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Drug Interactions between Caprelsa 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

Moderate

St. John's wort vandetanib

Applies to: st. john's wort and Caprelsa (vandetanib)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of vandetanib, which is a substrate of the isoenzyme. In 16 healthy male subjects, coadministration of rifampin (600 mg/day on days 1 to 31) and vandetanib (single 300 mg oral dose on day 10) resulted in an approximately 40% decrease in vandetanib exposure (AUC) and almost 50% decrease in half-life (from 217.6 hours to 116.3 hours) compared to vandetanib administered alone. There was no significant change in the peak plasma concentration (Cmax) of vandetanib. In the presence of rifampin, the Cmax and AUC of a metabolite, N-desmethylvandetanib, increased by 414% and 266%, respectively. Rifampin also increased the Cmax and AUC of another metabolite, vandetanib N-oxide, by approximately 179% and 126%, respectively. However, the plasma concentrations of vandetanib N-oxide were very low throughout, thus the change in absolute plasma levels induced by rifampin was actually quite small. The clinical implications of these changes are unknown. The two metabolites have shown in vitro pharmacologic activity in cellular assays against vascular endothelial growth factor and epidermal growth factor, with N-desmethylvandetanib exhibiting similar potency to parent drug and vandetanib N-oxide exhibiting less than 1/50 the activity of the parent drug.

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

References

  1. Martin P, Oliver S, Robertson J, Kennedy SJ, Read J, Duvauchelle T (2011) "Pharmacokinetic drug interactions with vandetanib during cadministration with rifampicin or itraconazole." Drugs R D, 11, p. 37-51
  2. (2011) "Product Information. Vandetanib (vandetanib)." Astra-Zeneca Pharmaceuticals

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.