Vienva

Vienva™ (levonorgestrel and ethinyl estradiol tablets USP, 0.1 mg/0.02 mg) are available as follows:

Each blister card contains 21 active tablets and 7 inactive tablets. The 21 active tablets are white, round, debossed with SZ on one side and L2 on the other side. The 7 inert tablets are peach, round, debossed with SZ on one side and J1 on the other side.

NDC 0781-5575-15, one carton containing 3 individual blister cartons

Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature].

Manufactured by Laboratorios Leon Farma S.A., Spain, For Sandoz Inc. Princeton, NJ 08540. Revised: May 2017

An increased risk of the following serious adverse reactions (see WARNINGS section for additional information) has been associated with the use of oral contraceptives:

Thromboembolic and thrombotic disorders and other vascular problems (including thrombophlebitis and venous thrombosis with or without pulmonary embolism, mesenteric thrombosis, arterial thromboembolism, myocardial infarction, cerebral hemorrhage, cerebral thrombosis), carcinoma of the reproductive organs and breasts, hepatic neoplasia (including hepatic adenomas or benign liver tumors), ocular lesions (including retinal vascular thrombosis), gallbladder disease, carbohydrate and lipid effects, elevated blood pressure, and headache including migraine.

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related (alphabetically listed):

• Acne
• Amenorrhea
• Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms
• Breast changes: tenderness, pain, enlargement, secretion
• Budd-Chiari syndrome
• Cervical erosion and secretion, change in
• Cholestatic jaundice
• Chorea, exacerbation of
• Colitis
• Contact lenses, intolerance to
• Corneal curvature (steepening), change in
• Dizziness
• Edema/fluid retention
• Erythema multiforme
• Erythema nodosum
• Gastrointestinal symptoms (such as abdominal pain, cramps, and bloating)
• Hirsutism
• Infertility after discontinuation of treatment, temporary
• Lactation, diminution in, when given immediately postpartum
• Libido, change in
• Melasma/chloasma which may persist
• Menstrual flow, change in
• Mood changes, including depression
• Nausea
• Nervousness
• Pancreatitis
• Porphyria, exacerbation of
• Rash (allergic)
• Scalp hair, loss of
• Serum folate levels, decrease in
• Spotting
• Systemic lupus erythematosus, exacerbation of
• Unscheduled bleeding
• Vaginitis, including candidiasis
• Varicose veins, aggravation of
• Vomiting
• Weight or appetite (increase or decrease), change in

The following adverse reactions have been reported in users of oral contraceptives:

• Cataracts
• Cystitis-like syndrome
• Dysmenorrhea
• Hemolytic uremic syndrome
• Hemorrhagic eruption
• Optic neuritis, which may lead to partial or complete loss of vision
• Premenstrual syndrome
• Renal function, impaired

Symptoms of oral contraceptive overdosage in adults and children may include nausea, vomiting, and drowsiness/fatigue; withdrawal bleeding may occur in females. There is no specific antidote and further treatment of overdose, if necessary, is directed to the symptoms.

Noncontraceptive Health Benefits

The following noncontraceptive health benefits related to the use of oral contraceptives are supported by epidemiological studies which largely utilized oral-contraceptive formulations containing doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol.

Effects On Menses

• Increased menstrual cycle regularity
• Decreased blood loss and decreased incidence of iron-deficiency anemia
• Decreased incidence of dysmenorrhea

Effects Related To Inhibition Of Ovulation

• Decreased incidence of functional ovarian cysts
• Decreased incidence of ectopic pregnancies

Effects From Long-Term Use

• Decreased incidence of fibroadenomas and fibrocystic disease of the breast
• Decreased incidence of acute pelvic inflammatory disease
• Decreased incidence of endometrial cancer
• Decreased incidence of ovarian cancer

Taking this medicine can increase your risk of blood clots, stroke, or heart attack. You are even more at risk if you have high blood pressure, diabetes, high cholesterol, or if you are overweight. Your risk of stroke or blood clot is highest during your first year of taking birth control pills. Your risk is also high when you restart this medicine after not taking it for 4 weeks or longer.

Smoking can greatly increase your risk of blood clots, stroke, or heart attack. Your risk increases the older you are and the more you smoke. You should not take this medicine if you smoke and are over 35 years old.

Do not use if you are pregnant. Stop using this medicine and tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills.

