Drug Interactions between Theobid and Zyflo
This report displays the potential drug interactions for the following 2 drugs:
- Theobid (theophylline)
- Zyflo (zileuton)
Interactions between your drugs
theophylline zileuton
Applies to: Theobid (theophylline) and Zyflo (zileuton)
ADJUST DOSE: Coadministration with zileuton may significantly increase the plasma concentrations of theophylline. The proposed mechanism is zileuton inhibition of theophylline metabolism via CYP450 1A2. In 16 healthy adult male volunteers, administration of theophylline 200 mg four times daily in combination with zileuton 800 mg twice daily for 5 days resulted in an approximately 73% increase in mean steady-state theophylline peak serum concentration (Cmax) and 92% increase in systemic exposure (AUC) compared to administration with placebo. In addition, the apparent plasma clearance of theophylline decreased by nearly 50%, the time to peak concentration (Tmax) delayed by 0.5 hours, and the half-life prolonged by 1.5 hours (24%) during coadministration with zileuton. Fourteen subjects reported 44 mild or moderately severe adverse events possibly or probably related to coadministration of zileuton, including three who withdrew from the study prematurely, compared to eight subjects who reported 8 such events during placebo coadministration.
MANAGEMENT: Caution is advised if theophylline is prescribed in combination with zileuton, particularly in the elderly and patients with chronic obstructive pulmonary disease, congestive heart failure or cirrhosis, as these patients generally have lower theophylline clearance rates and may be particularly vulnerable to theophylline toxicity. When zileuton is initiated in patients receiving theophylline, the theophylline dosage should be reduced by approximately one-half and theophylline levels closely monitored. Similarly, when initiating therapy with theophylline in patients receiving zileuton, the maintenance dosage and/or dosing interval of theophylline should be adjusted accordingly and guided by serum theophylline levels. Patients should be advised to notify their physician if they experience signs and symptoms suggestive of theophylline toxicity such as nausea, vomiting, diarrhea, headache, tremor, irritability, insomnia, seizures, palpitation, or arrhythmia.
References
- Granneman GR, Braeckman RA, Locke CS, Cavanaugh JH, Dube LM, Awni WM "Effect of zileuton on theophylline pharmacokinetics." Clin Pharmacokinet 29(suppl 2 (1995): 77-83
- "Product Information. Zyflo (zileuton)." Abbott Pharmaceutical PROD
- Lau R "Drug interactions with zileuton." Lancet 349 (1997): 1479-80
Drug and food interactions
theophylline food
Applies to: Theobid (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
- 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
- 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
- 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
theophylline food
Applies to: Theobid (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
- 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
- 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
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
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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