Metronidazole + Neomycin Sulphate + Polymyxin B + Nystatin interactions

Food & lifestyle

• alcohol

  Major

  Metabolism

  Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'.

  What to do: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

  9 sources

  1. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  2. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  3. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  4. "Product Information. Flagyl (metronidazole)." Searle (2001):
  5. Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  8. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc (2017):

Conditions

Conditions in which Metronidazole + Neomycin Sulphate + Polymyxin B + Nystatin needs care, as documented in this source.

• Colitis

  Major

  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.

  31 sources

  1. "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome (2002):
  3. "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome (2002):
  4. "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn (2002):
  5. "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  6. "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  7. "Product Information. Amoxil (amoxicillin)." SmithKline Beecham (2001):
  8. "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis (2001):
  10. "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn (2001):
  11. "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc (2003):
  12. "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals (2004):
  13. "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical (2007):
  14. "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc (2009):
  15. "Product Information. Vibativ (telavancin)." Theravance Inc (2009):
  16. "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals (2010):
  17. "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc (2022):
  18. "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc. (2014):
  19. "Product Information. Orbactiv (oritavancin)." The Medicines Company (2014):
  20. "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions (2017):
  21. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
  22. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):
  23. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  24. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  25. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  26. "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc. (2018):
  27. "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc (2019):
  28. "Product Information. Biaxin (clarithromycin)." AbbVie US LLC (2019):
  29. "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group (2021):
  30. "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals (2018):
  31. "Product Information. Priftin (rifapentine)." sanofi-aventis (2020):

• Colitis

  Major

  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.

  31 sources

  1. "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome (2002):
  3. "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome (2002):
  4. "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn (2002):
  5. "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  6. "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  7. "Product Information. Amoxil (amoxicillin)." SmithKline Beecham (2001):
  8. "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis (2001):
  10. "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn (2001):
  11. "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc (2003):
  12. "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals (2004):
  13. "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical (2007):
  14. "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc (2009):
  15. "Product Information. Vibativ (telavancin)." Theravance Inc (2009):
  16. "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals (2010):
  17. "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc (2022):
  18. "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc. (2014):
  19. "Product Information. Orbactiv (oritavancin)." The Medicines Company (2014):
  20. "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions (2017):
  21. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
  22. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):
  23. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  24. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  25. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  26. "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc. (2018):
  27. "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc (2019):
  28. "Product Information. Biaxin (clarithromycin)." AbbVie US LLC (2019):
  29. "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group (2021):
  30. "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals (2018):
  31. "Product Information. Priftin (rifapentine)." sanofi-aventis (2020):

• Colitis

  Major

  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.

  31 sources

  1. "Product Information. Omnipen (ampicillin)." Wyeth-Ayerst Laboratories (2002):
  2. "Product Information. Ceftin (cefuroxime)." Glaxo Wellcome (2002):
  3. "Product Information. Zinacef (cefuroxime)." Glaxo Wellcome (2002):
  4. "Product Information. Cleocin (clindamycin)." Pharmacia and Upjohn (2002):
  5. "Product Information. Macrobid (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  6. "Product Information. Macrodantin (nitrofurantoin)." Procter and Gamble Pharmaceuticals (2002):
  7. "Product Information. Amoxil (amoxicillin)." SmithKline Beecham (2001):
  8. "Product Information. Merrem (meropenem)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 31 sourcesShow fewer sources

  9. "Product Information. Coly-Mycin M Parenteral (colistimethate)." Parke-Davis (2001):
  10. "Product Information. Lincocin (lincomycin)." Pharmacia and Upjohn (2001):
  11. "Product Information. Cubicin (daptomycin)." Cubist Pharmaceuticals Inc (2003):
  12. "Product Information. Xifaxan (rifaximin)." Salix Pharmaceuticals (2004):
  13. "Product Information. Doribax (doripenem)." Ortho McNeil Pharmaceutical (2007):
  14. "Product Information. Penicillin G Procaine (procaine penicillin)." Monarch Pharmaceuticals Inc (2009):
  15. "Product Information. Vibativ (telavancin)." Theravance Inc (2009):
  16. "Product Information. Teflaro (ceftaroline)." Forest Pharmaceuticals (2010):
  17. "Product Information. Penicillin G Sodium (penicillin G sodium)." Sandoz Inc (2022):
  18. "Product Information. Dalvance (dalbavancin)." Durata Therapeutics, Inc. (2014):
  19. "Product Information. Orbactiv (oritavancin)." The Medicines Company (2014):
  20. "Product Information. Bicillin C-R (benzathine penicillin-procaine penicillin)." A-S Medication Solutions (2017):
  21. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Inc. (2017):
  22. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):
  23. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  24. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  25. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
  26. "Product Information. Aemcolo (rifamycin)." Aries Pharmaceuticals, Inc. (2018):
  27. "Product Information. Fetroja (cefiderocol)." Shionogi USA Inc (2019):
  28. "Product Information. Biaxin (clarithromycin)." AbbVie US LLC (2019):
  29. "Product Information. Zithromax (azithromycin)." Pfizer U.S. Pharmaceuticals Group (2021):
  30. "Product Information. E.E.S.-400 Filmtab (erythromycin)." Arbor Pharmaceuticals (2018):
  31. "Product Information. Priftin (rifapentine)." sanofi-aventis (2020):

