Nexesta Fe

Thrombotic Disorders and Other Vascular Problems

• Stop Nexesta Fe if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.

• Stop Nexesta Fe if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.

• If feasible, stop Nexesta 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 Nexesta 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.

Liver Disease

Impaired Liver Function

Do not use Nexesta 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 Nexesta Fe if jaundice develops.

Liver Tumors

Nexesta 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.

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

High Blood Pressure

Nexesta 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 Nexesta 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.

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.

Carbohydrate and Lipid Metabolic Effects

Carefully monitor prediabetic and diabetic women who take Nexesta 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.

Headache

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

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

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 Nexesta 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.

COC Use Before or During Early Pregnancy

Extensive epidemiologic 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 Nexesta Fe use if pregnancy is confirmed.

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

Depression

Carefully observe women with a history of depression and discontinue Nexesta Fe if depression recurs to a serious degree.

Carcinoma of the Breast and Cervix

• Nexesta Fe 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.

Effect on Binding Globulins

The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sec hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

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 healthcare.

Hereditary Angioedema

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

Chloasma

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

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

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 hormonal 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 EE increase AUC values for EE by approximately 20 to 25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors, such as itraconazole, 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]).

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 (5.12)].

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation

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

Interference 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

[See Warnings and Precautions (5.11) and Use in Specific Populations (8.1).]

NexestaTM Fe (neks-ey-stuh Fe)
(norethindrone and ethinyl estradiol tablets USP (chewable)
and ferrous fumarate tablets (chewable))

Important Information about taking Nexesta Fe

• Take 1 pill every day at the same time. Take the pills in the order directed on your blister pack.
• Both the white to off-white pills and the brown pills may be swallowed whole or chewed and swallowed. If the pill is chewed, drink a full glass (8 ounces) of liquid immediately after swallowing.
• 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 Nexesta Fe, talk to your healthcare provider. When you first start taking Nexesta Fe, 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 Nexesta Fe. 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 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 Nexesta Fe according to directions, or miss 2 periods in a row, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking Nexesta Fe.
• If you have vomiting or diarrhea within 3 to 4 hours of taking your pill, take another pill of the same color from your extra blister pack. If you do not have an extra blister pack, take the next pill in your blister pack. Continue taking all your remaining pills in order. Start the first pill of your next blister pack the day after finishing your current blister pack. This will be 1 day earlier than originally scheduled. Continue on your new schedule. 
• 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 and a spermicide, until you check with your healthcare provider.
• Stop taking Nexesta Fe 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 and spermicide) during this time period.

Before you start taking Nexesta Fe:

• Decide what time of day you want to take your pill. It is important to take it at the same time every day and in the order as directed on your blister pack.
• Have backup contraception (condoms and spermicide) available and if possible, an extra full pack of pills as needed.

When should I start taking Nexesta Fe?

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

• There are 2 ways to start taking your birth control pills. You can either start on a Sunday (Sunday Start) or on the first day (Day 1) of your natural menstrual period (Day 1 Start). Your healthcare provider should tell you when to start taking your birth control pill.
• If you use the Sunday Start, use non-hormonal back-up contraception such as condoms and spermicide for the first 7 days that you take Nexesta Fe. You do not need back-up contraception if you use the Day 1 Start.

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

• Start your new Nexesta Fe 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 Nexesta Fe and previously used a vaginal ring or transdermal patch:

• Start using Nexesta Fe on the day you would have reapplied the next ring or patch.

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

• Start taking Nexesta Fe on the day of removal of your implant or on the day when you would have had your next injection.

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

• Start taking Nexesta Fe 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 and spermicide for the first 7 days that you take Nexesta Fe.

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 Nexesta Fe?” above. Follow these instructions for either a Sunday Start or a Day 1 Start.

Sunday Start:

You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.

