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Drug Interactions between Bydureon and nalidixic acid

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

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Moderate

nalidixic acid exenatide

Applies to: nalidixic acid and Bydureon (exenatide)

MONITOR: Quinolone antibiotics may interfere with the therapeutic effects of insulin and other antidiabetic agents. The use of 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. Both hyperglycemia and hypoglycemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., sulfonylurea) or insulin. Although hyperglycemia is significantly more common and infection itself may be an underlying risk factor, hypoglycemia may cause greater morbidity and mortality. An internal safety review conducted by the U.S. Food and Drug Administration (FDA) identified at least 67 reports of severe hypoglycemia associated with quinolone use resulting in coma, death, or permanent and disabling injuries, primarily in elderly and diabetic patients with renal impairment and/or complicated infections. This is in addition to the numerous cases that have been reported for gatifloxacin, which led to its withdrawal from the U.S. market in 2008. Of the five quinolones that the FDA reviewed, levofloxacin had the most cases (44), followed by ciprofloxacin (12), moxifloxacin (9), ofloxacin (2), and gemifloxacin (0). Other quinolones such as nalidixic acid and norfloxacin, as well as some others that have never been marketed or are no longer marketed such as clinafloxacin and temafloxacin, have also been associated with dysglycemia, thus it is generally believed to be a class effect, albeit with varying risks amongst the individual agents. Available data also seem to indicate different time frames for the development of hypo- and hyperglycemia, with the former generally occurring within 1 to 3 days following quinolone initiation and the latter within 4 to 10 days later.

MANAGEMENT: Blood glucose should be closely monitored whenever quinolones are prescribed to diabetic patients, especially if they are elderly, have renal impairment, or are severely ill. Patients should be apprised of the increased risk of dysglycemia and be particularly alert to potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypoglycemia occurs, patients should initiate appropriate remedial therapy immediately, discontinue the quinolone, and contact their physician. Alternative antibiotics may need to be considered.

