Dosage & Administration
One capsule (elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in the morning and one capsule (elagolix 300 mg) in the evening for up to 24 months. (
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Oriahnn Prescribing Information
- Estrogen and progestin combinations, including ORIAHNN, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism, deep vein thrombosis, stroke and myocardial infarction, especially in women at increased risk for these events[see Warnings and Precautions (5.1 Thromboembolic Disorders and Vascular Events
ORIAHNN is contraindicated in women with current or history of thrombotic or thromboembolic disorders and in women at increased risk for these events
[see Contraindications(4)]. In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two thrombotic events occurred in 453 ORIAHNN-treated women (thrombosis in the calf and pulmonary embolism)[see Adverse Reactions(6.1)and Clinical Studies(14)]. Estrogen and progestin combinations, including the estradiol/norethindrone acetate component of ORIAHNN, increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at high risk for these events. In general, the risk is greatest among women over 35 years of age who smoke, and women with uncontrolled hypertension, dyslipidemia, vascular disease, or obesity.Discontinue ORIAHNN if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected. If feasible, discontinue ORIAHNN at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Stop ORIAHNN immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported in patients receiving estrogens and progestins.
)]. - ORIAHNN is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke and women with uncontrolled hypertension[see Contraindications (4 CONTRAINDICATIONS
ORIAHNN is contraindicated in women:
- With a high risk of arterial, venous thrombotic, or thromboembolic disorders[see Boxed Warning and Warnings and Precautions(5.1)]. Examples include women over 35 years of age who smoke, and women who are known to have:
○ current or history of deep vein thrombosis or pulmonary embolism
○ vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease)
○ thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
○ inherited or acquired hypercoagulopathies
○ uncontrolled hypertension
○ headaches with focal neurological symptoms or have migraine headaches with aura if over age 35 - Who are pregnant. Exposure to ORIAHNN early in pregnancy may increase the risk of early pregnancy loss[see Use in Specific Populations(8.1)].
- With known osteoporosis because of the risk of further bone loss[see Warnings and Precautions(5.2)].
- With current or history of breast cancer or other hormonally-sensitive malignancies, and with increased risk for hormonally-sensitive malignancies[see Warnings and Precautions(5.3)].
- With known hepatic impairment or disease[see Warnings and Precautions(5.5)].
- With undiagnosed abnormal uterine bleeding.
- With known anaphylactic reaction, angioedema, or hypersensitivity to ORIAHNN or any of its components.
- Taking inhibitors of organic anion transporting polypeptide (OATP)1B1 (a hepatic uptake transporter) that are known or expected to significantly increase elagolix plasma concentrations[see Drug Interactions(7.2)].
- High risk of arterial, venous thrombotic, or thromboembolic disorder.
- Pregnancy.
- Known osteoporosis.
- Current or history of breast cancer or other hormonally-sensitive malignancies.
- Known liver impairment or disease.
- Undiagnosed abnormal uterine bleeding.
- Known hypersensitivity to ingredients of ORIAHNN.
- Organic anion transporting polypeptide (OATP)1B1 inhibitors that are known or expected to significantly increase elagolix plasma concentrations.
)]. - With a high risk of arterial, venous thrombotic, or thromboembolic disorders
ORIAHNN is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.
Use of ORIAHNN should be limited to 24 months due to the risk of continued bone loss, which may not be reversible
- Exclude pregnancy before starting ORIAHNN or start ORIAHNN within 7 days from the onset of menses[see Use in Specific Populations(8.1)and(8.3)].
- The recommended dosage of ORIAHNN is:
○ One elagolix 300 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg capsule in the morning (AM), and
○ One elagolix 300 mg capsule in the evening (PM). - Take the morning and evening capsules at approximately the same time each day, with or without food.
- The recommended duration of treatment with ORIAHNN is 24 months[see Warnings and Precautions(5.2)].
ORIAHNN is contraindicated in women with known osteoporosis
In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3)
Consider the benefits and risks of ORIAHNN treatment in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, including taking medications that may decrease BMD (e.g., systemic or chronic inhaled corticosteroids, anticonvulsants, or proton pump inhibitors).
Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing ORIAHNN if the risk associated with bone loss exceeds the potential benefit of treatment. Limit the duration of use to 24 months to reduce the extent of bone loss
Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation for patients with inadequate dietary intake may be beneficial.
