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Drug Interactions between gatifloxacin and repaglinide

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

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Major

repaglinide gatifloxacin

Applies to: repaglinide and gatifloxacin

CONTRAINDICATED: Gatifloxacin may interfere with the therapeutic effects of insulin and other antidiabetic agents. The use of various quinolones has been associated with disturbances in blood glucose homeostasis possibly stemming from effects on pancreatic beta cell ATP-sensitive potassium channels that regulate insulin secretion. However, hypoglycemia and hyperglycemia have been reported more frequently with gatifloxacin than with other quinolones. Gatifloxacin-induced hypoglycemic episodes have generally occurred within the first 3 days of therapy and sometimes even after the first dose, while hyperglycemia usually occurred 4 to 10 days after initiation of therapy. Death has been reported in severe cases. Coadministration of gatifloxacin with sulfonylureas (most often glyburide) and/or other oral hypoglycemic agents has resulted in severe, refractory hypoglycemia and hypoglycemic coma. Elderly patients and patients with reduced renal function are particularly susceptible.

MANAGEMENT: The use of gatifloxacin is contraindicated in patients with diabetes mellitus. Other quinolones may be safer alternatives in such patients, although all quinolones should be used with caution. Blood glucose should be closely monitored whenever quinolones are prescribed to patients receiving insulin or other antidiabetic agents, especially if they are elderly or have renal impairment. Patients should learn to recognize the symptoms of hypoglycemia such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypo- or hyperglycemia occur during quinolone therapy, patients should initiate appropriate remedial therapy immediately, discontinue the antibiotic, and contact their physician.

References (27)
  1. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  2. Gajjar DA, LaCreta FP, Kollia GD, et al. (2000) "Effect of multiple-dose gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with noninsulin-dependent diabetes mellitus maintained with diet and exercise." Pharmacotherapy, 20 (6 Pt 2), s76-86
  3. Roberge RJ, Kaplan R, Frank R, Fore C (2000) "Glyburide-ciprofloxacin interaction with resistant hypoglycemia." Ann Emerg Med, 36, p. 160-3
  4. Rubinstein E (2001) "History of quinolones and their side effects." Chemotherapy, 47 Suppl 3, p. 3-8
  5. Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH (2002) "Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents." Am J Med, 113, p. 232-4
  6. Baker SE, Hangii MC (2002) "Possible gatifloxacin-induced hypoglycemia." Ann Pharmacother, 36, p. 1722-6
  7. (2003) "Hypoglycemia and hyperglycemia with fluoroquinolones." Med Lett Drugs Ther, 45, p. 64
  8. Donaldson AR, Vandiver JR, Finch CK (2004) "Possible gatifloxacin-induced hyperglycemia." Ann Pharmacother, 38, p. 602-5
  9. LeBlanc M, Belanger C, Cossette P (2004) "Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy." Pharmacotherapy, 24, p. 926-31
  10. Biggs WS (2004) "Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients." J Am Board Fam Pract, 16, p. 455-7
  11. Gavin JR 3rd, Kubin R, Choudhri S, et al. (2004) "Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies." Drug Saf, 27, p. 671-86
  12. Saraya A, Yokokura M, Gonoi T, Seino S (2004) "Effects of fluoroquinolones on insulin secretion and beta-cell ATP-sensitive K(+) channels." Eur J Pharmacol, 497, p. 111-7
  13. Lin G, Hays DP, Spillane L (2004) "Refractory hypoglycemia from ciprofloxacin and glyburide interaction." J Toxicol Clin Toxicol, 42, p. 295-7
  14. Khovidhunkit W, Sunthornyothin S (2004) "Hypoglycemia, hyperglycemia, and gatifloxacin." Ann Intern Med, 141, p. 969
  15. Happe MR, Mulhall BP, Maydonovitch CL, Holtzmuller KC (2004) "Gatifloxacin-induced hyperglycemia." Ann Intern Med, 141, p. 968-9
  16. Greenberg AL, Decerbo M, Fan J (2005) "Gatifloxacin therapy associated with hypoglycemia." Clin Infect Dis, 40, p. 1210-1
  17. Blommel AL, Lutes RA (2005) "Severe hyperglycemia during renally adjusted gatifloxacin therapy." Ann Pharmacother, 39, p. 1349-52
  18. Brogan SE, Cahalan MK (2005) "Gatifloxacin as a possible cause of serious postoperative hypoglycemia." Anesth Analg, 101, p. 635-6
  19. Graumlich JF, Habis S, Avelino RR, et al. (2005) "Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study." Pharmacotherapy, 25, p. 1296-302
  20. Frothingham R (2005) "Glucose homeostasis abnormalities associated with use of gatifloxacin." Clin Infect Dis, 41, p. 1269-76
  21. Bhasin R, Arce FC, Pasmantier R (2005) "Hypoglycemia associated with the use of gatifloxacin." Am J Med Sci, 330, p. 250-3
  22. McMorran M, Morrison H, Letourneau G (2006) Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3_e.html#1
  23. Park-Wyllie LY, Juurlink DN, Kopp A, et al. (2006) "Outpatient gatifloxacin therapy and dysglycemia in older adults." N Engl J Med, 354, p. 1352-61
  24. Zvonar R (2006) "Gatifloxacin-induced dysglycemia." Am J Health Syst Pharm, 63, p. 2087-2092
  25. Zhanel GG, Fontaine S, Adam H, et al. (2006) "A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections." Treat Respir Med, 5, p. 437-465
  26. Yip C, Lee AJ (2006) "Gatifloxacin-induced hyperglycemia: a case report and summary of the current literature." Clin Ther, 28, p. 1857-66
  27. Tomita T, Onishi M, Sato E, Kimura Y, Kihira K (2007) "Gatifloxacin induces augmented insulin release and intracellular insulin." Biol Pharm Bull, 30, p. 644-7

Drug and food interactions

Moderate

repaglinide food

Applies to: repaglinide

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 (32)
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  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "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, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
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 (2)
  1. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  2. Wallace AW, Victory JM, Amsden GW (2003) "Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers." J Clin Pharmacol, 43, p. 92-6

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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