Theophylline interactions

Food & lifestyle

• coffee

  Moderate

  Metabolism

  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.

  What to do: 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.

  3 sources

  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

Conditions

Conditions in which Theophylline needs care, as documented in this source.

• Epilepsy

  Major

  The use of theophyllines is considered by some manufacturers to be contraindicated in patients with underlying seizure disorders unless they are receiving adequate anticonvulsant therapy. Theophyllines may cause seizures, which have generally been associated with toxic drug levels but have also been reported at therapeutic concentrations in patients with head trauma or cerebral infarct. If theophylline therapy is administered in patients with these or other risk factors for seizures, serum drug levels should be monitored closely and maintained in the low therapeutic range. Intractable seizures and death have been reported during acute theophylline toxicity.

  11 sources

  1. Hendeles L, Weinberger M, Johnson G "Monitoring serum theophylline levels." Clin Pharmacokinet 3 (1978): 294-312
  2. Sessler CN "Theophylline toxicity: clinical features of 116 consecutive cases." Am J Med 88 (1990): 567-76
  3. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO "Inpatient theophylline toxicity: preventable factors." Ann Intern Med 114 (1991): 748-53
  4. Nakada T, Kwee IL, Lerner AM, Remler MP "Theophylline-induced seizures: clinical and pathophysiologic aspects." West J Med 138 (1983): 371-4
  5. Aderka D, Shavit G, Garfinkel D, et al. "Life-threatening theophylline intoxication in a hypothyroid patient." Respiration 44 (1983): 77-80
  6. Covelli HD, Knodel AR, Heppner BT "Predisposing factors to apparent theophylline-induced seizures." Ann Allergy 54 (1985): 411-5
  7. Bahls FH, Ma KK, Bird TD "Theophylline-associated seizures with "therapeutic" or low toxic serum concentrations: risk factors for serious outcome in adults." Neurology 41 (1991): 1309-12
  8. Albert S "Aminophylline toxicity." Pediatr Clin North Am 34 (1987): 61-73

  Show all 11 sourcesShow fewer sources

  9. Milgrom H, Bender B "Current issues in the use of theophylline." Am Rev Respir Dis 147 (1993): s33-9
  10. "Product Information. Theo-Dur (theophylline)." Schering Corporation (2001):
  11. Stewart JT "Prolongation of ECT-induced seizures with theophylline." J Am Geriatr Soc 44 (1996): 475

• Kidney Diseases

  Major

  The metabolites of theophylline, which are generally undetectable in patients with normal renal function, may accumulate in patients with renal impairment and contribute to the toxicity of theophylline. In addition, the plasma protein binding of theophylline may be significantly decreased in renal impairment, resulting in elevated free drug concentrations and further increasing the risk of toxicity. Therapy with theophyllines should be administered cautiously in patients with impaired renal function. Dosage adjustments and more intensive monitoring of serum theophylline concentrations may be required.

  8 sources

  1. Reidenberg MM, Restivo K "The binding of theophylline to serum proteins of hemodialysis patients." J Dial 3 (1979): 375-81
  2. Bauer LA, Bauer SP, Blouin RA "The effect of acute and chronic renal failure on theophylline clearance." J Clin Pharmacol 22 (1982): 65-8
  3. Shaw LM, Fields L, Mayock R "Factors influencing theophylline serum protein binding." Clin Pharmacol Ther 32 (1982): 490-6
  4. Leakey TE, Elias-Jones AC, Coates PE, Smith KJ "Pharmacokinetics of theophylline and its metabolites during acute renal failure: a case report." Clin Pharmacokinet 21 (1991): 400-8
  5. Nicot G, Charmes JP, Lachatre G, et al. "Theophylline toxicity risks and chronic renal failure." Int J Clin Pharmacol Ther Toxicol 27 (1989): 398-401
  6. Vanholder R, Van Landschoot N, De Smet R, Schoots A, Ringoir S "Drug protein binding in chronic renal failure: evaluation of nine drugs." Kidney Int 33 (1988): 996-1004
  7. Leopold D, Webb D, Buss DC, Fifield RA, Smith AP, Routledge PA "The ex vivo plasma protein binding of theophylline in renal disease." Br J Clin Pharmacol 19 (1985): 823-5
  8. Kraan J, Jonkman JH, Koeter GH, et al. "The pharmacokinetics of theophylline and enprofylline in patients with liver cirrhosis and in patients with chronic renal disease." Eur J Clin Pharmacol 35 (1988): 357-62

• Peptic Ulcer

  Major

  Methylxanthines are known to stimulate peptic acid secretion. Therapy with products containing methylxanthines should be administered with extreme caution in patients with active peptic ulcer disease. Some manufacturers consider their use to be contraindicated under such circumstance.

