Skip to main content

Drug Interactions between cimetidine and Diastat Pediatric

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

cimetidine diazePAM

Applies to: cimetidine and Diastat Pediatric (diazepam)

MONITOR: Administration of cimetidine with benzodiazepines may increase systemic exposure to benzodiazepines. The mechanism may be related to inhibition of CYP450 3A4 hepatic metabolism by cimetidine, a moderate inhibitor of this isoenzyme. This interaction has been reported for alprazolam, diazepam, triazolam, midazolam and chlordiazepoxide, but may also occur with other benzodiazepines. In one pharmacokinetic study, two groups of healthy subjects (n=8) were administered cimetidine (1 g daily) for 2 weeks, with the addition of either alprazolam (0.5 mg three times a day) or triazolam (0.5 mg nightly) during the second week of cimetidine administration. Concomitant administration with cimetidine led to statistically significant alterations in some of the pharmacokinetic parameters of the benzodiazepines. Alprazolam systemic exposure, (AUC [0 to infinity]) and Cmax increased by 73% and 82%, respectively, and clearance (L/h) decreased by 42%. Triazolam systemic exposure (AUC [0 to infinity]) and Cmax increased by 120% and 51%, respectively, half-life increased by 68%, and clearance (L/h) decreased by 55%. This interaction appears to be minimal with lorazepam, oxazepam, and temazepam. Ranitidine may increase or decrease benzodiazepine plasma levels; however, the effects are not expected to be clinically significant. This interaction has not been noted with other H2 antagonists.

MANAGEMENT: The US manufacturers of alprazolam, estazolam and triazolam recommend consideration of a dose reduction when these medicines are co-administered with cimetidine. The authors of the abovementioned pharmacokinetic study suggest either a reduction to the alprazolam dose by one-third or an increase to the dosage interval to twice daily when used concomitantly with cimetidine. Use of H2 antagonists and benzodiazepines that are not reported to interact may also be considered. Patients should be advised to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Gough PA, Curry SH, Araujo OE, Robinson JD, Dallman JJ "Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change." Br J Clin Pharmacol 14 (1982): 739-42
  2. Parker WA, MacLachlan RA "Prolonged hypnotic response to triazolam-cimetidine combination in an elderly patient." Drug Intell Clin Pharm 18 (1984): 980-1
  3. Klotz U, Arvela P, Rosenkranz B "Effect of single doses of cimetidine and ranitidine on the steady-state plasma levels of midazolam." Clin Pharmacol Ther 38 (1985): 652-5
  4. Desmond PV, Patwardhan RV, Schenker S, Speeg KV "Cimetidine impairs elimination of chlordiazepoxide ( librium) in man." Ann Intern Med 93 (1980): 266-8
  5. Klotz U, Reimann I "Delayed clearance of diazepam due to cimetidine." N Engl J Med 302 (1980): 1012-4
  6. Klotz U, Reimann I "Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam." Eur J Clin Pharmacol 18 (1980): 517-20
  7. Patwardhan RV, Johnson RF, Sinclair AP, Schenker S, Speeg KV "Lack of tolerance and rapid recovery of cimetidine-inhibited chlordiazepoxide (librium) elimination." Gastroenterology 81 (1981): 547-51
  8. Greenblatt DJ, Abernethy DR, Morse DS, Harmatz JS, Shader RI "Clinical importance of the interaction of diazepam and cimetidine." N Engl J Med 310 (1984): 1639-43
  9. Ruffalo RL, Thompson JF, Segal J "Cimetidine-benzodiazepine drug interaction." Am J Hosp Pharm 38 (1981): 1365-6
  10. Klotz U, Reimann IW, Ohnhaus EE "Effect of ranitidine on the steady state pharmacokinetics of diazepam." Eur J Clin Pharmacol 24 (1983): 357-60
  11. Andersson T, Andren K, Cederberg C, Edvardsson G, Heggelund A, Lundborg P "Effect of omeprazole and cimetidine on plasma diazepam levels." Eur J Clin Pharmacol 39 (1990): 51-4
  12. Sanders LD, Whitehead C, Gildersleve CD, Rosen M, Robinson JO "Interaction of H2-receptor antagonists and benzodiazepine sedation. A double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam." Anaesthesia 48 (1993): 286-92
  13. Britton ML, Waller ES "Central nervous system toxicity associated with concurrent use of triazolam and cimetidine." Drug Intell Clin Pharm 19 (1985): 666-8
  14. Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C "Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects." Int J Clin Pharmacol Ther Toxicol 23 (1985): 447-51
  15. Abernethy DR, Greenblatt DJ, Divoll M, Moschitto LJ, Harmatz JS, Shader RI "Interaction of cimetidine with the triazolobenzodiazepines alprazolam and triazolam." Psychopharmacology (Berl) 80 (1983): 275-8
  16. Greenblatt DJ, Locniskar A, Scavone JM, Blyden GT, Ochs HR, Harmatz JS, Shader RI "Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam." Anesth Analg 65 (1986): 176-80
  17. Wilson CM, Robinson FP, Thompson EM, Dundee JW, Elliott P "Effect of pretreatment with ranitidine on the hypnotic action of single doses of midazolam, temazepam and zopiclone. A clinical study." Br J Anaesth 58 (1986): 483-6
  18. Salonen M, Aantaa E, Aaltonen L, Kanto J "Importance of the interaction of midazolam and cimetidine." Acta Pharmacol Toxicol (Copenh) 58 (1986): 91-5
  19. Wrighton SA, Ring BJ "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res 11 (1994): 921-4
View all 19 references

Switch to consumer interaction data

Drug and food interactions

Moderate

diazePAM food

Applies to: Diastat Pediatric (diazepam)

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits intestinal rather than hepatic CYP450 3A4. 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 to avoid alcohol during benzodiazepine therapy. Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. 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
  3. "Product Information. Valium (diazepam)." Roche Laboratories PROD (2002):
  4. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  5. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  6. "Product Information. Doral (quazepam)." Wallace Laboratories PROD (2001):
  7. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie 49 (1994): 522-4
  8. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94
  9. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  10. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  11. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  12. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  13. Majeed A, Kareem A "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol 10 (1996): 395
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol 42 (1996): p662
  15. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  16. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  17. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet 23 (1998): 55-9
  18. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  19. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56
  20. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  21. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
  22. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  23. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  24. Eagling VA, Profit L, Back DJ "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol 48 (1999): 543-52
  25. Damkier P, Hansen LL, Brosen K "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol 48 (1999): 829-38
  26. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  27. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  28. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  29. Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58
  30. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  31. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  32. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
  33. 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
  34. Flanagan D "Understanding the grapefruit-drug interaction." Gen Dent 53 (2005): 282-5; quiz 286
View all 34 references

Switch to consumer interaction data

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

Switch to consumer interaction data

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

Switch to consumer interaction data

Minor

diazePAM food

Applies to: Diastat Pediatric (diazepam)

One study has reported a 22% reduction in diazepam plasma levels when coadministered with caffeine. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that changes to caffeine consumption habits may impact the efficacy of diazepam therapy.

References

  1. Ghoneim MM, Hinrichs JV, Chiang CK, Loke WH "Pharmacokinetic and pharmacodynamic interactions between caffeine and diazepam." J Clin Psychopharmacol 6 (1986): 75-80

Switch to consumer interaction data

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

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer