Drug Interactions between D-Tal and repotrectinib

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

D-Tal (atropine/hyoscyamine/phenobarbital/scopolamine)
repotrectinib

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Consumer
Professional

Interactions between your drugs

Major

PHENobarbital repotrectinib

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations and pharmacologic effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4 and is also a substrate of P-gp in vitro. Concomitant use with rifampin, a combined potent CYP450 3A4 and P-gp inducer, decreased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 79% and 92%, respectively. Data are not available for repotrectinib in combination with other, less potent CYP450 3A4 inducers. Reduced effectiveness of repotrectinib may occur.

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

References

"Product Information. Augtyro (repotrectinib)." Bristol-Myers Squibb ORIG-1 (2023):

Moderate

atropine hyoscyamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (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.

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Moderate

atropine scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (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.

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Moderate

PHENobarbital scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (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.

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Moderate

hyoscyamine scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (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.

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Drug and food interactions

Major

repotrectinib food

Applies to: repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. The proposed mechanism 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 repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (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. Increased exposure to repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures.

MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.