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Drug Interactions between Cipro XR and insulin aspart/insulin aspart protamine

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

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Major

ciprofloxacin insulin aspart

Applies to: Cipro XR (ciprofloxacin) and insulin aspart/insulin aspart protamine

MONITOR CLOSELY: 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 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. Pharmacokinetically, ciprofloxacin is also a known inhibitor of CYP450 1A2 and 3A4 and may inhibit the hepatic metabolism of glyburide. Hypoglycemia in association with elevated serum glyburide level occurred in a patient after one week of ciprofloxacin therapy.

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. Due to the risk of profound and potentially life-threatening hypoglycemia, particular caution is advised during concomitant use of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms 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. "Product Information. Cipro (ciprofloxacin)." Bayer PROD (2002):
  2. "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  4. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  5. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  6. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  7. Edwards DJ, Bowles SK, Svensson CK, Rybak MJ "Inhibition of drug metabolism by quinolone antibiotics." Clin Pharmacokinet 15 (1988): 194-204
  8. "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb PROD (2001):
  9. Gajjar DA, LaCreta FP, Kollia GD, et al. "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) (2000): s76-86
  10. Roberge RJ, Kaplan R, Frank R, Fore C "Glyburide-ciprofloxacin interaction with resistant hypoglycemia." Ann Emerg Med 36 (2000): 160-3
  11. Rubinstein E "History of quinolones and their side effects." Chemotherapy 47 Suppl 3 (2001): 3-8
  12. Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH "Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents." Am J Med 113 (2002): 232-4
  13. Baker SE, Hangii MC "Possible gatifloxacin-induced hypoglycemia." Ann Pharmacother 36 (2002): 1722-6
  14. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  15. "Hypoglycemia and hyperglycemia with fluoroquinolones." Med Lett Drugs Ther 45 (2003): 64
  16. Donaldson AR, Vandiver JR, Finch CK "Possible gatifloxacin-induced hyperglycemia." Ann Pharmacother 38 (2004): 602-5
  17. LeBlanc M, Belanger C, Cossette P "Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy." Pharmacotherapy 24 (2004): 926-31
  18. Biggs WS "Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients." J Am Board Fam Pract 16 (2004): 455-7
  19. Gavin JR 3rd, Kubin R, Choudhri S, et al. "Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies." Drug Saf 27 (2004): 671-86
  20. Saraya A, Yokokura M, Gonoi T, Seino S "Effects of fluoroquinolones on insulin secretion and beta-cell ATP-sensitive K(+) channels." Eur J Pharmacol 497 (2004): 111-7
  21. Lin G, Hays DP, Spillane L "Refractory hypoglycemia from ciprofloxacin and glyburide interaction." J Toxicol Clin Toxicol 42 (2004): 295-7
  22. Friedrich LV, Dougherty R "Fatal hypoglycemia associated with levofloxacin." Pharmacotherapy 24 (2004): 1807-12
  23. Khovidhunkit W, Sunthornyothin S "Hypoglycemia, hyperglycemia, and gatifloxacin." Ann Intern Med 141 (2004): 969
  24. Happe MR, Mulhall BP, Maydonovitch CL, Holtzmuller KC "Gatifloxacin-induced hyperglycemia." Ann Intern Med 141 (2004): 968-9
  25. Greenberg AL, Decerbo M, Fan J "Gatifloxacin therapy associated with hypoglycemia." Clin Infect Dis 40 (2005): 1210-1
  26. Blommel AL, Lutes RA "Severe hyperglycemia during renally adjusted gatifloxacin therapy." Ann Pharmacother 39 (2005): 1349-52
  27. Brogan SE, Cahalan MK "Gatifloxacin as a possible cause of serious postoperative hypoglycemia." Anesth Analg 101 (2005): 635-6
  28. Graumlich JF, Habis S, Avelino RR, et al. "Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study." Pharmacotherapy 25 (2005): 1296-302
  29. Frothingham R "Glucose homeostasis abnormalities associated with use of gatifloxacin." Clin Infect Dis 41 (2005): 1269-76
  30. Bhasin R, Arce FC, Pasmantier R "Hypoglycemia associated with the use of gatifloxacin." Am J Med Sci 330 (2005): 250-3
  31. McMorran M, Morrison H, Letourneau G "Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3_e.html#1" (2006):
  32. Park-Wyllie LY, Juurlink DN, Kopp A, et al. "Outpatient gatifloxacin therapy and dysglycemia in older adults." N Engl J Med 354 (2006): 1352-61
  33. Wang S, Rizvi AA "Levofloxacin-induced hypoglycemia in a nondiabetic patient." Am J Med Sci 331 (2006): 334-5
  34. Kanbay M, Aydogan T, Bozalan R, et al. "A rare but serious side effect of levofloxacin: hypoglycemia in a geriatric patient." Diabetes Care 29 (2006): 1716-7
  35. Zvonar R "Gatifloxacin-induced dysglycemia." Am J Health Syst Pharm 63 (2006): 2087-2092
  36. Zhanel GG, Fontaine S, Adam H, et al. "A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections." Treat Respir Med 5 (2006): 437-465
  37. Yip C, Lee AJ "Gatifloxacin-induced hyperglycemia: a case report and summary of the current literature." Clin Ther 28 (2006): 1857-66
  38. Tomita T, Onishi M, Sato E, Kimura Y, Kihira K "Gatifloxacin induces augmented insulin release and intracellular insulin." Biol Pharm Bull 30 (2007): 644-7
  39. Kelesidis T, Canseco E "Quinolone-induced hypoglycemia: a life-threatening but potentially reversible side effect." Am J Med 123 (2010): e5-6
  40. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
View all 40 references