You should not take birth control pills if you have:

• untreated or uncontrolled high blood pressure;

• heart disease (chest pain, coronary artery disease, history of heart attack, stroke, or blood clot);

• an increased risk of having blood clots due to a heart problem or a hereditary blood disorder;

• circulation problems (especially if caused by diabetes);

• a history of hormone-related cancer, or cancer of the breast, uterus/cervix, or vagina;

• unusual vaginal bleeding that has not been checked by a doctor;

• liver disease or liver cancer;

• severe migraine headaches (with aura, numbness, weakness, or vision changes), especially if you are older than 35;

• a history of jaundice caused by pregnancy or birth control pills; or

• if you smoke and are over 35 years old; or

• if you take any hepatitis C medication containing ombitasvir/paritaprevir/ritonavir (Technivie).

To make sure birth control pills are safe for you, tell your doctor if you have ever had:

• heart disease, high blood pressure, or if you are prone having blood clots;

• high cholesterol or triglycerides, or if you are overweight;

• depression;

• a seizure or migraine headache;

• diabetes, gallbladder disease;

• liver or kidney disease;

• irregular menstrual cycles; or

• fibrocystic breast disease, lumps, nodules, or an abnormal mammogram.

The hormones in birth control pills can pass into breast milk and may harm a nursing baby. This medicine may also slow breast milk production. Do not use if you are breast feeding a baby.

Do not smoke while taking birth control pills, especially if you are older than 35 years of age.

Birth control pills will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Other drugs may interact with birth control pills, including prescription and over-the-counter medicines, vitamins, and herbal products. Some drugs can make birth control pills less effective, which may result in pregnancy. Tell your doctor about all your current medicines and any medicine you start or stop using.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling more or less hungry.
• Dizziness.
• Weight gain.
• Headache.
• Upset stomach or throwing up.
• Cramps.
• Bloating.
• Enlarged breasts.
• Breast soreness.
• Hair loss.
• Pimples (acne).
• Period (menstrual) changes. These include spotting or bleeding between cycles.
• Lowered interest in sex.
• This medicine may cause dark patches of skin on your face. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Combination oral contraceptives should not be used in women with any of the following conditions:

• Thrombophlebitis or thromboembolic disorders • A history of deep-vein thrombophlebitis or thromboembolic disorders • Cerebrovascular or coronary artery disease (current or past history) • Valvular heart disease with thrombogenic complications • Thrombogenic rhythm disorders • Hereditary or acquired thrombophilias • Major surgery with prolonged immobilization • Diabetes with vascular involvement • Headaches with focal neurological symptoms • Uncontrolled hypertension • Known or suspected carcinoma of the breast or personal history of breast cancer • Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia • Undiagnosed abnormal genital bleeding • Cholestatic jaundice of pregnancy or jaundice with prior pill use • Hepatic adenomas or carcinomas, or active liver disease • Known or suspected pregnancy • Hypersensitivity to any of the components of levonorgestrel and ethinyl estradiol • Are receiving Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations (see Warnings, RISK OF LIVER ENZYME ELEVATIONS WITH CONCOMITANT HEPATITIS C TREATMENT).

Applies to ethinyl estradiol / levonorgestrel: oral tablet

Cardiovascular

Cardiovascular side effects of hypertension and edema have been attributed to the estrogen component of this combination product. Significant blood pressure increases generally occurred only in women receiving high-dose estrogen products (50 mcg or more of ethinyl estradiol or equivalent daily). Exogenous estrogens may exert cardioprotective effects due to favorable changes in lipid profiles, however, beneficial effects may be partially or completely offset by alterations in lipid profiles induced by exogenous progestins.[Ref]

Detailed information concerning the effects of oral contraceptive therapy on lipid metabolism is available in the Endocrine paragraph of this side effect monograph.

Early investigations of high dose estrogen combinations (50 mcg or more of ethinyl estradiol or equivalent daily) suggested that women may be at increased risk of cardiovascular complications (myocardial infarction, stroke, and vascular thrombosis, including venous thromboembolism). More recent investigations of low dose estrogen combinations have suggested that oral contraceptive use is not associated with an increased risk of serious cardiovascular complications in healthy non smoking women up to the age of 45. Oral contraceptive use for women aged 35 to 44 who smoke or who have preexisting systemic diseases that may affect the cardiovascular system is not recommended.

