Skip to Content

Flagyl ER (metronidazole) Disease Interactions

There are 7 disease interactions with Flagyl ER (metronidazole):

Major

Antibiotics (applies to Flagyl ER) colitis

Major Potential Hazard, Low plausibility. Applicable conditions: Colitis/Enteritis (Noninfectious)

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

References

  1. Moriarty HJ, Scobie BA "Pseudomembranous colitis in a patient on rifampicin and ethambutol." N Z Med J 04/23/80 (1980): 294-5
  2. Thomas E, Mehta JB "Pseudomembranous colitis due to oxacillin therapy." South Med J 77 (1984): 532-3
  3. Bauwens JE, McFarland LV, Melcher SA "Recurrent clostridium difficile disease following ciprofloxacin use." Ann Pharmacother 31 (1997): 1090
  4. Davies J, Beck E "Recurrent colitis following antibiotic-associated pseudomembranous colitis." Postgrad Med J 57 (1981): 599-601
  5. Dan M, Samra Z "Clostridium difficile colitis associated with ofloxacin therapy." Am J Med 87 (1989): 479
  6. Harmon T, Burkhart G, Applebaum H "Perforated pseudomembranous colitis in the breast-fed infant." J Pediatr Surg 27 (1992): 744-6
  7. Milstone EB, McDonald AJ, Scholhamer CF Jr "Pseudomembranous colitis after topical application of clindamycin." Arch Dermatol 117 (1981): 154-5
  8. Cone JB, Wetzel W "Toxic megacolon secondary to pseudomembranous colitis." Dis Colon Rectum 25 (1982): 478-82
  9. Burt RA "A review of the drug events reported by 12,917 patients treated with cephalexin." Postgrad Med J 59 (1983): 47-50,51-3
  10. Cannon SR, Dyson PH, Sanderson PJ "Pseudomembranous colitis associated with antibiotic prophylaxis in orthopaedic surgery." J Bone Joint Surg Br 70-B (1988): 600-2
  11. Miller DL, Sedlack JD, Holt RW "Perforation complicating rifampin-associated pseudomembranous enteritis." Arch Surg 124 (1989): 1082
  12. Wang C, Calandra GB, Aziz MA, Brown KR "Efficacy and safety of imipenem/cilastatin: a review of worldwide clinical experience." Rev Infect Dis 7 (1985): s528-36
  13. Miller SN, Ringler RP "Vancomycin-induced pseudomembranous colitis." J Clin Gastroenterol 9 (1987): 114-5
  14. Bernstein L "Adverse reaction to trimethoprim-sulfamethoxazole, with particular reference to long-term therapy." Can Med Assoc J 112 (1975): s96-8
  15. Calandra GB, Brown KR, Grad LC, et al "Review of adverse experiences and tolerability in the first 2,516 patients treated with imipenem/cilastatin." Am J Med 78 (1985): 73-8
  16. Pokorney BH, Nichols TW, Jr "Pseudomembranous colitis. A complication of sulfasalazine therapy in a patient with Crohn's colitis." Am J Gastroenterol 76 (1981): 374-6
  17. Sankarankutty M, McGeorge D, Galasko CS "Pseudomembranous colitis following cephradine prophylaxis." Postgrad Med J 58 (1982): 726-8
  18. Van Ness MM, Cattau EL Jr "Fulminant colitis complicating antibiotic-associated pseudomembranous colitis: case report and review of the clinical manifestations and treatment." Am J Gastroenterol 82 (1987): 374-7
  19. Hutcheon DF, Milligan FD, Yardley JH, Hendrix TR "Cephalosporin-associated pseudomembranous colitis." Am J Dig Dis 23 (1978): 321-6
  20. Gordin F, Gibert C, Schmidt ME "Clostridium difficile colitis associated with trimethoprim-sulfamethoxazole given as prophylaxis for pneumocystis carinii pneumonia." Am J Med 96 (1994): 94-5
  21. Bingley PJ, Harding GM "Clostridium difficile colitis following treatment with metronidazole and vancomycin." Postgrad Med J 63 (1987): 993-4
  22. Hinton NA "The effect of oral tetracycline HCl and doxycycline on the intestinal flora." Curr Ther Res Clin Exp 12 (1970): 341-52