One capsule (elagolix 300 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) in the morning and one capsule (elagolix 300 mg) in the evening for up to 24 months. (
- Exclude pregnancy before starting ORIAHNN or start ORIAHNN within 7 days from the onset of menses[see Use in Specific Populations(8.1)and(8.3)].
- The recommended dosage of ORIAHNN is:
○ One elagolix 300 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg capsule in the morning (AM), and
○ One elagolix 300 mg capsule in the evening (PM). - Take the morning and evening capsules at approximately the same time each day, with or without food.
- The recommended duration of treatment with ORIAHNN is 24 months[see Warnings and Precautions(5.2)].
ORIAHNN consists of two capsules:
- The morning (AM) capsule is white and yellow, printed with “EL300 AM” containing 300 mg elagolix, 1 mg estradiol, and 0.5 mg norethindrone acetate.
- The evening (PM) capsule is white and light blue, printed with “EL300 PM” containing 300 mg elagolix.
There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ORIAHNN during pregnancy. Healthcare providers are encouraged to register patients, or pregnant women may enroll themselves in the registry by calling 1-833-782-7241 or visiting https://www.bloompregnancyregistry.com.
Use of ORIAHNN is contraindicated in pregnant women. Exposure to elagolix early in pregnancy may increase the risk of early pregnancy loss. Discontinue ORIAHNN if pregnancy occurs during treatment.
The limited human data with the use of elagolix in pregnant women are insufficient to determine whether there is a risk for major birth defects or miscarriage
There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ORIAHNN during pregnancy. Healthcare providers are encouraged to register patients, or pregnant women may enroll themselves in the registry by calling 1-833-782-7241 or visiting https://www.bloompregnancyregistry.com.
Use of ORIAHNN is contraindicated in pregnant women. Exposure to elagolix early in pregnancy may increase the risk of early pregnancy loss. Discontinue ORIAHNN if pregnancy occurs during treatment.
The limited human data with the use of elagolix in pregnant women are insufficient to determine whether there is a risk for major birth defects or miscarriage
When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 12 times the maximum recommended human dose (MRHD). Spontaneous abortion and total litter loss were observed in rabbits at doses 4 and 7 times the MRHD. There were no structural abnormalities in the fetuses at exposures up to 25 and 7 times the MRHD for the rat and rabbit, respectively
There was one pregnancy reported in the 453 women who received ORIAHNN in the Phase 3 uterine fibroids clinical trials. The pregnancy resulted in a spontaneous abortion and the estimated fetal exposure to ORIAHNN occurred during the first 18 days of pregnancy.
Embryofetal development studies were conducted in the rat and rabbit. Elagolix was administered by oral gavage to pregnant rats (25 animals/dose) at doses of 0, 300, 600, and 1200 mg/kg/day and to rabbits (20 animals/dose) at doses of 0, 100, 150, and 200 mg/kg/day during the period of organogenesis (gestation day 6-17 in the rat and gestation day 7-20 in the rabbit).
In rats, maternal toxicity was present at all doses and included six deaths and decreases in body weight gain and food consumption. Increased postimplantation losses were present in the mid dose group, which was 12 times the MRHD based on AUC. In rabbits, three spontaneous abortions and a single total litter loss were observed at the highest maternally toxic dose, which was 7 times the MRHD based on AUC. A single total litter loss occurred at a lower non-maternally toxic dose of 150 mg/kg/day, which was 4 times the MRHD.
No fetal malformations were present at any dose level tested in either species even in the presence of maternal toxicity. At the highest doses tested, the exposure margins were 25 and 7 times the MRHD for the rat and rabbit, respectively. However, because elagolix binds poorly to the rat gonadotropin-releasing hormone (GnRH) receptor (~1000 fold less than to the human GnRH receptor), the rat study is unlikely to identify pharmacologically mediated effects of elagolix on embryofetal development. The rat study is still expected to provide information on potential non-target-related effects of elagolix.
In a pre- and postnatal development study in rats, elagolix was given in the diet to achieve doses of 0, 100, and 300 mg/kg/day (25 per dose group) from gestation day 6 to lactation day 20. There was no evidence of maternal toxicity. At the highest dose, two dams had total litter loss, and one failed to deliver. Pup survival was decreased from birth to postnatal day 4. Pups had lower birth weights, and lower body weight gains were observed throughout the pre-weaning period at 300 mg/kg/day. Smaller body size and effect on startle response were associated with lower pup weights at 300 mg/kg/day. Post-weaning growth, development, and behavioral endpoints were unaffected.
