Pazopanib with Dexlansoprazole Interaction Details
Brand Names Associated with Pazopanib
- Pazopanib
- Votrient®
Brand Names Associated with Dexlansoprazole
- Dexilant® (formerly available as Kapidex®)
- Dexlansoprazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 20, 2023
Interaction Effect
Reduction in pazopanib bioavailability
Interaction Summary
Oral pazopanib administered with a proton pump inhibitor may result in decreased pazopanib concentrations. When pazopanib and esomeprazole were coadministered, there was a decrease in mean AUC and Cmax of pazopanib. Since the absorption and solubility of pazopanib depends on an acidic environment and repeated administration of a proton pump inhibitor elevates gastric pH for an extended period, the absorption of pazopanib will be reduced with coadministration, which may result in subtherapeutic exposure of pazopanib in some patients. Concomitant use should be avoided. If coadministration is necessary, consider alternative dosing regimens that do not increase gastric pH at the time of pazopanib dosing (eg, late evening administration of pazopanib). However, in another study there were no significant effects on PFS or OS when coadministered in patients with metastatic renal cell carcinoma . Short acting antacids should be considered. Administration of pazopanib and antacids should be separated by several hours .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of pazopanib with a proton pump inhibitor should be avoided. The absorption and solubility of pazopanib depends on an acidic environment and will be reduced with coadministration of a proton pump inhibitor, which may result in subtherapeutic exposure of pazopanib in some patients. If concomitant use is necessary, consider alternative dosing regimens that do not increase gastric pH at the time of pazopanib dosing or administer pazopanib at a time when gastric pH is expected to be low, such as late evening. Short acting antacids should be considered in place of proton pump inhibitors. Administration of pazopanib and antacids should be separated by several hours .
Mechanism Of Interaction
Decreased solubility and absorption of pazopanib due to increased gastric pH by proton pump inhibitors
Literature Reports
A) In a retrospective cohort study in patients with metastatic renal cell carcinoma, concomitant use (n=66) of pazopanib and a proton pump inhibitor (esomeprazole, lansoprazole, omeprazole, pantoprazole) or a histamine-2 receptor antagonist (famotidine, ranitidine) compared with pazopanib alone (n=24) did not significantly reduce progression-free survival (PFS; 9 vs 11 months) or overall survival (OS; 28 vs 30.1 months). There was also no significant difference in patients receiving a proton pump inhibitor (n=57) compared with a histamine-2 receptor antagonist (n=9) on median PFS (11 vs 8 months) or median OS (27 vs 31 months) .
B) Coadministration of pazopanib and esomeprazole led to decreases in pazopanib mean AUC 24 hours post-dose (848 to 512 mcg x hr/mL) and mean Cmax (48.9 to 28.4 mcg/mL). Plasma samples were analyzed for 12 patients with advanced solid tumors who received oral pazopanib 800 mg once daily in the morning (at least 1 hour before or 2 hours after the morning meal) for 7 days and then received esomeprazole 40 mg once daily in the evening (at bedtime, about 3 hours after the evening meal) for 5 days. The mean AUC 24 hours post-dose and Cmax for pazopanib metabolites were also lower in the presence of esomeprazole. Concomitant use of esomeprazole may result in subtherapeutic exposure of pazopanib for some patients .
Pazopanib Overview
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Pazopanib is used to treat advanced renal cell carcinoma (RCC, a type of cancer that begins in the cells of the kidneys) in adults. Pazopanib is in a class of medications called kinase inhibitors. It works by slowing or stopping the spread of cancer cells.
Dexlansoprazole Overview
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Dexlansoprazole is used to treat the symptoms of gastroesophageal reflux disease (GERD; a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus [tube between the throat and stomach]) in adults and children 12 years of age and older. It is also used to treat esophagitis (swelling that may damage tissues of the esophagus) in adults and children 12 years of age and older. Dexlansoprazole is used for the maintenance treatment of esophagitis and healing in adults and children 12 years of age and older. Dexlansoprazole is in a class of medications called proton pump inhibitors. It works by decreasing the amount of acid made in the stomach.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.