Switch to consumer interaction data

Major

ciprofloxacin insulin aspart protamine

Applies to: Cipro XR (ciprofloxacin) and insulin aspart/insulin aspart protamine

MONITOR CLOSELY: 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 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. Pharmacokinetically, ciprofloxacin is also a known inhibitor of CYP450 1A2 and 3A4 and may inhibit the hepatic metabolism of glyburide. Hypoglycemia in association with elevated serum glyburide level occurred in a patient after one week of ciprofloxacin therapy.

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. Due to the risk of profound and potentially life-threatening hypoglycemia, particular caution is advised during concomitant use of insulin and insulin secretagogues (e.g., sulfonylureas, meglitinides). Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms 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. "Product Information. Cipro (ciprofloxacin)." Bayer PROD (2002):
  2. "Product Information. Noroxin (norfloxacin)." Merck & Co., Inc PROD (2001):
  3. "Product Information. Floxin (ofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  4. "Product Information. Levaquin (levofloxacin)." Ortho McNeil Pharmaceutical PROD (2001):
  5. "Product Information. Raxar (grepafloxacin)." Glaxo Wellcome PROD (2001):
  6. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  7. Edwards DJ, Bowles SK, Svensson CK, Rybak MJ "Inhibition of drug metabolism by quinolone antibiotics." Clin Pharmacokinet 15 (1988): 194-204
  8. "Product Information. Tequin (gatifloxacin)." Bristol-Myers Squibb PROD (2001):
  9. Gajjar DA, LaCreta FP, Kollia GD, et al. "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) (2000): s76-86
  10. Roberge RJ, Kaplan R, Frank R, Fore C "Glyburide-ciprofloxacin interaction with resistant hypoglycemia." Ann Emerg Med 36 (2000): 160-3
  11. Rubinstein E "History of quinolones and their side effects." Chemotherapy 47 Suppl 3 (2001): 3-8
  12. Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH "Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents." Am J Med 113 (2002): 232-4
  13. Baker SE, Hangii MC "Possible gatifloxacin-induced hypoglycemia." Ann Pharmacother 36 (2002): 1722-6
  14. "Product Information. Factive (gemifloxacin)." *GeneSoft Inc (2003):
  15. "Hypoglycemia and hyperglycemia with fluoroquinolones." Med Lett Drugs Ther 45 (2003): 64
  16. Donaldson AR, Vandiver JR, Finch CK "Possible gatifloxacin-induced hyperglycemia." Ann Pharmacother 38 (2004): 602-5
  17. LeBlanc M, Belanger C, Cossette P "Severe and resistant hypoglycemia associated with concomitant gatifloxacin and glyburide therapy." Pharmacotherapy 24 (2004): 926-31
  18. Biggs WS "Hypoglycemia and hyperglycemia associated with gatifloxacin use in elderly patients." J Am Board Fam Pract 16 (2004): 455-7
  19. Gavin JR 3rd, Kubin R, Choudhri S, et al. "Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies." Drug Saf 27 (2004): 671-86
  20. Saraya A, Yokokura M, Gonoi T, Seino S "Effects of fluoroquinolones on insulin secretion and beta-cell ATP-sensitive K(+) channels." Eur J Pharmacol 497 (2004): 111-7
  21. Lin G, Hays DP, Spillane L "Refractory hypoglycemia from ciprofloxacin and glyburide interaction." J Toxicol Clin Toxicol 42 (2004): 295-7
  22. Friedrich LV, Dougherty R "Fatal hypoglycemia associated with levofloxacin." Pharmacotherapy 24 (2004): 1807-12
  23. Khovidhunkit W, Sunthornyothin S "Hypoglycemia, hyperglycemia, and gatifloxacin." Ann Intern Med 141 (2004): 969
  24. Happe MR, Mulhall BP, Maydonovitch CL, Holtzmuller KC "Gatifloxacin-induced hyperglycemia." Ann Intern Med 141 (2004): 968-9
  25. Greenberg AL, Decerbo M, Fan J "Gatifloxacin therapy associated with hypoglycemia." Clin Infect Dis 40 (2005): 1210-1
  26. Blommel AL, Lutes RA "Severe hyperglycemia during renally adjusted gatifloxacin therapy." Ann Pharmacother 39 (2005): 1349-52
  27. Brogan SE, Cahalan MK "Gatifloxacin as a possible cause of serious postoperative hypoglycemia." Anesth Analg 101 (2005): 635-6
  28. Graumlich JF, Habis S, Avelino RR, et al. "Hypoglycemia in inpatients after gatifloxacin or levofloxacin therapy: nested case-control study." Pharmacotherapy 25 (2005): 1296-302
  29. Frothingham R "Glucose homeostasis abnormalities associated with use of gatifloxacin." Clin Infect Dis 41 (2005): 1269-76
  30. Bhasin R, Arce FC, Pasmantier R "Hypoglycemia associated with the use of gatifloxacin." Am J Med Sci 330 (2005): 250-3
  31. McMorran M, Morrison H, Letourneau G "Gatifloxacin (Tequin): hypoglycemia and hyperglycemia. http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v13n3_e.html#1" (2006):
  32. Park-Wyllie LY, Juurlink DN, Kopp A, et al. "Outpatient gatifloxacin therapy and dysglycemia in older adults." N Engl J Med 354 (2006): 1352-61
  33. Wang S, Rizvi AA "Levofloxacin-induced hypoglycemia in a nondiabetic patient." Am J Med Sci 331 (2006): 334-5
  34. Kanbay M, Aydogan T, Bozalan R, et al. "A rare but serious side effect of levofloxacin: hypoglycemia in a geriatric patient." Diabetes Care 29 (2006): 1716-7
  35. Zvonar R "Gatifloxacin-induced dysglycemia." Am J Health Syst Pharm 63 (2006): 2087-2092
  36. Zhanel GG, Fontaine S, Adam H, et al. "A Review of New Fluoroquinolones : Focus on their Use in Respiratory Tract Infections." Treat Respir Med 5 (2006): 437-465
  37. Yip C, Lee AJ "Gatifloxacin-induced hyperglycemia: a case report and summary of the current literature." Clin Ther 28 (2006): 1857-66
  38. Tomita T, Onishi M, Sato E, Kimura Y, Kihira K "Gatifloxacin induces augmented insulin release and intracellular insulin." Biol Pharm Bull 30 (2007): 644-7
  39. Kelesidis T, Canseco E "Quinolone-induced hypoglycemia: a life-threatening but potentially reversible side effect." Am J Med 123 (2010): e5-6
  40. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
View all 40 references

