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Interactions between Asciminib and Bosutinib

1 drug interaction and 16 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

bosutinib asciminib

Applies to: bosutinib and asciminib
Monitor

Coadministration with inhibitors of CYP450 3A4 and/or P-glycoprotein (P-gp) may increase the plasma concentrations of bosutinib, which is a substrate of the isoenzyme and efflux transporter. In 24 healthy volunteers, administration of a single 100 mg dose of bosutinib with the potent CYP450 3A4 and P-gp inhibitor ketoconazole (400 mg/day for 5 days) under fasting conditions resulted in a 5.2-fold increase in bosutinib peak plasma concentration (Cmax) and 8.6-fold increase in systemic exposure (AUC) compared to administration of bosutinib alone. Ketoconazole also decreased the mean apparent clearance of bosutinib by approximately 9-fold and increased the mean terminal half-life from 46.2 hours to 69.0 hours. No data are available for use with less potent CYP450 3A4 inhibitors or P-gp inhibitors.

Management

Caution is advised when bosutinib is used with CYP450 3A4 or P-gp inhibitors. Patients should be monitored more closely for development of adverse effects such as diarrhea, nausea, vomiting, abdominal pain, myelosuppression, hepatotoxicity, and fluid retention (e.g., pericardial effusion, pleural effusion, pulmonary edema, peripheral edema).

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2012) "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition.

It can be intentional, when combining drugs with similar actions adds demonstrated therapeutic benefit — or unintentional, such as when a patient sees multiple prescribers or fills prescriptions at more than one pharmacy, which can lead to adverse effects.

Duplication:

Bcr-abl tyrosine kinase inhibitors

The recommended maximum number of medicines in the 'BCR-ABL tyrosine kinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'BCR-ABL tyrosine kinase inhibitors' category:

  • asciminib
  • bosutinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

bosutinib Food/Lifestyle

Applies to: bosutinib
Adjust dosing interval

Food enhances the oral bioavailability of bosutinib. When given with a high-fat meal, bosutinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.8- and 1.7-fold, respectively.

Generally avoid

Coadministration with grapefruit juice is likely to increase the plasma concentrations of bosutinib, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

Management

Bosutinib should be administered with a meal. The consumption of grapefruit, grapefruit juice, and supplements that contain grapefruit extract should be avoided.

References (1)
  1. (2012) "Product Information. Bosulif (bosutinib)." Pfizer U.S. Pharmaceuticals Group
Moderate:

asciminib Food/Lifestyle

Applies to: asciminib
Adjust dosing interval

Food may reduce the oral bioavailability of asciminib. When a single 40 mg dose of asciminib was administered with a low-fat meal (400 calories; 25% fat) in healthy volunteers, asciminib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 30%, respectively, compared to asciminib administered in the fasted state. Administration with a high-fat meal (1000 calories; 50% fat) decreased the Cmax and AUC of asciminib by 68% and 62%, respectively.

Management

To ensure adequate asciminib exposures, food consumption should be avoided for at least 2 hours before and 1 hour after taking asciminib.

References (2)
  1. (2021) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals
  2. (2022) "Product Information. Scemblix (asciminib)." Novartis Pharmaceuticals UK Ltd, Scemblix 20 mg film-

Disease interactions

13 potential interactions Applies to: 12 conditions, including High Blood Pressure, Heart Failure, Diarrhea, Fluid Retention, and Liver Disease.

Bone Marrow Depression/Low Blood Counts

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Thrombocytopenia, aplastic anemia, agranulocytosis, and neutropenia occur with BCR-ABL tyrosine kinase inhibitors. Therapy with these drugs should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed every 1 to 2 weeks for the first month of therapy and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, reduce dose, or discontinue therapy as necessary.

Cardiovascular Conditions and Disorders

Major:

asciminib

Asciminib has a major potential interaction with Cardiovascular Conditions and Disorders.

