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Drug Interactions between Aldroxicon II and nirogacestat

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

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Interactions between your drugs

Major

aluminum hydroxide nirogacestat

Applies to: Aldroxicon II (aluminum hydroxide / magnesium hydroxide / simethicone) and nirogacestat

ADJUST DOSING INTERVAL: Concurrent administration of agents that increase gastric pH such as proton pump inhibitors (PPIs), histamine type 2 (H2)-receptor antagonists, or antacids may decrease the plasma concentrations of nirogacestat. According to the manufacturer, nirogacestat is poorly soluble at a pH of 6 or more. Reduced therapeutic efficacy may occur.

MANAGEMENT: The manufacturer advises that antacids may be preferable if the use of a gastric acid reducing agent is considered clinically necessary. Dosage of the antacid should be separated from nirogacestat by at least 2 hours.

References

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

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Major

magnesium hydroxide nirogacestat

Applies to: Aldroxicon II (aluminum hydroxide / magnesium hydroxide / simethicone) and nirogacestat

ADJUST DOSING INTERVAL: Concurrent administration of agents that increase gastric pH such as proton pump inhibitors (PPIs), histamine type 2 (H2)-receptor antagonists, or antacids may decrease the plasma concentrations of nirogacestat. According to the manufacturer, nirogacestat is poorly soluble at a pH of 6 or more. Reduced therapeutic efficacy may occur.

MANAGEMENT: The manufacturer advises that antacids may be preferable if the use of a gastric acid reducing agent is considered clinically necessary. Dosage of the antacid should be separated from nirogacestat by at least 2 hours.

References

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

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Drug and food interactions

Major

aluminum hydroxide food

Applies to: Aldroxicon II (aluminum hydroxide / magnesium hydroxide / simethicone)

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67

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Major

nirogacestat food

Applies to: nirogacestat

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

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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.