  23. Ring FA, Hershfield NB, Machin GA, Scott RB "Sulfasalazine-induced colitis complicating idiopathic ulcerative colitis." Can Med Assoc J 131 (1984): 43-5
  24. Saginur R, Hawley CR, Bartlett JG "Colitis associated with metronidazole therapy." J Infect Dis 141 (1980): 772-4
  25. Friedman RJ, Mayer IE, Galambos JT, Hersh T "Oxacillin-induced pseudomembranous colitis." Am J Gastroenterol 73 (1980): 445-7
  26. "Multum Information Services, Inc. Expert Review Panel"
  27. Midtvedt T, Carlstedt-Duke B, Hoverstad T, et al "Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects." Eur J Clin Invest 16 (1986): 11-7
  28. Leigh DA, Simmons K, Williams S "Gastrointestinal side effects following clindamycin and lincomycin treatment: a follow up study." J Antimicrob Chemother 6 (1980): 639-45
  29. Altamirano A, Bondani A "Adverse reactions to furazolidone and other drugs. A comparative review." Scand J Gastroenterol Suppl 169 (1989): 70-80
  30. Hecht JR, Olinger EJ "Clostridium difficile colitis secondary to intravenous vancomycin." Dig Dis Sci 34 (1989): 148-9
  31. Brause BD, Romankiewicz JA, Gotz V, Franklin JE Jr, Roberts RB "Comparative study of diarrhea associated with clindamycin and ampicillin therapy." Am J Gastroenterol 73 (1980): 244-8
  32. Boriello SP, Jones RH, Phillips I "Rifampicin-associated pseudomembranous colitis." Br Med J 281 (1980): 1180-1
  33. Klinger D, Radford P, Collin J "Pneumoperitoneum without faecal peritonitis in a patient with pseudomembranous colitis." Br Med J 288 (1984): 1271-2
  34. Saadah HA "Carbenicillin and pseudomembranous enterocolitis." Ann Intern Med 93 (1980): 645
  35. Lyon JA "Imipenem/cilastatin: the first carbapenem antibiotic." Drug Intell Clin Pharm 19 (1985): 894-8
  36. Daly JJ, Chowdary KV "Pseudomembranous colitis secondary to metronidazole." Dig Dis Sci 28 (1983): 573-4
  37. Trexler MF, Fraser TG, Jones MP "Fulminant pseudomembranous colitis caused by clindamycin phosphate vaginal cream." Am J Gastroenterol 92 (1997): 2112-3
  38. Edlund C, Brismar B, Nord CE "Effect of lomefloxacin on the normal oral and intestinal microflora." Eur J Clin Microbiol Infect Dis 1 (1990): 35-9
  39. O'Meara TF, Simmons RA "Carbenicillin and pseudomembranous enterocolitis." Ann Intern Med 92 (1980): 440-1
  40. Meadowcroft AM, Diaz PR, Latham GS "Clostridium difficile toxin-induced colitis after use of clindmycin phosphate vaginal cream." Ann Pharmacother 32 (1998): 309-11
  41. Ehrenpreis ED, Lievens MW, Craig RM "Clostridium difficile-associated diarrhea after norfloxacin." J Clin Gastroenterol 12 (1990): 188-9
  42. Osler T, Lott D, Bordley J, et al "Cefazolin-induced pseudomembranous colitis resulting in perforation of the sigmoid colon." Dis Colon Rectum 29 (1986): 140-3
  43. Parry MF, Rha CK "Pseudomembranous colitis caused by topical clindamycin phosphate." Arch Dermatol 122 (1986): 583-4
  44. Clissold SP, Todd PA, Campoli-Richards DM "Imipenem/cilastatin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy." Drugs 33 (1987): 185-241
  45. Sugarman B "Trimethoprim-sulfamethoxazole, pseudomembranous colitis, and spinal cord injury." South Med J 78 (1985): 711-3
  46. Golledge CL, Riley TV "Clostridium difficile-associated diarrhoea after doxycycline malaria prophylaxis." Lancet 345 (1995): 1377-8
  47. Edlund C, Lidbeck A, Kager L, Nord CE "Effect of enoxacin on colonic microflora of healthy volunteers." Eur J Clin Microbiol 6 (1987): 298-300
View all 47 references
Major

