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Drug Interactions between flurazepam and Omeclamox-Pak

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

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Interactions between your drugs

Moderate

clarithromycin flurazepam

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

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 (1986) "A pharmacokinetic drug interaction between erythromycin and triazolam." J Clin Psychopharmacol, 6, p. 297-9
  2. Warot D, Bergougnan L, Lamiable D, et al. (1987) "Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation." Eur J Clin Pharmacol, 32, p. 389-93
  3. Mattila MJ, Idanpaanheikkila JJ, Tornwall M, Vanakoski J (1993) "Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance." Pharmacol Toxicol, 73, p. 180-5
  4. Wrighton SA, Ring BJ (1994) "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res, 11, p. 921-4
  5. Amsden GW (1995) "Macrolides versus azalides: a drug interaction update." Ann Pharmacother, 29, p. 906-17
  6. Luurila H, Olkkola KT, Neuvonen PJ (1996) "Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam." Pharmacol Toxicol, 78, p. 117-22
  7. Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A (1996) "Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam." Arzneimittelforschung, 46, p. 213-7
  8. Yasui N, Otani K, Kaneko S, et al. (1996) "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, p. 514-9
  9. Yeates RA, Laufen H, Zimmermann T (1996) "Interaction between midazolam and clarithromycin: comparison with azithromycin." Int J Clin Pharmacol Ther, 34, p. 400-5
  10. Yeates RA, Laufen H, Zimmermann T, Schumacher T (1997) "Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin clarithromycin, and the azalide azithromycin." Int J Clin Pharmacol Ther, 35, p. 577-9
  11. Gorski JC, Jones DR, HaehnerDaniels BD, Hamman MA, OMara EM, Hall SD (1998) "The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin." Clin Pharmacol Ther, 64, p. 133-43
  12. Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y (2000) "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, p. 419-26
  13. Ito K, Ogihara K, Kanamitsu SI, Itoh T (2003) "Prediction of the in vivo interaction between midazolam and macrolides based on in vitro studies using human liver microsomes." Drug Metab Dispos, 31, p. 945-954
View all 13 references

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Moderate

flurazepam omeprazole

Applies to: flurazepam 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. (1990) "Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole." Clin Pharmacol Ther, 47, p. 79-85
  2. Gugler R, Jensen JC (1985) "Omeprazole inhibits oxidative drug metabolism: studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro." Gastroenterology, 89, p. 1235-41
  3. Andersson T, Andren K, Cederberg C, Edvardsson G, Heggelund A, Lundborg P (1990) "Effect of omeprazole and cimetidine on plasma diazepam levels." Eur J Clin Pharmacol, 39, p. 51-4
  4. Shader RI (1993) "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, p. 459
  5. Caraco Y, Tateishi T, Wood AJJ (1995) "Interethnic difference in omeprazole's inhibition of diazepam metabolism." Clin Pharmacol Ther, 58, p. 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 (1961) "Penicillin and erythromycin singly and in combination in scarlatina therapy and the interference between them." Antibiot Chemother, 11, p. 694-7
  2. Cohn JR, Jungkind DL, Baker JS (1980) "In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens." Antimicrob Agents Chemother, 18, p. 872-6
  3. Penn RL, Ward TT, Steigbigel RT (1982) "Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of listeria monocytogenes." Antimicrob Agents Chemother, 22, p. 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 (1999) "CYP2C19 genotypes and omeprazole metabolism after single and repeated dosing when combined with clarithromycin." Eur J Clin Pharmacol, 55, p. 43-7
  2. Gustavson LE, Kaiser JF, Edmonds AL, Locke CS, DeBartolo ML, Schneck DW (1995) "Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state." Antimicrob Agents Chemother, 39, p. 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 (1999) "Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans." Clin Pharmacol Ther, 66, p. 265-74

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Drug and food interactions

Moderate

flurazepam food

Applies to: flurazepam

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete 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. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 4 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 (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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.

See also

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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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