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Drug Interactions between pazopanib and Ron-Acid Plus

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

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Interactions between your drugs

Moderate

magaldrate PAZOPanib

Applies to: Ron-Acid Plus (magaldrate / simethicone) and pazopanib

GENERALLY AVOID: Coadministration with drugs that increase gastric pH may significantly decrease the oral bioavailability of pazopanib and reduce its concentrations in plasma. The solubility of pazopanib is pH-dependent, thus an increase in pH may interfere with its absorption. According to the product labeling, pazopanib is very slightly soluble at pH 1 and practically insoluble above pH 4 in aqueous media. When pazopanib (800 mg once daily in the morning) was coadministered with esomeprazole (40 mg once daily in the evening) for 5 days in 12 patients with advanced solid tumors, mean steady-state pazopanib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 40% each. The AUCs of three metabolites were also decreased. Mean steady-state trough concentration of pazopanib was reduced to 17.3 mcg/mL, which is close to the reported threshold of >=15 mcg/mL for clinical efficacy as suggested by a phase I trial of pazopanib. However, the potential for subtherapeutic pazopanib exposure in some patients cannot be excluded.

MANAGEMENT: Concomitant use of pazopanib with drugs that increase gastric pH should generally be avoided. If acid-suppression therapy is required, short-acting antacids should be considered, with dosing separated by several hours from pazopanib dosing. Some experts recommend administering pazopanib at least 1 hour before or 2 hours after antacids.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  3. "Product Information. Votrient (pazopanib)." GlaxoSmithKline (2009):
  4. Tan AR, Gibbon DG, Stein MN, et al. "Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors." Cancer Chemother Pharmacol 71 (2013): 1635-43
  5. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG "Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective." Lancet Oncol 15 (2014): e315-e326
  6. Yu G, Zheng QS, Wang DX, Zhou HH, Li GF "Drug interactions between tyrosine-kinase inhibitors and acid suppressive agents: more than meets the eye." Lancet Oncol 15 (2014): e469-70
View all 6 references

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Drug and food interactions

Major

PAZOPanib food

Applies to: pazopanib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of pazopanib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Although not studied, the interaction may increase the risk of QT interval prolongation and torsade de pointes arrhythmia as well as severe and fatal hepatotoxicity associated with the use of pazopanib.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of pazopanib. The mechanism of interaction is unknown. Administration of pazopanib with a high-fat or low-fat meal results in an approximately 2-fold increase in peak plasma concentration (Cmax) and systemic exposure (AUC).

MANAGEMENT: Patients treated with pazopanib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Pazopanib should be administered at least one hour before or two hours after a meal.

References

  1. "Product Information. Votrient (pazopanib)." GlaxoSmithKline (2009):

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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.

See also

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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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