Nitroimidazoles (applies to Flagyl ER) blood dyscrasias

Major Potential Hazard, Low plausibility. Applicable conditions: History - Blood Dyscrasias, Bone Marrow Depression/Low Blood Counts

The use of nitroimidazoles (e.g., metronidazole, tinidazole) has rarely been associated with hematologic adverse effects such as mild, transient leukopenia, thrombocytopenia, and bone marrow aplasia. The manufacturers recommend that therapy with nitroimidazoles be administered cautiously in patients with evidence of or a history of blood dyscrasias, and that total and differential leukocyte counts be performed before and after treatment with these drugs, particularly in patients receiving repeated courses of therapy.

References

  1. White CM, Price JJ, Hunt KM "Bone marrow aplasia associated with metronidazole." Br Med J 280 (1980): 647
  2. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc, Arlington Heights, IL.
  3. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
  4. Smith JA "Neutropenia associated with metronidazole therapy." Can Med Assoc J 123 (1980): 202
View all 4 references
Major

Nitroimidazoles (applies to Flagyl ER) neurologic toxicity

Major Potential Hazard, Moderate plausibility. Applicable conditions: CNS Disorder, Peripheral Neuropathy

The use of nitroimidazoles (e.g., metronidazole, tinidazole) has been associated with the development of nervous system toxicity including convulsive seizures and dose-related peripheral neuropathy, the latter characterized primarily by numbness or paresthesia of an extremity. Persistent peripheral neuropathy has been reported in some patients treated for prolonged periods. Other neurologic adverse effects include vertigo, incoordination, ataxia, confusion, agitation, hallucinations, and depression. Therapy with nitroimidazoles should be administered cautiously in patients with or predisposed to seizures or other nervous system abnormalities. Nitroimidazole therapy should be discontinued promptly if neurologic disturbances occur.

References

  1. Learned-Coughlin S "Peripheral neuropathy induced by metronidazole." Ann Pharmacother 28 (1994): 536
  2. Lawford R, Sorrell TC "Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report." Clin Infect Dis 19 (1994): 346-8
  3. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc, Arlington Heights, IL.
  4. Wienbren M, Perinpanayagam RM, Camba L, Lee CA "Convulsions and encephalopathy in a patient with leukaemia after treatment with metronidazole." J Clin Pathol 38 (1985): 1076
  5. Kusumi RK, Plouffe JF, Wyatt RH, Fass RJ "Central nervous sytem toxicity associated with metronidazole therapy." Ann Intern Med 93 (1980): 59-60
  6. Duffy LF, Daum F, Fisher SE, et al "Peripheral neuropathy in Crohn's disease patients treated with metronidazole." Gastroenterology 88 (1985): 681-4
  7. Alvarez RS, Richardson DA, Bent AE, Ostergard DR "Central nervous system toxicity related to prolonged metronidazole therapy." Am J Obstet Gynecol 145 (1983): 640-1
  8. Boyce EG, Cookson ET, Bond WS "Persistent metronidazole-induced peripheral neuropathy." DICP 24 (1990): 19-21
  9. Schentag JJ, Ziemniak JA, Greco JM, Rainstein M, Buckley RJ "Mental confusion in a patient treated with metronidazole: a concentration-related effect." Pharmacotherapy 2 (1982): 384-7
  10. Beloosesky Y, Grosman B, Marmelstein V, Grinblat J "Convulsions induced by metronidazole treatment for Clostridium difficile-associated disease in chronic renal failure." Am J Med Sci 319 (2000): 338-9
  11. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
  12. Schreiber W, Spernal J "Metronidazole-induced psychotic disorder." Am J Psychiatry 154 (1997): 1170-1
  13. Stahlberg D, Barany F, Einarsson K, Ursing B, Elmquist D, Persson A "Neurophysiologic studies of patients with Crohn's disease on long-term treatment with metronidazole." Scand J Gastroenterol 26 (1991): 219-24
  14. Ahmed A, Laes DJ, Bressler EL "Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy." Neurology 45 (1995): 588-9
View all 14 references
Moderate

Metronidazole (applies to Flagyl ER) alcoholism

Moderate Potential Hazard, Moderate plausibility.

