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Drug Interactions between cimetidine and Inderal LA

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

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Interactions between your drugs

Moderate

propranolol cimetidine

Applies to: Inderal LA (propranolol) and cimetidine

MONITOR: H2 antagonists such as cimetidine increase plasma concentrations of some oral beta-blockers. The mechanism may be related to inhibition of CYP450 metabolism of hepatically metabolized beta-blockers, and/or inhibition of renal tubular secretion of others. The potential inhibition of CYP450 enzymes by other H2 antagonists (ranitidine, famotidine, nizatidine) is significantly less than that of cimetidine and is not expected to be clinically significant.

MANAGEMENT: Clinical monitoring of patient response and tolerance is recommended when cimetidine is added to or discontinued from a beta-blocker regimen.

References

  1. Durant PA, Joucken K "Bronchospasm and hypotension during cardiopulmonary bypass after preoperative cimetidine and labetalol therapy." Br J Anaesth 56 (1984): 917-20
  2. Duchin KL, Stern MA, Willard DA, McKinstry DN "Kinetic interactions of nadolol and propranolol with cimetidine." Br J Clin Pharmacol 17 (1984): 486-7
  3. Duchin KL, Stern MA, Willard DA, McKinstry DN "Comparison of kinetic interactions of nadolol and propranolol with cimetidine." Am Heart J 108 (1984): 1084-6
  4. Houtzagers JJ, Streurman O, Regardh CG "The effect of pretreatment with cimetidine on the bioavailability and disposition of atenolol and metoprolol." Br J Clin Pharmacol 14 (1982): 67-72
  5. Kirch W, Spahn H, Kohler H, et al. "Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine." Klin Wochenschr 60 (1982): 1401-7
  6. Toon S, Davidson EM, Garstang FM, et al. "The racemic metoprolol H2-antagonist interaction." Clin Pharmacol Ther 43 (1988): 283-9
  7. Somogyi AA, Bochner F, Sallustio BC "Stereoselective inhibition of pindolol renal clearance by cimetidine in humans." Clin Pharmacol Ther 51 (1992): 379-87
  8. Spahn H, Kirch W, Hajdu P, et al. "Penbutolol pharmacokinetics: the influence of concomitant administration of cimetidine." Eur J Clin Pharmacol 29 (1986): 555-60
  9. Rey E, Jammet P, d'Athis P, et al. "Effect of cimetidine on the pharmacokinetics of the new beta-blocker betaxolol." Arzneimittelforschung 37 (1987): 953-6
  10. Daneshmend TK, Roberts CJ "The effects of enzyme induction and enzyme inhibition on labetalol pharmacokinetics." Br J Clin Pharmacol 18 (1984): 393-400
  11. Kirch W, Rose I, Klingmann I, Pabst J, Ohnhaus EE "Interaction of bisoprolol with cimetidine and rifampicin." Eur J Clin Pharmacol 31 (1986): 59-62
  12. Feely J, Wilkinson GR, Wood AJ "Reduction of liver blood flow and propranolol metabolism by cimetidine." N Engl J Med 304 (1981): 692-5
  13. Asgharnejad M, Powell R, Donn K, Danis M "The effect of cimetidine dose timing on oral propranolol kinetics in adults." Clin Pharmacol Ther 41 (1987): 203
  14. "Product Information. Tenormin (atenolol)." ICN Pharmaceuticals Inc PROD (2002):
  15. "Product Information. Corgard (nadolol)." Bristol-Myers Squibb PROD (2002):
  16. "Product Information. Cartrol (carteolol)." Abbott Pharmaceutical PROD (2001):
  17. "Product Information. Betapace (sotalol)." Berlex Laboratories PROD (2001):
  18. Seffart G ed. "Drug Dosage in Renal Insufficiency." Dordrecht, South Holland, : Kluwer Academic Publishers (1991):
  19. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
  20. Ishii Y, Nakamura K, Tsutsumi K, Kotegawa T, Nakano S, Nakatsuka K "Drug interaction between cimetidine and timolol ophthalmic solution: Effect on heart rate and intraocular pressure in healthy Japanese volunteers." J Clin Pharmacol 40 (2000): 193-9
View all 20 references

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Drug and food interactions

Moderate

propranolol food

Applies to: Inderal LA (propranolol)

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References

  1. Olanoff LS, Walle T, Cowart TD, et al. "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther 40 (1986): 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol 17 (1984): s45-50

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Moderate

propranolol food

Applies to: Inderal LA (propranolol)

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

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Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

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.

Further information

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