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Drug and food interactions

Moderate

ciprofloxacin food

Applies to: Cipro XR (ciprofloxacin)

ADJUST DOSING INTERVAL: Concurrent ingestion of dairy products (milk, yogurt) or calcium-fortified foods (i.e., cereal, orange juice) may decrease the activity of certain oral fluoroquinolone antibiotics. 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. One study reported an average 41% decrease in maximum plasma concentrations and a 38% decrease in AUC when ciprofloxacin was given with calcium-fortified orange juice instead of water. Administration of ciprofloxacin tablets with enteral nutrition may reduce its bioavailability and maximum serum concentrations. Data have been conflicting and variable by the type of enteral nutrition product, location of the feeding tube, and patient characteristics. Decreased absorption is expected if ciprofloxacin is given by jejunostomy tube.

MANAGEMENT: Oral ciprofloxacin should not be taken with dairy products or calcium-fortified foods alone, but may be taken with meals that contain these products. When taken alone, dairy products or calcium-fortified foods should be ingested at least 2 hours before or after ciprofloxacin administration. When ciprofloxacin tablets are administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 2 hours after the dose of ciprofloxacin is given. Patients should be monitored for altered antimicrobial efficacy and switched to intravenous ciprofloxacin if necessary. If no enteral route besides a jejunostomy tube is available, it is also recommended to switch to intravenous ciprofloxacin. According to the manufacturer, ciprofloxacin oral suspension should not be administered via nasogastric or feeding tubes due to its physical characteristics.

