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<p>Pazopanib, a multi-targeted tyrosine kinase inhibitor, is used for advanced renal cell carcinoma and soft tissue sarcoma. However, it is associated with dose-dependent adverse events (AEs), including hypertension, and gastrointestinal issues. Antacids like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are often co-administered, raising concerns about potential drug interactions. Pazopanib’s solubility and absorption are pH-dependent, with increased gastric pH potentially reducing its bioavailability. In this study, we analyzed VigiBase<sup>®</sup> data using multivariate logistic regression models and found significant interactions between pazopanib and antacids (PPIs, H2RAs, and others), suggesting reduced serious AE reporting, possibly due to lower pazopanib exposure. A secondary analysis of CYP3A4 inhibitors showed a non-significant trend for higher serious AEs, aligning with expected pharmacokinetic effects. These findings emphasize the need for caution when combining antacids with pazopanib, as it may reduce both toxicity and efficacy.</p>

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Pazopanib and antacids: insights from the WHO pharmacovigilance database

  • 期刊论文

  • 发表日期：

    2025年7月2日

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  • Kazuki Nishida,
  • Yao Liang,
  • Osamu Maeda,
  • Angélique Da Silva,
  • Yuichi Ando,
  • Basile Chrétien

摘要

Pazopanib, a multi-targeted tyrosine kinase inhibitor, is used for advanced renal cell carcinoma and soft tissue sarcoma. However, it is associated with dose-dependent adverse events (AEs), including hypertension, and gastrointestinal issues. Antacids like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are often co-administered, raising concerns about potential drug interactions. Pazopanib’s solubility and absorption are pH-dependent, with increased gastric pH potentially reducing its bioavailability. In this study, we analyzed VigiBase® data using multivariate logistic regression models and found significant interactions between pazopanib and antacids (PPIs, H2RAs, and others), suggesting reduced serious AE reporting, possibly due to lower pazopanib exposure. A secondary analysis of CYP3A4 inhibitors showed a non-significant trend for higher serious AEs, aligning with expected pharmacokinetic effects. These findings emphasize the need for caution when combining antacids with pazopanib, as it may reduce both toxicity and efficacy.