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Drug Interactions between osilodrostat and st. john's wort

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

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Interactions between your drugs

Major

St. John's wort osilodrostat

Applies to: st. john's wort and osilodrostat

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4 and/or 2B6 may decrease the plasma concentrations of osilodrostat, which is partially metabolized by these isoenzymes. According to the product labeling, multiple CYP450 isoenzymes (CYP450 3A4, 2B6, and 2D6) and UDP-glucuronosyltransferases contribute to osilodrostat metabolism, and no single pathway contributes greater than 25% to the total clearance. Some of the known potent CYP450 3A4 and 2B6 inducers also induce UDP-glucuronosyltransferases. Pharmacokinetic data for osilodrostat in combination with a potent inducer of one or more of these pathways have not been reported. Reduced therapeutic efficacy of osilodrostat may occur during coadministration. On the other hand, discontinuation of a potent CYP450 3A4 and/or 2B6 inducer during treatment with osilodrostat may result in increased osilodrostat plasma concentrations and increased risk of adverse effects such as hypocortisolism (which may lead to life-threatening adrenal insufficiency), QT prolongation (which may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death), and elevated androgen and 11-deoxycorticosterone levels (the latter of which may activate mineralocorticoid receptors and cause hypokalemia, edema, and hypertension).

MANAGEMENT: An increase in the dosage of osilodrostat may be required during concomitant use of a potent CYP450 3A4 and/or 2B6 inducer. Dosage adjustments should be based on clinical response and tolerance. Patients should have regular monitoring of 24-hour urine free cortisol and serum or plasma cortisol during treatment, as well as regular evaluations of their signs and symptoms. A reduction in dosage of osilodrostat may be required if the potent CYP450 3A4 and/or 2B6 inducer is discontinued during treatment with osilodrostat.

References

  1. (2020) "Product Information. Isturisa (osilodrostat)." Recordati Rare Diseases Inc
  2. (2022) "Product Information. Isturisa (osilodrostat)." Recordati Rare Diseases Australia Pty Ltd, ISTURISA PI v1.1
  3. (2021) "Product Information. Isturisa (osilodrostat)." Recordati Rare Diseases UK Ltd

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Drug and food interactions

Moderate

St. John's wort food

Applies to: st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. Patel S, Robinson R, Burk M (2002) "Hypertensive crisis associated with St. John's Wort." Am J Med, 112, p. 507-8

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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.

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