Orilissa

Gonadotropin Releasing Hormone Receptor Antagonist

Oral Administration Oral Solid Formulations

Administer orally at approximately the same time each day, with or without food.

Severe

suicidal ideation / Delayed / 0.2-0.2
bone fractures / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
angioedema / Rapid / Incidence not known

Moderate

hot flashes / Early / 24.0-46.0
osteopenia / Delayed / 2.0-21.0
depression / Delayed / 3.0-6.0
constipation / Delayed / 3.0-4.9
hypertriglyceridemia / Delayed / 0-4.0
hypercholesterolemia / Delayed / 0-4.0
osteoporosis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known

Mild

night sweats / Early / 24.0-46.0
headache / Early / 17.0-20.0
nausea / Early / 11.0-16.0
insomnia / Early / 6.0-9.0
amenorrhea / Delayed / 4.0-7.0
emotional lability / Early / 5.0-6.0
rash / Early / 5.8-5.8
anxiety / Delayed / 3.0-5.0
arthralgia / Delayed / 3.0-5.0
dizziness / Early / 3.0-4.9
irritability / Delayed / 3.0-4.9
libido decrease / Delayed / 3.0-4.9
abdominal pain / Early / 3.0-4.9
weight gain / Delayed / 3.0-4.9
diarrhea / Early / 3.0-4.9
back pain / Delayed / 0.2-0.2
menstrual irregularity / Delayed / Incidence not known
urticaria / Rapid / Incidence not known

Orilissa

Rx

Oral gonadotropin-releasing hormone (GnRH) receptor antagonist
Used for moderate to severe pain associated with endometriosis including menstrual and non-menstrual pelvic pain and dyspareunia
Contraindicated in patients with osteoporosis; may cause reduction in bone mineral density so treatment is limited to 24 months or less, depending on dosage chosen

For the treatment of moderate pain or severe pain associated with endometriosis, which may include endometriosis-related dyspareunia. Oral dosage Adult Females

Initiate at 150 mg PO once daily; maximum duration for this dose is 24 months. WOMEN WITH CO-EXISTING DYSPAREUNIA: Consider initiation at the higher dose of 200 mg PO twice daily; maximum duration of use is 6 months at this dose. Exclude pregnancy prior to initiating elagolix or start therapy within 7 days from the onset of menses. Use the lowest effective dose, taking into account the severity of symptoms and treatment objectives. Limit the duration of use as recommended to reduce the extent of bone loss.

Hepatic Impairment

Mild impairment (Child-Pugh A): No dosage adjustment required.
Moderate impairment (Child-Pugh B): Initiate with 150 mg PO once daily and limit use to no more than 6 months. Use of 200 mg PO twice daily is not recommended.
Severe impairment (Child-Pugh C): Use is contraindicated.

Renal Impairment

No dose adjustment is required in women with any degree of renal impairment or end-stage renal disease (including dialysis).

