Interactions between Revumenib and Tolterodine
1 drug interaction and 17 additional warnings found for the following 2 drugs:
- revumenib
- tolterodine
Drug interactions
Major drug interactions
Major:
tolterodine revumenib
Applies to: tolterodine and revumenib
Generally avoid
Revumenib causes dose-related prolongation of the QT interval. Coadministration with other agents that can prolong the QT interval may result in additive effects and an increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In clinical trials, QT interval prolongation was reported as an adverse reaction in 29% of patients treated with revumenib at the recommended dosage for relapsed or refractory acute leukemia with a KMT2A translocation. Additionally, Grade 3 QT interval prolongation occurred in 12% of those patients and a greater than 60 msec increase in Fridericia-corrected QT interval (QTcF) from baseline was reported in 18% of patients. 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, hypocalcemia). Moreover, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Management
It is recommended to avoid revumenib in combination with other drugs that can prolong the QT interval. If concomitant use cannot be avoided, obtain electrocardiograms (ECGs) when initiating, during concomitant use, and as clinically indicated. Serum electrolytes, including potassium, magnesium, and calcium, should be monitored before starting revumenib therapy and monthly during treatment. Revumenib should not be started if baseline QTc is greater than 450 msec. Likewise, treatment should be interrupted and adjusted in accordance with the product labeling in patients who develop QTc prolongation greater than 480 msec. 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. Permanently discontinue revumenib in patients who develop QTc interval prolongation with life-threatening arrhythmia.
References (1)
- (2024) "Product Information. Revuforj (revumenib)." Syndax Pharmaceuticals, Inc
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
revumenib Food/Lifestyle
Applies to: revumenib
Adjust dosing interval
In pharmacokinetic studies, revumenib was administered while fasting or with a low fat meal. Revumenib has not been studied with meals of higher fat content and the impact on its pharmacokinetic parameters is unknown.
Monitor
Grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges may increase the plasma concentrations of revumenib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. In pharmacokinetic studies in patients with relapsed or refractory acute leukemia, revumenib area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) increased 2-fold following concomitant use with the potent CYP450 3A4 inhibitors posaconazole, itraconazole, and voriconazole, and 2.5-fold following concomitant use with the potent CYP450 3A4 inhibitor cobicistat. However, clinically significant differences in revumenib pharmacokinetics were not observed when used concomitantly with the moderate CYP450 3A4 inhibitors fluconazole and isavuconazole. 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. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. Increased exposure to revumenib may increase the risk of QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.
Management
Due to the potential impact of high fat content meals on revumenib absorption and exposure, it is recommended that revumenib be administered while fasting or with a low fat meal (approximately 400-500 calories, with 25% of calories from fat). In addition, if grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, or Seville oranges are consumed during treatment with revumenib, assess patient tolerability and monitor for serious adverse effects (e.g., QT prolongation and torsade de pointes arrhythmia, differentiation syndrome, neutropenia, thrombocytopenia).
References (2)
- (2024) "Product Information. Quinoric (hydroxychloroquine)." Bristol Laboratories Ltd
- (2024) "Product Information. Revuforj (revumenib)." Syndax Pharmaceuticals, Inc
Disease interactions
16 potential interactions Applies to: 13 conditions, including Heart Failure, Arrhythmia, Hypokalemia, Myasthenia Gravis, and Dementia.
Arrhythmia
Moderate:
revumenib
Revumenib has a moderate potential interaction with Arrhythmia.
Revumenib can cause QTc interval prolongation. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia, prior to treatment, and perform a baseline ECG. This drug should not be initiated in patients with QTcF greater than 450 msec. Monitor with ECG during treatment (once a week during the first 4 weeks and then monthly). More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking other medications that can prolong the QTc interval.
Central Nervous System Disorders
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Central Nervous System Disorders.
Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.
Dementia
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Dementia.
Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.
Gastrointestinal Obstruction
Major:
tolterodine
Tolterodine has a major potential interaction with Gastrointestinal Obstruction.
The use of tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.
