Galbriela (norethindrone and ethinyl estradiol chewable tablet and ferrous fumarate chewable tablet) is indicated for use by women to prevent pregnancy. The efficacy of Galbriela in women with a body mass index (BMI) of > 35 kg/m 2 has not been evaluated. Galbriela is a combination of norethindrone, a progestin, and ethinyl estradiol, an estrogen, indicated for use by females of reproductive potential to prevent pregnancy.
( 1 ) The efficacy in females of reproductive potential with a body mass index (BMI) of > 35 kg/m 2 has not been evaluated. ( 1 , 8.8 )
Contraindications
Galbriela 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: o Smoke, if over age 35 [see Boxed Warning , and Warnings and Precautions (5.1) ] o Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions (5.1) ] o Have cerebrovascular disease [see Warnings and Precautions (5.1) ] o Have coronary artery disease [see Warnings and Precautions (5.1) ] o 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) ] o Have inherited or acquired hypercoagulopathies [see Warnings and Precautions (5.1) ] o Have uncontrolled hypertension [see Warnings and Precautions (5.5) ] o Have diabetes with vascular disease [see Warnings and Precautions (5.7) ] o Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions (5.8) ] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.2) ] Liver tumors, benign or malignant, or liver disease [see Warnings and Precautions (5.3) , Use in Specific Populations (8.7) , and Clinical Pharmacology (12.3) ] Undiagnosed abnormal uterine bleeding [see Warnings and Precautions (5.9) ] 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 (5.4) ] A high risk of arterial or venous thrombotic diseases.
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( 4 ) Undiagnosed abnormal uterine bleeding. ( 4 ) Breast cancer ( 4 ) Liver tumors or liver disease ( 4 ) Co-administration with Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir ( 4 )
Warnings and precautions
Vascular risks: Stop norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if a thrombotic event occurs. Stop at least 4 weeks before and 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 if jaundice occurs. ( 5.3 ) High blood pressure: Do not prescribe for women with uncontrolled hypertension or hypertension with vascular disease.
( 5.5 ) Carbohydrate and lipid metabolic effects: Monitor prediabetic and diabetic women taking norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable). Consider an alternate contraceptive method for women with uncontrolled dyslipidemia. ( 5.7 ) Headache: Evaluate significant change in headaches and discontinue if indicated. ( 5.8 ) Uterine bleeding: Evaluate irregular bleeding or amenorrhea.
( 5.9 )
5.1Thrombotic and Other Vascular Events
Stop norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if an arterial or deep venous thrombotic (VTE) event occurs. Although the use of COCs increases the risk of venous thromboembolism, pregnancy increases the risk of venous thromboembolism as much or more than the use of COCs. The risk of venous thromboembolism in women using COCs is 3 to 9 per 10,000 woman-years. The excess risk is highest during the first year of use of a COC.
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. The risk of thromboembolic disease due to oral contraceptives gradually disappears after COC use is discontinued. If feasible, stop norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism.
Start norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years of age), hypertensive women who also smoke.
COCs also increase the risk for stroke in women with other underlying risk factors. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Stop norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately.
5.2Malignant Neoplasms Breast Cancer Norethindrone
and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) are 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 Adverse Reactions (6.2) ]. Cervical Cancer 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.
5.3Liver Disease
Discontinue norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if jaundice develops. Steroid hormones may be poorly metabolized in patients with impaired liver function. 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. 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 attributable risk of liver cancers in COC users is less than one case per million users. Oral contraceptive-related cholestasis may occur in women with a history of pregnancy-related cholestasis.
Women with a history of COC-related cholestasis may have the condition recur with subsequent COC use.
5.4Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment
During clinical trials with 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 norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir [see Contraindications (4) ].
Norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) can be restarted approximately 2 weeks following completion of treatment with the Hepatitis C combination drug regimen.
5.5High Blood Pressure
For women with well-controlled hypertension, monitor blood pressure and stop norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if blood pressure rises significantly. Women with uncontrolled hypertension or hypertension with vascular disease should not use COCs. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use.
The incidence of hypertension increases with increasing concentration of progestin.
5.6Gallbladder Disease
Studies suggest the relative risk of developing gallbladder disease may be increased among COC users.
5.7Carbohydrate and Lipid Metabolic Effects
Carefully monitor prediabetic and diabetic women who are taking norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable). COCs may decrease glucose tolerance in a dose-related fashion. 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.
5.8Headache If
a woman taking norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) if indicated. An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.
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
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
No drug-drug interaction studies were conducted with norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable). 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 )
7.1Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products If
a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding.
Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: barbiturates bosentan carbamazepine felbamate griseofulvin oxcarbazepine phenytoin rifampin St. John's wort topiramate HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.
Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.
7.2Increase in Plasma Levels of Ethinyl Estradiol Associated with Co-Administered Drugs Co-administration
of atorvastatin and certain combination oral contraceptives containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.
7.3Concomitant Use with HCV Combination
Therapy – Liver Enzyme Elevation Do not co-administer norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions (5.4) ].
7.4Changes in Plasma Levels of Co-Administered Drugs
COCs containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
There is no use for contraception in pregnancy; therefore, norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) 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 COCs 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.
Adverse reactions
The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and smoking [see Boxed Warning , and Warnings and Precautions (5.1) ] Vascular events [see Warnings and Precautions (5.1) ] Liver disease [see Warnings and Precautions (5.3) ] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache The most common adverse reactions (≥ 2%) are nausea/vomiting (8.8%), headaches/migraine (7.5%), depression/mood complaints (4.1%), dysmenorrhea (3.9%), acne (3.2%), anxiety symptoms (2.4%), breast pain/tenderness (2.4%), and increased weight (2.3%).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Xiromed, LLC at 844-XIROMED (844-947-6633) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A phase 3 clinical trial evaluated the safety and efficacy of norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable) for pregnancy prevention.
The study was a multicenter, non-comparative, open-label study with a treatment duration of 12 months (thirteen 28-day cycles). A total of 1,677 women aged 18-46 were enrolled and took at least one dose of norethindrone and ethinyl estradiol tablets (chewable) and ferrous fumarate tablets (chewable). Adverse Reactions Leading to Study Discontinuation: 8.5% of the women discontinued from the clinical trial due to an adverse reaction.
The most common adverse reactions leading to discontinuation were nausea (1.0%), weight increase (0.8%), acne (0.8%), metrorrhagia (0.7%), altered mood (0.4%), hypertension (0.4%), irritability (0.3%), migraine (0.3%), decreased libido (0.3%) and mood swings (0.3%). Common Adverse Reactions (≥ 2% of all treated subjects): nausea/vomiting (8.8%), headaches/migraine (7.5%), depression/mood complaints (4.1%), dysmenorrhea (3.9%), acne (3.2%), anxiety symptoms (2.4%), breast pain/tenderness (2.4%), and increased weight (2.3%).
Serious Adverse Reactions: Hypertension, depression, cholecystitis, and deep vein thrombosis.
6.2Postmarketing 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.
Figure 1: Relevant Studies of Risk of Breast Cancer with Combined Oral Contraceptives
Composition
Active ingredients
ETHINYL ESTRADIOL 0.025MG; NORETHINDRONE 0.8MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Norethindrone and Ethinyl Estradiol and Ferrous Fumarate