  4 sources

  1. Stoller JL "Oesophageal ulceration and theophylline." Lancet 2 (1985): 328-9
  2. "Product Information. Theo-Dur (theophylline)." Schering Corporation (2001):
  3. Alterman P, Spiegel D, Feldman J, Yaretzky A "Histamine h2-receptor antagonists and chronic theophylline toxicity." Am Fam Physician 54 (1996): 1473
  4. "Product Information. Lufyllin (dyphylline)." Wallace Laboratories (2001):

• Diseases requiring hemodialysis

  Moderate

  Theophylline is removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

  8 sources

  1. Levy G, Gibson TP, Whitman W, Procknai J "Hemodialysis clearance of theophylline." JAMA 237 (1977): 1466-7
  2. Lee CS, Marbury TC, Perrin JH, Fuller TJ "Hemodialysis of theophylline in uremic patients." J Clin Pharmacol April (1979): 219-26
  3. Kradjan WA, Martin TR, Delaney CJ, et al. "Effect of hemodialysis on the pharmacokinetics of theophylline in chronic renal failure." Nephron 32 (1982): 40-4
  4. Anderson JR, Poklis A, McQueen RC, Purtell JN, Slavin RG "Effects of hemodialysis on theophylline kinetics." J Clin Pharmacol 23 (1983): 428-32
  5. Lee CS, Peterson JC, Marbury TC "Comparative pharmacokinetics of theophylline in peritoneal dialysis and hemodialysis." J Clin Pharmacol 23 (1983): 274-80
  6. Vaziri ND, Barton CH, Ness R, Clark D "Dialysability of theophylline." J Dial 2 (1978): 243-9
  7. Slaughter RL, Green L, Kohli R "Hemodialysis clearance of theophylline." Ther Drug Monit 4 (1982): 191-3
  8. Blouin RA, Bauer LA, Bustrack JA, Record KE, Bivins BA "Theophylline hemodialysis clearance." Ther Drug Monit 2 (1980): 221-3

• Gastroesophageal Reflux

  Moderate

  Methylxanthines increase gastric acidity and may also relax lower esophageal sphincter, which can lead to gastric reflux into the esophagus. Therapy with products containing methylxanthines should be administered cautiously in patients with significant gastroesophageal reflux.

  4 sources

  1. Stoller JL "Oesophageal ulceration and theophylline." Lancet 2 (1985): 328-9
  2. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  3. Alterman P, Spiegel D, Feldman J, Yaretzky A "Histamine h2-receptor antagonists and chronic theophylline toxicity." Am Fam Physician 54 (1996): 1473
  4. "Product Information. Lufyllin (dyphylline)." Wallace Laboratories (2001):

• Tachycardia

  Moderate

  The use of theophyllines is associated with an increase in heart rate which may progress to supraventricular tachycardia or ventricular arrhythmia at high serum drug concentrations. Appearance of cardiac adverse effects is generally an indication of theophylline toxicity, although patients with a history of tachyarrhythmias may be more susceptible to the chronotropic effect of these drugs. Therapy with theophyllines should be administered cautiously in such patients. Caution is also advised in patients with hypertension, hyperthyroidism, angina pectoris, or recent myocardial infarction, since high dosages of the drugs are associated with positive inotropic as well as chronotropic effects. Clinical monitoring of serum drug concentrations is recommended to prevent toxicity.

  12 sources

  1. Hendeles L, Weinberger M, Johnson G "Monitoring serum theophylline levels." Clin Pharmacokinet 3 (1978): 294-312
  2. Sessler CN "Theophylline toxicity: clinical features of 116 consecutive cases." Am J Med 88 (1990): 567-76
  3. Schiff GD, Hegde HK, LaCloche L, Hryhorczuk DO "Inpatient theophylline toxicity: preventable factors." Ann Intern Med 114 (1991): 748-53
  4. Marchlinski FE, Miller JM "Atrial arrhythmias exacerbated by theophylline: response to verapamil and evidence for triggered activity in man." Chest 88 (1985): 931-4
  5. Levine JH, Michael JR, Guarnieri T "Multifocal atrial tachycardia: a toxic effect of theophylline." Lancet 1 (1985): 12-4
  6. Taniguchi A, Ohe T, Shimorura K "Theophylline-induced ventricular tachycardia in a patient with chronic lung disease: sensitivity to verapamil." Chest 96 (1989): 958-9
  7. Bittar G, Friedman HS "The arrhythmogenicity of theophylline: a multivariate analysis of clinical determinants." Chest 99 (1991): 1415-20
  8. Patel AK, Skatrud JB, Thomsen JH "Cardiac arrhythmias due to oral aminophylline in patients with chronic obstructive pulmonary disease." Chest 80 (1981): 661-5

  Show all 12 sourcesShow fewer sources

  9. Albert S "Aminophylline toxicity." Pediatr Clin North Am 34 (1987): 61-73
  10. Milgrom H, Bender B "Current issues in the use of theophylline." Am Rev Respir Dis 147 (1993): s33-9
  11. Chazan R, Karwat K, Tyminska K, Tadeusiak W, Droszcz W "Cardiac arrhythmias as a result of intravenous infusions of theophylline in patients with airway obstruction." Int J Clin Pharmacol Ther 33 (1995): 170-5
  12. Mccarthy M "Theophylline, beta-agonists, and cardiovascular death." Lancet 349 (1997): 33