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Drug Interactions between Jynarque and osimertinib

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

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Interactions between your drugs

Minor

tolvaptan osimertinib

Applies to: Jynarque (tolvaptan) and osimertinib

Coadministration with osimertinib may alter the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. In vitro, osimertinib has been shown to be a competitive inhibitor as well as inducer of CYP450 3A4. However, a clinically significant inhibitory effect on CYP450 3A4 has not been demonstrated in clinical drug interaction studies. In a pharmacokinetic study of 49 patients with non-small cell lung cancer, coadministration of osimertinib with the sensitive CYP450 3A4 substrate simvastatin decreased the area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of simvastatin by approximately 9% and 23%, respectively. These reductions are also not considered clinically significant. Based on these observations, osimertinib may be administered with CYP450 3A4 substrates without the need for increased clinical monitoring.

References (5)
  1. (2024) "Product Information. Tagrisso (osimertinib)." Astra-Zeneca Pharmaceuticals
  2. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca Pharma Inc
  3. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca UK Ltd
  4. (2024) "Product Information. Tagrisso (osimertinib)." AstraZeneca Pty Ltd, 6
  5. Harvey RD, Aransay NR, Isambert N, Lee J, Arkenau T, vansteenkiste j, Dickinson PA, bui k, Weilert D, So K, thomas k, Vishwanathan K (2018) "Effect of multiple-dose osimertinib on the pharmacokinetics of simvastatin and rosuvastatin" Br J Clin Pharmacol, 84, p. 2877-88

Drug and food interactions

Moderate

tolvaptan food

Applies to: Jynarque (tolvaptan)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References (1)
  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

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.

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