Interactions between Adagrasib and Tucatinib
1 drug interaction and 6 additional warnings found for the following 2 drugs:
- adagrasib
- tucatinib
Drug interactions
Major drug interactions
Major:
tucatinib adagrasib
Applies to: tucatinib and adagrasib
Adjust dosing interval
Adagrasib can cause concentration-dependent, prolongation of the QT interval. Coadministration of potent CYP450 3A4 inhibitors before adagrasib has reached steady-state may significantly increase the plasma concentrations of adagrasib, which is primarily metabolized by the isoenzyme. From clinical studies, adagrasib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.4-fold and 4-fold, respectively, following concomitant use of a single dose of adagrasib (200 mg) with itraconazole, a potent CYP450 3A4 inhibitor. No clinically significant differences in the pharmacokinetics of adagrasib at steady state were predicted when used concomitantly with itraconazole. Elevated plasma concentrations of adagrasib may increase the risk for adverse effects such as QT prolongation, diarrhea, fatigue, musculoskeletal pain, hepatotoxicity, and renal impairment. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Management
Adagrasib manufacturer recommends avoiding its concomitant use with potent CYP450 3A4 inhibitors until adagrasib concentrations have reached steady state (after approximately 8 days). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References (1)
- (2022) "Product Information. Krazati (adagrasib)." Mirati Therapeutics, Inc.
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
adagrasib Food/Lifestyle
Applies to: adagrasib
Adjust dosing interval
Adagrasib can cause concentration-dependent, prolongation of the QT interval. Theoretically, coadministration with grapefruit juice before adagrasib has reached steady-state may significantly increase the plasma concentrations of adagrasib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, itraconazole. In a clinical drug interaction study, adagrasib peak plasma concentration (Cmax) and systemic exposure (AUC) were increased by 2.4-fold and 4-fold, respectively following concomitant use of a single dose of adagrasib (200 mg) with itraconazole. No clinically significant differences in the pharmacokinetics of adagrasib at steady state were predicted when used concomitantly with itraconazole. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to adagrasib may increase the risk of adverse effects such as QT prolongation, diarrhea, fatigue, musculoskeletal pain, hepatotoxicity, and renal impairment. Adagrasib pharmacokinetics were not significantly affected when administered with a high-fat meal.
Management
Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit or grapefruit juice until adagrasib concentrations have reached steady state (after approximately 8 days). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Adagrasib may be administered with or without food.
References (1)
- (2022) "Product Information. Krazati (adagrasib)." Mirati Therapeutics, Inc.
Disease interactions
5 potential interactions Applies to: 5 conditions, including Hyperkalemia, Liver Disease, Long QT Syndrome, Renal Dysfunction, and Pulmonary Impairment.
Hyperkalemia
Moderate:
tucatinib
Tucatinib has a moderate potential interaction with Hyperkalemia.
Tucatinib contains 60.6 mg potassium per 300 mg dose. This should be taken into consideration especially in patients with hyperkalemia or impaired kidney function who are on a controlled potassium diet.
Liver Disease
Moderate:
tucatinib
Tucatinib has a moderate potential interaction with Liver Disease.
Tucatinib is a hepatotoxic drug. Additionally, its exposure is increased in patients with severe hepatic impairment. This is the reason why the dosage must be reduced in these patients (Child-Pugh C). Consult the manufacturers prescribing information for details on dosage modification.
Long QT Syndrome
Moderate:
adagrasib
Adagrasib has a moderate potential interaction with Long QT Syndrome.
Adagrasib can cause QTc prolongation, which increases the risk of ventricular tachyarrhythmias or sudden death. Use should be avoided in patients with congenital long QT syndrome, in patients with concurrent QTc prolongation, and patients taking other medicines known to prolong the QTc interval. Monitor ECG and electrolytes prior to starting treatment and as indicated during therapy.
Pulmonary Impairment
Moderate:
adagrasib
Adagrasib has a moderate potential interaction with Pulmonary Impairment.
Adagrasib can cause interstitial lung disease (ILD)/pneumonitis which can be fatal. Patients should be monitored for new or worsening symptoms indicative of ILD/pneumonitis during treatment. Caution is advised in patients with pulmonary impairment.
Renal Dysfunction
Moderate:
tucatinib
Tucatinib has a moderate potential interaction with Renal Dysfunction.
Tucatinib contains 60.6 mg potassium per 300 mg dose. This should be taken into consideration especially in patients with hyperkalemia or impaired kidney function who are on a controlled potassium diet.
Report options
More resources
adagrasib
A total of 701 drugs are known to interact with adagrasib.
- Adagrasib is in the drug class miscellaneous antineoplastics.
- Adagrasib is used to treat Non Small Cell Lung Cancer.
tucatinib
A total of 547 drugs are known to interact with tucatinib.
- Tucatinib is in the drug class HER2 inhibitors.
- Tucatinib is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.