Maternal plasma concentrations in rats on lactation day 21 at 100 and 300 mg/kg/day (47 and 125 ng/mL) were 0.04-fold and 0.1-fold the maximal elagolix concentration (Cmax) in humans at the MRHD. Because the exposures achieved in rats were much lower than the human MRHD, this study is not predictive of potentially higher lactational exposure in humans.
When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 12 times the maximum recommended human dose (MRHD). Spontaneous abortion and total litter loss were observed in rabbits at doses 4 and 7 times the MRHD. There were no structural abnormalities in the fetuses at exposures up to 25 and 7 times the MRHD for the rat and rabbit, respectively
There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ORIAHNN during pregnancy. Healthcare providers are encouraged to register patients, or pregnant women may enroll themselves in the registry by calling 1-833-782-7241 or visiting https://www.bloompregnancyregistry.com.
Use of ORIAHNN is contraindicated in pregnant women. Exposure to elagolix early in pregnancy may increase the risk of early pregnancy loss. Discontinue ORIAHNN if pregnancy occurs during treatment.
The limited human data with the use of elagolix in pregnant women are insufficient to determine whether there is a risk for major birth defects or miscarriage
When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 12 times the maximum recommended human dose (MRHD). Spontaneous abortion and total litter loss were observed in rabbits at doses 4 and 7 times the MRHD. There were no structural abnormalities in the fetuses at exposures up to 25 and 7 times the MRHD for the rat and rabbit, respectively
There was one pregnancy reported in the 453 women who received ORIAHNN in the Phase 3 uterine fibroids clinical trials. The pregnancy resulted in a spontaneous abortion and the estimated fetal exposure to ORIAHNN occurred during the first 18 days of pregnancy.
Embryofetal development studies were conducted in the rat and rabbit. Elagolix was administered by oral gavage to pregnant rats (25 animals/dose) at doses of 0, 300, 600, and 1200 mg/kg/day and to rabbits (20 animals/dose) at doses of 0, 100, 150, and 200 mg/kg/day during the period of organogenesis (gestation day 6-17 in the rat and gestation day 7-20 in the rabbit).
In rats, maternal toxicity was present at all doses and included six deaths and decreases in body weight gain and food consumption. Increased postimplantation losses were present in the mid dose group, which was 12 times the MRHD based on AUC. In rabbits, three spontaneous abortions and a single total litter loss were observed at the highest maternally toxic dose, which was 7 times the MRHD based on AUC. A single total litter loss occurred at a lower non-maternally toxic dose of 150 mg/kg/day, which was 4 times the MRHD.
No fetal malformations were present at any dose level tested in either species even in the presence of maternal toxicity. At the highest doses tested, the exposure margins were 25 and 7 times the MRHD for the rat and rabbit, respectively. However, because elagolix binds poorly to the rat gonadotropin-releasing hormone (GnRH) receptor (~1000 fold less than to the human GnRH receptor), the rat study is unlikely to identify pharmacologically mediated effects of elagolix on embryofetal development. The rat study is still expected to provide information on potential non-target-related effects of elagolix.
In a pre- and postnatal development study in rats, elagolix was given in the diet to achieve doses of 0, 100, and 300 mg/kg/day (25 per dose group) from gestation day 6 to lactation day 20. There was no evidence of maternal toxicity. At the highest dose, two dams had total litter loss, and one failed to deliver. Pup survival was decreased from birth to postnatal day 4. Pups had lower birth weights, and lower body weight gains were observed throughout the pre-weaning period at 300 mg/kg/day. Smaller body size and effect on startle response were associated with lower pup weights at 300 mg/kg/day. Post-weaning growth, development, and behavioral endpoints were unaffected.
Maternal plasma concentrations in rats on lactation day 21 at 100 and 300 mg/kg/day (47 and 125 ng/mL) were 0.04-fold and 0.1-fold the maximal elagolix concentration (Cmax) in humans at the MRHD. Because the exposures achieved in rats were much lower than the human MRHD, this study is not predictive of potentially higher lactational exposure in humans.