Some investigators have suggested that even low dose products may result in adverse lipid metabolism and a woman's cardiovascular risk factors should be assessed before a decision is made to use oral contraceptive combinations.

The frequency of both subarachnoid hemorrhage and thrombotic stroke has been increased in women taking oral contraceptive hormones, however, the risk of these effects with low dose formulations appear to be very small for young women without underlying cardiovascular disease or other risk factors.[Ref]

General

Women taking oral contraceptive combinations have experienced several noncontraceptive health benefits. These benefits have included protection against two malignant neoplasms (endometrial carcinoma and ovarian cancer). In addition, use of oral contraceptive combinations has decreased the frequency of benign breast tumors, the risk of ovarian cysts, the risk of ectopic pregnancy, menstrual irregularity, the incidences of iron deficiency anemia, dysmenorrhea, and pelvic inflammatory disease.

Many of the adverse effects experienced by women on oral contraceptive combination products are related to a relative excess or deficiency of the estrogen and progestin components of these formulations. The following categorizes many of the frequent adverse effects by relative excess or deficiency of these components.

Progestin Excess:

Acne, oily skin
Breast tenderness
Depression
Tiredness, fatigue
Hair loss
Hypertension
Increased appetite
Weight gain
Cholestatic jaundice

Progestin Deficiency:

Late breakthrough bleeding
Amenorrhea
Hypermenorrhea

Estrogen Excess:

Nausea
Headache
Melasma
Hypertension
Breast tenderness
Edema

Estrogen Deficiency:

Early/midcycle breakthrough bleeding
Increased spotting
Hypomenorrhea[Ref]

A number of studies have suggested that use of oral contraceptives decreased the risk of ovarian cancer. Specifically, the risk of epithelial ovarian cancers is decreased by 40%. The protection against ovarian cancer may last for 10 to 15 years after discontinuation of oral contraceptives. After long term use (12 years), the risk of ovarian cancer is decreased by as much as 80%.

The risk of endometrial cancer is decreased by approximately 50%. Protection may last for 15 years after discontinuation and may be greatest for nulliparous women who may be at higher risk for endometrial carcinoma than other women.

The incidence of hospitalization for pelvic inflammatory disease has been approximately 50% lower in women taking oral contraceptives. The reason for the decrease in the frequency (or severity) of pelvic inflammatory disease in women taking oral contraceptives has not been fully elucidated.

Some recent studies have suggested that the decrease in frequency of functional ovarian cysts reported with some older formulations may not occur in women taking newer low dose formulations.

One recent study (The Nurses' Health Study) has suggested that long term use of oral contraceptives is safe and does not adversely affect long term risk for mortality.[Ref]

Gastrointestinal

Nausea, a relatively common gastrointestinal side effect, has occurred in approximately 10% of treated women during the first cycles of therapy. Some early reports suggested an association between oral contraceptive use and gallbladder disease.[Ref]

Cases of oral contraceptive induced esophageal ulceration and geographic tongue have been reported rarely.

More recent studies have suggested that the risk of gallbladder disease is minimal.[Ref]

Oncologic

Oral contraceptive combinations have been studied extensively for oncologic side effects. A number of studies have examined a possible relationship between the use of oral contraceptives and the development of breast cancer. Many of the studies have reported conflicting results. A committee of the World Health Organization evaluated these studies and the risks of breast cancer and concluded that: "Numerous studies have found no overall association between oral contraceptive use and risk of breast cancer." In addition, the same committee also examined a possible relationship between oral contraceptive use and neoplasms of the uterine cervix and concluded that: "There are insufficient data to draw any firm conclusions regarding the effects of combined oral contraceptives on the risk of cervical adenocarcinoma."[Ref]

The World Health Organization committee also noted that some studies "have found a weak association between long-term use of oral contraceptives and breast cancer diagnosed before the age of 36, and perhaps up to the age 45....It is unclear whether this observed association is attributable to bias, the development of new cases of cancer, or accelerated growth of existing cancers."

The World Health Organization committee further concluded that there is no increased risk of breast cancer in women over the age of 45 who have previously taken oral contraceptives. In addition, studies suggest that use of oral contraceptives does not place specific groups of women (like those with a family history of breast cancer) at higher or lower risk, and variations in the hormonal content of oral contraceptives do not influence the risk of breast cancer.

