Aurovela 24 Fe Norethindrone Acetate and Ethinyl Estradiol and Ferrous Fumarate Kit, 1 pouch — NDC 65862-934-87 (Billing 65862-0934-87)

5 WARNINGS AND PRECAUTIONS Thrombotic Disorders and Other Vascular Problems: Stop norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if a thrombotic event occurs. Stop at least 4 weeks before 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 norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if jaundice occurs. ( 5.2 ) High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if blood pressure rises significantly. ( 5.4 ) Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets.

Consider an alternative contraceptive method for women with uncontrolled dyslipidemia. ( 5.6 ) Headache: Evaluate significant change in headaches and discontinue norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if indicated. ( 5.7 ) Bleeding Irregularities and Amenorrhea: Evaluate irregular bleeding or amenorrhea.

( 5.8 )

5.1Thrombotic Disorders and Other Vascular Problems Stop norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate 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 norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate 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 the following prolonged immobilization. Start norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate 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 a COCs and when restarting oral contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after COC 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.

5.2Liver Disease Impaired Liver Function Do not use norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets 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 norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets if jaundice develops.

Liver Tumors Norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets are contraindicated in women with benign and malignant liver tumors [see Contraindications (4) ] . Hepatic adenomas are asso… [Excerpted — this section continues on DailyMed.]

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 The most common adverse reactions (greater than or equal to 2%) were: headache, vaginal candidiasis, nausea, menstrual cramps, breast tenderness, mood changes, bacterial vaginitis, acne, and weight gain.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 practice. The safety of norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets were evaluated in 743 subjects who participated in an open-label, randomized, active-controlled, multicenter clinical trial of norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets for contraception.

This trial examined healthy, non-pregnant volunteers aged 18 to 45 years, who were sexually active and had a body mass index of less than or equal to 35 kg/m 2 . Subjects were followed for up to six 28-day cycles providing a total of 3,823 treatment-cycles of exposure. Common Adverse Reactions ( greater than or equal to 2% of all subjects): The most common adverse reactions reported by at least 2% of the 743 women using norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets were the following, in order of decreasing incidence: headache (6.3%), vaginal candidiasis (6.1%), nausea (4.6%), menstrual cramps (4.4%), breast tenderness (3.4%), mood changes (including mood swings (2.2%) and depression (1.1%), bacterial vaginitis (3.1%), acne (2.7%), and weight gain (2.0%).

Adverse Reactions Leading to Study Discontinuation : Among the 743 women using norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets, 46 women (6.2%) withdrew because of an adverse event. Adverse events occurring in 3 or more subjects leading to discontinuation of treatment were, in decreasing order: abnormal bleeding (0.9%), nausea (0.8%), mood changes (0.8%), menstrual cramps (0.4%), increased blood pressure (0.4%), and irregular bleeding (0.4%).

6.2Postmarketing Experience Five studies that compared breast cancer risk between ever-users (current or past use) of COCs and never-users of COCs reported no association between ever use of COCs and breast cancer risk, with effect estimates ranging from 0.90 to 1.12 (Figure 1). Three studies compared breast cancer risk between current or recent COC users (<6 months since last use) and never users of COCs (Figure 1). One of these studies reported no association between breast cancer risk and COC use.

The other two studies found an increased relative risk of 1.19 to 1.33 with current or recent use. Both of these studies found an increased risk of breast cancer with current use of longer duration, with relative risks ranging from 1.03 with less than one year of COC use to approximately 1.4 with more than 8 to 10 years of COC use. Figure 1: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives RR = relative risk; OR = odds ratio; HR = hazard ratio. “ever COC” are females with current or past COC use; “never COC use” are females that never used COCs.

The following adverse reactions have been identified during post approval use of norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets. Because these reactions are reported voluntarily from a po… [Excerpted — this section continues on DailyMed.]

7 DRUG INTERACTIONS Consult the labeling of concurrently used drugs to obtain further information about interactions with oral contraceptives or the potential for enzyme alterations. 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 method or alternative method of contraception when enzyme inducers are used with COCs. (7.1)

7.1Effects 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 oral contraceptives including phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St.

John’s wort. Interactions between COCs 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.

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 to 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 or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]).

7.2Effects 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, and temazepam. 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) ].

7.3Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Co-administration of Aurovela 24 Fe with HCV drug combinations containing ombitasvir/ paritaprevir/ritonavir, with or without dasabuvir is contraindicated due to potential for ALT elevations [see Warnings and Precautions (5.3) ]. Co-administration of Aurovela 24 Fe and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations.

7.4Interactions with Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation f… [Excerpted — this section continues on DailyMed.]