Wymzya Fe

• CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use.
• This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.
• For this reason, COCs are contraindicated in women who are over 35 years of age and smoke [see CONTRAINDICATIONS ( 4 )] .
• WARNING:
• CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See Full Prescribing Information for complete boxed warning.
• WYMZYA Fe is contraindicated in women over 35 years old who smoke.
• ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use.
• ( 4 )

• 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 )] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Pregnancy ( 4 ) Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )

• Thrombotic Disorders and Other Vascular Problems:
• Stop WYMZYA Fe 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 WYMZYA Fe if jaundice occurs ( 5.2 ) High blood pressure :
• If used in women with well-controlled hypertension, monitor blood pressure and stop WYMZYA Fe if blood pressure rises significantly.
• ( 5.4 ) Carbohydrate and lipid metabolic effects :
• Monitor prediabetic and diabetic women taking WYMZYA Fe.
• Consider an alternative contraceptive method for women with uncontrolled dyslipidemia ( 5.6 ) Headache :
• Evaluate significant change in headaches and discontinue WYMZYA Fe if indicated (5.7 ) Bleeding Irregularities and Amenorrhea :
• Evaluate irregular bleeding or amenorrhea ( 5.8 )
• 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.
• 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 )] .
• 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.
• 5.9 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 WYMZYA 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 )] .
• 5.10 Depression Carefully observe women with a history of depression and discontinue WYMZYA Fe if depression recurs to a serious degree.
• 5.11 Malignant Neoplasms Breast Cancer WYMZYA Fe is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see CONTRAINDICATIONS ( 4 )] .
• Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk.
• Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer.
• However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use [see POSTMARKETING EXPERIENCE ( 6.2 )] .
• Cervical Cancer 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.
• 5.12 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.
• 5.13 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.
• 5.14 Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.
• 5.15 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 WYMZYA Fe.

• There is little or no increased risk of birth defects in women who inadvertently use COCs during early 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 low dose COCs prior to conception or during early pregnancy.
• Do not use COCs to induce withdrawal bleeding as a test for pregnancy.
• Do not use COCs during pregnancy to treat threatened or habitual abortion.
• Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child.
• COCs can reduce milk production in breastfeeding mothers.
• This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women.
• Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
• IN SPECIFIC POPULATIONS Nursing mothers: Advise use of another contraceptive method.
• WYMZYA Fe can decrease milk production.
• ( 8.3 )
• 8.1 Pregnancy There is little or no increased risk of birth defects in women who inadvertently use COCs during early 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 low dose COCs prior to conception or during early pregnancy.
• Do not use COCs to induce withdrawal bleeding as a test for pregnancy.
• Do not use COCs during pregnancy to treat threatened or habitual abortion.
• 8.3 Nursing Mothers Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child.
• COCs can reduce milk production in breastfeeding mothers.
• This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women.
• Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.
• 8.4 Pediatric Use Safety and efficacy of WYMZYA Fe have been established in women of reproductive age.
• Efficacy is expected to be the same in post-pubertal adolescents under the age of 18 years as for users 18 years and older.
• Use of this product before menarche is not indicated.
• 8.5 Geriatric Use WYMZYA Fe has not been studied in postmenopausal women and is not indicated in this population.
• 8.6 Hepatic Impairment The pharmacokinetics of WYMZYA Fe has not been studied in women with hepatic impairment.
• However, steroid hormones may be poorly metabolized in patients with hepatic impairment.
• 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 [see CONTRAINDICATIONS ( 4 ) and WARNINGS AND PRECAUTIONS ( 5.2 )].
• 8.7 Renal Impairment The pharmacokinetics of WYMZYA Fe has not been studied in women with renal impairment.

• Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
• Drugs or herbal products that induce certain enzymes, including 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 )
• 7.1 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]).
• 7.2 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 )] .
• 7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer WYMZYA 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 ) ].
• 7.4 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.

There have been no reports of serious ill effects from overdosage of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.