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Drug Interactions between cimetidine and nisoldipine

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

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Interactions between your drugs

Moderate

cimetidine nisoldipine

Applies to: cimetidine and nisoldipine

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

Drug and food interactions

Moderate

nisoldipine food

Applies to: nisoldipine

GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability. Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice. Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels. Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References (19)
  1. Edgar B, Bailey D, Bergstrand R, Johnsson G, Regardh CG (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. (2002) "Product Information. Plendil (felodipine)." Merck & Co., Inc
  3. (2002) "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals
  4. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  5. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. (2001) "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals
  10. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  11. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  12. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  13. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  14. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  15. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  16. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  17. Ho PC, Ghose K, Saville D, Wanwimolruk S (2000) "Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers." Eur J Clin Pharmacol, 56, p. 693-8
  18. Fuhr U, Muller-Peltzer H, Kern R, et al. (2002) "Effects of grapefruit juice and smoking on verapamil concentrations in steady state." Eur J Clin Pharmacol, 58, p. 45-53
  19. Cerner Multum, Inc. "UK Summary of Product Characteristics."
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 (2)
  1. Feely J, Wood AJ (1982) "Effects of cimetidine on the elimination and actions of ethanol." JAMA, 247, p. 2819-21
  2. Hansten PD (1992) "Effects of H2-receptor antagonists on blood alcohol levels." JAMA, 267, p. 2469
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 (2)
  1. (2001) "Product Information. Tagamet (cimetidine)." SmithKline Beecham
  2. Broughton LJ, Rodgers HJ (1981) "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol, 12, p. 155-9
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)
  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 165-9

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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