In general, studies evaluating the potential risk of cervical cancer in patients taking oral contraceptives have been complicated by the large number of confounding factors which make investigations into the epidemiology of this neoplasm difficult. Some studies have suggested that women taking oral contraceptives are at increased risk of dysplasia, epidermoid carcinoma, and adenocarcinoma of the cervix. However, other studies have not found such an association.[Ref]

Endocrine

Endocrine effects have included complex alterations in plasma lipid profiles.[Ref]

All progestins which occur in commercially available oral contraceptive combinations have adverse effects on lipid profiles. These progestins exert antiestrogen and androgen effects and decrease HDL (and HDL2) cholesterol levels and increase LDL cholesterol levels. The estrogen component of oral contraceptive combinations exert opposing effects. Consequently, alterations in lipid profiles are related to the relative amount and potency of the specific estrogen and progestin in a given product. (Levonorgestrel exerts potent progestin, antiestrogen, and androgen effects.)[Ref]

Hepatic

The rate of death due to hepatocellular carcinoma in the United States has not changed during the last 25 years (a time during which use of oral contraceptive hormones has increased dramatically).

A committee of the World Health Organization has reported that in developing countries where hepatitis B virus infection and hepatocellular carcinoma are common, "short term use of oral contraceptives does not appear to be associated with an increased risk. Data on the effects of long term use are scarce."

A recent Italian case control study of women with hepatocellular carcinoma has suggested that the relative risk of hepatocellular carcinoma is 2.2 for oral contraceptive users compared to women who never used oral contraceptives.

A similar American case control study from 1989 also reported a strong association between oral contraceptive use and hepatocellular carcinoma but concluded that: "If this observed association is causal, the actual number of cases of liver cancer in the United States attributable to oral contraceptive use is small. Therefore, these findings do not have public health importance in the United States and other Western nations."[Ref]

Hepatic side effects have included focal nodular hyperplasia, intrahepatic cholestasis, liver cell adenomas, hepatic granulomas, hepatic hemangiomas and well differentiated hepatocellular carcinomas, which have been reported rarely in association with estrogen therapy and therapy with oral contraceptive combinations.[Ref]

Hematologic

Cases of venous thrombosis, pulmonary embolism (sometimes fatal), and arterial thrombosis have been reported rarely.

Previous thrombotic disease is considered a contraindication to use of oral contraceptive combinations.[Ref]

A hematologic concern has been the risk of thromboembolism associated with exogenous estrogens. Because the dose of exogenous estrogens is low in most commercially available preparations, the risk of thromboembolism is minimal for most women. Risk is greater in women who are over age 35, smoke, and/or with a history of previous thrombotic diseases. The incidence of venous thrombosis in women with inherited clotting defects has been greater and developed sooner (within the first six months to one year of therapy).[Ref]

Genitourinary

A common genitourinary side effect has been breakthrough bleeding and spotting, especially during the first several cycles of oral contraceptive use. Nonhormonal causes of such bleeding should be excluded. In addition, oral contraceptive use may cause conception delay.[Ref]

Some women have experienced oligomenorrhea and amenorrhea following termination or oral contraceptive use.[Ref]

Psychiatric

Psychiatric side effects have included depression and precipitation of panic disorder.[Ref]

Immunologic

Immunologic side effects have included rare cases of oral contraceptive induced systemic lupus erythematosus.[Ref]

Nervous system

Nervous system side effects have been rare. A case of chorea has been reported in association with oral contraceptives.[Ref]

Ocular

Ocular side effects have included rare cases of retinal thrombosis. In addition, the manufacturers of oral contraceptive products report that some patients have developed changes in contact lens tolerance.[Ref]

Respiratory

A case of fatal pulmonary venooclusive disease has been reported.[Ref]

Metabolic

Despite the potentially adverse effects of oral contraceptives on lipid levels and glucose tolerance, some investigators have suggested that young diabetic women without existing vascular disease or severe lipidemias may be candidates for low dose oral contraceptive combinations with appropriate clinical monitoring of patient response and tolerance.[Ref]

Metabolic side effects have resulted in altered carbohydrate metabolism. The suggested effect that oral contraceptive combinations may have on glucose tolerance has been varied. Decreased glucose tolerance has been observed, however, studies with low dose preparations have suggested that decreased glucose tolerance due to oral contraceptive combinations generally has been minimal.[Ref]

Some side effects of Vienva may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.