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Drug Interactions between Dy-G and Utibron Neohaler

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

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Interactions between your drugs

Moderate

dyphylline indacaterol

Applies to: Dy-G (dyphylline / guaifenesin) and Utibron Neohaler (glycopyrrolate / indacaterol)

MONITOR: Concomitant use of beta-2 adrenergic agonists with theophylline may increase the risk and/or severity of hypokalemia and adverse cardiovascular effects such as palpitation, tachycardia, and blood pressure elevation. Adverse events, especially hypokalemia, may be more likely with systemic or nebulized formulations of beta-2 agonists or high dosages of theophylline. Beta-2 agonists can cause clinically significant but usually transient decreases in serum potassium concentrations, while hypokalemia associated with theophylline often occurs in toxicity. Serious events including rare cases of cardiorespiratory arrest and intestinal pseudo-obstruction have been reported in association with hypokalemia induced by these agents. Moreover, since QT prolongation is a possible side effect of beta-2 agonists, development of hypokalemia may potentiate the risk of torsade de pointes and other serious arrhythmias. Pharmacokinetically, some beta-2 agonists given systemically may decrease the plasma concentrations of theophylline. Albuterol, isoproterenol, and terbutaline have been specifically implicated, usually increasing theophylline clearance by approximately 10% to a third, although some studies with albuterol and terbutaline failed to demonstrate a significant effect on theophylline pharmacokinetics. The interaction also did not occur in studies with fenoterol, formoterol, and metaproterenol. A case report describes a significant increase in theophylline clearance during intravenous administration of albuterol in a 19-month-old child with severe asthma, who subsequently required a threefold increase in theophylline dosage. Theophylline clearance decreased by 50% upon discontinuation of albuterol. In another case, a greater than 4-fold increase in theophylline clearance was reported following the intravenous administration of isoproterenol and methylprednisolone in a critically patient receiving aminophylline and nebulized terbutaline.

MANAGEMENT: Although theophylline and beta-2 agonists are commonly used together to produce bronchodilation, it may be appropriate to monitor patient response as well as serum potassium level, blood pressure and heart rate during coadministration, especially if the beta-2 agonist is administered systemically or by nebulizer. Close monitoring is particularly important in patients with severe asthma, since the potential increases in blood pressure and heart rate may have more serious consequences in the presence of hypoxemia or hypercapnia due to increased myocardial oxygen consumption. Patients should be advised to notify their physician if they experience worsening of their respiratory condition or potential signs and symptoms of hypokalemia such as fatigue, weakness, myalgia, muscle cramps, numbness, tingling, abdominal pain, constipation, palpitation, and irregular heartbeat.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  2. Coleman JJ, Vollmer WM, Barker AF, et al. "Cardiac arrhythmias during the combined use of beta-adrenergic agonist drugs and theophylline." Chest 90 (1986): 45-51
  3. Cusack BJ, Nielson CP, Morgan ME, Vestal RE "Additive effect of theophylline on the cardiac response to isoproterenol." Clin Pharmacol Ther 41 (1987): 289-96
  4. Deenstra M, Haalboom JR, Struyvenberg A "Decrease of plasma potassium due to inhalation of beta-2 agonists: absence of an additional effect of intravenous theophylline." Eur J Clin Invest 18 (1988): 162-5
  5. Jonkman JH, Borgstrom L, van der Boon WJ, de Noord OE "Theophylline-terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects." Br J Clin Pharmacol 26 (1988): 285-93
  6. Garty M, Paul-Keslin L, Ilfeld DN, et al. "Increased theophylline clearance in asthmatic patients due to terbutaline." Eur J Clin Pharmacol 36 (1989): 25-8
  7. Amitai Y, Glustein J, Godfrey S "Enhancement of theophylline clearance by oral albuterol." Chest 102 (1992): 786-9
  8. Amirav I, Amitai Y, Avital A, Godfrey S "Enhancement of theophylline clearance by intravenous albuterol." Chest 94 (1988): 444-5
  9. Whyte KF, Reid C, Addis GJ, Whitesmith R, Reid JL "Salbutamol induced hypokalaemia: the effect of theophylline alone and in combination with adrenaline." Br J Clin Pharmacol 25 (1988): 571-8
  10. Kelly HW "Controversies in asthma therapy with theophylline and the beta2-adrenergic agonists." Clin Pharm 3 (1984): 386-95
  11. Griffith JA, Kozloski GD "Isoproterenol-theophylline interaction: possible potentiation by other drugs." Clin Pharm 9 (1990): 54-7
  12. Chow OK, Fung KP "Slow-release terbutaline and theophylline for the long-term therapy of children with asthma: a Latin square and factorial study of drug effects and interactions." Pediatrics 84 (1989): 119-25
  13. Smith SR, Kendall MJ "Potentiation of the adverse effects of intravenous terbutaline by oral theophylline." Br J Clin Pharmacol 21 (1986): 451-3
  14. Josephson GW, Kennedy HL, MacKenzie EJ, Gibson G "Cardiac dysrhythmias during the treatment of acute asthma. A comparison of two treatment regimens by a double blind protocol." Chest 78 (1980): 429-35
  15. "Interactions between methyl xanthines and beta adrenergic agonists." FDA Drug Bull 11 (1981): 19-20
  16. Conrad KA, Woodworth JR "Orciprenaline does not alter theophylline elimination." Br J Clin Pharmacol 12 (1981): 756-7
  17. Lombardi TP, Bertino JS, Goldberg A, Middleton E, Slaughter RL "The effects of a beta-2 selective adrenergic agonist and a beta- nonselective antagonist on theophylline clearance." J Clin Pharmacol 27 (1987): 523-9
  18. O'Rourke PP, Crone RK "Effect of isoproterenol on measured theophylline levels." Crit Care Med 12 (1984): 373-5
  19. Hemstreet MP, Miles MV, Rutland RO "Effect of intravenous isoproterenol on theophylline kinetics." J Allergy Clin Immunol 69 (1982): 360-4
  20. Danzinger Y, Garty M, Volwitz B, Ilfeld D, Varsano I, Rosenfeld JB "Reduction of serum theophylline levels by terbutaline in children with asthma." Clin Pharmacol Ther 37 (1985): 469-71
  21. Rachelefsky GS, Katz RM, Mickey MR Jr, Siegel SC "Metaproterenol and theophylline in asthmatic children." Ann Allergy 45 (1980): 207-12
  22. "Product Information. Brovana (arformoterol)." Sepracor Inc (2006):
  23. "Product Information. Arcapta Neohaler (indacaterol)." Novartis Pharmaceuticals (2011):
  24. Dawson KP, Fergusson DM "Effects of oral theophylline and oral salbutamol in the treatment of asthma." Arch Dis Child 57 (1982): 674-6
  25. Flatt A, Burgess C, Windom H, Beasley R, Purdie G, Crane J "The cardiovascular effects of inhaled fenoterol alone and during treatment with oral theophylline." Chest 96 (1989): 1317-20
  26. "Product Information. Striverdi Respimat (olodaterol)." Boehringer Ingelheim (2014):
View all 26 references

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Drug and food interactions

Moderate

glycopyrrolate food

Applies to: Utibron Neohaler (glycopyrrolate / indacaterol)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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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.

See also

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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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