• Dehydration

  Major

  Adequate hydration is crucial to minimize the risk of oto- and nephrotoxicity associated with the use of aminoglycosides. Dehydration should preferably be corrected prior to initiation of therapy. In patients who may be at risk for dehydration, such as those with severe and/or prolonged diarrhea or vomiting, fluid status should be monitored closely. If signs of renal irritation develop during therapy, hydration should be increased as indicated, accompanied by a reduction in dosage if necessary. Therapy should be withdrawn if urinary output decreases progressively or azotemia increases.

  6 sources

  1. "Product Information. Amikin (amikacin)." Bristol-Myers Squibb (2002):
  2. "Product Information. Garamycin (gentamicin)." Schering-Plough Corporation (2007):
  3. "Product Information. Netromycin (netilmicin)." Schering Corporation (2002):
  4. "Product Information. Streptomycin Sulfate (streptomycin)." Pfizer U.S. Pharmaceuticals
  5. "Product Information. Nebcin (tobramycin)." Lilly, Eli and Company (2001):
  6. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):

• Gastroenteritis

  Major

  The use of neomycin oral solution is contraindicated in patients with inflammatory or ulcerative gastrointestinal diseases because of the potential for enhanced absorption of neomycin. Like other aminoglycosides, neomycin is potentially oto- and nephrotoxic, and systemic exposure should be avoided if possible.

  1 source

  1. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):

• Hematologic Diseases

  Major

  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.

  4 sources

  1. Smith JA "Neutropenia associated with metronidazole therapy." Can Med Assoc J 123 (1980): 202
  2. White CM, Price JJ, Hunt KM "Bone marrow aplasia associated with metronidazole." Br Med J 280 (1980): 647
  3. "Product Information. Flagyl (metronidazole)." Searle (2002):
  4. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):

• Intestinal Obstruction

  Major

  The use of oral aminoglycosides is contraindicated in patients with intestinal obstruction. Orally administered aminoglycosides are poorly absorbed from the gastrointestinal tract and primarily eliminated unchanged in the feces. Drug retention and enhanced systemic absorption may occur in the presence of intestinal obstruction, increasing the risk of oto- and nephrotoxicity associated with these drugs.

  3 sources

  1. Ristuccia AM, Cunha BA "The aminoglycosides." Med Clin North Am 66 (1982): 303-12
  2. "Product Information. Humatin (paromomycin)." Parke-Davis (2001):
  3. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):

• Kidney Diseases

  Major

  Aminoglycosides are potentially oto- and nephrotoxic. Eighth cranial nerve damage may manifest as vestibular and/or auditory toxicities, including dizziness, nystagmus, vertigo, ataxia, tinnitus, and varying degrees of hearing impairment. Nephrotoxicity is usually evidenced by tubular necrosis; increases in BUN, nonprotein nitrogen, and serum creatinine concentration; decreases in urine specific gravity and creatinine clearance; proteinuria; and cells or casts in the urine. Rarely, renal electrolyte wasting may occur, resulting in hypocalcemia, hypomagnesemia, and hypokalemia that may be associated with paresthesia, tetany, confusion, and positive Chvostek and Trousseau signs. Although aminoglycoside- induced nephrotoxicity is generally reversible following discontinuation of the drug, death from uremia has occurred rarely. Therapy with aminoglycosides should be administered cautiously at reduced dosages in patients with renal impairment, since they may be at increased risk for oto- and nephrotoxicity due to drug accumulation. To minimize the risk of toxicity, patients should be adequately hydrated, the usual aminoglycoside dosage should not be exceeded, use with other neuro- and nephrotoxic agents should be avoided, and peak and trough serum aminoglycoside concentrations should be periodically determined and dosage adjusted to maintain desired levels. Renal and eighth cranial nerve function should be closely monitored, and the dosage reduced or therapy withdrawn if toxicity develops.

