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Pazopanib CAN be Co-Administered with the Following Agents1

  • CYP1A2 substrates, CYP2C9 substrates (e.g. warfarin), CYP2C19 substrates (e.g. omeprazole)1,2

Pazopanib CAN be Co-Administered with the Following Agents, IF Administered with Caution

  • UGT1A1 substrates (e.g. irinotecan)2
  • Taxanes: paclitaxel1,2
  • Simvastatin (insufficient data on other statins)1,2
  • Anti-arrhythmic agents and other drugs that may prolong the QT interval1,2

Pazopanib CANNOT be Co-Administered with the Following Agents

  • Strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin), grapefruit1,2
  • CYP3A4 inducers (e.g. rifampicin)1,2
  • Potent P-gp or BCRP inhibitors or inducers1,2
  • CYP substrates with narrow therapeutic windows that are metabolised by CYP3A4, CYP2D6, or CYP2C81
  • Drugs that raise gastric pH (avoid)1,3

Additional important information when prescribing pazopanib

If co-administration of pazopanib and strong CYP3A4 inhibitors is warranted, reduce the pazopanib dose to 400 mg.1,2,4,5

If administration of a strong CYP3A4 inducer (or chronic use) is unavoidable, do not use pazopanib.1,5

Concomitant use of pazopanib and simvastatin increases the risk of ALT elevations and should be undertaken with caution and close monitoring.1,3

Avoid co-administration of pazopanib and medicines that increase gastric pH.1,2

Consider short-acting antacids in place of PPIs and H2 receptor antagonists, and separate antacid and pazopanib dosing by several hours.1,4

If concomitant use of a PPI is medically necessary, take pazopanib without food once daily in the evening concomitantly with the PPI.3

If concomitant use of an H2-receptor antagonist is medically necessary, take pazopanib without food ≥2 hours before, or ≥10 hours after, the H2-receptor antagonist dose.1

Monitor patients with a history of QT interval prolongation, those taking medications that may prolong the QT interval, and those with relevant pre-existing cardiac disease.1,2 If indicated, an ECG should be obtained 24-48 hours before and 1 week after initiating concomitant therapy.4

Care should be taken when co-administering pazopanib with other oral BCRP and P-gp substrates, as inhibition of BCRP and P-gp by pazopanib in the gastrointestinal tract cannot be excluded.2

References

  1. Food and Drug Administration. Pazopanib (VOTRIENT) Prescribing information. 2015.
  2. European Medicines Agency. Pazopanib (VOTRIENT) Summary of Product Characteristics. 2015.
  3. European Medicines Agency. Nintedanib (VARGATEF). Summary of Product Characteristics. 2015.
  4. van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol 2014; 15: e315-326.
  5. Teo YL, Ho HK, Chan A. Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations. Br J Clin Pharmacol 2015; 79: 241-253.

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