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Drug Interactions between Bel-Phen-Ergot and nirogacestat

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

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Interactions between your drugs

Major

PHENobarbital nirogacestat

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital) and nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with moderate to potent CYP450 3A4 inducers may significantly decrease the plasma concentration and pharmacologic effects of nirogacestat, which is primarily metabolized by the isoenzyme. Coadministration of multiple doses of nirogacestat (150 mg twice daily) with the potent CYP450 3A4 inducer rifampin is predicted to decrease the systemic exposure (AUC) of nirogacestat by 85%. In addition, administration of multiple doses of nirogacestat (150 mg twice daily) with the moderate CYP450 3A4 inducer efavirenz is predicted to decrease the AUC of nirogacestat by 67%. Reduced therapeutic efficacy of nirogacestat may occur.

MANAGEMENT: According to the manufacturer, concomitant use of nirogacestat with moderate to potent CYP450 3A4 inducers should be avoided.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):
Moderate

ergotamine PHENobarbital

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital) and Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital)

PHENobarbital may reduce the blood levels and effects of ergotamine. Contact your doctor if your symptoms worsen or your condition changes during treatment with these medications. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring 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.

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Moderate

ergotamine nirogacestat

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital) and nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with nirogacestat may increase the plasma concentrations and therapeutic effects of drugs that are substrates of CYP450 3A4. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index. The proposed mechanism is decreased clearance due to nirogacestat-mediated inhibition of CYP450 3A4. Concomitant use of the sensitive CYP450 3A4 substrate midazolam with multiple doses of nirogacestat (150 mg twice daily) is predicted to increase the systemic exposure (AUC) and peak plasma concentration (Cmax) of midazolam by 2.07-fold and 1.77-fold, respectively.

MANAGEMENT: According to the manufacturer, concomitant use of nirogacestat with sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index (e.g., ergot alkaloids, colchicine, fentanyl, macrolide immunosuppressants, midazolam, triazolam, vinca alkaloids) is not recommended.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):

Drug and food interactions

Major

nirogacestat food

Applies to: nirogacestat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit, grapefruit juice, Seville oranges, and starfruit may significantly increase the plasma concentrations and pharmacologic effects of nirogacestat. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Coadministration of multiple doses of nirogacestat (150 mg twice daily) with the moderate CYP450 3A4 inhibitors erythromycin and fluconazole are predicted to increase the AUC of nirogacestat by 2.73-fold and 3.18-fold, respectively. The interaction has not been studied with grapefruit, Seville oranges, or starfruit. 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 systemic exposure to nirogacestat may increase the risk of adverse effects including diarrhea, ovarian toxicity, hepatotoxicity, electrolyte abnormalities, and non-melanoma skin cancers.

MANAGEMENT: Patients treated with nirogacestat should avoid consumption of grapefruit, grapefruit juice, Seville oranges, starfruit, or any supplement containing grapefruit.

References

  1. "Product Information. Ogsiveo (nirogacestat)." SpringWorks Therapeutics, Inc. (2023):
Major

PHENobarbital food

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital)

Ask your doctor before using PHENobarbital together with ethanol, this can add to dizziness, drowsiness and other side effects of PHENobarbital. Be careful if you drive or do activities that require you to be awake and alert. Talk with your doctor before using any medications together, or drinking alcohol with PHENobarbital. 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

ergotamine food

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital)

Grapefruit juice may increase the blood levels of certain medications such as ergotamine. You may want to limit your consumption of grapefruit and grapefruit juice during treatment with ergotamine. 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.

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Moderate

belladonna food

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital)

Ask your doctor before using belladonna together with ethanol. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking belladonna. You should be warned not to exceed recommended dosages and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. 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

ergotamine food

Applies to: Bel-Phen-Ergot (belladonna / ergotamine / phenobarbital)

Nicotine may increase the effects of ergotamine in narrowing the blood vessels and decreasing blood flow. A severe decrease in blood flow to the brain and other parts of the body can lead to dangerous side effects. Contact your doctor immediately if you experience coldness, paleness, discoloration, numbness, tingling, or pain in your hands or feet; muscle pain or weakness; severe or worsening headache; blurred vision; severe abdominal pain; chest pain; or shortness of breath while using these 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.

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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.