  59 sources

  1. Beauchamp D, Gourde P, Theriault G, Bergeron MG "Age-dependent gentamicin experimental nephrotoxicity." J Pharmacol Exp Ther 260 (1992): 444-9
  2. Dahlgren JG, Anderson ET, Hewitt WL "Gentamicin blood levels: a guide to nephrotoxicity." Antimicrob Agents Chemother 8 (1975): 58-62
  3. Fanning WL, Gump D, Jick H "Gentamicin and cephalothin-associated rises in blood urea nitrogen." Antimicrob Agents Chemother 10 (1976): 80-2
  4. Madhavan T, Yaremchuk K, Levin N, et al. "Effect of renal failure and dialysis on the serum concentration of the aminoglycoside amikacin." Antimicrob Agents Chemother 10 (1976): 464-5
  5. Plantier J, Forrey AW, O'Neill MA, Blair AD, Christopher TG, Cutler RE "Pharmacokinetics of amikacin in patients with normal or impaired renal function: radioenzymatic acetylation assay." J Infect Dis 134 Suppl (1976): s323-30
  6. McHenry MC, Wagner JG, Hall PM, Vidt DG, Gavan TL "Pharmacokinetics of amikacin in patients with impaired renal function." J Infect Dis 134 Suppl (1976): s343-54
  7. Sarubbi FA, Hull JH "Amikacin serum concentrations: prediction of levels and dosage guidelines." Ann Intern Med 89 (1978): 612-8
  8. Bock BV, Edelstein PH, Meyer RD "Prospective comparative study of efficacy and toxicity of netilmicin and amikacin." Antimicrob Agents Chemother 17 (1980): 217-25