Abacavir; Dolutegravir; Lamivudine: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with elagolix can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If elagolix is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Elagolix is a weak to moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of oxycodone as needed. If elagolix is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Major) Concomitant use of elagolix 200 mg twice daily and adagrasib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and adagrasib to 6 months. Coadministration may increase elagolix exposure. Elagolix is a CYP3A substrate; adagrasib is a strong inhibitor of CYP3A. Coadministration of elagolix with another strong CYP3A inhibitor increased the AUC of elagolix by 120%.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with elagolix is necessary. If elagolix is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a weak to moderate CYP3A4 inducer like elagolix with alfentanil, a CYP3A4 substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Amiodarone: (Moderate) Monitor for decreased efficacy of amiodarone if coadministration with elagolix is necessary. Coadministration may decrease amiodarone plasma concentrations. Amiodarone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Atorvastatin: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Benazepril: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Celecoxib: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Olmesartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as clarithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Clarithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to clarithromycin in a patient receiving elagolix. (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Apalutamide: (Moderate) Concomitant use of elagolix and apalutamide may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; apalutamide is a strong inducer of CYP3A.
Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, caution is advisable during coadministration of a CYP3A4 inducer, such as elagolix. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. A dose adjustment of aripiprazole may be needed. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Aspirin, ASA; Omeprazole: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of oxycodone as needed. If elagolix is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as atazanavir is contraindicated. Coadministration may increase elagolix plasma concentrations and decrease atazanavir concentrations. Elagolix is a substrate of CYP3A and OATP1B1, and a weak to moderate CYP3A4 inducer. Atazanavir is a strong inhibitor of CYP3A and a CYP3A4 substrate, and it inhibits OATP1B1. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Atazanavir; Cobicistat: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as atazanavir is contraindicated. Coadministration may increase elagolix plasma concentrations and decrease atazanavir concentrations. Elagolix is a substrate of CYP3A and OATP1B1, and a weak to moderate CYP3A4 inducer. Atazanavir is a strong inhibitor of CYP3A and a CYP3A4 substrate, and it inhibits OATP1B1. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Atogepant: (Major) Avoid use of atogepant and elagolix when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with elagolix. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Avacopan: (Major) Avoid concomitant use of avacopan and elagolix due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Avanafil: (Major) Coadministration of avanafil with elagolix is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil was not evaluated, plasma concentrations may decrease.
Avapritinib: (Major) Avoid coadministration of avapritinib with elagolix due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A4 substrate and elagolix is a weak-to-moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease the AUC and Cmax of avapritinib by 62% and 55%, respectively.
Axitinib: (Major) Avoid coadministration of axitinib with elagolix if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A4 induction potential is recommended. Axitinib is a CYP3A4/5 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Bedaquiline: (Major) Avoid coadministration of elagolix with bedaquiline due to decreased plasma exposure to bedaquiline. Bedaquiline is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased bedaquiline exposure by approximately 20%. The AUC and Cmax of the primary metabolite of bedaquiline (M2) were increased by 70% and 80%, respectively.
Belzutifan: (Moderate) Monitor for anemia and hypoxia if concomitant use of elagolix with belzutifan is necessary due to increased plasma exposure of belzutifan which may increase the incidence and severity of adverse reactions. Reduce the dose of belzutifan as recommended if anemia or hypoxia occur. Belzutifan is a CYP2C19 substrate and elagolix is a CYP2C19 inhibitor.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking elagolix. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving elagolix. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving elagolix. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; elagolix inhibits P-gp.
Brigatinib: (Major) Avoid coadministration of brigatinib with elagolix due to decreased plasma exposure to brigatinib which may result in decreased efficacy; concentrations of elagolix may also increase. If concomitant use is unavoidable, after 7 days of concomitant treatment with elagolix, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose; monitor for an increase in elagolix-related adverse reactions. After discontinuation of elagolix, resume the brigatinib dose that was tolerated prior to initiation of elagolix. Brigatinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%. Elagolix is also a P-glycoprotein (P-gp) substrate. Brigatinib is a P-gp inhibitor in vitro and may have the potential to increase concentrations of P-gp substrates.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and elagolix are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; elagolix is a weak to moderate inducer of CYP3A4.
Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with elagolix is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If elagolix is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with elagolix is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If elagolix is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Buspirone: (Moderate) Monitor for decreased efficacy of buspirone if elagolix is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Cabotegravir; Rilpivirine: (Major) The concomitant use of elagolix and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Elagolix is a weak to moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Capmatinib: (Major) Avoid coadministration of capmatinib and elagolix due to the risk of decreased capmatinib exposure, which may reduce its efficacy. Capmatinib is a CYP3A substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased capmatinib exposure by 44%.
Carbamazepine: (Moderate) Concomitant use of elagolix and carbamazepine may result in decreased concentrations of elagolix and/or carbamazepine; monitor for decreased efficacy of both drugs with coadministration. Elagolix is a CYP3A substrate and a weak to moderate inducer; carbamazepine is a strong inducer and substrate of CYP3A4.
Cariprazine: (Major) Coadministration of cariprazine with elagolix is not recommended as the net effect of CYP3A4 induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Coadministration of cariprazine with CYP3A4 inducers has not been evaluated.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of tramadol as needed. If elagolix is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Ceritinib: (Major) Concomitant use of elagolix 200 mg twice daily and ceritinib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ceritinib to 6 months. Elagolix is a CYP3A substrate and ceritinib is a strong inhibitor of CYP3A. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Chloramphenicol: (Major) Concomitant use of elagolix 200 mg twice daily and chloramphenicol for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and chloramphenicol to 6 months. Elagolix is a CYP3A substrate; chloramphenicol is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with elagolix can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If elagolix is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Elagolix is a weak to moderate inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Cisapride: (Moderate) Monitor for decreased efficacy of cisapride if coadministration with elagolix is necessary; coadministration may result in decreased plasma concentrations of cisapride. Elagolix is a weak to moderate CYP3A4 inducer and cisapride is a CYP3A4 substrate.
Citalopram: (Moderate) CItalopram 20 mg/day is the maximum recommended dose for patients taking concomitant CYP2C19 inhibitors because of the risk of QT prolongation. Elagolix is a weak CYP2C19 inhibitor and a weak to moderate CYP3A4 inducer and citalopram is a CYP2C19 and CYP3A4 substrate. The net effect of elagolix on citalopram exposure is not clear.
Clarithromycin: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as clarithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Clarithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to clarithromycin in a patient receiving elagolix.
