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Interactions between Adagrasib and S-Pack DM

1 drug interaction and 4 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

dextromethorphan adagrasib

Applies to: S-Pack DM (dextromethorphan / guaifenesin) and adagrasib
Monitor

Coadministration with CYP450 2D6 inhibitors may increase the plasma concentrations of dextromethorphan, which is primarily metabolized by this isoenzyme. Approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent are extensive metabolizers of CYP450 2D6 and may be affected by this interaction. Coadministration of dextromethorphan (60 mg orally, once) with the CYP450 2D6 inhibitor panobinostat (20 mg orally once a day on days 3, 5, and 8) in 14 patients with advanced cancer had a highly variable effect on dextromethorphan levels, increasing the peak plasma concentration (Cmax) of dextromethorphan by 20% to 200% and total systemic exposure (AUC 0 to infinity) by 20% to 130%, compared to dextromethorphan given alone. The moderate CYP450 2D6 inhibitor asunaprevir, given at 200 mg twice daily, also increased the Cmax and AUC of a single 30 mg dose of dextromethorphan by 2.7- and 3.9-fold, respectively, in 17 study subjects.

Management

Caution should be exercised if these drugs must be used together. Patients should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required. Additional consultation with individual product labeling may be advisable for further guidance.

References (13)
  1. Funck-Brentano C, Jacqz-Aigrain E, Leenhardt A, Roux A, Poirier JM, Jaillon P (1991) "Influence of amiodarone on genetically determined drug metabolism in humans." Clin Pharmacol Ther, 50, p. 259-66
  2. (2015) "Product Information. Farydak (panobinostat)." Novartis Pharmaceuticals
  3. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc
  4. (2024) "Product Information. Bisolvon Dry (dextromethorphan)." Sanofi-Aventis Australia Pty Ltd
  5. (2025) "Product Information. Abiraterone Acetate (abiraterone)." BluePoint Laboratories
  6. (2025) "Product Information. Theraflu Severe Cold Relief+Chest Congestion (acetaminophen/dextromethorphan/diphenhydramine/guaifenesin)." Haleon
  7. (2014) "Product Information. CINFATOS (dextrometorfano)." LABORATORIOS CINFA, S.A.
  8. (2025) "Product Information. Auvelity (bupropion-dextromethorphan)." Axsome Therapeutics, Inc.
  9. (2019) "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc, DM 29
  10. Sager JE, Lutz JD, Foti RS, Davis C, Kunze KL, Isoherranen N (2014) "Fluoxetine and norfluoxetine mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19 and CYP3A4." Clin Pharmacol and Therapeutic, 95, p. 653-62
  11. (2025) "Product Information. Benylin Dry Coughs (dextromethorphan)." McNeil Products Ltd
  12. (2017) "Product Information. Sunvepra (asunaprevir)." Bristol-Myers Squibb Canada Inc
  13. (2025) "Product Information. Amiodarone Hydrochloride (amiodarone)." Fresenius Kabi USA, LLC, DM 6

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)
  1. (2022) "Product Information. Krazati (adagrasib)." Mirati Therapeutics, Inc.

Moderate food/lifestyle interactions

Moderate:

dextromethorphan Food/Lifestyle

Applies to: S-Pack DM (dextromethorphan / guaifenesin)
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.

Disease interactions

2 potential interactions Applies to: 2 conditions, including Long QT Syndrome and Pulmonary Impairment.

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.

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More resources

adagrasib

A total of 701 drugs are known to interact with adagrasib.

S-Pack DM

A total of 375 drugs are known to interact with S-Pack DM.

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.

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