Zovia 1/35 Ethynodiol Diacetate and Ethinyl Estradiol Tablets Kit — NDC 51862-894-06 (Billing 51862-0894-06)

WARNING SIGNALS If any of these adverse effects occur while you are taking oral contraceptives, call your doctor immediately: ● Sharp chest pain, coughing up blood, or sudden shortness of breath (indicating a possible blood clot in the lung). ● Pain in the calf (indicating a possible blood clot in the leg). ● Crushing chest pain or heaviness in the chest (indicating a possible heart attack). ● Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, or numbness in an arm or leg (indicating a possible stroke). ● Sudden partial or complete loss of vision (indicating a possible blood clot in the blood vessels of the eye). ● Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast).

Ask your doctor or health care provider to show you how to examine your own breasts. ● Severe pain or tenderness or a mass in the stomach area (indicating a possible ruptured liver tumor). ● Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression). ● Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems). ● Unusual swelling. ● Other unusual conditions.

SIDE EFFECTS OF ORAL CONTRACEPTIVES 1. Vaginal bleeding. Spotting.

This is a slight staining between your menstrual periods that may not even require a pad. Some women spot even though they take their pills exactly as directed. Many women spot although they have never taken the pills.

Spotting does not mean that your ovaries are releasing an egg. Spotting may be the result of irregular pill-taking. Getting back on schedule will usually stop it.

If you should spot while taking the pills, you should not be alarmed, because spotting usually stops by itself within a few days. It seldom occurs after the first pill cycle. Consult your doctor if spotting persists for more than a few days or if it occurs after the second cycle.

Unexpected (breakthrough) bleeding. Unexpected (breakthrough) bleeding does not mean that your ovaries have released an egg. It seldom occurs, but when it does happen it is most common in the first pill cycle.

It is a flow much like a regular period, requiring the use of a pad or tampon. If you experience breakthrough bleeding use a pad or tampon and continue with your schedule. Usually your periods will become regular within a few cycles.

Breakthrough bleeding will seldom bother you again. Consult your doctor or health care provider if breakthrough bleeding is heavy, does not stop within a week, or if it occurs after the second cycle. 2.

Contact lenses. If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your doctor or health care provider. 3.

Fluid retention or raised blood pressure. Oral contraceptives may cause edema (fluid retention), with swelling of the fingers or ankles. If you experience fluid retention, contact your doctor or health care provider.

Some women develop high blood pressure while on the pill, which ordinarily, but not always, returns to the original levels when the pill is stopped. High blood pressure predisposes one to strokes, heart attacks, kidney disease, and other diseases of the blood vessels. 4.

Melasma. A spotty darkening of the skin is possible, particularly of the face. This may persist after the pill is discontinued.

5. Other side effects. Other side effects may include nausea and vomiting, change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, and vaginal infections.

If any of these, or other, side effects occur, call your doctor or health care provider.

WARNINGS The use of oral contraceptives is associated with increased risk of several serious conditions including venous and arterial thromboembolism, thrombotic and hemorrhagic stroke, myocardial infarction, liver tumors or other liver lesions, and gallbladder disease. The risk of morbidity and mortality increases significantly in the presence of other risk factors such as hypertension, hyperlipidemia, obesity, and diabetes mellitus. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these and other risks.

The information contained herein is principally based on studies carried out in patients who used oral contraceptives with formulations containing higher amounts of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lesser amounts of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective casecontrol studies and prospective cohort studies.

Case-control studies provide an estimate of the relative risk of a disease, which is defined as the ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk (or odds ratio) does not provide information about the actual clinical occurrence of a disease. Cohort studies provide a measure of both the relative risk and the attributable risk.

The latter is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence or incidence of a disease in the subject population. For further information, the reader is referred to a text on epidemiological methods.

1. Thromboembolic disorders and other vascular problems. a. Myocardial infarction.

An increased risk of myocardial infarction has been associated with oral contraceptive use. 2-21 This increased risk is primarily in smokers or in women with other underlying risk factors for coronary artery disease such as hypertension, obesity, diabetes, and hypercholesterolemia. The relative risk for myocardial infarction in current oral contraceptive users has been estimated to be 2 to 6.

The risk is very low under the age of 30. However, there is the possibility of a risk of cardiovascular disease even in very young women who take oral contraceptives. Smoking in combination with oral contraceptive use has been reported to contribute substantially to the risk of myocardial infarction in women in their mid-thirties or older, with smoking accounting for the majority of excess cases.

