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Drug Interactions between gatifloxacin and Norpace CR

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

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Major

disopyramide gatifloxacin

Applies to: Norpace CR (disopyramide) and gatifloxacin

CONTRAINDICATED: Quinolones such as ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, and sparfloxacin may cause dose-related prolongation of the QT interval in some patients. Coadministration with other agents that can prolong the QT interval may result in elevated risk of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, because of additive arrhythmogenic potential related to their effects on cardiac conduction. Torsade de pointes have been reported in a few patients receiving sparfloxacin alone and with antiarrhythmic agents like amiodarone and disopyramide. There have also been isolated case reports of clinically significant interactions with sotalol, a class III antiarrhythmic agent, for both gatifloxacin and moxifloxacin. Ciprofloxacin, levofloxacin, lomefloxacin, norfloxacin, and ofloxacin alone have been associated with extremely rare cases of torsade de pointes and ventricular tachycardia.

MANAGEMENT: Product labeling for certain quinolones recommends avoiding concomitant therapy with class IA (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, dofetilide, ibutilide, sotalol) antiarrhythmic agents, as well as bepridil.

References

  1. "Product Information. Maxaquin (lomefloxacin)." Searle PROD (2002):
  2. "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  4. Thomas M, Maconochie JG, Fletcher E "The dilemma of the prolonged QT interval in early drug studies." Br J Clin Pharmacol 41 (1996): 77-81
  5. Jaillon P, Morganroth J, Brumpt I, Talbot G "Overview of electrocardiographic and cardiovascular safety data for sparfloxacin. Sparfloxacin Safety Group." J Antimicrob Chemother 37(suppl a) (1996): 161-7
  6. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  7. Zix JA, GeerdesFenge HF, Rau M, Vockler J, Borner K, Koeppe P, Lode H "Pharmacokinetics of sparfloxacin and interaction with cisapride and sucralfate." Antimicrob Agents Chemother 41 (1997): 1668-72
  8. "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer PROD (2001):
  9. Demolis JL, Charransol A, Funck-Brentano C, Jaillon P "Effects of a single oral dose of sparfloxacin on ventricular repolarization in healthy volunteers." Br J Clin Pharmacol 41 (1996): 499-503
  10. Dupont H, Timsit JF, Souweine B, Gachot B, Wolff M, Regnier B "Torsades de pointe probably related to sparfloxacin." Eur J Clin Microbiol Infect Dis 15 (1996): 350-1
  11. Lipsky BA, Dorr MB, Magner DJ, Talbot GH "Safety profile of sparfloxacin, a new fluoroquinolone antibiotic." Clin Ther 21 (1999): 148-59
  12. Samaha FF "QTC interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin." Am J Med 107 (1999): 528-9
  13. "Product Information. Avelox (moxifloxacin)." Bayer PROD (2001):
  14. "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb PROD (2001):
  15. Siepmann M, Kirch W "Drug points - Tachycardia associated with moxifloxacin." Br Med J 322 (2001): 23
  16. Owens RC "Risk assessment for antimicrobial agent-induced QTc interval prolongation and torsades de pointes." Pharmacotherapy 21 (2001): 301-19
  17. Iannini PB, Circiumaru I "Gatifloxacin-induced QTc prolongation and ventricular tachycardia." Pharmacotherapy 21 (2001): 361-2
  18. Demolis JL, Kubitza D, Tenneze L, Funck-Bretano C "Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects." Clin Pharmacol Ther 68 (2000): 658-66
  19. Iannini PB, Doddamani S, Byazrova E, Curciumaru I, Kramer H "Risk of torsades de pointes with non-cardiac drugs." BMJ 322 (2001): 46-7
  20. Ball P "Quinolone-induced QT interval prolongation: a not-so-unexpected class effect." J Antimicrob Chemother 45 (2000): 557-9
  21. Kang J, Wang L, Chen XL, Triggle DJ, Rampe D "Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG." Mol Pharmacol 59 (2001): 122-6
  22. White CM, Grant EM, Quintiliani R "Moxifloxacin does increase the corrected QT interval." Clin Infect Dis 33 (2001): 1441-2
  23. Frothingham R "Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin." Pharmacotherapy 21 (2001): 1468-72
  24. Bertino JS Jr, Owens RC Jr, Carnes TD, Iannini PB "Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors." Clin Infect Dis 34 (2002): 861-3
  25. Oliphant CM, Green GM "Quinolones: a comprehensive review." Am Fam Physician 65 (2002): 455-64
  26. Owens RC Jr, Ambrose PG "Torsades de pointes associated with fluoroquinolones." Pharmacotherapy 22 (2002): 663-8; discussion 668-72
  27. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  28. Noel GJ, Natarajan J, Chien S, Hunt TL, Goodman DB, Abels R "Effects of three fluoroquinolones on QT interval in healthy adults after single doses." Clin Pharmacol Ther 73 (2003): 292-303
  29. Ansari SR, Chopra N "Gatifloxacin and Prolonged QT Interval." Am J Med Sci 327 (2004): 55-6
  30. Iannini PB "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf 1 (2002): 121-8
  31. Owens RC "QT Prolongation with Antimicrobial Agents : Understanding the Significance." Drugs 64 (2004): 1091-124
  32. Katritsis D, Camm AJ "Quinolones: cardioprotective or cardiotoxic." Pacing Clin Electrophysiol 26 (2003): 2317-20
  33. Stahlmann R "Clinical toxicological aspects of fluoroquinolones." Toxicol Lett 127 (2002): 269-77
  34. Makaryus AN, Byrns K, Makaryus MN, Natarajan U, Singer C, Goldner B "Effect of ciprofloxacin and levofloxacin on the QT interval: is this a significant "clinical" event?" South Med J 99 (2006): 52-6
  35. Dale KM, Lertsburapa K, Kluger J, White CM "Moxifloxacin and torsade de pointes." Ann Pharmacother 41 (2007): 336-40
  36. Falagas ME, Rafailidis PI, Rosmarakis ES "Arrhythmias associated with fluoroquinolone therapy." Int J Antimicrob Agents 29 (2007): 374-9
  37. Tsikouris JP, Peeters MJ, Cox CD, Meyerrose GE, Seifert CF "Effects of three fluoroquinolones on QT analysis after standard treatment courses." Ann Noninvasive Electrocardiol 11 (2006): 52-6
View all 37 references

