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Drug Interactions between Equaline Heartburn Relief and Tedrigen

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

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Moderate

raNITIdine theophylline

Applies to: Equaline Heartburn Relief (ranitidine) and Tedrigen (ephedrine / phenobarbital / theophylline)

MONITOR: Cimetidine may increase theophylline plasma concentrations by as much as 70%. The mechanism is related to inhibition of liver CYP450 enzymes responsible for theophylline metabolism. Although controlled studies have not demonstrated an interaction with ranitidine, famotidine, or nizatidine, and they do not have enzyme-inhibiting properties, there have been rare case reports of increased theophylline concentrations and/or toxicity with each of these agents. Patients with chronic obstructive pulmonary disease, congestive heart failure, or cirrhosis may have slower theophylline clearance rates; therefore, they may be at greater risk of developing theophylline toxicity.

MANAGEMENT: Clinical monitoring of patient response, tolerance, and laboratory theophylline serum concentrations is recommended. Patients should be advised to report any signs of theophylline toxicity including nausea, vomiting, diarrhea, headache, restlessness, insomnia, or irregular heartbeat to their physician.

References

  1. Schwartz JI, Bachmann KA, Bond LW, Mahajan VK "Impact of cimetidine on the pharmacokinetics of the theophylline." Clin Pharm 1 (1982): 534-8
  2. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part II)." Clin Pharmacokinet 20 (1991): 135-50
  3. Campbell MA, Plachetka JR, Jackson JE, Moon JF, Finley PR "Cimetidine decreases theophylline clearance." Ann Intern Med 95 (1981): 68-9
  4. Bauman JH, Kimelblatt BJ, Caraccio TR, Silverman HM, Simon GI, Beck GJ "Cimetidine-theophylline interaction: report of four patients." Ann Allergy 48 (1982): 100-2
  5. Hsu K, Garton A, Sproule BJ, Tam YK, Leggatt D, Herbert FA "The influence of orally administered cimetidine and theophylline on the elimination of each drug in patients with chronic airways obstruction." Am Rev Respir Dis 130 (1984): 740-3
  6. Powell JR, Rogers JF, Wargin WA, Cross RE, Eshelman FN "Inhibition of theophylline clearance by cimetidine but not ranitidine." Arch Intern Med 144 (1984): 484-6
  7. Anderson JR, Poklis A, Slavin RG "A fatal case of theophylline intoxication." Arch Intern Med 143 (1983): 559-60
  8. Boehning W "Effect of cimetidine and ranitidine on plasma theophylline in patients with chronic obstructive airways disease treated with theophylline and corticosteroids." Eur J Clin Pharmacol 38 (1990): 43-5
  9. Jackson JE, Powell JR, Wandell M, Bentley J, Dorr R "Cimetidine decreases theophylline clearance." Am Rev Respir Dis 123 (1981): 615-7
  10. Kelly HW "Lack of evidence for reduction of theophylline clearance by ranitidine." Am J Med 86 (1989): 629-32
  11. Lofgren RP, Gilbertson RA "Cimetidine and theophylline." Ann Intern Med 96 (1982): 378
  12. Reitberg DP, Bernhard H, Schentag JJ "Alteration of theophylline clearance and half-life by cimetidine in normal volunteers." Ann Intern Med 95 (1981): 582-5
  13. Fenje PC, Isles AF, Baltodano A, MacLeod SM, Soldin S "Interaction of cimetidine and theophylline in two infants." Can Med Assoc J 126 (1982): 1178
  14. Weinberger MM, Smith G, Milavetz G, Hendeles L "Decreased clearance of theophylline due to cimetidine ." N Engl J Med 304 (1981): 672
  15. Lin JH, Chremos AN, Chiou R, Yeh KC, Williams R "Comparative effect of famotidine and cimetidine on the pharmacokinetics of theophylline in normal volunteers." Br J Clin Pharmacol 24 (1987): 669-72
  16. Dal Negro R, Pomari C, Turco P "Famotidine and theophylline pharmacokinetics. An unexpected cimetidine-like interaction in patients with chronic obstructive pulmonary disease." Clin Pharmacokinet 24 (1993): 255-8
  17. Fernandes E, Melewicz FM "Ranitidine and theophylline." Ann Intern Med 100 (1984): 459
  18. Roy AK, Cuda MP, Levine RA "Induction of theophylline toxicity and inhibition of clearance rates by ranitidine." Am J Med 85 (1988): 525-7
  19. Skinner MH, Lenert L, Blaschke TF "Theophylline toxicity subsequent to ranitidine administration: a possible drug-drug interaction." Am J Med 86 (1989): 129-32
  20. Hegman GW, Gilbert RP "Ranitidine-theophylline interaction--fact or fiction?" Ann Pharmacother 25 (1991): 21-5
  21. Kelly HW, Powell JR, Donohue JF "Ranitidine at very large doses does not inhibit theophylline elimination." Clin Pharmacol Ther 39 (1986): 577-81
  22. Ohashi K, Sakamoto K, Sudo T, Tateishi T, Fujimura A, Shiga T, Ebihara A "Effects of diltiazem and cimetidine on theophylline oxidative metabolism." J Clin Pharmacol 33 (1993): 1233-7
  23. Bachmann KA, Sullivan TJ, Jauregui L, Reese J, Miller K, Levine L "Drug interactions of h-2-receptor antagonists." Scand J Gastroenterol 29 (1994): 14-9
  24. Bachmann K, Sullivan TJ, Reese JH, Jauregui L, Miller K, Scott M, Yeh KC, Stepanavage M, King JD, Schwartz J "Controlled study of the putative interaction between famotidine and theophylline in patients with chronic obstructive pulmonary disease." J Clin Pharmacol 35 (1995): 529-35
  25. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  26. Pride M, Deamer RL "Over-the-counter cimetidine and theophylline interaction." Am Fam Physician 52 (1995): 2180
  27. Kehoe WA, Sands CD, Long LF, et al. "Effect of ranitidine on theophylline metabolism in healthy Koreans living in China." Ann Pharmacother 30 (1996): 133-7
  28. Loi CM, Parker BM, Cusack BJ, Vestal RE "Aging and drug interactions .3. individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism in healthy male and female nonsmokers." J Pharmacol Exp Ther 280 (1997): 627-37
  29. Verdiani P, Di Carlo S, Baronti A "Famotidine effects on theophylline pharmacokinetics in subjects affected by COPD: comparison with cimetidine and placebo." Chest 94 (1988): 807-10
View all 29 references