Clozapine: (Moderate) Monitor for loss of clozapine effectiveness if coadministered with elagolix. Consideration should be given to increasing the clozapine dose if necessary. When elagolix is discontinued, reduce the clozapine dose based on clinical response. Elagolix is a weak to moderate inducer of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine.
Cobicistat: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with elagolix due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and elagolix is a weak to moderate inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Codeine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with elagolix can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor for reduced efficacy of codeine and signs of opioid withdrawal; consider increasing the dose of codeine as needed. If elagolix is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Elagolix is a weak to moderate CYP3A4 inducer.
Colchicine: (Major) Avoid concomitant use of colchicine and elagolix due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elagolix is a P-gp inhibitor.
Cyclosporine: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cyclosporine is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cyclosporine inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with elagolix, a P-gp inhibitor. Although coadministration may have no effect on the pharmacokinetics of dabigatran in healthy subjects, patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like elagolix in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with elagolix, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Daclatasvir: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as daclatasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Daclatasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Daridorexant: (Major) Avoid concomitant use of daridorexant and elagolix. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darolutamide: (Contraindicated) Coadministration of elagolix with darolutamide is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and darolutamide is an OATP1B1 inhibitor.
Darunavir: (Major) Concomitant use of elagolix 200 mg twice daily and darunavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and darunavir to 6 months. Monitor for elagolix-related side effects and reduced response to darunavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; darunavir is a strong inhibitor of CYP3A and a sensitive CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease darunavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Darunavir; Cobicistat: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Major) Concomitant use of elagolix 200 mg twice daily and darunavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and darunavir to 6 months. Monitor for elagolix-related side effects and reduced response to darunavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; darunavir is a strong inhibitor of CYP3A and a sensitive CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease darunavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Major) Concomitant use of elagolix 200 mg twice daily and darunavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and darunavir to 6 months. Monitor for elagolix-related side effects and reduced response to darunavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; darunavir is a strong inhibitor of CYP3A and a sensitive CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease darunavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Deflazacort: (Major) Avoid concomitant use of deflazacort and elagolix. Concurrent use may significantly decrease concentrations of 21-desDFZ , the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; elagolix is a weak to moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of another strong CYP3A4 inducer resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Delavirdine: (Major) Concomitant use of elagolix 200 mg twice daily and delavirdine for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and delavirdine to 6 months. Monitor for elagolix-related side effects and reduced response to delavirdine. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; delavirdine is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease delavirdine concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Desogestrel; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Diazepam: (Minor) Coadministration of elagolix with diazepam may theoretically increase plasma concentrations of diazepam. Elagolix is a weak CYP2C19 inhibitor and diazepam is a CYP2C19 sensitive substrate. Monitor for diazepam-related adverse effects during coadministration with elagolix.
Dienogest; Estradiol valerate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Digoxin: (Moderate) Clinical monitoring is recommended for digoxin when coadministered with elagolix. Monitor heart rate, clinical status and serum digoxin concentrations periodically and as clinically indicated. Elagolix is an inhibitor of P-glycoprotein (P-gp), and digoxin is a P-gp substrate. During drug interaction studies, the coadministration of elagolix with digoxin resulted in an increase in digoxin peak concentrations by a mean of 1.71 ( range, 1.53 to 1.91) and mean AUC of 1.26 (range 1.17 to 1.35).
Diltiazem: (Moderate) Use caution and careful monitoring when coadministering elagolix with diltiazem; diltiazem exposure and effect may be decreased. Dose adjustments should be made for diltiazem based on clinical response. Elagolix is a weak to moderate CYP3A4 inducer. Diltiazem is a CYP3A4 substrate.
Disopyramide: (Moderate) Monitor disopyramide serum concentrations and for loss of efficacy when coadministration with elagolix is necessary. Disopyramide exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and disopyramide is a CYP3A4 substrate.
Docetaxel: (Moderate) Monitor for decreased docetaxel efficacy when coadministration with elagolix is necessary. Docetaxel exposure may be decreased during concurrent use. Elagolix is a weak to moderate CYP3A4 inducer and docetaxel is a CYP3A4 substrate.
Dolutegravir: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Dolutegravir; Lamivudine: (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Dolutegravir; Rilpivirine: (Major) The concomitant use of elagolix and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Elagolix is a weak to moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate. (Moderate) Dolutegravir plasma concentrations may be reduced when administered concurrently with elagolix; thereby increasing the risk for HIV treatment failures or the development of viral-resistance. Data are insufficient to make dosing recommendations; however, predictions regarding this interaction can be made based on the drugs metabolic pathways. Elagolix is a weak to moderate inducer of CYP3A, dolutegravir is partially metabolized by this isoenzyme.
Doravirine: (Moderate) Concurrent administration of doravirine and elagolix may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and elagolix may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Drospirenone: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Drospirenone; Estetrol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Drospirenone; Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Drospirenone; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Duvelisib: (Major) Avoid concomitant use of duvelisib with elagolix. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When elagolix has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with elagolix. Duvelisib is a CYP3A substrate; elagolix is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elacestrant: (Major) Avoid concurrent use of elacestrant and elagolix due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix; Estradiol; Norethindrone acetate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with elagolix should be avoided if possible. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. Elagolix is a weak to moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. (Major) If possible, avoid concurrent administration of grazoprevir with elagolix. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response. Elagolix is a weak to moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A.
Elexacaftor; tezacaftor; ivacaftor: (Contraindicated) Coadministration of elagolix with elexacaftor is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and elexacaftor is a strong OATP1B1 inhibitor.
Eltrombopag: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eltrombopag is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Eltrombopag is an inhibitor of OATP1B1 in vitro and can increase the systemic exposure of other drugs that are substrates of OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Eluxadoline: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as eluxadoline is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of OATP1B1. Eluxadoline inhibits OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as cobicistat is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Cobicistat is a combined inhibitor; it is a potent inhibitor of CYP3A and inhibits OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) The concomitant use of elagolix and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomita

nt use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Elagolix is a weak to moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) The concomitant use of elagolix and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Elagolix is a weak to moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Enasidenib: (Contraindicated) Coadministration of elagolix with enasidenib is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and enasidenib is a strong OATP1B1 inhibitor.
Encorafenib: (Contraindicated) Coadministration of elagolix with encorafenib is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and encorafenib is a strong OATP1B1 inhibitor.
Entrectinib: (Major) Avoid coadministration of entrectinib with elagolix due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer. Coadministration of a moderate CYP3A4 inducer is predicted to reduce the entrectinib AUC by 56%.
Enzalutamide: (Moderate) Concomitant use of elagolix and enzalutamide may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; enzalutamide is a strong inducer of CYP3A.
Erdafitinib: (Major) If coadministration of erdafitinib and elagolix is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If elagolix must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If elagolix is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer.
Erlotinib: (Major) There may be a risk of reduced erlotinib efficacy when coadministered with elagolix; however, the risk has not been clearly defined. If coadministration is necessary, consider increasing the erlotinib dose by 50 mg increments at 2-week intervals as tolerated, to a maximum of 450 mg. Erlotinib is a CYP3A4 substrate, and elagolix is a weak to moderate CYP3A4 inducer.
Erythromycin: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as erythromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Erythromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to erythromycin in a patient receiving elagolix.
Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Estradiol; Levonorgestrel: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Estradiol; Norethindrone: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Estradiol; Norgestimate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Ethinyl Estradiol; Norelgestromin: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Ethinyl Estradiol; Norethindrone Acetate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Ethinyl Estradiol; Norgestrel: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Etonogestrel; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with elagolix is necessary. The dose of everolimus may need to be adjusted. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Elagolix is a weak to moderate CYP3A4 inducer; it may also increase plasma concentrations of P-gp substrates. Coadministration with CYP3A4 inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Fedratinib: (Major) Avoid coadministration of fedratinib with elagolix as concurrent use may decrease fedratinib exposure which may result in decreased therapeutic response. Fedratinib is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Coadministration of fedratinib with another moderate CYP3A4 inducer decreased the overall exposure of fedratinib by 47%.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if coadministration with elagolix is necessary. If elagolix is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A4 inducer like elagolix with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Finerenone: (Major) Avoid concurrent use of finerenone and elagolix due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
Flibanserin: (Major) Coadministration of elagolix with flibanserin is not recommended due to decreased plasma exposure to flibanserin which may result in decreased efficacy. Flibanserin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant administration with a moderate CYP3A4 inducer decreased flibanserin exposures by approximately 21%.
Fosamprenavir: (Moderate) Monitor for decreased fosamprenavir efficacy if coadministered with elagolix. Concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Fosamprenavir is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Fosphenytoin: (Moderate) Concomitant use of elagolix and fosphenytoin may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; fosphenytoin is a strong inducer of CYP3A.
Fostemsavir: (Contraindicated) Coadministration of elagolix with fostemsavir is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and fostemsavir is an OATP1B1 inhibitor.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and elagolix due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer.
Gemfibrozil: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as gemfibrozil is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Glasdegib: (Major) Avoid coadministration of glasdegib and elagolix due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily; or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after elagolix has been discontinued for 7 days. Glasdegib is a CYP3A substrate; elagolix is a weak to moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer was predicted to decrease the glasdegib AUC value by 55%.
Glecaprevir; Pibrentasvir: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as glecaprevir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Glecaprevir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as pibrentasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Pibrentasvir inhibits both OATP1B1 and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking elagolix due to increased elagolix exposure. Elagolix is a CYP3A substrate; grapefruit juice is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Guanfacine: (Major) Elagolix may significantly decrease guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if these agents are taken together, doubling the recommended dose of guanfacine should be considered; if elagolix is added in a patient already receiving guanfacine, this escalation should occur over 1 to 2 weeks. If elagolix is discontinued, decrease the guanfacine ER dosage back to the recommended dose over 1 to 2 weeks. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is primarily metabolized by CYP3A4, and elagolix is a weak to moderate CYP3A4 inducer.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with elagolix can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal; consider increasing the dose of hydrocodone as needed. If elagolix is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with elagolix. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of oxycodone as needed. If elagolix is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Major) Concomitant use of elagolix 200 mg twice daily and idelalisib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and idelalisib to 6 months. Elagolix is a CYP3A substrate; idelalisib is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Indinavir: (Major) Concomitant use of elagolix 200 mg twice daily and indinavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and indinavir to 6 months. Monitor for elagolix-related side effects and reduced response to indinavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; indinavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease indinavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Infigratinib: (Major) Avoid concurrent use of infigratinib and elagolix. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer.
Isavuconazonium: (Major) The concomitant use of elagolix and isavuconazonium may lead to decreased isavuconazonium concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of isavuconazonium efficacy. Elagolix is a weak to moderate CYP3A4 inducer; isavuconazonium is a sensitive CYP3A4 substrate. The use of isavuconazonium is contraindicated with strong CYP3A4 inducers; however, the manufacturer does not provide guidance for moderate inducers.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin.
Isoniazid, INH; Rifampin: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin.
Itraconazole: (Major) Concomitant use of elagolix 200 mg twice daily and itraconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and itraconazole to 6 months. Monitor for elagolix-related side effects and reduced response to itraconazole. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; itraconazole is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease itraconazole concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Ketoconazole: (Major) Concomitant use of elagolix 200 mg twice daily and ketoconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ketoconazole to 6 months. Coadministration may increase elagolix exposure. Elagolix is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the AUC of elagolix by 120%.
Lansoprazole: (Minor) Coadministration of elagolix with lansoprazole may theoretically increase plasma concentrations of lansoprazole. Monitor for lansoprazole-related adverse effects during coadministration with elagolix. Elagolix is a weak CYP2C19 inhibitor and lansoprazole is a CYP2C19 sensitive substrate.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as clarithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Clarithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to clarithromycin in a patient receiving elagolix. (Minor) Coadministration of elagolix with lansoprazole may theoretically increase plasma concentrations of lansoprazole. Monitor for lansoprazole-related adverse effects during coadministration with elagolix. Elagolix is a weak CYP2C19 inhibitor and lansoprazole is a CYP2C19 sensitive substrate.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with elagolix is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and elagolix is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and elagolix due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If elagolix is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of elagolix. Larotrectinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with elagolix unless the benefits outweigh the risks due to unpredictable lefamulin exposure. Lefamulin is a CYP3A4 and P-gp substrate; elagolix is both an inducer of CYP3A4 as well as a P-gp inhibitor. The net effect on lefamulin concentrations is unclear.