References

  1. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  2. (2001) "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc
  3. (2001) "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical
  4. (2001) "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical
  5. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  6. (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
  7. Edwards DJ, Bowles SK, Svensson CK, Rybak MJ (1988) "Inhibition of drug metabolism by quinolone antibiotics." Clin Pharmacokinet, 15, p. 194-204
  8. (2001) "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb
  9. 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
  10. Roberge RJ, Kaplan R, Frank R, Fore C (2000) "Glyburide-ciprofloxacin interaction with resistant hypoglycemia." Ann Emerg Med, 36, p. 160-3
  11. Rubinstein E (2001) "History of quinolones and their side effects." Chemotherapy, 47 Suppl 3, p. 3-8
  12. 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
  13. Baker SE, Hangii MC (2002) "Possible gatifloxacin-induced hypoglycemia." Ann Pharmacother, 36, p. 1722-6
  14. (2003) "Product Information. Factive (gemifloxacin)." *GeneSoft Inc
  15. (2003) "Hypoglycemia and hyperglycemia with fluoroquinolones." Med Lett Drugs Ther, 45, p. 64
  16. Donaldson AR, Vandiver JR, Finch CK (2004) "Possible gatifloxacin-induced hyperglycemia." Ann Pharmacother, 38, p. 602-5
  17. LeBlanc M, Belanger C, Cossette P (2004) "Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy." Pharmacotherapy, 24, p. 926-31
  18. Biggs WS (2004) "Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients." J Am Board Fam Pract, 16, p. 455-7
  19. 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
  20. 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
  21. Lin G, Hays DP, Spillane L (2004) "Refractory hypoglycemia from ciprofloxacin and glyburide interaction." J Toxicol Clin Toxicol, 42, p. 295-7
  22. Friedrich LV, Dougherty R (2004) "Fatal hypoglycemia associated with levofloxacin." Pharmacotherapy, 24, p. 1807-12
  23. Khovidhunkit W, Sunthornyothin S (2004) "Hypoglycemia, hyperglycemia, and gatifloxacin." Ann Intern Med, 141, p. 969
  24. Happe MR, Mulhall BP, Maydonovitch CL, Holtzmuller KC (2004) "Gatifloxacin-induced hyperglycemia." Ann Intern Med, 141, p. 968-9
  25. Greenberg AL, Decerbo M, Fan J (2005) "Gatifloxacin therapy associated with hypoglycemia." Clin Infect Dis, 40, p. 1210-1
  26. Blommel AL, Lutes RA (2005) "Severe hyperglycemia during renally adjusted gatifloxacin therapy." Ann Pharmacother, 39, p. 1349-52
  27. Brogan SE, Cahalan MK (2005) "Gatifloxacin as a possible cause of serious postoperative hypoglycemia." Anesth Analg, 101, p. 635-6
  28. 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
  29. Frothingham R (2005) "Glucose homeostasis abnormalities associated with use of gatifloxacin." Clin Infect Dis, 41, p. 1269-76
  30. Bhasin R, Arce FC, Pasmantier R (2005) "Hypoglycemia associated with the use of gatifloxacin." Am J Med Sci, 330, p. 250-3
  31. 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
  32. 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
  33. Wang S, Rizvi AA (2006) "Levofloxacin-induced hypoglycemia in a nondiabetic patient." Am J Med Sci, 331, p. 334-5
  34. Kanbay M, Aydogan T, Bozalan R, et al. (2006) "A rare but serious side effect of levofloxacin: hypoglycemia in a geriatric patient." Diabetes Care, 29, p. 1716-7
  35. Zvonar R (2006) "Gatifloxacin-induced dysglycemia." Am J Health Syst Pharm, 63, p. 2087-2092
  36. 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
  37. Yip C, Lee AJ (2006) "Gatifloxacin-induced hyperglycemia: a case report and summary of the current literature." Clin Ther, 28, p. 1857-66
  38. 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
  39. Kelesidis T, Canseco E (2010) "Quinolone-induced hypoglycemia: a life-threatening but potentially reversible side effect." Am J Med, 123, e5-6
  40. (2017) "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc.
  41. (2021) "Product Information. Ciprofloxacin Hydrochloride (ciprofloxacin)." Aurobindo Pharma USA Inc
  42. FDA. Food and Drug Admnistration (2023) FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes. https://www.fda.gov/drugs/drug-safety-and-availability/fda-reinforces-safety-information-about
View all 42 references

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Drug and food interactions

Moderate

exenatide food

Applies to: Bydureon (exenatide)

ADJUST DOSING INTERVAL: Exenatide slows gastric emptying and may reduce the extent and rate of absorption of concomitantly administered oral medications. When acetaminophen 1000 mg was administered simultaneously with exenatide 10 mcg and also one hour, 2 hours, and 4 hours after exenatide injection, acetaminophen systemic exposure (AUC) was decreased by 21%, 23%, 24%, and 14%, respectively; peak plasma concentration (Cmax) was decreased by 37%, 56%, 54%, and 41%, respectively; and time to peak plasma concentration (Tmax) was increased from 0.6 hours in the control period to 0.9 hours, 4.2 hours, 3.3 hours, and 1.6 hours, respectively. These values were not significantly changed when acetaminophen was given one hour before exenatide injection.

MANAGEMENT: Concomitantly administered oral medications that are dependent on threshold concentrations for efficacy (e.g., antibiotics, contraceptives) or that require rapid gastrointestinal absorption (e.g., hypnotics, pain medications) should be administered at least 1 hour before exenatide. If such medications are to be administered with food, patients should be advised to take them with a meal or snack when exenatide is not administered.

References

  1. (2005) "Product Information. Byetta (exenatide)." Amylin Pharmaceuticals Inc

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Moderate

nalidixic acid food

Applies to: nalidixic acid

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of nalidixic acid. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of nalidixic acid by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract.

MANAGEMENT: When coadministration cannot be avoided, nalidixic acid should be dosed at least 2 hours before or 2 hours after polyvalent cation-containing products to minimize the potential for interaction.