There was one pregnancy reported in the 453 women who received ORIAHNN in the Phase 3 uterine fibroids clinical trials. The pregnancy resulted in a spontaneous abortion and the estimated fetal exposure to ORIAHNN occurred during the first 18 days of pregnancy.
Embryofetal development studies were conducted in the rat and rabbit. Elagolix was administered by oral gavage to pregnant rats (25 animals/dose) at doses of 0, 300, 600, and 1200 mg/kg/day and to rabbits (20 animals/dose) at doses of 0, 100, 150, and 200 mg/kg/day during the period of organogenesis (gestation day 6-17 in the rat and gestation day 7-20 in the rabbit).
In rats, maternal toxicity was present at all doses and included six deaths and decreases in body weight gain and food consumption. Increased postimplantation losses were present in the mid dose group, which was 12 times the MRHD based on AUC. In rabbits, three spontaneous abortions and a single total litter loss were observed at the highest maternally toxic dose, which was 7 times the MRHD based on AUC. A single total litter loss occurred at a lower non-maternally toxic dose of 150 mg/kg/day, which was 4 times the MRHD.
No fetal malformations were present at any dose level tested in either species even in the presence of maternal toxicity. At the highest doses tested, the exposure margins were 25 and 7 times the MRHD for the rat and rabbit, respectively. However, because elagolix binds poorly to the rat gonadotropin-releasing hormone (GnRH) receptor (~1000 fold less than to the human GnRH receptor), the rat study is unlikely to identify pharmacologically mediated effects of elagolix on embryofetal development. The rat study is still expected to provide information on potential non-target-related effects of elagolix.
In a pre- and postnatal development study in rats, elagolix was given in the diet to achieve doses of 0, 100, and 300 mg/kg/day (25 per dose group) from gestation day 6 to lactation day 20. There was no evidence of maternal toxicity. At the highest dose, two dams had total litter loss, and one failed to deliver. Pup survival was decreased from birth to postnatal day 4. Pups had lower birth weights, and lower body weight gains were observed throughout the pre-weaning period at 300 mg/kg/day. Smaller body size and effect on startle response were associated with lower pup weights at 300 mg/kg/day. Post-weaning growth, development, and behavioral endpoints were unaffected.
Maternal plasma concentrations in rats on lactation day 21 at 100 and 300 mg/kg/day (47 and 125 ng/mL) were 0.04-fold and 0.1-fold the maximal elagolix concentration (Cmax) in humans at the MRHD. Because the exposures achieved in rats were much lower than the human MRHD, this study is not predictive of potentially higher lactational exposure in humans.
ORIAHNN is contraindicated in women:
- With a high risk of arterial, venous thrombotic, or thromboembolic disorders [see Boxed Warning and Warnings and Precautions(5.1 Thromboembolic Disorders and Vascular Events
ORIAHNN is contraindicated in women with current or history of thrombotic or thromboembolic disorders and in women at increased risk for these events
[see Contraindications(4)]. In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two thrombotic events occurred in 453 ORIAHNN-treated women (thrombosis in the calf and pulmonary embolism)[see Adverse Reactions(6.1)and Clinical Studies(14)]. Estrogen and progestin combinations, including the estradiol/norethindrone acetate component of ORIAHNN, increase the risk of thrombotic or thromboembolic disorders, including pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction, especially in women at high risk for these events. In general, the risk is greatest among women over 35 years of age who smoke, and women with uncontrolled hypertension, dyslipidemia, vascular disease, or obesity.Discontinue ORIAHNN if an arterial or venous thrombotic, cardiovascular, or cerebrovascular event occurs or is suspected. If feasible, discontinue ORIAHNN at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Stop ORIAHNN immediately if there is sudden unexplained partial or complete loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis as these have been reported in patients receiving estrogens and progestins.
)]. Examples include women over 35 years of age who smoke, and women who are known to have:
○ current or history of deep vein thrombosis or pulmonary embolism
○ vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease)
○ thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
○ inherited or acquired hypercoagulopathies
○ uncontrolled hypertension
○ headaches with focal neurological symptoms or have migraine headaches with aura if over age 35 - Who are pregnant. Exposure to ORIAHNN early in pregnancy may increase the risk of early pregnancy loss [see Use in Specific Populations(8.1 PregnancyPregnancy Exposure Registry
There is a pregnancy registry that monitors pregnancy outcomes in women exposed to ORIAHNN during pregnancy. Healthcare providers are encouraged to register patients, or pregnant women may enroll themselves in the registry by calling 1-833-782-7241 or visiting https://www.bloompregnancyregistry.com.