Leflunomide: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as leflunomide is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. The active metabolite of leflunomide, which is responsible for virtually all of its activity, inhibits OATP1B1 in vivo and is expected to increase concentrations of drugs that are substrates for OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Lemborexant: (Major) Avoid coadministration of lemborexant and elagolix as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and elagolix due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. Lenacapavir is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%.
Leniolisib: (Contraindicated) Coadministration of elagolix with leniolisib is contraindicated as concurrent use may increase elagolix exposure and risk for adverse effects. Concomitant use may also decrease leniolisib exposure which may reduce its efficacy. Elagolix is a substrate of OATP1B1 and a moderate CYP3A inducer; leniolisib is an OATP1B1 inhibitor and a CYP3A substrate. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Letermovir: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as letermovir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Letermovir inhibits OATP1B1 and is expected to increase concentrations of drugs that are substrates for OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Leuprolide; Norethindrone: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Levamlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Levoketoconazole: (Major) Concomitant use of elagolix 200 mg twice daily and ketoconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ketoconazole to 6 months. Coadministration may increase elagolix exposure. Elagolix is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased the AUC of elagolix by 120%.
Levonorgestrel: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Levonorgestrel; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Lidocaine: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Lidocaine; Epinephrine: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and elagolix may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; elagolix is a weak to moderate CYP3A4 inducer.
Lonafarnib: (Contraindicated) Concurrent use of lonafarnib and elagolix is contraindicated as use may decrease lonafarnib exposure and efficacy. Elagolix exposure and the risk for elagolix-related adverse effects may also be increased. If concurrent use is necessary, limit elagolix therapy to a maximum duration of six months in patients receiving 150 mg daily or one month in patients receiving 200 mg twice daily. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; elagolix is a CYP3A4 substrate and moderate CYP3A4 inducer. Coadministration of elagolix with another strong CYP3A4 inhibitor increased elagolix exposure by 120%.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with elagolix. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with elagolix. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as lopinavir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of OATP1B1. Lopinavir inhibits OATP1B1. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Major) Concomitant use of elagolix 200 mg twice daily and ritonavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ritonavir to 6 months. Monitor for elagolix-related side effects and reduced response to ritonavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; ritonavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease ritonavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Lorlatinib: (Major) Avoid concomitant use of lorlatinib and elagolix due to decreased plasma concentrations of lorlatinib, which may reduce its efficacy. If concomitant use is necessary, increase the dose of lorlatinib to 125 mg PO once daily. Lorlatinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of elagolix and lumacaftor; ivacaftor may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; lumacaftor; ivacaftor is a strong inducer of CYP3A.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of elagolix and lumacaftor; ivacaftor may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; lumacaftor; ivacaftor is a strong inducer of CYP3A.
Lumateperone: (Major) Avoid coadministration of lumateperone and elagolix as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with elagolix due to risk for reduced mavacamten efficacy. There is also risk for increased adverse reactions due to mavacamten. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and elagolix is a weak CYP2C19 inhibitor and moderate CYP3A inducer. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall exposure by 48%.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with elagolix is necessary; elagolix may induce methadone metabolism. Consider increasing the dose of methadone if clinically warranted, with consideration of the long half-life of methadone. If elagolix is discontinued, consider a dose reduction of methadone and frequently monitor for signs or respiratory depression and sedation. Methadone is a substrate of CYP 3A4 and 2C19. Elagolix is a weak to moderate CYP3A4 inducer and a weak CYP2C19 inhibitor. Concomitant use of methadone with CYP3A4 inducers can decrease methadone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Midazolam: (Moderate) Monitor for altered response to midazolam therapy. Consider increasing the dose of midazolam and individualize therapy based on the patients response. Elagolix is a weak to moderate CYP3A4 inducer and has been shown to decrease the mean peak concentration (Cmax) and exposure (AUC) of midazolam in drug interaction studies.
Midostaurin: (Contraindicated) Coadministration of elagolix with midostaurin is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and midostaurin is an OATP1B1 inhibitor.
Mifepristone: (Major) Concomitant use of elagolix 200 mg twice daily and mifepristone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and mifepristone to 6 months. Elagolix is a CYP3A substrate; mifepristone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Mitapivat: (Major) Avoid coadministration of mitapivat with elagolix, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mitotane: (Moderate) Concomitant use of elagolix and mitotane may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; mitotane is a strong inducer of CYP3A.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and elagolix. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with elagolix is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and elagolix is a weak-to-moderate CYP3A4 inducer.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and elagolix. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor.
Nefazodone: (Major) Concomitant use of elagolix 200 mg twice daily and nefazodone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and nefazodone to 6 months. Elagolix is a CYP3A substrate; nefazodone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Nelfinavir: (Major) Concomitant use of elagolix 200 mg twice daily and nelfinavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and nelfinavir to 6 months. Monitor for elagolix-related side effects and reduced response to nelfinavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; nelfinavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease nelfinavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Neratinib: (Major) Avoid concomitant use of elagolix with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A4 inducer may decrease neratinib exposure by 52%.
Nirmatrelvir; Ritonavir: (Major) Concomitant use of elagolix 200 mg twice daily and ritonavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ritonavir to 6 months. Monitor for elagolix-related side effects and reduced response to ritonavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; ritonavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease ritonavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of elagolix is necessary. Concomitant use of nirmatrelvir and elagolix may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with elagolix due to decreased plasma concentrations of nisoldipine. Nisoldipine is a CYP3A4 substrate and enzalutamide is a elagolix weak to moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Norethindrone: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Norethindrone; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice d aily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Norgestimate; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Norgestrel: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Olaparib: (Major) Avoid coadministration of olaparib with elagolix due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and elagolix is a weak to moderate CYP3A4 inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and elagolix due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and elagolix. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Omeprazole: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Omeprazole; Sodium Bicarbonate: (Moderate) Coadministration of elagolix with omeprazole may increase plasma concentrations of omeprazole. Consider dosage reduction of omeprazole when elagolix is used concomitantly with higher doses of omeprazole, e.g., in patients with Zollinger-Ellison syndrome; however, no dose adjustments are needed for omeprazole at doses of 40 mg once daily or lower. Elagolix is a weak CYP2C19 inhibitor and omeprazole is a CYP2C19 sensitive substrate.
