Interactions between Adagrasib and Ceo-Two
1 drug interaction and 10 additional warnings found for the following 2 drugs:
- adagrasib
- Ceo-Two (potassium bitartrate/sodium bicarbonate)
Drug interactions
Moderate drug interactions
Moderate:
potassium bitartrate adagrasib
Applies to: Ceo-Two (potassium bitartrate / sodium bicarbonate) and adagrasib
Monitor
Bowel cleansing as well as overuse of certain laxatives may cause electrolyte loss and increase the risk of torsade de pointes ventricular arrhythmia in patients treated with drugs that prolong the QT interval. Electrolyte disturbances including hypokalemia and hypomagnesemia have been reported with laxative abuse and are known risk factors for torsade de pointes associated with QT interval prolongation.
Management
Patients treated with drugs that prolong the QT interval should exercise caution when self-medicating with laxatives. The recommended dosage and duration of use should not be exceeded. Patients treated with lactulose for more than six months should be monitored periodically for electrolyte imbalance. 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 (4)
- Chin RL (1998) "Laxative-induced hypokalemia." Ann Emerg Med, 32, p. 517-8
- Muller-Lissner SA (1993) "Adverse effects of laxatives: fact and fiction." Pharmacology, 47, p. 138-45
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Schaefer DC, Cheskin LJ (1998) "Constipation in the elderly." Am Fam Physician, 58, p. 907-14
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
9 potential interactions Applies to: 9 conditions, including Heart Failure, Inflammatory Bowel Disease, Fluid Retention, Long QT Syndrome, and Renal Dysfunction.
Alkalosis
Moderate:
Ceo-Two
The sodium bicarbonate in Ceo-Two has a moderate potential interaction with Alkalosis.
Alkalinizing agents act as proton acceptors and/or dissociate to provide bicarbonate ions. Elimination of bicarbonate is decreased in patients with renal impairment and can result in metabolic alkalosis. Symptoms of metabolic alkalosis include hyperirritability or tetany, arrhythmia, and/or seizures (altered pH = altered calcium), or lactic acidosis due to impaired oxygen release. Therapy with alkalinizing agents should be administered with extreme caution in patients with compromised renal function. Clinical monitoring of renal function, acid/base balance and electrolytes is recommended.
Fluid Retention
Major:
Ceo-Two
The sodium bicarbonate in Ceo-Two has a major potential interaction with Fluid Retention.
Alkalinizing agents containing sodium can induce sodium and water retention and result in hypernatremia, hypokalemia, hyperosmolality, edema and aggravation of congestive heart failure. Therapy with sodium- containing alkalinizing agents should not be used in patients with hypernatremia or fluid retention. Clinical monitoring of acid/base balance and electrolytes prior to, during, a following completion of therapy with alkalinizing agents is recommended.
Gastrointestinal Obstruction
Major:
Ceo-Two
The potassium bitartrate in Ceo-Two has a major potential interaction with Gastrointestinal Obstruction.
The use of laxatives is contraindicated in patients with intestinal obstruction disorders. Patients with intestinal obstruction disorders may need their underlying condition treated to correct the constipation. Some laxatives require reduction in the colon to their active form to be effective which may be a problem in patients with intestinal obstruction.
Heart Failure
Major:
Ceo-Two
The sodium bicarbonate in Ceo-Two has a major potential interaction with Heart Failure.
Alkalinizing agents containing sodium can induce sodium and water retention and result in hypernatremia, hypokalemia, hyperosmolality, edema and aggravation of congestive heart failure. Therapy with sodium- containing alkalinizing agents should not be used in patients with hypernatremia or fluid retention. Clinical monitoring of acid/base balance and electrolytes prior to, during, a following completion of therapy with alkalinizing agents is recommended.
Hypernatremia
Major:
Ceo-Two
The sodium bicarbonate in Ceo-Two has a major potential interaction with Hypernatremia.
Alkalinizing agents containing sodium can induce sodium and water retention and result in hypernatremia, hypokalemia, hyperosmolality, edema and aggravation of congestive heart failure. Therapy with sodium- containing alkalinizing agents should not be used in patients with hypernatremia or fluid retention. Clinical monitoring of acid/base balance and electrolytes prior to, during, a following completion of therapy with alkalinizing agents is recommended.
Inflammatory Bowel Disease
Major:
Ceo-Two
The potassium bitartrate in Ceo-Two has a major potential interaction with Inflammatory Bowel Disease.
The use of laxatives is contraindicated in patients with inflammatory bowel disease. Patients with inflammatory bowel disease may experience colonic perforation with use of stimulant laxatives.
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:
Ceo-Two
The sodium bicarbonate in Ceo-Two has a moderate potential interaction with Renal Dysfunction.
Alkalinizing agents act as proton acceptors and/or dissociate to provide bicarbonate ions. Elimination of bicarbonate is decreased in patients with renal impairment and can result in metabolic alkalosis. Symptoms of metabolic alkalosis include hyperirritability or tetany, arrhythmia, and/or seizures (altered pH = altered calcium), or lactic acidosis due to impaired oxygen release. Therapy with alkalinizing agents should be administered with extreme caution in patients with compromised renal function. Clinical monitoring of renal function, acid/base balance and electrolytes is recommended.
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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.
Ceo-Two
A total of 405 drugs are known to interact with Ceo-Two.
- Ceo-two is in the drug class laxatives.
- Ceo-two is used to treat Constipation.
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
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