Interactions between Adagrasib and Cyclobenzaprine
1 drug interaction and 15 additional warnings found for the following 2 drugs:
- adagrasib
- cyclobenzaprine
Drug interactions
Moderate drug interactions
Moderate:
cyclobenzaprine adagrasib
Applies to: cyclobenzaprine and adagrasib
Monitor
Coadministration with adagrasib may increase the plasma concentrations of drugs that are metabolized by the CYP450 3A4, 2D6 or 2C9 enzymatic pathways or are substrates of the P-glycoprotein (P-gp) efflux membrane transporter. When adagrasib 400 mg twice daily (two-thirds the approved recommended dosage) was administered with midazolam (a sensitive CYP450 3A4 substrate) and dextromethorphan (a sensitive CYP450 2D6 substrate) in pharmacokinetic studies, midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 4.8- and 21-fold, respectively, while dextromethorphan Cmax and AUC increased by 1.9- and 1.8-fold, respectively. Adagrasib at the approved recommended dosage of 600 mg twice daily is predicted to increase midazolam Cmax by 3.1-fold and AUC by 31-fold; dextromethorphan Cmax by 1.7-fold and AUC by 2.4-fold; warfarin (a sensitive CYP450 2C9 substrate) Cmax by 1.1-fold and AUC by 2.9-fold; and digoxin (a P-gp substrate) Cmax by 1.9-fold and AUC by 1.5-fold. These results suggest that adagrasib is a potent inhibitor of CYP450 3A4 and may be a moderate inhibitor of CYP450 2D6 and 2C9 at the approved recommended dosage of 600 mg twice daily.
Management
Caution is advised when adagrasib is used concomitantly with drugs that are substrates of CYP450 3A4, CYP450 2D6, CYP450 2C9 and/or P-gp, particularly sensitive substrates or those with a narrow therapeutic range. Substitution for these medications is recommended when possible, or initiate with lower dosages and monitor patient clinical response/tolerance and titrate accordingly if coadministration is required. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration and for any dosage adjustments that may be required.
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.
Moderate food/lifestyle interactions
Moderate:
cyclobenzaprine Food/Lifestyle
Applies to: cyclobenzaprine
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)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- 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.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Disease interactions
13 potential interactions Applies to: 13 conditions, including Heart Failure, Hypotension, Hyperthyroidism, Urinary Retention, and Long QT Syndrome.
Cardiovascular Conditions and Disorders
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Cardiovascular Conditions and Disorders.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
Cerebrovascular Insufficiency
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Cerebrovascular Insufficiency.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
Dehydration
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Dehydration.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
Gastrointestinal Obstruction
Moderate:
cyclobenzaprine
Cyclobenzaprine has a moderate potential interaction with Gastrointestinal Obstruction.
Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.
Glaucoma/Intraocular Hypertension
Moderate:
cyclobenzaprine
Cyclobenzaprine has a moderate potential interaction with Glaucoma/Intraocular Hypertension.
Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.
Heart Failure
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Heart Failure.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
History - Cerebrovascular Disease
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with History - Cerebrovascular Disease.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
History - Myocardial Infarction
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with History - Myocardial Infarction.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
Hyperthyroidism
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Hyperthyroidism.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
Hypotension
Major:
cyclobenzaprine
Cyclobenzaprine has a major potential interaction with Hypotension.
The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.
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.
Urinary Retention
Moderate:
cyclobenzaprine
Cyclobenzaprine has a moderate potential interaction with Urinary Retention.
Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.
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.
cyclobenzaprine
A total of 466 drugs are known to interact with cyclobenzaprine.
- Cyclobenzaprine is in the drug class skeletal muscle relaxants.
-
Cyclobenzaprine is used to treat the following conditions:
- Back Pain
- Chronic Myofascial Pain (off-label)
- Fibromyalgia
- Migraine (off-label)
- Muscle Spasm
- Pain
- Sciatica
- Temporomandibular Joint Disorder (off-label)
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.