  Show all 59 sourcesShow fewer sources

  9. Lerner SA, Schmitt BA, Seligsohn R, Matz G "Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin." Am J Med 80 Suppl 6 (1986): 98-104
  10. Williams PJ, Hull JH, Sarubbi FA, Rogers JF, Wargin WA "Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin." J Clin Pharmacol 26 (1986): 79-86
  11. Emanuelli G, Anfossi G, Calcamuggi G, Marcarino C, Lanzio M "Urinary enzyme release following aminoglycoside administration in single low dose." Enzyme 39 (1988): 119-22
  12. Contreras AM, Gamba G, Cortes J, et al. "Serial trough and peak amikacin levels in plasma as predictors of nephrotoxicity." Antimicrob Agents Chemother 33 (1989): 973-6
  13. French MA, Cerra FB, Plaut ME, Schentag JJ "Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients." Antimicrob Agents Chemother 19 (1981): 147-52
  14. Pijck J, Hallynck T, Soep H, Baert L, Daniels R, Boelaert J "Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance." J Infect Dis 134 (1976): s331-41
  15. Solberg CO, Madsen ST, Digranes A, et al. "High dose netilmicin therapy: efficacy, tolerance and tissue penetration." J Antimicrob Chemother 6 (1980): 133-41
  16. Bhattacharya BK, Gorringe H, Farr MJ "Netilmicin and nephrotoxicity." Lancet 2 (1983): 216-7
  17. Bergeron MG, Lessard C, Ronald A, Stiver G, Van Roogen CE, Chadwick P "Three to eight weeks of therapy with netilmicin: toxicity in normal and diabetic patients." J Antimicrob Chemother 12 (1983): 245-8
  18. Bernstein JM, Gorse GJ, Linzmayer MI, et al. "Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients." Arch Intern Med 146 (1986): 2329-34
  19. Matzke GR, Millikin, Kovarik JM "Variability in pharmacokinetic values for gentamicin, tobramycin, and netilmicin in patients with renal insufficiency." Clin Pharm 8 (1989): 800-6
  20. Herrero A, Alarco FR, Diez JM, Mahiques E, Domingo JV "Pharmacokinetics of netilmicin in renal insufficiency and hemodialysis." Int J Clin Pharmacol Ther Toxicol 26 (1988): 84-7
  21. Craig WA, Gudmundsson S, Reich RM "Netilmicin sulfate: a comparative evaluation of antimicrobial activity, pharmacokinetics, adverse reactions and clinical efficacy." Pharmacotherapy 3 (1983): 305-15
  22. Luft FC, Brannon DR, Stropes LL, Costello RJ, Sloan RS, Maxwell DR "Pharmacokinetics of netilmicin in patients with renal impairment and in patients on dialysis." Antimicrob Agents Chemother 14 (1978): 403-7
  23. Humbert G, Leroy A, Fillastre JP, Oksenhendler G "Pharmacokinetics of netilmicin in the presence of normal or impaired renal function." Antimicrob Agents Chemother 14 (1978): 40-4
  24. Russo ME, Atkin-Thor E "Gentamicin and ticarcillin in subjects with end-stage renal disease." Clin Nephrol 15 (1981): 175-80
  25. Federspil P, Schatzle W, Tiesler E "Pharmacokinetics and ototoxicity of gentamicin, tobramycin and amikacin." J Infect Dis 134 (1976): s200-5
  26. Smith CR, Lipsky JJ, Laskin OL, et al. "Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin." N Engl J Med 302 (1980): 1106-9
  27. Kumin GD "Clinical nephrotoxicity of tobramycin and gentamicin." JAMA 244 (1980): 1808-10
  28. Keys TF, Kurtz SB, Jones JD, Muller SM "Renal toxicity during therapy with gentamicin or tobramycin." Mayo Clin Proc 56 (1981): 556-9
  29. Schentag JJ, Cerra FB, Plaut ME "Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients." Antimicrob Agents Chemother 21 (1982): 721-6
  30. Pines A, Goldhammer E, Kaplinsky N, Frankl O "Hypopotassemia associated with tobramycin treatment." Infection 10 (1982): 101-
  31. Tablan OC, Reyes MP, Rintelmann WF, Lerner AM "Renal and auditory toxicity of high-dose, prolonged therapy with gentamicin and tobramycin in pseudomonas endocarditis." J Infect Dis 149 (1984): 257-63
  32. Watson AJ, Watson MM, Keogh JA "Metabolic abnormalities associated with tobramycin therapy." Isr J Med Sci 153 (1984): 96-9
  33. Gatell JM, SanMiguel JG, Araujo V, et al. "Prospective randomized double-blind comparison of nephrotoxicity and auditory toxicity of tobramycin and netilmicin." Antimicrob Agents Chemother 26 (1984): 766-9
  34. Cimino MA, Rotstein C, Slaughter RL, Emrich LJ "Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy." Am J Med 83 (1987): 1091-7
  35. Contrepois A, Brion N, Garaud JJ, et al. "Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans." Antimicrob Agents Chemother 27 (1985): 520-4
  36. Wilkinson R, Lucas GL, Heath DA, et al. "Hypomagnesaemic tetany associated with prolonged treatment with aminoglycosides." Br Med J 292 (1986): 818-9
  37. Pedersen SS, Jensen J, Osterhammel D, Osterhammel P "Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis." Antimicrob Agents Chemother 31 (1987): 594-9
  38. Kunin CM, Finland M "Persistence of antibiotics in blood of patients with acute renal failure. III. Penicillin, streptomycin, erythromycin and kanamycin." J Clin Invest 38 (1959): 1509-19
  39. Yoshikawa TT, Nagami PH "Adverse drug reactions in TB therapy: risks and recommendations." Geriatrics 37 (1982): 61-3, 67-8
  40. Siegenthaler WE, Bonetti A, Luthy R "Aminoglycoside antibiotics in infectious diseases: an overview." Am J Med 80 (1986): 2-14
  41. Ristuccia AM, Cunha BA "The aminoglycosides." Med Clin North Am 66 (1982): 303-12
  42. Trollfors B, Alestig K, Krantz I, Norrby R "Quantitative nephrotoxicity of gentamicin in nontoxic doses." J Infect Dis 141 (1980): 306-9
  43. Letona JM, Barbolla L, Frieyro E, et al. "Immune haemolytic anaemia and renal failure induced by streptomycin." Br J Haematol 35 (1977): 561-71
  44. McQueen EG "Antibiotic allergy and acute renal failure." N Z Med J 64 (1965): 561-3
  45. Gyselnyck AM, Forrey A, Cutler R "Pharmacokinetics of gentamicin: distribution and plasma and renal clearance." J Infect Dis 124 (1971): s70
  46. Jaffe, Meyers BR, Hirschman SZ "Pharmacokinetics of tobramycin in patients with stable renal impairment, patients undergoing peritoneal dialysis, and patients on chronic hemodialysis." Antimicrob Agents Chemother 5 (1974): 611-6
  47. Schentag JJ, Lasezkay G, Cumbo TJ, et al. "Accumulation pharmacokinetics of tobramycin." Antimicrob Agents Chemother 13 (1978): 649-56
  48. Pechere JC, Dugal R, Pechere MM "Pharmacokinetics of netilmicin in renal insufficiency and haemodialysis." Clin Pharmacokinet 3 (1978): 395-406
  49. "Product Information. Amikin (amikacin)." Bristol-Myers Squibb (2002):
  50. "Product Information. Garamycin (gentamicin)." Schering-Plough Corporation (2007):
  51. "Product Information. Netromycin (netilmicin)." Schering Corporation (2002):
  52. "Product Information. Streptomycin Sulfate (streptomycin)." Pfizer U.S. Pharmaceuticals
  53. "Product Information. Nebcin (tobramycin)." Lilly, Eli and Company (2001):
  54. Gilbert DN, Bennett WM "Use of antimicrobial agents in renal failure." Infect Dis Clin North Am 3 (1989): 517-31
  55. Matz GJ, Naunton RF "Ototoxic drugs and poor renal function." JAMA 206 (1968): 2119
  56. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  57. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):
  58. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  59. "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated (2018):