Glaucoma/Intraocular Hypertension
Major:
tolterodine
Tolterodine has a major potential interaction with Glaucoma/Intraocular Hypertension.
The use of tolterodine is contraindicated in patients with uncontrolled angle-closure (narrow angle) glaucoma. Tolterodine exerts anticholinergic activity and can result in increased intraocular pressure and loss of accommodation.
Heart Failure
Moderate:
revumenib
Revumenib has a moderate potential interaction with Heart Failure.
Revumenib can cause QTc interval prolongation. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia, prior to treatment, and perform a baseline ECG. This drug should not be initiated in patients with QTcF greater than 450 msec. Monitor with ECG during treatment (once a week during the first 4 weeks and then monthly). More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking other medications that can prolong the QTc interval.
Hypokalemia
Moderate:
revumenib
Revumenib has a moderate potential interaction with Hypokalemia.
Revumenib can cause QTc interval prolongation. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia, prior to treatment, and perform a baseline ECG. This drug should not be initiated in patients with QTcF greater than 450 msec. Monitor with ECG during treatment (once a week during the first 4 weeks and then monthly). More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking other medications that can prolong the QTc interval.
Liver Disease
Moderate:
revumenib
Revumenib has a moderate potential interaction with Liver Disease.
Revumenib has not been studied in patients with severe liver or renal impairment.
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Liver Disease.
Tolterodine undergoes biotransformation in the liver of extensive metabolizers to an active metabolite. Poor metabolizers have a greater concentration of active parent and less active metabolite, however the net activity of tolterodine is expected to be the same. The pharmacokinetic disposition of tolterodine can be significantly altered in patients with hepatic dysfunction. Therapy with tolterodine should be administered cautiously in patients with severe hepatic impairment and dosage should be reduced to no greater than 1 mg twice daily.
Long QT Syndrome
Moderate:
revumenib
Revumenib has a moderate potential interaction with Long QT Syndrome.
Revumenib can cause QTc interval prolongation. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia, prior to treatment, and perform a baseline ECG. This drug should not be initiated in patients with QTcF greater than 450 msec. Monitor with ECG during treatment (once a week during the first 4 weeks and then monthly). More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking other medications that can prolong the QTc interval.
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Long QT Syndrome.
Tolterodine has been associated with QT prolongation. The effect on QT interval correlates with plasma concentration of tolterodine. Caution is recommended when prescribing this agent to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.
Magnesium Imbalance
Moderate:
revumenib
Revumenib has a moderate potential interaction with Magnesium Imbalance.
Revumenib can cause QTc interval prolongation. Correct electrolyte imbalances such as hypokalemia and hypomagnesemia, prior to treatment, and perform a baseline ECG. This drug should not be initiated in patients with QTcF greater than 450 msec. Monitor with ECG during treatment (once a week during the first 4 weeks and then monthly). More frequent ECG monitoring may be necessary in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those taking other medications that can prolong the QTc interval.
Myasthenia Gravis
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Myasthenia Gravis.
Tolterodine acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors. Caution is recommended when using this agent in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.
Renal Dysfunction
Moderate:
revumenib
Revumenib has a moderate potential interaction with Renal Dysfunction.
Revumenib has not been studied in patients with severe liver or renal impairment.
Moderate:
tolterodine
Tolterodine has a moderate potential interaction with Renal Dysfunction.
The renal elimination of tolterodine and active metabolite is limited and a prolonged half-life is not anticipated in patients with renal impairment. However, the pharmacokinetic disposition of tolterodine has not been evaluated in patients with renal impairment and it is recommended that tolterodine be administered cautiously in patients with compromised renal function.
Urinary Retention
Major:
tolterodine
Tolterodine has a major potential interaction with Urinary Retention.
The use of tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.
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revumenib
A total of 580 drugs are known to interact with revumenib.
- Revumenib is in the drug class miscellaneous antineoplastics.
- Revumenib is used to treat the following conditions:
tolterodine
A total of 667 drugs are known to interact with tolterodine.
- Tolterodine is in the drug class urinary antispasmodics.
- Tolterodine 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
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