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Drug Interactions between Omeclamox-Pak and Valrelease

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

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Interactions between your drugs

Moderate

clarithromycin diazePAM

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Valrelease (diazepam)

MONITOR: Macrolide antibiotics may increase and prolong the CNS effects of certain benzodiazepines. The mechanism is inhibition of CYP450 3A4 hepatic oxidation of the benzodiazepines. Midazolam, triazolam, and alprazolam have been specifically studied in this regard. Lorazepam, oxazepam, and temazepam are hepatically conjugated and are not expected to interact. Azithromycin and dirithromycin do not inhibit CYP450 isoenzymes.

MANAGEMENT: Patients receiving this combination should be monitored for excessive or prolonged sedation. Non-interacting benzodiazepines or antimicrobials may be considered as alternatives.

References

  1. Phillips JP, Antal EJ, Smith RB "A pharmacokinetic drug interaction between erythromycin and triazolam." J Clin Psychopharmacol 6 (1986): 297-9
  2. Warot D, Bergougnan L, Lamiable D, et al. "Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation." Eur J Clin Pharmacol 32 (1987): 389-93
  3. Mattila MJ, Idanpaanheikkila JJ, Tornwall M, Vanakoski J "Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance." Pharmacol Toxicol 73 (1993): 180-5
  4. 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
  5. Amsden GW "Macrolides versus azalides: a drug interaction update." Ann Pharmacother 29 (1995): 906-17
  6. Luurila H, Olkkola KT, Neuvonen PJ "Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam." Pharmacol Toxicol 78 (1996): 117-22
  7. Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A "Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam." Arzneimittelforschung 46 (1996): 213-7
  8. Yasui N, Otani K, Kaneko S, et al. "A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3a4 in alprazolam metabolism." Clin Pharmacol Ther 59 (1996): 514-9
  9. Yeates RA, Laufen H, Zimmermann T "Interaction between midazolam and clarithromycin: comparison with azithromycin." Int J Clin Pharmacol Ther 34 (1996): 400-5
  10. Yeates RA, Laufen H, Zimmermann T, Schumacher T "Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin clarithromycin, and the azalide azithromycin." Int J Clin Pharmacol Ther 35 (1997): 577-9
  11. Gorski JC, Jones DR, HaehnerDaniels BD, Hamman MA, OMara EM, Hall SD "The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin." Clin Pharmacol Ther 64 (1998): 133-43
  12. Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y "Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4." Pharmaceut Res 17 (2000): 419-26
  13. Ito K, Ogihara K, Kanamitsu SI, Itoh T "Prediction of the in vivo interaction between midazolam and macrolides based on in vitro studies using human liver microsomes." Drug Metab Dispos 31 (2003): 945-954
View all 13 references

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Moderate

diazePAM omeprazole

Applies to: Valrelease (diazepam) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

MONITOR: Omeprazole may increase the pharmacologic effects and serum levels of certain benzodiazepines via hepatic enzyme inhibition. Diazepam and triazolam are the only benzodiazepines that have been specifically studied in this regard.

MANAGEMENT: Patient should be observed for increased sedation. Reduced benzodiazepine dosage may be indicated, especially in the elderly. Benzodiazepines not metabolized via oxidation (i.e., lorazepam, oxazepam, temazepam) are not expected to interact and may be considered as alternatives.

References

  1. Andersson T, Cederberg C, Edvardsson G, et al. "Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole." Clin Pharmacol Ther 47 (1990): 79-85
  2. Gugler R, Jensen JC "Omeprazole inhibits oxidative drug metabolism: studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro." Gastroenterology 89 (1985): 1235-41
  3. 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
  4. Shader RI "I recently saw a patient taking omeprazole for a duodenal ulcer who was wobbly and sedated by the small doses of diazepam that he had previously tolerated - how is this explained." J Clin Psychopharmacol 13 (1993): 459
  5. Caraco Y, Tateishi T, Wood AJJ "Interethnic difference in omeprazole's inhibition of diazepam metabolism." Clin Pharmacol Ther 58 (1995): 62-72
View all 5 references

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Minor

amoxicillin clarithromycin

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

References

  1. Strom J "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother 11 (1961): 694-7
  2. Cohn JR, Jungkind DL, Baker JS "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother 18 (1980): 872-6
  3. Penn RL, Ward TT, Steigbigel RT "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother 22 (1982): 289-94

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Minor

clarithromycin omeprazole

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole) and Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

References

  1. Zhou Q, Yamamoto I, Fukuda T, Ohno M, Sumida A, Azuma J "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol 55 (1999): 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother 39 (1995): 2078-83
  3. Furuta T, Ohashi K, Kobayashi K, Iida I, Yoshida H, Shirai N, Takashima M, Kosuge K, Hanai H, Chiba K, Ishizaki T, Kaneko E "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther 66 (1999): 265-74

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Drug and food interactions

Moderate

diazePAM food

Applies to: Valrelease (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

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Minor

clarithromycin food

Applies to: Omeclamox-Pak (amoxicillin / clarithromycin / omeprazole)

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother 42 (1998): 927-9

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Minor

diazePAM food

Applies to: Valrelease (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

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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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