Blisovi 24 Fe

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.

Some drugs can make birth control pills less effective, which may result in pregnancy. Other drugs may be affected by birth control pills. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with ethinyl estradiol and norethindrone. Give a list of all your medicines to any healthcare provider who treats you.

• It is used to prevent pregnancy.
• It is used to treat pimples (acne).
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists. This medicine may need to be stopped before certain types of surgery as your doctor has told you. If Blisovi 24 Fe is stopped, your doctor will tell you when to start taking this medicine again after your surgery or procedure.
• This medicine may raise the chance of blood clots, a stroke, or a heart attack. Talk with the doctor.
• Talk with your doctor if you will need to be still for long periods of time like long trips, bedrest after surgery, or illness. Not moving for long periods may raise your chance of blood clots.
• Some studies have shown the risk of breast cancer is raised in women taking birth control pills, especially at a younger age. This includes birth control pills that have drugs like this one in them. The risk was also linked to how long the birth control pills were taken. One study showed the risk of breast cancer was also raised in women who took birth control pills within the past 10 years. Talk with the doctor.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Be sure to have regular breast exams and gynecology check-ups. Your doctor will tell you how often to have these. You will also need to do breast self-exams as your doctor has told you. Talk with your doctor.
• If you are allergic to tartrazine, talk with your doctor. Some products have tartrazine.
• If you drink grapefruit juice or eat grapefruit often, talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Blisovi 24 Fe.
• Certain drugs, herbal products, or health problems could cause this medicine to not work as well. Be sure your doctor knows about all of your drugs and health problems.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• This medicine may raise the chance of blood clots. The chance is highest during the first year of using Blisovi 24 Fe. The chance is also highest when starting to use hormone-based birth control again after not using it for 4 weeks or more. Talk with the doctor.
• If you are taking this medicine for pimples (acne), you need to be at least 15 years of age.
• If you have any signs of pregnancy or if you have a positive pregnancy test, call your doctor right away.

Use Blisovi 24 Fe (ethinyl estradiol, norethindrone, and ferrous fumarate) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Follow how to use as you have been told by the doctor or read the package insert.
• Take this medicine at the same time of day.
• Take with or without food. Take with food if it causes an upset stomach.
• Do not skip doses, even if you do not have sex very often.
• If you throw up or have diarrhea, Blisovi 24 Fe may not work as well to prevent pregnancy. Use an extra form of birth control, like condoms, until you check with your doctor.
• If you miss 2 periods in a row, take a pregnancy test before starting a new cycle.

What do I do if I miss a dose?

• If a dose is missed, check the package insert or call the doctor to find out what to do. If using this medicine to prevent pregnancy, another form of birth control may need to be used for some time to prevent pregnancy.

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.
• Stomach cramps.
• Bloating.
• Enlarged breasts.
• Breast soreness.
• Hair loss.
• 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.
• Period (menstrual) changes. These include lots of bleeding, spotting, or bleeding between cycles.

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 your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Blisovi 24 Fe, please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Blisovi 24 Fe. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Blisovi 24 Fe.

Review Date: October 4, 2017

Blisovi™ 24 Fe is indicated for use by women to prevent pregnancy [see CLINICAL STUDIES (14)].

The efficacy of Blisovi 24 Fe in women with a body mass index (BMI) of > 35 kg/m2 has not been evaluated.

Thrombotic Disorders and Other Vascular Problems

• Stop Blisovi 24 Fe if an arterial thrombotic event or venous thromboembolic (VTE) event occurs.
• Stop Blisovi 24 Fe 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 Blisovi 24 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 Blisovi 24 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 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.

Liver Disease

Impaired Liver Function

Do not use Blisovi 24 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 Blisovi 24 Fe if jaundice develops.

Liver Tumors

Blisovi 24 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 per 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.

High Blood Pressure

Blisovi 24 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 Blisovi 24 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 are taking Blisovi 24 Fe. COCs may decrease glucose tolerance.

Consider alternative contraception for women with uncontrolled dyslipidemias. 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 Blisovi 24 Fe develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Blisovi 24 Fe if indicated.

Consider discontinuation of Blisovi 24 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.

In a clinical trial of Blisovi 24 Fe, the frequency and duration of unscheduled bleeding and/or spotting was assessed in 743 women (3,823 28-day cycles). A total of 10 subjects (1.3%) discontinued Blisovi 24 Fe, at least in part, due to bleeding or spotting. Based on data from the clinical trial, [24 to 38%] of women using Blisovi 24 Fe experienced unscheduled bleeding per cycle in the six months of the trial. The percent of women who experienced unscheduled bleeding tended to decrease over time.

Amenorrhea and Oligomenorrhea

Women who use Blisovi 24 Fe may experience absence of withdrawal bleeding, even if they are not pregnant. In the clinical trial with Blisovi 24 Fe, 31 to 41% of the women using Blisovi 24 Fe did not have a withdrawal menses in at least one of 6 cycles of use.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 Blisovi 24 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 Blisovi 24 Fe if depression recurs to a serious degree.

Carcinoma of the Breast and Cervix

Blisovi 24 Fe is contraindicated in women who currently have or have had breast cancer because breast cancer is a 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 COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these 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, sex 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 Blisovi 24 Fe.

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

Clinical 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 Blisovi 24 Fe was evaluated in 743 subjects who participated in an open-label, randomized, active-controlled, multicenter clinical trial of Blisovi 24 Fe 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 ≤ 35 kg/m2. Subjects were followed for up to six 28-day cycles providing a total of 3,823 treatment-cycles of exposure.

Common Adverse Reactions (≥ 2% of all subjects)

The most common adverse reactions reported by at least 2% of the 743 women using Blisovi 24 Fe 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 Blisovi 24 Fe, 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%).

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Blisovi 24 Fe. Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure.

Cardiovascular

Chest pain, palpitations, tachycardia, angina pectoris, myocardial infarction.

Endocrine Disorders

Hypothyroidism, hyperthyroidism.

Eye Disorders

Blurred vision, visual impairment, transient blindness, corneal thinning, change in corneal curvature (steepening).

GI Disorders

Nausea, vomiting, abdominal pain, constipation, pancreatitis.

Hepatobiliary Disorders

Cholelithiasis, cholecystitis, hepatic adenoma, hemangioma of liver.

Immune System Disorders

Anaphylactic reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms.

Infections

Vaginal infection.

Metabolism and Nutrition Disorders

Change in weight or appetite (increase or decrease). hypoglycemia, diabetes mellitus, anemia.

Musculoskeletal and Connective Tissue Disorders

Myalgia.

Skin and Subcutaneous Disorders

Alopecia, rash (generalized and allergic), pruritus, skin discoloration, night sweats, swelling face or lips, hirsutism, skin burning sensation, erythema multiforme, erythema nodosum, hemorrhagic eruption.

Nervous System Disorders

Headache, dizziness, migraine, hyperesthesia, paraesthesia, hypoaesthesia, somnolence, loss of consciousness, sensory disturbance.

Psychiatric Disorders

Mood swings, depression, insomnia, anxiety, suicidal ideation, panic attack, changes in libido, bipolar disorder, dissociation, homicidal ideation.

Renal and Urinary Disorders

Pollakiuria, dysuria, cystitis-like syndrome.

Reproductive System and Breast Disorders

Breast changes (tenderness, pain, enlargement, and secretion), premenstrual syndrome, ovarian cyst, pelvic pain, ovarian cyst ruptured, pelvic fluid collection.

Vascular Disorders

Hot flush, thrombosis/embolism (coronary artery, pulmonary, cerebral, deep vein), migraine, transient ischemic attack, ischemic stroke.