Oral Contraceptives: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of oxycodone as needed. If elagolix is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Pacritinib: (Major) Avoid concurrent use of pacritinib with elagolix due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and elagolix. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and elagolix due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime if perampanel is added to elagolix therapy; increase the dose as tolerated in 2 mg increments no more than weekly, based on clinical response. If elagolix is added or withdrawn from perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Perampanel is a CYP3A substrate and elagolix is a moderate CYP3A inducer.
Perindopril; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Phenobarbital: (Moderate) Concomitant use of elagolix and phenobarbital may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; phenobarbital is a strong inducer of CYP3A.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of elagolix and phenobarbital may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; phenobarbital is a strong inducer of CYP3A.
Phenytoin: (Moderate) Concomitant use of elagolix and phenytoin may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; phenytoin is a strong inducer of CYP3A.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends avoiding concomitant use of pimavanserin with moderate CYP3A4 inducers, such as elagolix. Moderate inducers of CYP3A4 can reduce pimavanserin exposure, potentially decreasing the effectiveness of pimavanserin.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and elagolix due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. If concomitant use is necessary, an empiric pirtobrutinib dosage increase is required. If the current dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Pirtobrutinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%.
Posaconazole: (Major) Concomitant use of elagolix 200 mg twice daily and posaconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and posaconazole to 6 months. Elagolix is a CYP3A substrate; posaconazole is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Pralsetinib: (Major) Avoid concomitant use of elagolix with pralsetinib due to the risk of altered pralsetinib exposure which may reduce its efficacy or increase the risk of adverse reactions. Pralsetinib is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45% and coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Praziquantel: (Moderate) Monitor for reduced response to praziquantel if coadministered with elagolix. Concomitant use may produce therapeutically ineffective concentrations of praziquantel. In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Elagolix is a weak to moderate CYP3A4 inducer.
Pretomanid: (Major) Avoid coadministration of pretomanid with elagolix as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer decreased pretomanid exposure by 35%.
Primidone: (Moderate) Concomitant use of elagolix and primidone may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; phenobarbital, the active metabolite of primidone, is a strong inducer of CYP3A.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and elagolix due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and elagolix is a P-gp inhibitor.
Quizartinib: (Major) Avoid concomitant use of elagolix with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Rabeprazole: (Minor) Coadministration of elagolix with rabeprazole may theoretically increase plasma concentrations of rabeprazole. Monitor for rabeprazole-related adverse effects during coadministration with elagolix. Elagolix is a weak CYP2C19 inhibitor and rabeprazole is a CYP2C19 sensitive substrate.
Ranolazine: (Contraindicated) Coadministration of elagolix and ranolazine is contraindicated. Concurrent use may decrease elagolix exposure resulting in reduced therapeutic response. Ranolazine is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Coadministration of a strong CYP3A4 inducer decreased the plasma concentrations of ranolazine by approximately 95%.
Relugolix: (Major) Avoid concomitant use of relugolix and oral elagolix. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer elagolix at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and elagolix is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral elagolix. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer elagolix at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-gp substrate and elagolix is a P-gp inhibitor. (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Ribociclib: (Major) Concomitant use of elagolix 200 mg twice daily and ribociclib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ribociclib to 6 months. Elagolix is a CYP3A substrate; ribociclib is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Ribociclib; Letrozole: (Major) Concomitant use of elagolix 200 mg twice daily and ribociclib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ribociclib to 6 months. Elagolix is a CYP3A substrate; ribociclib is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Rifampin: (Contraindicated) The use of rifampin with elagolix is contraindicated. Concomitant use of elagolix and organic anion transporting polypeptide (OATP) 1B1 inhibitors such as rifampin increase exposure to elagolix. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. During drug interaction studies, a single dose of rifampin increased the mean AUC of elagolix by 5.58-fold. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. While induction of CYP3A by rifampin may also occur, particularly with continued use, it appears that elagolix is more influenced by the OATP1B1 activity of rifampin as AUC remained elevated by a mean of 1.65-fold with continued use of rifampin.
Rifapentine: (Moderate) Monitor for decreased efficacy of elagolix if coadministration with rifapentine is necessary. Concurrent use may decrease elagolix exposure. Elagolix is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with elagolix is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and elagolix is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) The concomitant use of elagolix and rilpivirine may lead to decreased rilpivirine concentrations and loss of virologic response. Consider use of an alternative agent. If concomitant use of these agents is unavoidable, monitor patients for loss of rilpivirine efficacy. Elagolix is a weak to moderate CYP3A4 inducer and rilpivirine is a moderately sensitive CYP3A4 substrate.
Rimegepant: (Major) Avoid coadministration of rimegepant with elagolix; concurrent use may alter rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate and elagolix is a weak to moderate CYP3A4 inducer and P-gp inhibitor.
Ripretinib: (Major) Avoid coadministration of ripretinib with elagolix. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of elagolix. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and elagolix is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritonavir: (Major) Concomitant use of elagolix 200 mg twice daily and ritonavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ritonavir to 6 months. Monitor for elagolix-related side effects and reduced response to ritonavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; ritonavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease ritonavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and elagolix may result in increases in rivaroxaban exposure and may increase bleeding risk. Elagolix is an inhibitor of P-gp, and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Rosuvastatin: (Moderate) Monitor for a decrease in rosuvastatin efficacy during concomitant use with elagolix and adjust the rosuvastatin dose as appropriate. Concomitant use has been observed to decrease rosuvastatin overall exposure by 40%.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for a decrease in rosuvastatin efficacy during concomitant use with elagolix and adjust the rosuvastatin dose as appropriate. Concomitant use has been observed to decrease rosuvastatin overall exposure by 40%.
Saquinavir: (Major) Concomitant use of elagolix 200 mg twice daily and saquinavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and saquinavir to 6 months. Monitor for elagolix-related side effects and reduced response to saquinavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; saquinavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease saquinavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Segesterone Acetate; Ethinyl Estradiol: (Major) During use of elagolix, females of childbearing potential should use non-hormonal methods of contraception for the duration of treatment and for 28 days following the discontinuation of therapy. Estrogen-containing injectable, implantable, transdermal, vaginal or oral contraceptives are expected to reduce the efficacy of elagolix. The effect of progestin-only contraceptives on elagolix is not known. However, elagolix is a weak to moderate inducer of CYP3A4, and many estrogens and progestins are metabolized via this enzyme. Thus, elagolix may decrease plasma concentrations of hormonal contraceptives. Coadministration of elagolix 200 mg twice daily and a combined oral contraceptive (COC) containing 0.1 mg levonorgestrel decreases the plasma concentrations of levonorgestrel by 27%, potentially affecting contraceptive efficacy. Coadministration of elagolix with COCs containing norethindrone acetate did not show reduction in plasma concentrations of norethindrone. Elagolix may also increase contraceptive concentrations. Coadministration of a COC (containing 20 mcg ethinyl estradiol/0.1 mg levonorgestrel) following administration of elagolix 200 mg twice daily for 14 days increases the plasma ethinyl estradiol concentration by 2.2-fold compared to this COC alone; this may lead to increased risk of ethinyl estradiol-related adverse events including thromboembolic disorders and vascular events.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and elagolix due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with other moderate CYP3A4 inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and elagolix due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with a moderate CYP3A4 inducer is predicted to decrease selumetinib exposure by 38%.
