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Drug Interaction Report

2 potential interactions and/or warnings found for the following 3 drugs:

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Interactions between your drugs

Moderate

levalbuterol ivabradine

Applies to: levalbuterol, ivabradine

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. 1987;23:65-71.
  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. 1977;116:861-9.
  3. Hastwell G, Lambert BE. The effect of oral salbutamol on serum potassium and blood sugar. Br J Obstet Gynaecol. 1978;85:767-9.
  4. Hypokalaemia due to salbutamol overdosage. Br Med J (Clin Res Ed). 1981;283:500-1.
  5. Kantola I, Tarssanen L. Hypokalemia from usual salbutamol dosage . Chest. 1986;89:619-20.
  6. Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE. Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet. 1990;336:1396-9.
  7. Gross TL, Sokol RJ. Severe hypokalemia and acidosis: a potential complication of beta- adrenergic treatment. Am J Obstet Gynecol. 1980;138:1225-6.
  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. 1990;141:575-9.
  9. Hurlbert BJ, Edelman JD, David K. Serum potassium levels during and after terbutaline. Anesth Analg. 1981;60:723-5.
  10. Bengtsson B, Fagerstrom PO. Extrapulmonary effects of terbutaline during prolonged administration. Clin Pharmacol Ther. 1982;31:726-32.
  11. Gelmont DM, Balmes JR, Yee A. Hypokalemia induced by inhaled bronchodilators. Chest. 1988;94:763-6.
  12. Sanders JP, Potter DE, Ellis S, Bee DE, Grant JA. Metabolic and cardiovascular effects of carbuterol and metaproterenol. J Allergy Clin Immunol. 1977;60:174-9.
  13. Product Information. Proventil (albuterol). Schering Corporation. 2002;PROD.
  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. 1990;103:259-61.
  15. Product Information. Serevent (salmeterol). Glaxo Wellcome. PROD.
  16. Product Information. Maxair (pirbuterol). 3M Pharmaceuticals. 2001;PROD.
  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. 1994;14:729-33.
  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. 1994;106:1654-9.
  19. Braden GL, vonOeyen PT, Germain MJ, Watson DJ, Haag BL. Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences. Kidney Int. 1997;51:1867-75.
  20. Rakhmanina NY, Kearns GL, Farrar HC. Hypokalemia in an asthmatic child from abuse of albuterol metered dose inhaler. Pediatr Emerg Care. 1998;14:145-7.
  21. Product Information. Xopenex (levalbuterol). Sepracor Inc. 2001;PROD.
  22. Product Information. Foradil (formoterol). Novartis Pharmaceuticals. 2001;PROD.
  23. Ferguson GT, Funck-Brentano C, Fischer T, Darken P, Reisner C. Cardiovascular Safety of Salmeterol in COPD. Chest. 2003;123:1817-24.
  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. 2006;28:582-90.
  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. 2001;86:45-51.
  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. 1998;31:1400-5.
  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

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No other interactions were found between your selected drugs. However, this does not necessarily mean no other interactions exist. Always consult your healthcare provider.

Drug and food interactions

Major

ivabradine food

Applies to: ivabradine

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of ivabradine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. According to the product labeling, administration with grapefruit juice (quantity unknown) resulted in an approximately twofold increase in ivabradine systemic exposure (AUC). Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

ADJUST DOSING INTERVAL: Food delays the absorption of ivabradine by approximately 1 hour and increases plasma exposure by 20% to 40% compared to fasting conditions.

MANAGEMENT: Patients treated with ivabradine should avoid or limit consumption of grapefruit or grapefruit juice. The manufacturer recommends taking ivabradine with meals to reduce variability in exposure.

References

  1. Cerner Multum, Inc. UK Summary of Product Characteristics.
  2. Cerner Multum, Inc. Australian Product Information.
  3. Product Information. Corlanor (ivabradine). Amgen USA. 2015.

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Therapeutic duplication warnings

No duplication 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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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.