WYMZYA Fe: Package Insert and Label Information

WYMZYA FE — norethindrone and ethinyl estradiol
Lupin Pharmaceuticals, Inc.

1 INDICATIONS AND USAGE

WYMZYA ^TM Fe is indicated for use by females of reproductive potential to prevent pregnancy.

2 DOSAGE AND ADMINISTRATION

2.1 How to Start WYMZYA Fe

WYMZYA Fe is dispensed in a blister [see HOW SUPPLIED/STORAGE AND HANDLING (16)]. WYMZYA Fe 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 WYMZYA Fe

WYMZYA Fe (white active tablets and brown placebo tablets) may be swallowed whole or chewed and swallowed. If the tablet is chewed, the patient should drink a full glass (8 ounces) of liquid immediately after swallowing.

Table 1: Instructions for Administration of WYMZYA Fe

Starting CHCs 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: ● WYMZYA Fe active tablets are white (Day 1 to Day 21). ● WYMZYA Fe placebo tablets are brown (Day 22 to Day 28).	Day 1 Start: ● Take first white active tablet on the first day of menses. ● Take subsequent white active tablets once daily at the same time each day for a total of 21 days. ● Take one brown placebo 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 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 WYMZYA Fe. ● Take subsequent white active tablets once daily at the same time each day for a total of 21 days. ● Take one brown placebo 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 WYMZYA Fe from another hormonal contraceptive	Start on the same day that a new pack of the previous hormonal contraceptive would have started.
Switching from another contraceptive method to WYMZYA Fe	Start WYMZYA Fe :
● 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 WYMZYA Fe after Abortion or Miscarriage

First-trimester:

• After a first-trimester abortion or miscarriage, WYMZYA Fe may be started immediately. An additional method of contraception is not needed if WYMZYA Fe is started within 5 days after termination of the pregnancy.
• If WYMZYA Fe 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 WYMZYA Fe.

Second-trimester:

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start WYMZYA Fe, 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 WYMZYA Fe. [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1), and FDA-APPROVED PATIENT LABELING.]

Starting WYMZYA Fe after Childbirth

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

2.3 Missed Tablets

Table 2: Instructions for Missed WYMZYA Fe Tablets

● If one white 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 white 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 white active tablets are missed in Week 3 or three or more white 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

WYMZYA Fe [norethindrone and ethinyl estradiol tablets USP (chewable) and ferrous fumarate tablets] is available in blister.

Each blister contains 28 tablets in the following order:

• 21 white to off-white, round (active), flat face, beveled edge tablets debossed with “LU” on one side and “M21” on the other side and each containing 0.4 mg norethindrone and 35 mcg ethinyl estradiol.
• 7 brown, mottled, round (non-hormonal placebo), flat face, beveled edge tablets debossed with “LU” on one side and “M22” on the other side and each containing 75 mg ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose.

4 CONTRAINDICATIONS

WYMZYA Fe 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 have migraine headaches with aura [see WARNINGS AND PRECAUTIONS (5.7)]

5 WARNINGS AND PRECAUTIONS

5.1 Thrombotic Disorders and Other Vascular Problems

• Stop WYMZYA Fe if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
• Stop WYMZYA Fe if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
• If feasible, stop WYMZYA Fe 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 the following prolonged immobilization.
• Start WYMZYA Fe 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 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). The 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 WYMZYA Fe in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of 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 WYMZYA Fe if jaundice develops.

Liver Tumors

WYMZYA Fe 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 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 ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN),including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications, such as COCs. Discontinue WYMZYA Fe prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see CONTRAINDICATIONS (4) ].

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

5.4 High Blood Pressure

WYMZYA Fe 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 WYMZYA Fe 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 with extended duration of use. The incidence of hypertension increases with increasing concentrations 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 take WYMZYA Fe. 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 WYMZYA Fe develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue WYMZYA Fe if indicated.

Consider discontinuation of WYMZYA Fe in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event).

5.8 Bleeding Irregularities and Amenorrhea

Unscheduled Bleeding and Spotting

Unscheduled (breakthrough or intracyclic) bleeding and spotting sometimes occur in patients on COCs, especially during the first three months of use. If bleeding persists or occurs after previously regular cycles, 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 contraceptive product.

Amenorrhea and Oligomenorrhea

Women who use WYMZYA Fe may experience amenorrhea. Some women may experience amenorrhea or oligomenorrhea after discontinuation of COCs, especially when such a condition was preexistent.

If scheduled (withdrawal) bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy.