Blisovi 24 Fe
norethindrone acetate and ethinyl estradiol · Kit
Uses
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/m 2 has not been evaluated. Blisovi 24 Fe is a combination of norethindrone acetate, a progestin, and ethinyl estradiol, an estrogen, indicated for use by women to prevent pregnancy. (1) The efficacy of Blisovi 24 Fe in women with a body mass index (BMI) of >35 kg/m 2 has not been evaluated. ( 1 , 8.8 )
Dosage and administration
Take one tablet by mouth at the same time every day for 28 days ( 2.1 ) Take tablets in the order directed on the blister pack ( 2.1 ) Blisovi 24 Fe may be administered without regard to meals ( 12.3 ) 2.1 How to Start Blisovi 24 Fe Blisovi 24 Fe is dispensed in a blister card [see HOW SUPPLIED/STORAGE AND HANDLING ( 16 )] . Blisovi 24 Fe may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception must be used until after the first 7 consecutive days of administration. 2.2 How to Take Blisovi 24 Fe Table 1: Instructions for Administration of Blisovi 24 Fe Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Day 1 Start: ● Take first white active tablet without regard to meals on the first day of menses. Important: Consider the possibility of ovulation and conception prior to initiation of this product. ● Take subsequent active tablets once daily at the same time each day for a total of 24 days. Tablet Color: ● Blisovi 24 Fe active tablets are white (Day 1 to Day 24). ● Take one brown inactive tablet daily for 4 days and at the same time of day that active tablets were taken. ● Blisovi 24 Fe inactive tablets are brown (Day 25 to Day 28). ● Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet). Sunday Start: For each 28-day course, take in the following order: ● Take the white active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non- hormonal contraception (such as condoms and spermicide) for the first 7 days of the patient's first cycle pack of Blisovi 24 Fe. ● Take subsequent active tablets once daily at the same time each day for a total of 24 days. ● Take one brown tablet (ferrous fumarate) daily for the following 4 days and at the same time of day that active tablets were taken. A scheduled period should occur during the 4 days that the brown tablets are taken. ● Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to Blisovi 24 Fe from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. S w itching from another contraceptive method to Blisovi 24 Fe Start Blisovi 24 Fe: ● Transdermal patch ● On the day when next application would have been scheduled. ● Vaginal ring ● On the day when next insertion would have been scheduled ● Injection ● On the day when next injection would have been scheduled ● Intrauterine contraceptive ● On the day of removal ● If the IUD is not removed on first day of the patient's menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. ● Implant ● On the day of removal Starting Blisovi 24 Fe after Abortion or Miscarriage First-trimester: After a first-trimester abortion or miscarriage, Blisovi 24 Fe may be started immediately. An additional method of contraception is not needed if Blisovi 24 Fe is started immediately. If Blisovi 24 Fe is not started within 5 days after termination of the pregnancy, the patient must use additional non-hormonal contraception (such as condoms and spermicide) for the first 7 days of her first 28-day course of Blisovi 24 Fe. Second-trimester: Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Blisovi 24 Fe following the instructions in Table 1 for Sunday start. Use additional non-hormonal contraception (such as condoms and spermicide) for the first 7 days of the patient's first 28-day course of Blisovi 24 Fe [see CONTRAINDICATIONS ( 4 ) and WARNINGS AND PRECAUTIONS ( 5.1 ). Starting Blisovi 24 Fe after Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Blisovi 24 Fe following the instructions in Table 1 for women not currently using hormonal contraception. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Blisovi 24 Fe [see CONTRAINDICATIONS ( 4 ), WARNINGS AND PRECAUTIONS ( 5.1 ), USE IN SPECIFIC POPULATIONS ( 8.1 and 8.2 ]. 2.3 Missed Tablets Table 2: Instructions for Missed Blisovi 24 Fe Tablets ● If one active tablet is missed in Weeks 1, 2 or 3 Take the tablet as soon as possible. Take the next pill at the regular time and continue taking one tablet a day until the pack is finished. Back-up contraception is not needed ● If two consecutive active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) must be used as back-up if the patient has sex within 7 days after missing tablets . ● If two consecutive active tablets are missed in Week 3 or Week 4 or three or more consecutive active tablets are missed at any time Day 1 Start : Throw out the rest of the pack and start a new pack that same day. Sunday Start : Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) must be used as back-up if the patient has sex within 7 days after missing 3 tablets. 2.4 Advice in Case of Gastrointestinal Disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures must be taken.
Dosage forms and strengths
Blisovi 24 Fe (norethindrone acetate and ethinyl estradiol tablets and ferrous fumarate tablets) is available in blister packs. Each blister pack (28 tablets) contains in the following order: 24 white to off-white, round, flat face beveled edged (active) tablets debossed with "LU" on one side and "N21" on the other side and each containing 1 mg norethindrone acetate and 20 mcg ethinyl estradiol. 4 brown mottled, round, flat face beveled edge (non-hormonal placebo) tablets debossed with "LU" on one side and "M22" on the other side and each containing 75 mg ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose. Blisovi 24 Fe consists of 28 tablets in the following order ( 3 ): 24 white tablets (active), each containing 1 mg norethindrone acetate and 20 mcg ethinyl estradiol 4 brown tablets (non-hormonal placebo), each containing 75 mg ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose.
Contraindications
Blisovi 24 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 )] ■ Women over age 35 with any migraine headaches [see WARNINGS AND PRECAUTIONS ( 5.7 )] Liver tumors, benign or malignant, or liver disease [see WARNINGS AND PRECAUTIONS ( 5.2 )] Undiagnosed abnormal uterine bleeding [see WARNINGS AND PRECAUTIONS ( 5.8 )] Current diagnosis of, or history of, breast cancer, which may be hormone sensitive [see WARNINGS AND PRECAUTIONS (5.11)] Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS AND PRECAUTIONS ( 5.3 )] A high risk of arterial or venous thrombotic diseases ( 4 ) Liver tumors or liver disease ( 4 ) Undiagnosed abnormal uterine bleeding ( 4 ) Breast cancer ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )
Warnings and precautions
Thrombotic Disorders and Other Vascular Problems: Stop Blisovi 24 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 Blisovi 24 Fe if jaundice occurs. ( 5.2 ) High blood pressure: If used in women with well-controlled hypertension, monitor blood pressure and stop Blisovi 24 Fe if blood pressure rises significantly. ( 5.4 ) Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking Blisovi 24 Fe . Consider an alternative contraceptive method for women with uncontrolled dyslipidemia. ( 5.6 ) Headache: Evaluate significant change in headaches and discontinue Blisovi 24 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 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. 5.2 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. 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 Blisovi 24 Fe prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see CONTRAINDICATIONS ( 4 )] . Blisovi 24 Fe can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen. 5.4 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. 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 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. 5.7 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).
Side effects
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 (≥ 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 Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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/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 (≥ 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%). 6.2 Postmarketing 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 - 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 - 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 8-10 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 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. 1
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 ) 7.1 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 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/ritnoavir, 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]). 7.2 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, 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 )]. 7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Co-administration of Blisovi 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 Blisovi 24 Fe and glecaprevir/pibrentasvir is not recommended due to potential for ALT elevations. 7.4 Interactions 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.
Use in specific populations
Lactation: Advise use of another contraceptive method. Blisovi 24 Fe can decrease milk production. ( 8.2 ) 8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Blisovi 24 Fe should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. Data Human Data Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. 8.2 Lactation Risk Summary Contraceptive hormones and/or metabolites are present in human milk. CHCs can reduce milk production in breastfeeding females. This reduction can occur at any time but is less likely to occur once breastfeeding is well-established. When possible, advise the nursing female to use other methods of contraception until she discontinues breastfeeding [see Dosage and Administration ( 2.2 )]. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Blisovi 24 Fe and any potential adverse effects on the breastfed child from Blisovi 24 Fe or from the underlying maternal condition. 8.4 Pediatric Use Safety and efficacy of Blisovi 24 Fe have been established in women of reproductive age. Efficacy is expected to be the same in postpubertal 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 Blisovi 24 Fe has not been studied in postmenopausal women and is not indicated in this population. 8.6 Hepatic Impairment The pharmacokinetics of Blisovi 24 Fe has not been studied in subjects 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 Blisovi 24 Fe has not been studied in women with renal impairment. 8.8 Body Mass Index The safety and efficacy of Blisovi 24 Fe in women with a body mass index (BMI) > 35 kg/m 2 has not been evaluated [see CLINICAL STUDIES ( 14 )].
Pregnancy
8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Blisovi 24 Fe should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively. Data Human Data Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy.
Pediatric use
8.4 Pediatric Use Safety and efficacy of Blisovi 24 Fe have been established in women of reproductive age. Efficacy is expected to be the same in postpubertal adolescents under the age of 18 years as for users 18 years and older. Use of this product before menarche is not indicated.
Geriatric use
8.5 Geriatric Use Blisovi 24 Fe has not been studied in postmenopausal women and is not indicated in this population.
Overdosage
There have been no reports of serious ill effects from overdose of oral contraceptives, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.
