Nilotinib with Ranitidine Interaction Details

Brand Names Associated with Nilotinib

Brand Names Associated with Ranitidine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 19, 2023

Interaction Effect

Reduction in nilotinib bioavailability

Interaction Summary

The solubility of nilotinib is pH-dependent, and absorption and subsequent bioavailability may be reduced when coadministered with a H2 blocker, which raises the pH of the upper gastrointestinal tract. In healthy subjects, when a single 400 mg-dose of nilotinib was administered 2 hours before and 10 hours after famotidine (an H2 blocker) there were no significant changes in nilotinib pharmacokinetics. There was also no significant change in the efficacy of nilotinib observed with concurrent administration of a proton pump inhibitor (PPI) or H2 blocker for any duration compared with patients with no PPI or H2 blocker use during a retrospective review of 2 clinical trials (n=748) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase . If concurrent use is required, it is recommended to administer the H2 blocker approximately 10 hours before or 2 hours after nilotinib .

Severity

Moderate

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

If concurrent use of nilotinib and an H2 blocker is required, it is recommended to administer the H2 blocker approximately 10 hours before or 2 hours after nilotinib.

Mechanism Of Interaction

Decreased solubility and absorption of nilotinib due to increased pH of the upper gastrointestinal tract caused by H2 blockers

Literature Reports

A) Major molecular response (MMR) rates at 12 months were not affected by concurrent administration of proton pump inhibitors (PPI) or H2 blockers with nilotinib, according to a retrospective analysis of patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase enrolled in a phase 3 study (n=492). PPIs included esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole; H2 blockers included cimetidine, famotidine, and ranitidine. MMR at 12 months was achieved in 49.6% (59 of 119) of patients who received nilotinib and a PPI or H2 blocker for any duration compared with 41% (53 of 373) of patients who did not receive any PPI or H2 blocker (p=0.13). Median duration of concurrent use was 137 days for PPIs and 33 days for H2 blockers while on nilotinib therapy, with 9.3% (46 of 492) of patients receiving concurrent therapy for more than 50% of the study period .

B) Major cytogenic response (MCyR) and complete cytogenic response (CCyR) rates at 12 months were not affected by concurrent administration of proton pump inhibitors (PPI) or H2 blockers with nilotinib, according to a retrospective analysis of imatinib-experienced patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase enrolled in a phase 2 study (n=256). PPIs included esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole; H2 blockers included cimetidine, famotidine, and ranitidine. MCyR at 12 months was achieved in 64% (55 of 86) of patients who received nilotinib and a PPI or H2 blocker for any duration compared with 57.6% (98 of 170) of patients who did not receive any PPI or H2 blocker (p=0.4), and CCyR at 12 months was achieved in 45.3% (39 of 86) and 38.2% (65 of 170) of patients (p=0.34), respectively. Median duration of concurrent use was 177 days for PPIs and 96 days for H2 blockers while on nilotinib therapy, with 23% (59 of 256) of patients receiving concurrent therapy for more than 50% of the study period .

Nilotinib Overview

• Nilotinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells) who have recently found to have this condition in adults and children 1 year of age and older. It is also used to treat certain types of CML in adults whose disease could not be treated successfully with imatinib (Gleevec) or adults who cannot take imatinib because of side effects. Nilotinib is also used to treat certain types of CML in children 1 year of age or older whose disease could not be treated successfully with other tyrosine kinase inhibitor therapies or who cannot take these medications because of side effects. Nilotinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Ranitidine Overview

• Ranitidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter ranitidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Ranitidine is in a class of medications called H₂ blockers. It decreases the amount of acid made in the stomach.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.