Nitroimidazoles (e.g., metronidazole, tinidazole) may inhibit alcohol dehydrogenase and occasionally precipitate a disulfiram-like reaction in patients who consume alcohol while being treated. Symptoms may include nausea, vomiting, flushing, sweating, headache, abdominal cramps, and hypotension. Patients should be instructed to avoid alcohol-containing products during nitroimidazole therapy and for at least 48 to 72 hours after the last dose. Therapy with nitroimidazoles should be administered cautiously in patients who might be prone to acute alcohol intake. An alternative therapy may be appropriate.

References

  1. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
  2. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc, Arlington Heights, IL.
  3. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  4. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  5. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
View all 6 references
Moderate

Metronidazole (applies to Flagyl ER) dialysis

Moderate Potential Hazard, High plausibility. Applicable conditions: hemodialysis

Metronidazole and its metabolites are moderately removed by hemodialysis. Doses should either be scheduled for administration after dialysis or supplemental doses be given after dialysis.

References

  1. Kreeft JH, Ogilvie RI, Dufresne LR "Metronidazole kinetics in dialysis patients." Surgery 93 (1983): 149-53
  2. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
  3. Roux AF, Moirot E, Delhotal B, et al "Metronidazole kinetics in patients with acute renal failure on dialysis: a cumulative study." Clin Pharmacol Ther 36 (1984): 363-8
  4. Somogyi A, Kong C, Sabto J, Gurr FW, Spicer WJ, McLean AJ "Disposition and removal of metronidazole in patients undergoing haemodialysis." Eur J Clin Pharmacol 25 (1983): 683-7
  5. Lau AH, Chang CW, Sabatini S "Hemodialysis clearance of metronidazole and its metabolites." Antimicrob Agents Chemother 29 (1986): 235-8
View all 5 references
Moderate

Metronidazole (applies to Flagyl ER) liver disease

Moderate Potential Hazard, High plausibility.

Metronidazole is extensively metabolized by the liver to both pharmacologically active and inactive compounds. The plasma clearance of metronidazole may be decreased and the half-life prolonged in patients with impaired hepatic function. Therapy with metronidazole should be administered cautiously at reduced dosages in patients with severe liver disease.

References

  1. Loft S, Dossing M, Poulsen HE, et al "Influence of dose and route of administration on disposition of metronidazole and its major metabolites." Eur J Clin Pharmacol 30 (1986): 467-73
  2. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.
  3. Loft S, Sonne J, Dossing M, Andreasen PB "Metronidazole pharmacokinetics in patients with hepatic encephalopathy." Scand J Gastroenterol 22 (1987): 117-23
  4. Jensen JC, Gugler R "Single- and multiple-dose metronidazole kinetics." Clin Pharmacol Ther 34 (1983): 481-7
  5. Lau AH, Evans R, Chang CW, Seligsohn R "Pharmacokinetics of metronidazole in patients with alcoholic liver disease." Antimicrob Agents Chemother 31 (1987): 1662-4
  6. Farrell G, Baird-Lambert J, Cvejic M, Buchanan N "Disposition and metabolism of metronidazole in patients with liver failure." Hepatology 4 (1984): 772-6
View all 6 references
Moderate

Metronidazole (applies to Flagyl ER) sodium

Moderate Potential Hazard, High plausibility. Applicable conditions: Congestive Heart Failure, Hypertension, Fluid Retention, Hypernatremia

Flagyl I.V. RTU (brand of metronidazole ready-to-use injection) contains 14 mEq of sodium per each 500 mg dose of metronidazole. The sodium content should be considered when this product is used in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

References

  1. "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL.

Flagyl ER (metronidazole) drug interactions

There are 326 drug interactions with Flagyl ER (metronidazole)

Flagyl ER (metronidazole) alcohol/food interactions

There are 2 alcohol/food interactions with Flagyl ER (metronidazole)

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.