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Drug interactions of Sotorasib

1.Effects of Other Drugs on Sotorasib

Acid-Reducing Agents

The solubility of sotorasib is pH-dependent. Coadministration of Sotorasib with gastric acid-reducing agents  decreased sotorasib concentrations, which may reduce the efficacy of sotorasib.  Avoid coadministration of Sotorasib with proton pump inhibitors (PPIs), H2 receptor antagonists, and locally acting antacids. If coadministration with an acid-reducing agent cannot be avoided, administer Sotorasib 4  hours before or 10 hours after administration of a locally acting antacid.

Strong CYP3A4 Inducers

Sotorasib is a CYP3A4 substrate. Coadministration of Sotorasib with a strong CYP3A4 inducer decreased  sotorasib concentrations, which may reduce the efficacy of sotorasib. Avoid  coadministration of Sotorasib with strong CYP3A4 inducers.

2.Effects of Sotorasib on Other Drugs

CYP3A4 Substrates

Sotorasib is a CYP3A4 inducer. Coadministration of Sotorasib with a CYP3A4 substrate decreased its plasma  concentrations, which may reduce the efficacy of the substrate. Avoid  coadministration of Sotorasib with CYP3A4 sensitive substrates, for which minimal concentration changes may  lead to therapeutic failures of the substrate. If coadministration cannot be avoided, increase the sensitive CYP3A4  substrate dosage in accordance with its Prescribing Information.  

P-glycoprotein (P-gp) Substrates

Sotorasib is a P-gp inhibitor. Coadministration of Sotorasib with a P-gp substrate increased its plasma  concentrations, which may increase the adverse reactions of the substrate.  Avoid coadministration of Sotorasib with P-gp substrates, for which minimal concentration changes may lead to serious toxicities. If coadministration cannot be avoided, decrease the P-gp substrate dosage in accordance with its  Prescribing Information.  

Breast Cancer Resistance Protein (BCRP) Substrates

Sotorasib is a BCRP-inhibitor. Coadministration of Sotorasib with a BCRP substrate increased its plasma  concentrations, which may increase the risk of adverse reactions of the  substrate. When coadministered with Sotorasib, monitor for adverse reactions of the BCRP substrate and  decrease the BCRP substrate dosage in accordance with its Prescribing Information.

from FDA，2023.04