Sildenafil: (Moderate) Monitor for reduced therapeutic effect of sildenafil if coadministered with elagolix. Concurrent use may decrease sildenafil plasma concentrations. Sildenafil is a sensitive CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer. Population pharmacokinetic analysis of data from patients in clinical trials indicated approximately 3-fold the sildenafil clearance when it was coadministered with weak CYP3A inducers.
Siponimod: (Moderate) Concomitant use of siponimod and elagolix is not recommended for patients with CYP2C9*1/*3 and *2/*3 genotypes due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; elagolix is a moderate CYP3A4 inducer. Across different CYP2C9 genotypes, a moderate CYP3A4 inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of elagolix. Concomitant use may alter sirolimus exposure resulting in decreased efficacy or increased risk for sirolimus-related adverse effects. Sirolimus is a CYP3A and P-gp substrate and elagolix is a moderate CYP3A inducer and P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as velpatasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Velpatasvir is an inhibitor of OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as velpatasvir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Velpatasvir is an inhibitor of OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as voxilaprevir is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Voxilaprevir is an inhibitor of OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Solifenacin: (Minor) Monitor for decreased efficacy of solifenacin if coadministration with elagolix is necessary. Solifenacin is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Studies have not been conducted to evaluate the effect of CYP3A4 inducers on solifenacin, but inducers of CYP3A4 may decrease solifenacin plasma concentrations.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and elagolix; sonidegib exposure may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
St. John's Wort, Hypericum perforatum: (Moderate) Concomitant use of elagolix and St. John's Wort may result in decreased concentrations of elagolix; monitor for decreased efficacy with coadministration. Elagolix is a CYP3A substrate; St. John's Wort is a strong inducer of CYP3A.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if elagolix must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of sufentanil injection as needed. If elagolix is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tacrolimus: (Moderate) Monitor tacrolimus whole blood trough concentrations when tacrolimus is administered with elagolix; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus whole blood concentrations. Tacrolimus is metabolized mainly by CYP3A enzymes; elagolix is a weak to moderate CYP3A4 inducer.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with elagolix is necessary. Talazoparib is a P-gp substrate and elagolix is a P-gp inhibitor.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with elagolix as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer.
Telmisartan; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with elagolix is necessary. Amlodipine is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Teriflunomide: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as teriflunomide is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Teriflunomide inhibits OATP1B1 in vivo and is expected to increase concentrations of drugs that are substrates for OATP1B1. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density.
Tipranavir: (Major) Concomitant use of elagolix 200 mg twice daily and tipranavir for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and tipranavir to 6 months. Monitor for elagolix-related side effects and reduced response to tipranavir. Elagolix is a CYP3A substrate and a weak to moderate CYP3A4 inducer; tipranavir is a strong inhibitor of CYP3A and a CYP3A4 substrate. Coadministration may increase elagolix plasma concentrations and decrease tipranavir concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Topotecan: (Major) Avoid coadministration of elagolix with oral topotecan due to increased topotecan exposure; elagolix may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and elagolix is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of tramadol as needed. If elagolix is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with elagolix is necessary; consider increasing the dose of tramadol as needed. If elagolix is discontinued, consider a dose reduction of tramadol and frequently monitor for signs or respiratory depression and sedation. Tramadol is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease tramadol levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Trofinetide: (Contraindicated) Coadministration of elagolix with trofinetide is contraindicated as concurrent use may increase elagolix exposure. Elagolix is a substrate of OATP1B1 and trofinetide is a strong OATP1B1 inhibitor.
Tucatinib: (Major) Concomitant use of elagolix 200 mg twice daily and tucatinib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and tucatinib to 6 months. Coadministration may increase elagolix exposure. Elagolix is a CYP3A4 substrate; tucatinib is a strong inhibitor of CYP3A4. Coadministration of elagolix with another strong CYP3A4 inhibitor increased the AUC of elagolix by 120%.
Ubrogepant: (Major) Ubrogepant dose adjustment is necessary if coadministered with elagolix as concurrent use may decrease ubrogepant exposure and efficacy or increase ubrogepant exposure and side effects. Ubrogepant is a CYP3A4 and P-gp substrate; elagolix is a moderate CYP3A4 inducer and a P-gp inhibitor.
Venetoclax: (Major) Avoid coadministration of venetoclax with elagolix due to decreased plasma concentrations of venetoclax. Venetoclax is a CYP3A4 substrate and elagolix is a weak to moderate CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer decreased venetoclax exposure by 71%.
Voclosporin: (Major) Avoid coadministration of voclosporin with elagolix. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A4 substrate and elagolix is a moderate CYP3A4 inducer. Coadministration with moderate CYP3A4 inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan; Amoxicillin: (Major) Avoid concomitant use of vonoprazan and elagolix due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Concomitant use of elagolix and strong organic anion transporting polypeptide (OATP) 1B1 inhibitors such as clarithromycin is contraindicated. Use of elagolix with drugs that inhibit OATP1B1 may increase elagolix plasma concentrations. Elagolix is a substrate of CYP3A, P-gp, and OATP1B1. Clarithromycin significantly inhibits OATP1B1, and also inhibits CYP3A and P-gp. Another OATP1B1 potent inhibitor increased elagolix AUC in the range of 2- to 5.58-fold. Increased elagolix concentrations increase the risk for dose-related side effects, including loss of bone mineral density. Consider an alternative to clarithromycin in a patient receiving elagolix. (Major) Avoid concomitant use of vonoprazan and elagolix due to decreased plasma concentrations of vonoprazan, which may reduce its efficacy. Vonoprazan is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Vonoprazan exposures are predicted to be 50% lower when coadministered with a moderate CYP3A4 inducer.
Voriconazole: (Major) Concomitant use of elagolix 200 mg twice daily and voriconazole for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and voriconazole to 6 months. Monitor for elagolix-related side effects and increased or reduced response to voriconazole. Elagolix is a CYP3A substrate, a weak to moderate CYP3A4 inducer, and a weak CYP2C19 inhibitor; voriconazole is a strong inhibitor of CYP3A, a CYP3A4 substrate, and a CYP2C19 sensitive substrate. Coadministration may increase elagolix plasma concentrations and increase or decrease voriconazole concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Voxelotor: (Major) Avoid coadministration of voxelotor and elagolix as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Voxelotor is a substrate of CYP3A; elagolix is a moderate CYP3A inducer. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with elagolix is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. Elagolix is a moderate CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and elagolix due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if elagolix is discontinued. Zanubrutinib is a CYP3A substrate and elagolix is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.
Zolpidem: (Moderate) Monitor for reduced therapeutic response to zolpidem is coadministration with elagolix is necessary. Zolpidem exposure may be decreased. Zolpidem is a CYP3A4 substrate; elagolix is a weak to moderate CYP3A4 inducer.

