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Drug Interactions between Diltiazem Hydrochloride SR and Leader Heartburn Relief

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

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Interactions between your drugs

Moderate

dilTIAZem cimetidine

Applies to: Diltiazem Hydrochloride SR (diltiazem) and Leader Heartburn Relief (cimetidine)

MONITOR: Coadministration with cimetidine may increase the plasma concentrations of calcium channel blockers that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by cimetidine.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if cimetidine is used in combination with calcium channel blockers that are metabolized by CYP450 3A4 such as diltiazem, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine, and verapamil. Dose reductions of 40% to 50% may be considered, if necessary. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis. Other H2-receptor antagonists may be safer alternatives, since they have not been shown to significantly affect CYP450 3A4 metabolism. However, there have been isolated reports of interaction between ranitidine and calcium channel blockers including nifedipine and nitrendipine.

References

  1. Mikus G, Eichelbaum M, Fischer C, et al. "Interaction of verapamil and cimetidine: stereochemical aspects of drug metabolism, drug disposition and drug action." J Pharmacol Exp Ther 253 (1990): 1042-8
  2. Wing LM, Miners JO, Lillywhite KJ "Verapamil disposition: effects of sulphinpyrazone and cimetidine." Br J Clin Pharmacol 19 (1985): 385-91
  3. Smith MS, Benyunes MC, Bjornsson TD, et al. "Influence of cimetidine on verapamil kinetics and dynamics." Clin Pharmacol Ther 36 (1984): 551-4
  4. Muck W, Wingender W, Seiberling M, Woelke E, Ramsch KD, Kuhlmann J "Influence of the H2-receptor antagonists cimetidine and ranitidine on the pharmacokinetics of nimodipine in healthy volunteers." Eur J Clin Pharmacol 42 (1992): 325-8
  5. Kirch W, Ramsch K, Janisch HD, Ohnhaus EE "The influence of two histamine H2-receptor antagonists, cimetidine and ranitidine, on the plasma levels and clinical effect of nifedipine and metoprolol." Arch Toxicol Suppl 7 (1984): 256-9
  6. Smith SR, Kendall MJ, Lobo J, et al. "Ranitidine and cimetidine; drug interactions with single dose and steady-state nifedipine administration." Br J Clin Pharmacol 23 (1987): 311-5
  7. Kirch W, Hutt HJ, Heidemann H, et al. "Drug interactions with nitrendipine." J Cardiovasc Pharmacol 6 (1984): s982-5
  8. Janzon K, Edgar B, Lundborg P, Regardh CG "The influence of cimetidine and spironolactone on the pharmacokinetics and haemodynamic effects of felodipine in healthy subjects." Acta Pharmacol Toxicol (Copenh) 59 (1986): 98
  9. Winship LC, McKenney JM, Wright JT, Wood JH, Goodman RP "The effect of ranitidine and cimetidine on single-dose diltiazem pharmacokinetics." Pharmacotherapy 5 (1985): 16-9
  10. Smith SR, Kendall MJ, Lobo J, Beerahee A, Jack DB, Wilkins MR "Ranitidine and cimetidine; drug interactions with single dose and steady-state nifedipine administration." Br J Clin Pharmacol 23 (1987): 311-5
  11. Schwartz JB, Upton RA, Lin ET, Willias RL, Benet LZ "Effect of cimetidine or ranitidine administration on nifedipine pharmacokinetics and pharmacodynamics." Clin Pharmacol Ther 43 (1988): 673-80
  12. Khan A, Langley SJ, Mullins FG, Dixon JS, Toon S "The pharmacokinetics and pharmacodynamics of nifedipine at steady state during concomitant administration of cimetidine or high dose ranitidine." Br J Clin Pharmacol 32 (1991): 519-22
  13. Loi CM, Rollins DE, Dukes GE, Peat MA "Effect of cimetidine on verapamil disposition." Clin Pharmacol Ther 37 (1985): 654-7
  14. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  15. Renwick AG, Le Vie J, Challenor VF, Waller DG, Gruchy B, George CF "Factors affecting the pharmacokinetics of nifedipine." Eur J Clin Pharmacol 32 (1987): 351-5
  16. Agencia Española de Medicamentos y Productos Sanitarios Healthcare "Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html" (2008):
View all 16 references

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Drug and food interactions

Moderate

dilTIAZem food

Applies to: Diltiazem Hydrochloride SR (diltiazem)

MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects. Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water. The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water. In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours. The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase. Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain. Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

References

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A "Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects." Pharmazie 49 (1994): 675-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Christensen H, Asberg A, Holmboe AB, Berg KJ "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers." Eur J Clin Pharmacol 58 (2002): 515-520
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 5 references

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Moderate

dilTIAZem food

Applies to: Diltiazem Hydrochloride SR (diltiazem)

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 references

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Minor

cimetidine food

Applies to: Leader Heartburn Relief (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: Leader Heartburn Relief (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: Leader Heartburn Relief (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

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

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