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Moderate

theophylline PHENobarbital

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline) and Tedrigen (ephedrine / phenobarbital / theophylline)

MONITOR: Barbiturates may decrease serum levels and therapeutic effects of the methylxanthines. The mechanism is barbiturate induction of CYP450 3A4 and 1A2 hepatic metabolism of methylxanthines.

MANAGEMENT: Close observation for clinical and laboratory evidence of decreased methylxanthine effect is indicated if these drugs must be used together. Patients should be advised to notify their physician if they experience a worsening of their respiratory symptoms.

References

  1. Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80
  2. Bukowskyj M, Nakatsu K, Munt PW "Theophylline reassessed." Ann Intern Med 101 (1984): 63-73
  3. Landay RA, Gonzalez MA, Taylor JC "Effect of phenobarbital on theophylline disposition." J Allergy Clin Immunol 62 (1978): 27-9
  4. Dahlqvist R, Steiner E, Koike Y, von Bahr C, Lind M, Billing B "Induction of theophylline metabolism by pentobarbital." Ther Drug Monit 11 (1989): 408-10
View all 4 references

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Minor

theophylline ePHEDrine

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline) and Tedrigen (ephedrine / phenobarbital / theophylline)

Ephedrine-methylxanthine combinations are used for the treatment of asthma but the efficacy of the combination has been questioned. This combination may lead to increased xanthine side effects. The mechanism is unknown, but may be related to synergistic pharmacologic effects. Patients using this combination should be closely monitored for side effects such as nausea, vomiting, tachycardia, nervousness, or insomnia. If side effects are noted, the dosage of the xanthine may need to be decreased.

References

  1. Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ "Interaction of ephedrine and theophylline." Clin Pharmacol Ther 17 (1975): 585-92
  2. Sims JA, doPico GA, Reed CE "Bronchodilating effect of oral theophylline-ephedrine combination." J Allergy Clin Immunol 62 (1978): 15-21
  3. Tinkelman DG, Avner SE "Ephedrine therapy in asthmatic children. Clinical tolerance and absence of side effects." JAMA 237 (1977): 553-7
  4. Weinberger MM, Brousky EA "Evaluation of oral bronchodilator therapy in asthmatic children: bronchodilators in asthmatic children." J Pediatr 84 (1974): 421-7
  5. Badiei B, Faciane J, Sly M "Effect of throphylline, ephedrine and theri combination upon exercise-induced airway obstruction." Ann Allergy 35 (1975): 32-6
View all 5 references

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Drug and food interactions

Major

PHENobarbital food

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

theophylline food

Applies to: Tedrigen (ephedrine / phenobarbital / 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

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Moderate

theophylline food

Applies to: Tedrigen (ephedrine / phenobarbital / 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

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Moderate

ePHEDrine food

Applies to: Tedrigen (ephedrine / phenobarbital / theophylline)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 references

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Minor

raNITIdine food

Applies to: Equaline Heartburn Relief (ranitidine)

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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.

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

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