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Drug Interactions between Advair Diskus and gepirone

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

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Interactions between your drugs

Moderate

salmeterol gepirone

Applies to: Advair Diskus (fluticasone / salmeterol) and gepirone

Consumer information for this interaction is not currently available.

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

  1. Whyte KF, Addis GJ, Whitesmith R, Reid JL "The mechanism of salbutamol-induced hypokalaemia." Br J Clin Pharmacol 23 (1987): 65-71
  2. Larsson S, Svedmyr N "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 (1977): 861-9
  3. Hastwell G, Lambert BE "The effect of oral salbutamol on serum potassium and blood sugar." Br J Obstet Gynaecol 85 (1978): 767-9
  4. "Hypokalaemia due to salbutamol overdosage." Br Med J (Clin Res Ed) 283 (1981): 500-1
  5. Kantola I, Tarssanen L "Hypokalemia from usual salbutamol dosage ." Chest 89 (1986): 619-20
  6. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE "Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma." Lancet 336 (1990): 1396-9
  7. Gross TL, Sokol RJ "Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment." Am J Obstet Gynecol 138 (1980): 1225-6
  8. Clifton GD, Hunt BA, Patel RC, Burki NK "Effects of sequential doses of parenteral terbutaline on plasma levels of potassium and related cardiopulmonary responses." Am Rev Respir Dis 141 (1990): 575-9
  9. Hurlbert BJ, Edelman JD, David K "Serum potassium levels during and after terbutaline." Anesth Analg 60 (1981): 723-5
  10. Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32
  11. Gelmont DM, Balmes JR, Yee A "Hypokalemia induced by inhaled bronchodilators." Chest 94 (1988): 763-6
  12. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA "Metabolic and cardiovascular effects of carbuterol and metaproterenol." J Allergy Clin Immunol 60 (1977): 174-9
  13. "Product Information. Proventil (albuterol)." Schering Corporation PROD (2002):
  14. Windom H, Grainger J, Burgess C, Crane J, Pearce N, Beasley R "A comparison of the haemodynamic and hypokalaemic effects of inhaled pirbuterol and salbutamol." N Z Med J 103 (1990): 259-61
  15. "Product Information. Serevent (salmeterol)." Glaxo Wellcome PROD
  16. "Product Information. Maxair (pirbuterol)." 3M Pharmaceuticals PROD (2001):
  17. Dickens GR, Mccoy RA, West R, Stapczynski JS, Clifton GD "Effect of nebulized albuterol on serum potassium and cardiac rhythm in patients with asthma or chronic obstructive pulmonary disease." Pharmacotherapy 14 (1994): 729-33
  18. Tveskov C, Djurhuus MS, Klitgaard NAH, Egstrup K "Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta(2)-adrenergic stimulation with terbutaline in healthy subjects." Chest 106 (1994): 1654-9
  19. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL "Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences." Kidney Int 51 (1997): 1867-75
  20. Rakhmanina NY, Kearns GL, Farrar HC "Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler." Pediatr Emerg Care 14 (1998): 145-7
  21. "Product Information. Xopenex (levalbuterol)." Sepracor Inc PROD (2001):
  22. "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals PROD (2001):
  23. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C "Cardiovascular Safety of Salmeterol in COPD." Chest 123 (2003): 1817-24
  24. Milic M, Bao X, Rizos D, Liu F, Ziegler MG "Literature review and pilot studies of the effect of qt correction formulas on reported beta(2)-agonist-induced QTc prolongation." Clin Ther 28 (2006): 582-90
  25. "Product Information. Brovana (arformoterol)." Sepracor Inc (2006):
  26. Lowe MD, Rowland E, Brown MJ, Grace AA "Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium." Heart 86 (2001): 45-51
  27. Sun ZH, Swan H, Vitasalo M, Toivonen L "Effects of epinephrine and phenylephrine on QT interval dispersion in congenital long QT syndrome." J Am Coll Cardiol 31 (1998): 1400-5
  28. "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals (2011):
  29. "Product Information. Breo Ellipta (fluticasone-vilanterol)." GlaxoSmithKline (2013):
  30. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):
View all 30 references
Minor

fluticasone salmeterol

Applies to: Advair Diskus (fluticasone / salmeterol) and Advair Diskus (fluticasone / salmeterol)

Information for this minor interaction is available on the professional version.

Drug and food interactions

Moderate

gepirone food

Applies to: gepirone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. 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 other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.

MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.

References

  1. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):
  2. FDA. U.S. Food and Drug Administration "Grapefruit juice and some drugs don't mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix" (2024):
  3. Chen M, Zhou S, Fabriaga E, Zhang P, Zhou Q "Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326888/" (2024):
  4. Kiani J, Imam SZ "Medicinal importance of grapefruit juice and its interaction with various drugs. https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-33" (2024):
View all 4 references

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.

Further information

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