Description
Blisovi 24 Fe is a combination oral contraceptive for oral administration consisting of active tablets containing norethindrone acetate, a progestin, and ethinyl estradiol, an estrogen, and placebo tablets containing ferrous fumarate, which serve no therapeutic purpose. Each active white tablet contains 1 mg norethindrone acetate and 20 mcg ethinyl estradiol. Inactive ingredients include acacia, confectioner's sugar, corn starch, lactose monohydrate, magnesium stearate and talc. Each placebo brown tablet contains 75 mg ferrous fumarate, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate, and sucrose. The ferrous fumarate tablets do not serve any therapeutic purpose. Ferrous fumarate tablets are not USP for dissolution. The chemical name of ethinyl estradiol is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The empirical formula of ethinyl estradiol is C 20 H 24 O 2 and the structural formula is: The chemical name of norethindrone acetate is 17-hydroxy-19-nor-17α-pregn-4-en-20-yn-3-one acetate. The empirical formula of norethindrone acetate is C 22 H 28 O 3 and the structural formula is: "FDA approved dissolution test specifications differ from USP" image-1 image-2
Mechanism of action
12.1 Mechanism of Action CHCs prevent pregnancy primarily by suppressing ovulation.
How supplied
16.1 How Supplied Blisovi 24 Fe is available in a blister pack (NDC 68180-864-71) containing 28 tablets packed in a pouch (NDC 68180-864-71). Such three pouches are packaged in a carton (NDC 68180-864-73). Each blister pack (28 tablets) contains in the following order: 24 white to off-white, round, flat face beveled edged (active) tablets debossed with "LU" on one side and "N21" on the other side and each containing 1 mg norethindrone acetate and 20 mcg ethinyl estradiol. 4 brown mottled, round, flat face beveled edge (non-hormonal placebo) tablets debossed with "LU" on one side and "M22" on the other side and each containing 75 mg ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose. 16.2 Storage Conditions Store at 20° C to 25° C (68° F to 77° F); excursions permitted from 15 to 30° C (59 to 86° F) [see USP Controlled Room Temperature]. Protect from light. Keep this drug and all drugs out of the reach of children.
Storage
16.1 How Supplied Blisovi 24 Fe is available in a blister pack (NDC 68180-864-71) containing 28 tablets packed in a pouch (NDC 68180-864-71). Such three pouches are packaged in a carton (NDC 68180-864-73). Each blister pack (28 tablets) contains in the following order: 24 white to off-white, round, flat face beveled edged (active) tablets debossed with "LU" on one side and "N21" on the other side and each containing 1 mg norethindrone acetate and 20 mcg ethinyl estradiol. 4 brown mottled, round, flat face beveled edge (non-hormonal placebo) tablets debossed with "LU" on one side and "M22" on the other side and each containing 75 mg ferrous fumarate. The ferrous fumarate tablets do not serve any therapeutic purpose.
Patient information
Counsel patients to read the FDA-approved Patient Labeling (Patient Information and Instructions for Use). Counsel patients about the following information: Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see BOXED WARNING]. Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see WARNINGS AND PRECAUTIONS ( 5.1 )]. Blisovi 24 Fe does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Blisovi 24 Fe is not to be used during pregnancy; if pregnancy occurs during use of Blisovi 24 Fe instruct the patient to stop further use [see WARNINGS AND PRECAUTIONS ( 5.9 )]. Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed [see DOSAGE AND ADMINISTRATION ( 2.2 )]. Use a back-up or alternative method of contraception when enzyme inducers are used with Blisovi 24 Fe [see DRUG INTERACTIONS ( 7.1 )]. COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see USE IN SPECIFIC POPULATIONS ( 8.2 )]. Women who start COCs postpartum, and who has not yet had a period, must use an additional method of contraception until she has taken a white tablet for 7 consecutive days [see DOSAGE AND ADMINISTRATION ( 2.2 )]. Amenorrhea may occur. Consider pregnancy in the event of amenorrhea at the time of the first missed period. Rule out pregnancy in the event of amenorrhea in two or more consecutive cycles [see WARNINGS AND PRECAUTIONS ( 5.8 )]. Distributed by: Lupin Pharmaceuticals, Inc. Naples, FL 34108 United States Manufactured by: Lupin Limited Pithampur (M.P.) - 454 775 INDIA Revised: December 2024 image
Label text from the FDA structured product label by Lupin Pharmaceuticals, Inc. (revised Nov 18, 2025). Long sections are shortened; the complete label is on DailyMed.
Blisovi 24 Fe NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68180-864 | Kit | Lupin Pharmaceuticals, Inc. | ANDA |
Frequently asked questions
What is Blisovi 24 Fe used for?
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/m 2 has not been evaluated. Blisovi 24 Fe is a combination of norethindrone acetate, a progestin, and ethinyl estradiol, an estrogen, indicated for use by women to prevent pregnancy. (1) The efficacy of Blisovi 24 Fe in…
What are the side effects of 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… See the full label for the complete list.
Who makes Blisovi 24 Fe?
Blisovi 24 Fe is listed by 1 labeler in the FDA NDC directory, including Lupin Pharmaceuticals, Inc..