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Drug Interactions between cisapride and Symbicort

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

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Moderate

cisapride formoterol

Applies to: cisapride and Symbicort (budesonide / formoterol)

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 (1987) "The mechanism of salbutamol-induced hypokalaemia." Br J Clin Pharmacol, 23, p. 65-71
  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
View all 30 references

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Minor

budesonide formoterol

Applies to: Symbicort (budesonide / formoterol) and Symbicort (budesonide / formoterol)

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.

References

  1. (2001) "Product Information. Foradil (formoterol)." Novartis Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
View all 4 references

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Drug and food interactions

Major

cisapride food

Applies to: cisapride

CONTRAINDICATED: Coadministration with grapefruit juice may increase the plasma concentrations of cisapride. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a study of 14 healthy volunteers, administration with 250 mL of grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cisapride (10 mg single dose) by 34% and 39%, respectively, compared to water. A second single-dose study involving 12 healthy volunteers demonstrated an increase of 68% and 51% in cisapride Cmax and AUC, respectively, compared to water. In another 10 healthy volunteers, repeated ingestion of double-strength grapefruit juice (200 mL three times a day for 2 days, then with a 10 mg dose of cisapride and at 0.5 and 1.5 hours afterwards) resulted in an 81% and 144% increase in mean cisapride Cmax and AUC, respectively, compared to water. A high degree of intersubject variability in the grapefruit juice effect was observed in all three studies, but no patient experienced any changes in heart rate, blood pressure, or QT interval. However, high plasma levels of cisapride have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death.

GENERALLY AVOID: Coadministration with red wine may increase the plasma concentrations of cisapride in susceptible individuals. The exact mechanism of interaction is unknown but is believed to involve inhibition of CYP450 3A4 in the gut wall similar to grapefruit juice. In 12 healthy volunteers, administration with 250 mL of red wine (cabernet sauvignon) produced only minor and statistically insignificant changes in cisapride pharmacokinetics compared to water. However, one subject had a doubling in cisapride AUC and Cmax with red wine. The same subject also had the largest interaction with grapefruit juice, which suggests that a significant interaction may occur in certain individuals, perhaps those with a preexisting high intestinal CYP450 3A4 content.

MANAGEMENT: Patients receiving cisapride therapy should avoid the consumption of grapefruits and grapefruit juice. Because a significant interaction may occur with red wine in the occasional patient, red wine should preferably be avoided also during cisapride therapy.

References

  1. (2001) "Product Information. Propulsid (cisapride)." Janssen Pharmaceuticals
  2. Bran S, Murray WA, Hirsch IB, Palmer JP (1995) "Long QT syndrome during high-dose cisapride." Arch Intern Med, 155, p. 765-8
  3. Lewin MB, Bryant RM, Fenrich AL, Grifka RG (1996) "Cisapride-induced long QT interval." J Pediatr, 128, p. 279-81
  4. Hill SL, Evangelista JK, Pizzi AM, Mobassaleh M, Fulton DR, Berul CI (1998) "Proarrhythmia associated with cisapride in children." Pediatrics, 101, p. 1053-6
  5. Gross AS, Goh YD, Addison RS, Shenfield GM (1999) "Influence of grapefruit juice on cisapride pharmacokinetics." Clin Pharmacol Ther, 65, p. 395-401
  6. Kivisto KT, Lilja TJ, Backman JT, Neuvonen PJ (1999) "Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride." Clin Pharmacol Ther, 66, p. 448-53
  7. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  8. Desta Z, Soukhova N, Mahal SK, Flockhart DA (2000) "Interaction of cisapride with the human cytochrome P450 system: metabolism and inhibition studies." Drug Metab Dispos, 28, p. 789-800
  9. Michalets EL, Williams CR (2000) "Drug interactions with cisapride: clinical implications." Clin Pharmacokinet, 39, p. 49-75
  10. Offman EM, Freeman DJ, Dresser GK, Munoz C, Bend JR, Bailey DG (2001) "Red wine-cisapride interaction: Comparison with grapefruit juice." Clin Pharmacol Ther, 70, p. 17-23
View all 10 references

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Moderate

budesonide food

Applies to: Symbicort (budesonide / formoterol)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

MANAGEMENT: Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

References

  1. (2001) "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc

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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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