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Drug Interactions between amoxicillin / clarithromycin / omeprazole and sparfloxacin

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

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Interactions between your drugs

Major

clarithromycin sparfloxacin

Applies to: amoxicillin / clarithromycin / omeprazole and sparfloxacin

CONTRAINDICATED: Sparfloxacin may cause dose-related prolongation of the QT interval in some patients. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Torsade de pointes has been reported in a few patients receiving sparfloxacin alone and with antiarrhythmic agents like amiodarone and disopyramide.

MANAGEMENT: Coadministration of sparfloxacin with other drugs that can prolong the QT interval is considered contraindicated.

References (21)
  1. Thomas M, Maconochie JG, Fletcher E (1996) "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol, 41, p. 77-81
  2. Jaillon P, Morganroth J, Brumpt I, Talbot G (1996) "Overview of electrocardiographic and cardiovascular safety data for sparfloxacin. Sparfloxacin Safety Group." J Antimicrob Chemother, 37(suppl a), p. 161-7
  3. Zix JA, GeerdesFenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H (1997) "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother, 41, p. 1668-72
  4. (2001) "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer
  5. Demolis JL, Charransol A, Funck-Brentano C, Jaillon P (1996) "Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers." Br J Clin Pharmacol, 41, p. 499-503
  6. Dupont H, Timsit JF, Souweine B, Gachot B, Wolff M, Regnier B (1996) "Torsades de pointe probably related to sparfloxacin." Eur J Clin Microbiol Infect Dis, 15, p. 350-1
  7. Lipsky BA, Dorr MB, Magner DJ, Talbot GH (1999) "Safety profile of sparfloxacin, a new fluoroquinolone antibiotic." Clin Ther, 21, p. 148-59
  8. Owens RC (2001) "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy, 21, p. 301-19
  9. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H (2001) "Risk of torsades de pointes with non-cardiac drugs." BMJ, 322, p. 46-7
  10. Ball P (2000) "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother, 45, p. 557-9
  11. Kang J, Wang L, Chen XL, Triggle DJ, Rampe D (2001) "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol, 59, p. 122-6
  12. Oliphant CM, Green GM (2002) "Quinolones: a comprehensive review." Am Fam Physician, 65, p. 455-64
  13. Owens RC Jr, Ambrose PG (2002) "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy, 22, 663-8; discussion 668-72
  14. Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
  15. Owens RC (2004) "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs, 64, p. 1091-124
  16. Katritsis D, Camm AJ (2003) "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol, 26, p. 2317-20
  17. Stahlmann R (2002) "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett, 127, p. 269-77
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  19. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  20. Falagas ME, Rafailidis PI, Rosmarakis ES (2007) "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents, 29, p. 374-9
  21. Cerner Multum, Inc. "Australian Product Information."
Minor

amoxicillin clarithromycin

Applies to: amoxicillin / clarithromycin / omeprazole and 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 (3)
  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
Minor

clarithromycin omeprazole

Applies to: amoxicillin / clarithromycin / omeprazole and 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 (3)
  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

Drug and food interactions

Minor

clarithromycin food

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

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.

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

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