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Drug Interactions between dabrafenib and liraglutide

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

liraglutide dabrafenib

Applies to: liraglutide and dabrafenib

MONITOR: Coadministration with dabrafenib may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4 and/or 2C9, including many antidiabetic agents such as nateglinide, repaglinide, linagliptin, saxagliptin, and sulfonylureas. Dabrafenib has been found in vitro and in vivo to be an inducer of CYP450 3A4 and 2C9 using the probe substrates midazolam and warfarin, respectively. Onset of induction is likely to occur after 3 days of repeat dosing with dabrafenib; however, transient inhibition of these isoenzymes may be observed during the first few days of treatment. According to the product labeling, hyperglycemia is a commonly reported side effect during treatment with dabrafenib, which may require dosage increases of insulin and oral hypoglycemic agents or initiation of such therapy. It is unclear whether dabrafenib itself can impair glucose metabolism, or if the hyperglycemia is primarily due to a pharmacokinetic interaction between dabrafenib and some antidiabetic agents.

MANAGEMENT: Caution is advised when dabrafenib is prescribed to patients with diabetes, particularly those receiving antidiabetic agents that are metabolized by CYP450 3A4 and/or 2C9. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of dabrafenib, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to notify their physician if their blood glucose is consistently high or if they experience symptoms of severe hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should be observed for hypoglycemia when dabrafenib is withdrawn from their therapeutic regimen.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2013) "Product Information. Tafinlar (dabrafenib)." GlaxoSmithKline

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Drug and food interactions

Moderate

liraglutide food

Applies to: liraglutide

MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can delay gastric emptying, which may impact the absorption of concomitantly administered oral medications. Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others. According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel. Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin). The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be dose- and time-dependent, with the greatest effect observed after a single 5 mg dose but diminished after subsequent doses. When acetaminophen was administered following a single 5 mg dose of tirzepatide, acetaminophen peak plasma concentration (Cmax) was decreased by 50% and its median time to peak plasma concentration (Tmax) delayed by 1 hour. However, no significant impact on acetaminophen Cmax and Tmax was observed after 4 consecutive weekly doses of tirzepatide (5 mg/5 mg/8 mg/10 mg), and the overall exposure (AUC) of acetaminophen was unaffected. Tirzepatide at lower doses of 0.5 mg and 1.5 mg also had minimal effects on acetaminophen exposure.

MANAGEMENT: Although no specific dosage adjustment of concomitant medications is generally recommended based on available data, potential clinical impact on some oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics). Pharmacologic response to concomitantly administered oral medications should be monitored more closely following initiation, dose adjustment, or discontinuation of a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.

References

  1. (2005) "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc
  2. (2010) "Product Information. Victoza (liraglutide)." Novo Nordisk Pharmaceuticals Inc
  3. (2014) "Product Information. Tanzeum (albiglutide)." GlaxoSmithKline
  4. (2014) "Product Information. Trulicity (dulaglutide)." Eli Lilly and Company
  5. (2016) "Product Information. Adlyxin (lixisenatide)." sanofi-aventis
  6. (2022) "Product Information. Ozempic (1 mg dose) (semaglutide)." Novo Nordisk Pharmaceuticals Inc
  7. (2023) "Product Information. Mounjaro (tirzepatide)." Eli Lilly and Company Ltd
  8. (2023) "Product Information. Mounjaro (tirzepatide)." Lilly, Eli and Company
  9. Eli Lilly Canada Inc. (2023) Product monograph including patient medication information MOUNJARO tirzepatide injection. https://pdf.hres.ca/dpd_pm/00068421.PDF
View all 9 references

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Moderate

dabrafenib food

Applies to: dabrafenib

ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.

References

  1. (2013) "Product Information. Tafinlar (dabrafenib)." GlaxoSmithKline

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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

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