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of norgestimate and ethinyl estradiol tablets USP.

Second-trimester:

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start norgestimate and ethinyl estradiol tablets USP, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient’s first cycle pack of norgestimate and ethinyl estradiol tablets USP.[see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1), and FDA-APPROVED PATIENT LABELING.]

Starting Norgestimate and Ethinyl Estradiol Tablets USP after Childbirth

• Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with norgestimate and ethinyl estradiol tablets USP following the instructions in Table 1 for women not currently using hormonal contraception.
• Norgestimate and ethinyl estradiol tablets USP are not recommended for use in lactating women [see USE IN SPECIFIC POPULATIONS (8.3)].
• If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of norgestimate and ethinyl estradiol tablets USP [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1), USE IN SPECIFIC POPULATIONS (8.1 and 8.3), and FDA-APPROVED PATIENT LABELING].

Blister Pack:

SET THE DAY

□ Day 1 Start:

• Six different day label strips of the week have been provided with this pack in order to accommodate a Day-1 Start regimen.
• Pick the day label strip that starts with the first day of your period. Place this day label strip over the area that has the days of the week (starting with Sunday) pre-printed on the blister

□ Sunday Start:

• Each blister has been preprinted with the days of the week, starting with Sunday, to facilitate a Sunday-Start regimen. (Refer figure below).

Remove pill “1” by pushing down on the pill. The pill will come out through a hole in the back of the strip.

The patient should wait 24 hours to take the next pill. Continue to take one pill each day until all the pills have been taken.

When your blister is empty, you will start a new blister on the day after pill “28.” The first pill in every refill will always be taken on the same day of the week, no matter when the patient’s next period starts.

2.3 Missed Tablets

Table 2 : Instructions for Missed Norgestimate and Ethinyl Estradiol Tablets USP
● If one active tablet is missed in Weeks 1, 2, or 3	Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.
● If two active tablets are missed in Week 1 or Week 2	Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non – hormonal contraception ( such as condoms and spermicide ) should be used as back – up if the patient has sex within 7 days after missing tablets .
● If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3	Day 1 start: Throw out the rest of the pack and start a new pack that same day.Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non – hormonal contraception ( such as condoms and spermicide ) should be used as back – up if the patient has sex within 7 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 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-APPROVED PATIENT LABELING].

3 DOSAGE FORMS AND STRENGTHS

Norgestimate and ethinyl estradiol tablets are available in a blister. Each blister contains 28 tablets in the following order:

• 21 blue, round, film coated tablets, debossed with “E27” on one side and “LU” on the other side of the tablet contains 0.25 mg norgestimate and 0.035 mg ethinyl estradiol
• 7 green round, biconvex, film coated tablets (non-hormonal placebo) debossed with ‘LU’ on one side and “E24” on the other side contains inert ingredients

4 CONTRAINDICATIONS

Norgestimate and ethinyl estradiol tablets is contraindicated in females who are known to have or develop the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include 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)]
• 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)]
• Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive[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 Thromboembolic Disorders and Other Vascular Problems

• Stop norgestimate and ethinyl estradiol tablets if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
• Stop norgestimate and ethinyl estradiol tablets if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately [see ADVERSE REACTIONS (6.2)].
• If feasible, stop norgestimate and ethinyl estradiol tablets at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization.
• Start norgestimate and ethinyl estradiol tablets 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 COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. 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.