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)].
- 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)].
ORIAHNN is indicated for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal women.
Limitation of Use:
Use of ORIAHNN should be limited to 24 months due to the risk of continued bone loss, which may not be reversible [see Dosage and Administration ( 2.1) and Warnings and Precautions ( 5.2)].
2.1 Important Dosing Information
- 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)].
2.2 Missed Dose
Instruct the patient to take the missed dose of ORIAHNN within 4 hours of the time that it was supposed to be taken and then the next dose at the usual time. If more than 4 hours have passed since a capsule is usually taken, instruct the patient not to take the missed dose and take the next dose at the usual time. Take only one morning capsule and one evening capsule per day.
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.
8.1 Pregnancy
Pregnancy 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 Summary
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 [see Data].
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 [see Data].
Data
Human Data
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.
Animal Data
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.
8.2 Lactation
Risk Summary
There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. When estrogen and progestins are administered to lactating women, these compounds and/or their metabolites are detected in human milk and can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well established. Advise the nursing female to use non-hormonal contraception until she discontinues breast-feeding. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for ORIAHNN and any potential adverse effects on the breast-fed child from ORIAHNN or from the underlying maternal condition [see Data].
Data
There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogen and progestin have been identified in the breast milk of women receiving estrogen and progestin combinations.
There are no adequate animal data on excretion of elagolix in milk.
8.3 Females and Males of Reproductive Potential
Based on the mechanism of action of elagolix, there is a risk of early pregnancy loss if ORIAHNN is administered to a pregnant woman [see Use in Specific Populations ( 8.1), Clinical Pharmacology ( 12.1)].
Pregnancy Testing
ORIAHNN may delay the ability to recognize the occurrence of a pregnancy because it may reduce the intensity, duration, and amount of menstrual bleeding [see Adverse Reactions ( 6.1)]. Exclude pregnancy before initiating treatment with ORIAHNN. Perform pregnancy testing if pregnancy is suspected during treatment with ORIAHNN and discontinue treatment if pregnancy is confirmed [see Contraindications ( 4) and Warnings and Precautions ( 5.8)].
Contraception
Advise women to use non-hormonal contraception during treatment with ORIAHNN and for 28 days after discontinuing ORIAHNN [see Warnings and Precautions ( 5.8)].
8.4 Pediatric Use
Safety and effectiveness of ORIAHNN in pediatric patients have not been established.
8.6 Renal Impairment
No dose adjustment of ORIAHNN is required in women with any degree of renal impairment or end-stage renal disease (including women on dialysis) [see Clinical Pharmacology ( 12.3)].
8.7 Hepatic Impairment
ORIAHNN is contraindicated in women with any hepatic impairment or disease [see Contraindications ( 4)]. The use of estradiol (a component of ORIAHNN) in patients with hepatic impairment, compared to patients with normal hepatic function, is expected to increase the blood levels of estradiol and increase the risk of estradiol-associated adverse reactions. Additionally, the use of elagolix (a component of ORIAHNN) in patients with moderate and severe hepatic impairment, compared to patients with normal hepatic function, increased elagolix exposures 3-fold and 7-fold, respectively, and this increases the risk of elagolix-associated adverse reactions [see Clinical Pharmacology ( 12.3)].
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)].