Drug Interactions between Spasquid and suzetrigine

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

Spasquid (atropine/hyoscyamine/phenobarbital/scopolamine)
suzetrigine

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Consumer
Professional

Interactions between your drugs

Major

PHENobarbital suzetrigine

Applies to: Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine) and suzetrigine

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent and moderate inducers of CYP450 3A4 may significantly 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%. Reduced efficacy of suzetrigine may occur.

MANAGEMENT: Concomitant use of suzetrigine with potent or moderate CYP450 3A4 inducers should generally be avoided.

Moderate

atropine hyoscyamine

Applies to: Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine) and Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine)

Using atropine together with hyoscyamine may increase side effects such as drowsiness, blurred vision, dry mouth, heat intolerance, flushing, decreased sweating, difficulty urinating, abdominal cramping, constipation, irregular heartbeat, confusion, and memory problems. Side effects may be more likely to occur in the elderly or those with a debilitating condition. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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

atropine scopolamine

Applies to: Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine) and Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine)

Using atropine together with scopolamine may increase side effects such as drowsiness, blurred vision, dry mouth, heat intolerance, flushing, decreased sweating, difficulty urinating, abdominal cramping, constipation, irregular heartbeat, confusion, and memory problems. Side effects may be more likely to occur in the elderly or those with a debilitating condition. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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

PHENobarbital scopolamine

Applies to: Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine) and Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine)

Using PHENobarbital together with scopolamine may increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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

hyoscyamine scopolamine

Applies to: Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine) and Spasquid (atropine / hyoscyamine / phenobarbital / scopolamine)

Using hyoscyamine together with scopolamine may increase side effects such as drowsiness, blurred vision, dry mouth, heat intolerance, flushing, decreased sweating, difficulty urinating, abdominal cramping, constipation, irregular heartbeat, confusion, and memory problems. Side effects may be more likely to occur in the elderly or those with a debilitating condition. You should avoid or limit the use of alcohol while being treated with these medications. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medications affect you. Talk to your doctor if you have any questions or concerns. 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.

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.

Major