References

  1. "Product Information. Neggram (nalidixic acid)." Sanofi Winthrop Pharmaceuticals

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Moderate

nalidixic acid food

Applies to: nalidixic acid

MONITOR: Coadministration with certain quinolones may increase the plasma concentrations and pharmacologic effects of caffeine due to inhibition of the CYP450 1A2 metabolism of caffeine. Quinolones that may inhibit CYP450 1A2 include ciprofloxacin, enoxacin, grepafloxacin, nalidixic acid, norfloxacin, pipemidic acid, and pefloxacin (not all commercially available). In healthy volunteers, enoxacin (100 to 400 mg twice daily) increased systemic exposure (AUC) of caffeine by 2- to 5-fold and reduced its clearance by approximately 80%. Pipemidic acid (400 to 800 mg twice daily) increased AUC of caffeine by 2- to 3-fold and reduced its clearance by approximately 60%. Ciprofloxacin (250 to 750 mg twice daily) increased AUC and elimination half-life of caffeine by 50% to over 100%, and reduced its clearance by 30% to 50%. Norfloxacin 400 mg twice daily increased caffeine AUC by 16%, while 800 mg twice daily increased caffeine AUC by 52% and reduced its clearance by 35%. Pefloxacin (400 mg twice daily) has been shown to reduce caffeine clearance by 47%.

MANAGEMENT: Patients using caffeine-containing products should be advised that increased adverse effects such as headache, tremor, restlessness, nervousness, insomnia, tachycardia, and blood pressure increases may occur during coadministration with quinolones that inhibit CYP450 1A2. Caffeine intake should be limited when taking high dosages of these quinolones. If an interaction is suspected, other quinolones such as gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, and ofloxacin may be considered, since they are generally believed to have little or no effect on CYP450 1A2 or have been shown not to interact with caffeine.

References

  1. Polk RE (1989) "Drug-drug interactions with ciprofloxacin and other fluoroquinolones." Am J Med, 87, s76-81
  2. Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML (1989) "Interaction between oral ciprofloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 33, p. 474-8
  3. Harder S, Fuhr U, Staib AH, Wolf T (1989) "Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations." Am J Med, 87, p. 89-91
  4. Carbo ML, Segura J, De la Torre R, et al. (1989) "Effect of quinolones on caffeine disposition." Clin Pharmacol Ther, 45, p. 234-40
  5. (1993) "Product Information. Penetrax (enoxacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  6. Mahr G, Sorgel F, Granneman GR, et al. (1992) "Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine." Clin Pharmacokinet, 22, p. 90-7
  7. (2002) "Product Information. Cipro (ciprofloxacin)." Bayer
  8. (2001) "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc
  9. Staib AH, Stille W, Dietlein G, et al. (1987) "Interaction between quinolones and caffeine." Drugs, 34 Suppl 1, p. 170-4
  10. Stille W, Harder S, Micke S, et al. (1987) "Decrease of caffeine elimination in man during co-administration of 4-quinolones." J Antimicrob Chemother, 20, p. 729-34
  11. Harder S, Staib AH, Beer C, Papenburg A, Stille W, Shah PM (1988) "4-Quinolones inhibit biotransformation of caffeine." Eur J Clin Pharmacol, 35, p. 651-6
  12. Nicolau DP, Nightingale CH, Tessier PR, et al. (1995) "The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine." Drugs, 49 Suppl 2, p. 357-9
  13. (2001) "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome
  14. Carrillo JA, Benitez J (2000) "Clinically significant pharmacokinetic interactions between dietary caffeine and medications." Clin Pharmacokinet, 39, p. 127-53
  15. Fuhr U, Wolff T, Harder S, Schymanski P, Staib AH (1990) "Quinolone inhibition of cytochrome P-450 dependent caffeine metabolism in human liver microsomes." Drug Metab Dispos, 18, p. 1005-10
  16. Kinzig-Schippers M, Fuhr U, Zaigler M, et al. (1999) "Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2." Clin Pharmacol Ther, 65, p. 262-74
  17. Healy DP, Schoenle JR, Stotka J, Polk RE (1991) "Lack of interaction between lomefloxacin and caffeine in normal volunteers." Antimicrob Agents Chemother, 35, p. 660-4
View all 17 references

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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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