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Drug Interactions between revumenib and Xopenex Concentrate

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

levalbuterol revumenib

Applies to: Xopenex Concentrate (levalbuterol) and revumenib

MONITOR: Beta-2 adrenergic agonists can cause dose-related prolongation of the QT interval and potassium loss. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. 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). Clinically significant prolongation of QT interval and hypokalemia occur infrequently when beta-2 agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is recommended if beta-2 agonists are used in combination with other drugs that can prolong the QT interval. 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 (30)
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  2. Larsson S, Svedmyr N (1977) "Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol inasthmatics." Am Rev Respir Dis, 116, p. 861-9
  3. Hastwell G, Lambert BE (1978) "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol, 85, p. 767-9
  4. (1981) "Hypokalaemia due to salbutamol overdosage." Br Med J (Clin Res Ed), 283, p. 500-1
  5. Kantola I, Tarssanen L (1986) "Hypokalemia from usual salbutamol dosage ." Chest, 89, p. 619-20
  6. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE (1990) "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet, 336, p. 1396-9
  7. Gross TL, Sokol RJ (1980) "Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment." Am J Obstet Gynecol, 138, p. 1225-6
  8. Clifton GD, Hunt BA, Patel RC, Burki NK (1990) "Effects of sequential doses of parenteral terbutaline on plasma levels of potassium and related cardiopulmonary responses." Am Rev Respir Dis, 141, p. 575-9
  9. Hurlbert BJ, Edelman JD, David K (1981) "Serum potassium levels during and after terbutaline." Anesth Analg, 60, p. 723-5
  10. Bengtsson B, Fagerstrom PO (1982) "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther, 31, p. 726-32
  11. Gelmont DM, Balmes JR, Yee A (1988) "Hypokalemia induced by inhaled bronchodilators." Chest, 94, p. 763-6
  12. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA (1977) "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol, 60, p. 174-9
  13. (2002) "Product Information. Proventil (albuterol)." Schering Corporation
  14. Windom H, Grainger J, Burgess C, Crane J, Pearce N, Beasley R (1990) "A comparison of the haemodynamic and hypokalaemic effects of inhaled pirbuterol and salbutamol." N Z Med J, 103, p. 259-61
  15. "Product Information. Serevent (salmeterol)." Glaxo Wellcome
  16. (2001) "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals
  17. Dickens GR, Mccoy RA, West R, Stapczynski JS, Clifton GD (1994) "Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease." Pharmacotherapy, 14, p. 729-33
  18. Tveskov C, Djurhuus MS, Klitgaard NAH, Egstrup K (1994) "Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta(2)-adrenergic stimulation with terbutaline in healthy subjects." Chest, 106, p. 1654-9
  19. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL (1997) "Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences." Kidney Int, 51, p. 1867-75
  20. Rakhmanina NY, Kearns GL, Farrar HC (1998) "Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler." Pediatr Emerg Care, 14, p. 145-7
  21. (2001) "Product Information. Xopenex (levalbuterol)." Sepracor Inc
  22. (2001) "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals
  23. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C (2003) "Cardiovascular Safety of Salmeterol in COPD." Chest, 123, p. 1817-24
  24. Milic M, Bao X, Rizos D, Liu F, Ziegler MG (2006) "Literature review and pilot studies of the effect of qt correction formulas on reported beta(2)-agonist-induced QTc prolongation." Clin Ther, 28, p. 582-90
  25. (2006) "Product Information. Brovana (arformoterol)." Sepracor Inc
  26. Lowe MD, Rowland E, Brown MJ, Grace AA (2001) "Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium." Heart, 86, p. 45-51
  27. Sun ZH, Swan H, Vitasalo M, Toivonen L (1998) "Effects of epinephrine and phenylephrine on QT interval dispersion in congenital long QT syndrome." J Am Coll Cardiol, 31, p. 1400-5
  28. (2011) "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals
  29. (2013) "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline
  30. (2014) "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim

Drug and food interactions

Moderate

revumenib food

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)
  1. (2024) "Product Information. Quinoric (hydroxychloroquine)." Bristol Laboratories Ltd
  2. (2024) "Product Information. Revuforj (revumenib)." Syndax Pharmaceuticals, Inc

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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.

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