Cardiovascular toxicity has been reported with asciminib in patients with preexisting cardiovascular conditions or risk factors for cardiovascular disease. Reports of cardiovascular toxicity have included ischemia, arterial thrombotic and embolic conditions, and cardiac failure. Arrhythmia, including QTc prolongation, has been reported. Monitor patients with history of cardiovascular risk factors for cardiovascular signs and symptoms. Treat as clinically indicated. For cardiovascular toxicity, temporarily withhold, reduce dose, or permanently discontinue therapy, based on persistence of cardiovascular toxicity.

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Cardiovascular events (including arterial vascular occlusive events, peripheral arterial occlusive disease, and ischemic cerebrovascular events) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitors. Patients should seek immediate medical attention if acute signs or symptoms of cardiovascular events occur. Cardiovascular status should be evaluated, and cardiovascular risk factors should be monitored and actively managed during treatment.

Dehydration

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Dehydration.

Adequate hydration might be necessary during therapy with bosutinib as diarrhea, nausea, vomiting, and abdominal pain occur with treatment. Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement. To manage gastrointestinal toxicity, withhold, dose reduce, or discontinue bosutinib as necessary.

Diarrhea

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Diarrhea.

Adequate hydration might be necessary during therapy with bosutinib as diarrhea, nausea, vomiting, and abdominal pain occur with treatment. Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement. To manage gastrointestinal toxicity, withhold, dose reduce, or discontinue bosutinib as necessary.

Fluid Retention

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Fluid Retention.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Heart Failure

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Heart Failure.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

High Blood Pressure

Moderate:

asciminib

Asciminib has a moderate potential interaction with High Blood Pressure.

The use of asciminib may cause hypertension. Blood pressure should be well-controlled prior to initiating asciminib and treated as needed with standard anti-hypertensive therapy. For persistent hypertension despite anti-hypertensive medications, temporarily withhold, reduce dose, or permanently discontinue therapy, based on the persistence of hypertension.

Liver Disease

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Liver Disease.

Bosutinib is primarily metabolized by the CYP 450 3A4. Therapy with bosutinib should be administered cautiously in patients with hepatic impairment and the starting dose should be 200 mg daily in patients with baseline hepatic impairment. The manufacturer recommends performing hepatic enzyme tests monthly for the first three months of bosutinib treatment and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, reduce dose, or discontinue bosutinib as necessary.

Pancreatitis

Major:

asciminib

Asciminib has a major potential interaction with Pancreatitis.

Asciminib can cause increases in serum lipase. Patients with a previous history of pancreatitis might be at increased risk and should be monitored carefully for lipase elevations and any abdominal symptoms. Serum lipase should be monitored monthly and as clinically indicated. If lipase and amylase elevations are accompanied by abdominal symptoms, hold therapy, and rule out pancreatitis.

Pleural Effusion

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Pleural Effusion.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Renal Dysfunction

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Renal Dysfunction.

An on-treatment decline in estimated glomerular filtration rate (eGFR) has occurred in patients treated with bosutinib. The manufacturer recommends reducing the bosutinib starting dose in patients with severe (CrCl) less than 30 mL/min) or moderate (CrCl 30 to 50 mL/min) renal impairment at baseline. Consider dose adjustment in patients with baseline and treatment emergent renal impairment. It is recommended to monitor patients for renal function at baseline and during therapy with bosutinib, with particular attention to those patients who have preexisting renal impairment or risk factors for renal dysfunction.

Vomiting

Moderate:

bosutinib

Bosutinib has a moderate potential interaction with Vomiting.

Adequate hydration might be necessary during therapy with bosutinib as diarrhea, nausea, vomiting, and abdominal pain occur with treatment. Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement. To manage gastrointestinal toxicity, withhold, dose reduce, or discontinue bosutinib as necessary.

More resources

asciminib

A total of 773 drugs are known to interact with asciminib.

bosutinib

A total of 597 drugs are known to interact with bosutinib.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.