• Take pill 1 on the Sunday after your period starts.
• If your period starts on a Sunday, take pill “1” that day and refer to Day 1 Start instructions below.
• Take 1 pill every day in the order on the blister pack at the same time each day for 28 days.
• After taking the last pill on Day 28 from the blister pack, start taking the first pill from a new pack, on the same day of the week as the first pack (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 and spermicide for the first 7 days of the first cycle that you take Nexesta Fe.

Day 1 Start:

You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.

• Take 1 pill every day in the order of the blister pack, at the same time each day, for 28 days.
• After taking the last pill on Day 28 from the blister pack, start taking the first pill from a new pack, on the same day of the week as the first pack. Take the first pill in the new pack whether or not you are having your period.

Instructions for using your pill pack:

Step 1.

Look at your Nexesta Fe pill pack. See Figure A.

The Nexesta Fe pill pack has:

• 21 white to off-white (active) pills with hormone for Week 1 through Week 3.
• 7 brown (inactive) pills without hormones for Week 4.

Figure A

Step 2.

Find:

• where on your pack to start taking pills
• in what order to take your pills (follow the arrows)
• the week numbers

Step 3.

Remove the white to off-white pill by pressing the pill through the foil in the bottom of the pill pack. See Figure B. Continue taking the white to off-white pills for 21 days.

Figure B

Step 4.

On the first day of Week 4 start taking the brown pills. Take the brown pill for 7 days. Your period should start during this time.

Step 5.

When you have taken all of the brown pills in your pill pack, get a new pill pack and start taking the white to off-white pills.

• For a Day 1 start:

Begin your next pill pack on the same day of the week as your first cycle pill pack.

• For a Sunday Start:

Begin your next pill pack on Sunday.

What should I do if I miss any Nexesta Fe pills?

If you miss 1 pill in Weeks 1, 2, or 3, 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 pills in Week 1 or Week 2 of your pack, follow these steps:

• Take the 2 missed pills as soon as possible and the next 2 pills the next day.
• Then continue to take 1 pill every day until you finish the pack.
• Use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after missing your pills.

If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:

• If you are a Day 1 Starter:
• Throw out the rest of the pill pack and start a new pack that same day.
• If you are a Sunday Starter:
• Keep taking 1 pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of pills that same day.
• You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
• You could become pregnant if you have sex during the first 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as a condom and spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

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

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810

Manufactured by:
Aurobindo Pharma Limited
Unit-VII (SEZ)
Mahaboob Nagar (Dt)-509302
India

Revised: 08/2017

NDC 65862-926-87

NexestaTM Fe
(Norethindrone and Ethinyl Estradiol Tablets USP
 (Chewable) 0.4 mg/0.035 mg
and Ferrous Fumarate Tablets (Chewable))

Each of the 21 WHITE TO OFF-WHITE tablets contains
norethindrone USP 0.4 mg and ethinyl estradiol USP
0.035 mg. Each of the 7 BROWN tablets contains ferrous
fumarate USP 75 mg.

Ferrous Fumarate tablets are not USP for dissolution and
assay.

This product (like all oral contraceptives) is intended
to prevent pregnancy. It does not protect against HIV
infection (AIDS) and other sexually transmitted diseases.

Rx only           Contains 1 Blister of 28 Tablets Each

AUROBINDO

NDC 65862-926-58

NexestaTM Fe

(Norethindrone and Ethinyl Estradiol Tablets USP (Chewable)
0.4 mg/0.035 mg
 and Ferrous Fumarate Tablets (Chewable))

Each of the 21 WHITE TO OFF-WHITE tablets contains norethindrone USP
0.4 mg and ethinyl estradiol USP 0.035 mg. Each of the 7 BROWN tablets
contains ferrous fumarate USP 75 mg.

Ferrous Fumarate tablets are not USP for dissolution and assay

This product (like all oral contraceptives) is intended to prevent pregnancy. It does not
 protect against HIV infection (AIDS) and other sexually transmitted diseases.

Rx only           Conatins 5 Pouches of 28 Tablets Each