References

  1. "Product Information. Cipro (ciprofloxacin)." Bayer PROD (2002):
  2. Yuk JH, Nightingale CH, Sweeney KR, Quintiliani R, Lettieri JT, Forst RW "Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding." Antimicrob Agents Chemother 33 (1989): 1118-20
  3. Yuk JH, Nightingale CH, Quintiliani R "Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition." Diagn Microbiol Infect Dis 13 (1990): 99-102
  4. Noer BL, Angaran DW "The effect of enteral feedings on ciprofloxacin pharmacokinetics." Pharmacotherapy 10 (1990): 254
  5. Neuhofel AL, Wilton JH, Victory JM, Hejmanowsk LG, Amsden GW "Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction." J Clin Pharmacol 42 (2002): 461-6
  6. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67
View all 6 references

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Moderate

insulin aspart food

Applies to: insulin aspart/insulin aspart protamine

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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Moderate

insulin aspart protamine food

Applies to: insulin aspart/insulin aspart protamine

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand 656 (1981): 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol 24 (1983): 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia 24 (1983): 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A "Interaction of ethanol and glipizide in humans." Diabetes Care 10 (1987): 683-6
  5. "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  6. "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals PROD (2002):
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM "The pharmacology of sulfonylureas." Am J Med 70 (1981): 361-72
  9. "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care 25(Suppl 1) (2002): S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 10 references

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Moderate

ciprofloxacin food

Applies to: Cipro XR (ciprofloxacin)

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. 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 quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide.

MANAGEMENT: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations.

References

  1. Polk RE, Helay DP, Sahai J, Drwal L, Racht E "Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers." Antimicrob Agents Chemother 33 (1989): 1841-4
  2. Nix DE, Watson WA, Lener ME, et al. "Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin." Clin Pharmacol Ther 46 (1989): 700-5
  3. Garrelts JC, Godley PJ, Peterie JD, Gerlach EH, Yakshe CC "Sucralfate significantly reduces ciprofloxacin concentrations in serum." Antimicrob Agents Chemother 34 (1990): 931-3
  4. Frost RW, Lasseter KC, Noe AJ, Shamblen EC, Lettieri JT "Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin." Antimicrob Agents Chemother 36 (1992): 830-2
  5. Yuk JH "Ciprofloxacin levels when receiving sucralfate." J Am Geriatr Soc 262 (1989): 901
  6. Deppermann KM, Lode H, Hoffken G, Tschink G, Kalz C, Koeppe P "Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid." Antimicrob Agents Chemother 33 (1989): 1901-7
  7. Campbell NR, Kara M, Hasinoff BB, Haddara WM, McKay DW "Norfloxacin interaction with antacids and minerals." Br J Clin Pharmacol 33 (1992): 115-6
  8. Parpia SH, Nix DE, Hejmanowski LG, Goldstein HR, Wilton JH, Schentag JJ "Sucralfate reduces the gastrointestinal absorption of norfloxacin." Antimicrob Agents Chemother 33 (1989): 99-102
  9. Nix DE, Wilton JH, Ronald B, Distlerath L, Williams VC, Norman A "Inhibition of norfloxacin absorption by antacids." Antimicrob Agents Chemother 34 (1990): 432-5
  10. Akerele JO, Okhamafe AO "Influence of oral co-administered metallic drugs on ofloxacin pharmacokinetics." J Antimicrob Chemother 28 (1991): 87-94
  11. Wadworth AN, Goa KL "Lomefloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use." Drugs 42 (1991): 1018-60
  12. Shimada J, Shiba K, Oguma T, et al. "Effect of antacid on absorption of the quinolone lomefloxacin." Antimicrob Agents Chemother 36 (1992): 1219-24
  13. Sahai J, Healy DP, Stotka J, Polk RE "The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin." Br J Clin Pharmacol 35 (1993): 302-4
  14. Lehto P, Kivisto KT "Effect of sucralfate on absorption of norfloxacin and ofloxacin." Antimicrob Agents Chemother 38 (1994): 248-51
  15. Noyes M, Polk RE "Norfloxacin and absorption of magnesium-aluminum." Ann Intern Med 109 (1988): 168-9
  16. Grasela TH Jr, Schentag JJ, Sedman AJ, et al. "Inhibition of enoxacin absorption by antacids or ranitidine." Antimicrob Agents Chemother 33 (1989): 615-7
  17. Lehto P, Kivisto KT "Different effects of products containing metal ions on the absorption of lomefloxacin." Clin Pharmacol Ther 56 (1994): 477-82
  18. Spivey JM, Cummings DM, Pierson NR "Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction." Pharmacotherapy 16 (1996): 314-6
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  21. "Product Information. Zagam (sparfloxacin)." Rhone Poulenc Rorer PROD (2001):
  22. "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals PROD (2001):
  23. Teng R, Dogolo LC, Willavize SA, Friedman HL, Vincent J "Effect of Maalox and omeprazole on the bioavailability of trovafloxacin." J Antimicrob Chemother 39 Suppl B (1997): 93-7
  24. Zix JA, Geerdes-Fenge 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
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  32. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
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Moderate

ciprofloxacin food

Applies to: Cipro XR (ciprofloxacin)

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

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