Orilissa Oral Tab: 150mg, 200mg

Adults

150 mg/day for up to 24 months or 400 mg/day PO for up to 6 months for endometriosis.

Geriatric

Safety and efficacy have not been established.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Elagolix is an oral reverisble gonadotropin-releasing hormone (GnRH) receptor antagonist that inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Elagolix administration results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones, estradiol and progesterone. Estrogen plays an important role in the pathophysiology of endometriosis; estrogen promotes endometrial tissue proliferation and peritoneal implantation of endometrial tissue, and stimulates inflammation. The clinical result of the actions of elagolix is a reduction in the proliferation of endometrial tissue and subsequently, pain related to the disease.

Elagolix is administered orally. Elagolix is 80% bound to plasma proteins. The blood to plasma ratio is 0.6. The apparent mean volume of distribution at steady state is large, showing extensive tissue distribution. Elagolix is eliminated primarily through hepatic metabolism. The major metabolic pathway is via CYP3A4; minor pathways include CYP2D6, CYP2C8, and uridine glucuronosyl transferases (UGTs). Disposition of the drug is also dependent on hepatic organic anion transporting polypeptide (OATP) 1B1. Less than 3% of an elagolix dose is excreted in the urine and 90% is excreted in the feces. The mean oral clearance (% coefficient of variation or CV) is 123 (21) L/hour and 144 (43) L/hour for the 150 mg once daily and 200 mg twice daily regimens, respectively. The terminal half-life is approximately 4 to 6 hours.[63387]
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, OATP1B1, P-glycoprotein (P-gp), CYP2C19
Elagolix is a substrate of CYP3A4, P-gp, and OATP1B1. Medications that inhibit or induce CYP3A can affect elagolix exposure. Disposition of the drug is dependent on OATP1B1. Potent OATP1B1 inhibitors are expected to significantly increase elagolix concentrations and exposure. The effect of concomitant use of P-gp inhibitors or inducers on the pharmacokinetics of elagolix is unknown. In addition, elagolix may influence the pharmacokinetics of other drugs. Elagolix is a weak to moderate inducer of CYP3A4 and is also an inhibitor of P-gp. Elagolix is a weak inhibitor of CYP2C19. Elagolix coadministration may increase plasma concentrations of drugs that are CYP2C19 substrates.[63387]

Oral Route

The mean Cmax [peak concentration (%CV)] is 574 (29) ng/mL following an elagolix dose of 150 mg PO once daily and is 774 (68) ng/mL following a dose of 200 mg PO twice daily. The time to peak concentration (Tmax) is 1 hour. The mean AUC (%CV) for 200 mg twice daily is 1725 (57) ng x hour/mL and for 150 mg PO once daily is 1292 (31) ng x hour/mL. The AUC and Cmax are decreased by 24% and 36%, respectively, after ingestion a high-fat meal; however, the drug may be given with or without food.

Pregnancy

Elagolix is contraindicated for use during pregnancy; based on the mechanism of action, elagolix may increase the risk of early pregnancy loss. Exclude pregnancy before initiating treatment with elagolix, either by pregnancy testing or by initiating the drug within 7 days of the onset of menses. Advise patients to contact their physician immediately if there is any reason to suspect pregnancy during treatment. If a pregnancy test is positive, the physician and patient must discuss the risks to the pregnancy and fetus. 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. Although 2 cases of congenital malformations out of 49 pregnancies were reported in clinical trials with elagolix, no pattern was identified and miscarriages were reported at a similar incidence across treatment groups. In 1 case of infant cleft palate, the mother was treated with elagolix 150 mg daily and the estimated fetal exposure to elagolix occurred during the first 30 days of pregnancy. In 1 case of infant tracheoesophageal fistula, the mother was treated with elagolix 150 mg daily and the estimated fetal exposure to elagolix occurred during the first 15 days of pregnancy. Although the duration of fetal exposure was limited in elagolix clinical trials, there were no apparent decreases in birth weights associated with elagolix in comparison to placebo. The effect of elagolix on labor and obstetric delivery is not known. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to elagolix; information about the registry can be obtained by calling 1-833-782-7241 or by visiting https://www.bloompregnancyregistry.com.[63387]

Use elagolix with caution during breast-feeding. There is no information on the presence of elagolix or its metabolites in human milk, the effects on the breast-fed child, or the effects on milk production. There are no adequate animal data on the excretion of elagolix in milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated maternal condition.