Skip to main content

Drug Interactions between Constant-T and Stiolto Respimat

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

theophylline olodaterol

Applies to: Constant-T (theophylline) and Stiolto Respimat (olodaterol / tiotropium)

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

Switch to consumer interaction data

Drug and food interactions

Moderate

theophylline food

Applies to: Constant-T (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

ADJUST DOSING INTERVAL: Administration of theophylline with continuous enteral nutrition may reduce the serum levels or the rate of absorption of theophylline. The mechanism has not been reported. In one case, theophylline levels decreased by 53% in a patient receiving continuous nasogastric tube feedings and occurred with both theophylline tablet and liquid formulations, but not with intravenous aminophylline.

MANAGEMENT: When administered to patients receiving continuous enteral nutrition , some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 1 hour after the dose of theophylline is given; rapid-release formulations are preferable, and theophylline levels should be monitored.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  3. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

Switch to consumer interaction data

Moderate

theophylline food

Applies to: Constant-T (theophylline)

GENERALLY AVOID: Coadministration with caffeine may increase the serum concentrations of theophylline. The proposed mechanism involves competitive inhibition of theophylline metabolism via CYP450 1A2, as well as metabolic conversion of caffeine to theophylline in vivo and saturation of theophylline metabolism at higher serum concentrations. In six healthy male volunteers (all smokers), serum concentrations of theophylline (administered as aminophylline 400 mg single oral dose) were significantly higher following consumption of caffeine (2 to 7 cups of instant coffee over 24 hours, equivalent to approximately 120 to 630 mg of caffeine) than after caffeine deprivation for 48 hours. Caffeine consumption also increased the apparent elimination half-life of theophylline by an average of 32% and reduced its total body clearance by 23%. In another study, steady-state concentration and area under the concentration-time curve of theophylline (1200 mg intravenously over 24 hours) increased by 23% and 40%, respectively, in eight healthy volunteers following administration of caffeine (300 mg orally three times a day).

MANAGEMENT: Given the narrow therapeutic index of theophylline, patients should limit or avoid significant fluctuations in their intake of pharmacologic as well as dietary caffeine.

References

  1. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  2. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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

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

Medical Disclaimer