22 Mortality rates associated with circulatory disease have been shown to increase substantially in smokers, especially in those 35 years of age and older among women who use oral contraceptives (see Figure 1, Table 2). Figure 1 . Circulatory disease mortality rates per 100,000 woman-years by age, smoking status, and oral contraceptive use.

14 Adapted from Layde and Beral. 14 Oral contraceptives may compound the effects of well-known cardiovascular risk factors such as hypertension, diabetes, hyperlipidemias, hypercholesterolemia, age, cigarette smoking, and obesity. In particular, some progestogens decrease HDL cholesterol 23-31 and cause glucose intolerance, while estrogens may create a state of hyperinsulinism.

32 Oral contraceptives have been shown to increase blood pressure among some users (see WARNING No. 10 ). Similar effects on risk factors have been associated with an increased risk of heart disease. b.

Thromboembolism. An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established.17, 33-51 Case-control studies have estimated the relative risk to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS ): ● Thrombophlebitis and thrombosis ● Arterial thromboembolism ● Pulmonary embolism ● Myocardial infarction and coronary thrombosis ● Cerebral hemorrhage ● Cerebral thrombosis ● Hypertension ● Gallbladder disease ● Benign and malignant liver tumors, and other hepatic lesions There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed: ● Mesenteric thrombosis ● Neuro-ocular lesions (e.g., retinal thrombosis and optic neuritis) The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: ● Nausea ● Vomiting ● Gastrointestinal symptoms (such as abdominal cramps and bloating) ● Breakthrough bleeding ● Spotting ● Change in menstrual flow ● Amenorrhea during or after use ● Temporary infertility after discontinuation of use ● Edema ● Chloasma or melasma, which may persist ● Breast changes: tenderness, enlargement, secretion ● Change in weight (increase or decrease) ● Change in cervical erosion or secretion ● Diminution in lactation when given immediately postpartum ● Cholestatic jaundice ● Migraine ● Rash (allergic) ● Mental depression ● Reduced tolerance to carbohydrates ● Vaginal candidiasis ● Change in corneal curvature (steepening) ● Intolerance to contact lenses The following adverse reactions or conditions have been reported in users of oral contraceptives and the association has been neither confirmed nor refuted: ● Premenstrual syndrome ● Cataracts ● Changes in appetite ● Cystitis-like syndrome ● Headache ● Nervousness ● Dizziness ● Hirsutism ● Loss of scalp hair ● Erythema multiforme ● Erythema nodosum ● Hemorrhagic eruption ● Vaginitis ● Porphyria ● Impaired renal function ● Hemolytic uremic syndrome ● Acne ● Changes in libido ● Colitis ● Budd-Chiari syndrome ● Endocervical hyperplasia or ectropion

PRECAUTIONS 1. Physical examination and follow-up. It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives.

The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen, and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy.

Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. 2. Lipid disorders.

Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. 3.

Liver function. If jaundice develops in any woman receiving oral contraceptives, they should be discontinued. Steroids may be poorly metabolized in patients with impaired liver function and should be administered with caution in such patients.

Cholestatic jaundice has been reported after combined treatment with oral contraceptives and troleandomycin. Hepatotoxicity following a combination of oral contraceptives and cyclosporine has also been reported. 4.

Fluid retention. Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions that might be aggravated by fluid retention, such as convulsive disorders, migraine syndrome, asthma, or cardiac, hepatic, or renal dysfunction.

5. Emotional disorders. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree.

6. Contact lenses. Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

7. Drug interactions. Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin.

A similar association, though less marked, has been suggested for barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines. Administration of troglitazone concomitantly with a combination oral contraceptive (estrogen and progestin) reduced the plasma concentrations of both hormones by approximately 30%. This could result in loss of contraceptive efficacy.

Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Zovia 1/35 with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations (see Warnings , RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT ). 8. Laboratory test interactions.

Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: a. Increased prothrombin and factors VII, VIII, IX and X; decreased antithrombin III; increased platelet aggregability. b. Increased thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay.

Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered. c. Other binding proteins may be elevated in the serum. d. Sex-steroid binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged. e.

Triglycerides and phospholipids may be increased. f. Glucose tolerance may be decreased. g. Serum folate levels may be depressed.

This may be of clinical significance if a woman becomes pregnant s… [Excerpted — this section continues on DailyMed.]