Risk SummaryUse of ORIAHNN is contraindicated in pregnant women. Exposure to elagolix early in pregnancy may increase the risk of early pregnancy loss. Discontinue ORIAHNN if pregnancy occurs during treatment.
The limited human data with the use of elagolix in pregnant women are insufficient to determine whether there is a risk for major birth defects or miscarriage
[seeData].When pregnant rats and rabbits were orally dosed with elagolix during the period of organogenesis, postimplantation loss was observed in pregnant rats at doses 12 times the maximum recommended human dose (MRHD). Spontaneous abortion and total litter loss were observed in rabbits at doses 4 and 7 times the MRHD. There were no structural abnormalities in the fetuses at exposures up to 25 and 7 times the MRHD for the rat and rabbit, respectively
[seeData].DataHuman DataThere was one pregnancy reported in the 453 women who received ORIAHNN in the Phase 3 uterine fibroids clinical trials. The pregnancy resulted in a spontaneous abortion and the estimated fetal exposure to ORIAHNN occurred during the first 18 days of pregnancy.
Animal DataEmbryofetal development studies were conducted in the rat and rabbit. Elagolix was administered by oral gavage to pregnant rats (25 animals/dose) at doses of 0, 300, 600, and 1200 mg/kg/day and to rabbits (20 animals/dose) at doses of 0, 100, 150, and 200 mg/kg/day during the period of organogenesis (gestation day 6-17 in the rat and gestation day 7-20 in the rabbit).
In rats, maternal toxicity was present at all doses and included six deaths and decreases in body weight gain and food consumption. Increased postimplantation losses were present in the mid dose group, which was 12 times the MRHD based on AUC. In rabbits, three spontaneous abortions and a single total litter loss were observed at the highest maternally toxic dose, which was 7 times the MRHD based on AUC. A single total litter loss occurred at a lower non-maternally toxic dose of 150 mg/kg/day, which was 4 times the MRHD.
No fetal malformations were present at any dose level tested in either species even in the presence of maternal toxicity. At the highest doses tested, the exposure margins were 25 and 7 times the MRHD for the rat and rabbit, respectively. However, because elagolix binds poorly to the rat gonadotropin-releasing hormone (GnRH) receptor (~1000 fold less than to the human GnRH receptor), the rat study is unlikely to identify pharmacologically mediated effects of elagolix on embryofetal development. The rat study is still expected to provide information on potential non-target-related effects of elagolix.
In a pre- and postnatal development study in rats, elagolix was given in the diet to achieve doses of 0, 100, and 300 mg/kg/day (25 per dose group) from gestation day 6 to lactation day 20. There was no evidence of maternal toxicity. At the highest dose, two dams had total litter loss, and one failed to deliver. Pup survival was decreased from birth to postnatal day 4. Pups had lower birth weights, and lower body weight gains were observed throughout the pre-weaning period at 300 mg/kg/day. Smaller body size and effect on startle response were associated with lower pup weights at 300 mg/kg/day. Post-weaning growth, development, and behavioral endpoints were unaffected.
Maternal plasma concentrations in rats on lactation day 21 at 100 and 300 mg/kg/day (47 and 125 ng/mL) were 0.04-fold and 0.1-fold the maximal elagolix concentration (Cmax) in humans at the MRHD. Because the exposures achieved in rats were much lower than the human MRHD, this study is not predictive of potentially higher lactational exposure in humans.
)]. - With known osteoporosis because of the risk of further bone loss [see Warnings and Precautions(5.2 Bone Loss
ORIAHNN is contraindicated in women with known osteoporosis
[see Contraindications (4)]. ORIAHNN may cause a decrease in bone mineral density (BMD) in some patients. BMD loss is greater with increasing duration of use and may not be completely reversible after stopping treatment[see Adverse Reactions(6.1)].In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3)
[see Clinical Studies(14)], seven out of 453 (1.5%) ORIAHNN-treated women experienced fractures, including one (0.2%) with a fragility fracture, compared to one out of 196 (0.5%) placebo-treated women (patient had a non-fragility fracture). Five of the seven ORIAHNN-treated women reported these fractures in the post-treatment follow-up period. The impact of BMD decreases on long-term bone health and future fracture risk in premenopausal women is unknown.Consider the benefits and risks of ORIAHNN treatment in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, including taking medications that may decrease BMD (e.g., systemic or chronic inhaled corticosteroids, anticonvulsants, or proton pump inhibitors).