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Drug and food interactions

Moderate

disopyramide food

Applies to: Norpace CR (disopyramide)

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: 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. 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
  4. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  5. 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
  6. 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
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  8. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  9. 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
  10. 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
  11. Majeed A, Kareem A "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol 10 (1996): 395
  12. 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
  13. 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
  14. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  15. 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
  16. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  17. 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
  18. 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
  19. 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
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  21. 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
  22. 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
  23. 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
  24. 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
  25. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  26. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. Flanagan D "Understanding the grapefruit-drug interaction." Gen Dent 53 (2005): 282-5; quiz 286
View all 32 references

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Minor

gatifloxacin food

Applies to: gatifloxacin

Concurrent ingestion of calcium-fortified foods (i.e., cereal, orange juice) may alter the bioavailability of gatifloxacin. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. Data have been conflicting: One study has reported no effect with milk coadministration. Another study reported a modest decrease in gatifloxacin bioavailability (13.5% decrease in Cmax,12% decrease in AUC, 15% increase in total clearance) when taken with 12 ounces of calcium-fortified orange juice instead of water, which could be clinically significant if the infecting organisms have borderline susceptibilities. The manufacturer states that gatifloxacin may be taken without regard to food, milk, or calcium. Clinicians should be aware of the possibility of an interaction if subtherapeutic effects are observed.

References

  1. "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb PROD (2001):
  2. Wallace AW, Victory JM, Amsden GW "Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers." J Clin Pharmacol 43 (2003): 92-6

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Minor

disopyramide food

Applies to: Norpace CR (disopyramide)

Ethanol significantly increases the renal elimination of disopyramide, apparently by inducing diuresis (inhibition of antidiuretic hormone). Limited data show that ethanol does not, however, significantly affect the elimination half-life or total plasma clearance of disopyramide. No special precautions appear to be necessary.

References

  1. Olsen H, Bredesen JE, Lunde PK "Effect of ethanol intake on disopyramide elimination by healthy volunteers." Eur J Clin Pharmacol 25 (1983): 103-5

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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.

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