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Drug Interactions between elagolix / estradiol / norethindrone and suzetrigine

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

estradiol elagolix

Applies to: elagolix / estradiol / norethindrone and elagolix / estradiol / norethindrone

Estradiol and other estrogen-containing medications may reduce the effectiveness of elagolix in treating your condition. If you require contraception, it is recommended that you use a non-hormonal form of contraception during treatment with elagolix and for one week after its discontinuation. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Moderate

estradiol suzetrigine

Applies to: elagolix / estradiol / norethindrone and suzetrigine

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with suzetrigine may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is increased metabolic clearance due to induction of CYP450 3A4 by suzetrigine. When midazolam, a sensitive CYP450 3A4 substrate, was administered with suzetrigine given at 50 mg every 12 hours to steady state, mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 37% and 48%, respectively. These results suggest weak to borderline moderate induction of CYP450 3A4 by suzetrigine.

MANAGEMENT: Caution is advised when suzetrigine is used concomitantly with drugs that are substrates of CYP450 3A4, particularly sensitive substrates or those for which minimal concentration changes may lead to therapeutic failure. If coadministration is required, dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever suzetrigine is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration with a CYP450 3A4 inducer like suzetrigine and for any dosage adjustments that may be required.

Moderate

norethindrone elagolix

Applies to: elagolix / estradiol / norethindrone and elagolix / estradiol / norethindrone

Elagolix may reduce the blood levels and effects of norethindrone. If you are using low-dose oral contraceptives, you may have an increased risk of breakthrough bleeding and unintended pregnancy. You should discuss the use of alternative or additional methods of birth control with your healthcare provider. If you take hormone replacement for menopause, notify your doctor if your medication is no longer controlling your symptoms or you experience abnormal bleeding. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Moderate

elagolix suzetrigine

Applies to: elagolix / estradiol / norethindrone and suzetrigine

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of suzetrigine and M6-SUZ, a major active metabolite whose systemic exposure (AUC) at steady state is approximately 3 times that of the parent drug but exhibits 3.7-fold less potency in blocking the NaV1.8 voltage-gated sodium channels responsible for transmission of pain signals to the spinal cord and brain. Both suzetrigine and M6-SUZ are primarily metabolized by CYP450 3A4. When a single dose of suzetrigine was administered with the potent CYP450 3A4 inducer rifampin at steady state, mean suzetrigine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 80% and 93%, respectively, while mean Cmax of M6-SUZ increased by 30% and AUC decreased by 85%. Coadministration with efavirenz, a moderate CYP450 3A4 inducer, is predicted to decrease the mean Cmax and AUC of suzetrigine by 29% and 63%, respectively, while the mean Cmax of M6-SUZ is predicted to increase by 30% and AUC to decrease by 60%. The interaction has not been studied with other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of suzetrigine should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

Drug and food interactions

Major

suzetrigine food

Applies to: suzetrigine

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations of suzetrigine and M6-SUZ, a major active metabolite whose systemic exposure (AUC) at steady state is approximately 3 times that of the parent drug but exhibits 3.7-fold less potency in blocking the NaV1.8 voltage-gated sodium channels responsible for transmission of pain signals to the spinal cord and brain. The proposed mechanism for the interaction is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When a single dose of suzetrigine was administered with itraconazole, a potent CYP450 3A4 inhibitor, mean suzetrigine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.5- and 4.8-fold, respectively, while mean Cmax of M6-SUZ decreased by 32% and AUC increased by 4.4-fold. Coadministration of fluconazole, a moderate CYP450 3A4 inhibitor, with suzetrigine dosed according to the manufacturer's recommended dosage modification is predicted to increase the mean Cmax and AUC of suzetrigine by 1.4- and 1.5-fold, respectively, while the mean Cmax and AUC of M6-SUZ are predicted to increase by 1.1- and 1.2-fold, respectively, compared to suzetrigine administered at the regular recommended dosage without fluconazole. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

ADJUST DOSE INTERVAL: Food may delay the absorption of suzetrigine without impacting the overall systemic exposures to parent drug and M6-SUZ. Administration of suzetrigine 100 mg (the first dose) with a high-fat meal (800 to 1000 calories; 50% from fat), a moderate-fat meal (600 calories; 30% from fat), and a low-fat meal (<=500 calories; <=25% from fat) resulted in decreased initial plasma concentrations of suzetrigine and M6-SUZ compared to administration in a fasted state. The median time to reach peak plasma concentration (Tmax) for suzetrigine and M6-SUZ when administered with either a high-fat or moderate-fat meal was 5 hours and 24 hours, respectively, versus 3 hours and 8 to 10 hours, respectively, when administered in the fasted state. The Cmax and AUC of suzetrigine and M6-SUZ were not affected by any of the meal conditions, including a high-fat meal consumed one hour after suzetrigine. Administration of the second suzetrigine dose of 50 mg with or without regard to meals is also predicted to have no effect on the systemic exposures of suzetrigine and M6-SUZ.

MANAGEMENT: Patients should avoid consumption of foods or drinks containing grapefruit during treatment with suzetrigine. The starting dose of 100 mg should be taken on an empty stomach at least 1 hour before or 2 hours after food, although clear liquids (e.g., water, apple juice, vegetable broth, tea, black coffee) may be consumed during this time. Subsequent doses may be taken with or without food.

Moderate

norethindrone food

Applies to: elagolix / estradiol / norethindrone

Grapefruit juice may increase the blood levels of certain medications such as norethindrone. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with norethindrone. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.

Minor

estradiol food

Applies to: elagolix / estradiol / norethindrone

Information for this minor interaction is available on the professional version.

Minor

norethindrone food

Applies to: elagolix / estradiol / norethindrone

Information for this minor interaction is available on the professional version.

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.