Assessment of BMD by dual-energy X-ray absorptiometry (DXA) is recommended at baseline and periodically thereafter. Consider discontinuing ORIAHNN if the risk associated with bone loss exceeds the potential benefit of treatment. Limit the duration of use to 24 months to reduce the extent of bone loss
[see Indications and Usage(1)and Dosage and Administration(2.1)].Although the effect of supplementation with calcium and vitamin D was not studied, such supplementation for patients with inadequate dietary intake may be beneficial.
)]. - With current or history of breast cancer or other hormonally-sensitive malignancies, and with increased risk for hormonally-sensitive malignancies [see Warnings and Precautions(5.3 Hormonally-Sensitive Malignancies
ORIAHNN is contraindicated in women with current or history of breast cancer and in women at increased risk for hormonally-sensitive malignancies, such as those with mutations in BRCA genes
[see Contraindications(4)].In the Phase 3 clinical trials (Studies UF-1, UF-2, and UF-3), two (0.4%) cases of breast cancer in 453 ORIAHNN-treated women were observed. No breast cancer cases were seen in placebo-treated women
[see Adverse Reactions(6.1)].The use of estrogen alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. Surveillance measures, such as breast examinations and regular mammography, are recommended. Discontinue ORIAHNN if a hormonally-sensitive malignancy is diagnosed.
)]. - With known hepatic impairment or disease [see Warnings and Precautions(5.5 Hepatic Impairment and Transaminase ElevationsContraindication in Patients with Hepatic Impairment
ORIAHNN is contraindicated in women with known hepatic impairment or disease
[see Contraindications(4), Use in Specific Populations(8.7), and Clinical Pharmacology(12.3)].Transaminase ElevationsIn Phase 3 placebo-controlled clinical trials (Studies UF-1 and UF-2), elevations (> 3 times the upper limit of the reference range) in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 1.1% (4/379) and 1.3% (5/379) of ORIAHNN-treated patients, respectively, compared to no elevations in placebo. Transaminases peaked at 8 times the upper limit for ALT and 6 times the upper limit for AST. No pattern in time to onset of these liver transaminase elevations was identified. Transaminase levels returned to baseline within 4 months after peak values in these patients.
Instruct patients to promptly seek medical attention in case of symptoms or signs that may reflect liver injury, such as jaundice
[see Adverse Reactions(6.1)].)]. - With undiagnosed abnormal uterine bleeding.
- With known anaphylactic reaction, angioedema, or hypersensitivity to ORIAHNN or any of its components.
- Taking inhibitors of organic anion transporting polypeptide (OATP)1B1 (a hepatic uptake transporter) that are known or expected to significantly increase elagolix plasma concentrations [see Drug Interactions(7.2 Potential for Other Drugs to Affect ORIAHNN
Elagolix (a component of ORIAHNN) is a substrate of CYP3A, P-gp, and OATP1B1; estradiol and norethindrone acetate are metabolized partially by CYP3A
[see Clinical Pharmacology(12.3)]. Concomitant use of ORIAHNN with:- Strong CYP3A inducers may decrease elagolix, estradiol, and norethindrone plasma concentrations and may result in a decrease of the therapeutic effects of ORIAHNN.
- Rifampin is not recommended. The concomitant use of rifampin increased plasma concentrations of elagolix[see Clinical Pharmacology(12.3)].
- Strong CYP3A inhibitors are not recommended. Concomitant use of ORIAHNN with strong CYP3A inhibitors may increase elagolix, estradiol, and norethindrone plasma concentrations and increase the risk of adverse reactions.
- OATP1B1 inhibitors that are known or expected to significantly increase elagolix plasma concentrations is contraindicated due to increased risk of elagolix-associated adverse reactions[see Contraindications(4)].
)]. - Strong CYP3A inducers may decrease elagolix, estradiol, and norethindrone plasma concentrations and may result in a decrease of the therapeutic effects of ORIAHNN.