• Kidney Diseases

  Major

  Albuminuria, cellular casts/cylindruria, and azotemia are generally seen in patients with nephrotoxicity due to polymyxin B sulfate; nephrotoxic reactions have also included rising blood levels without any increase in dosage. Renal function should be carefully determined, and the dosage should be reduced in patients with renal damage and nitrogen retention. Polymyxin B sulfate should be discontinued if urine output decreases and BUN increases.Neurotoxic reactions with polymyxin B sulfate may be shown by drowsiness, irritability, weakness, perioral paresthesia, numbness of the extremities, ataxia, and blurring of vision; such reactions are generally associated with high serum levels found in patients with impaired renal function and/or nephrotoxicity. The neurotoxicity of polymyxin B sulfate can lead to respiratory paralysis from neuromuscular blockade, particularly when administered soon after anesthesia and/or muscle relaxants. If signs of respiratory paralysis develop, respiration should be assisted as required and polymyxin B sulfate should be discontinued.Baseline renal function should be determined before therapy, and renal function and blood polymyxin B sulfate levels should be monitored frequently during parenteral therapy. Coadministration with or sequential use of other neurotoxic and/or nephrotoxic agents should be avoided.

  1 source

  1. "Product Information. Polymyxin B Sulfate (polymyxin B sulfate)." AuroMedics Pharma LLC (2022):

• Neuromuscular Diseases

  Major

  Aminoglycosides can cause dose-related neuromuscular blockade and muscle weakness, particularly in patients with neuromuscular disease or hypocalcemia and in patients receiving general anesthetics, neuromuscular blocking agents, or massive transfusions of citrate-anticoagulated blood. Although aminoglycoside- induced neuromuscular blockade is generally self-limiting, it may rarely result in respiratory paralysis. Neomycin is thought to be the most potent neuromuscular blocking agent in the class. However, the risk is greatest with intraperitoneal or intrapleural instillation of large doses or rapid intravenous administration of parenteral aminoglycosides. Therapy with aminoglycosides should be administered cautiously in patients with neuromuscular disorders (e.g., myasthenia gravis, parkinsonian syndrome, botulism) or hypocalcemia. If signs of respiratory paralysis occur during aminoglycoside therapy, the drug should be discontinued and mechanical respiratory assistance provided if necessary.

  11 sources

  1. Kaeser HE "Drug-induced myasthenic syndromes." Acta Neurol Scand 70 (1984): 39-47
  2. Ristuccia AM, Cunha BA "The aminoglycosides." Med Clin North Am 66 (1982): 303-12
  3. "Product Information. Amikin (amikacin)." Bristol-Myers Squibb (2002):
  4. "Product Information. Garamycin (gentamicin)." Schering-Plough Corporation (2007):
  5. "Product Information. Netromycin (netilmicin)." Schering Corporation (2002):
  6. "Product Information. Streptomycin Sulfate (streptomycin)." Pfizer U.S. Pharmaceuticals
  7. "Product Information. Nebcin (tobramycin)." Lilly, Eli and Company (2001):
  8. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):
  10. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  11. "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated (2018):

• Neurotoxicity Syndromes

  Major

  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.

  14 sources

  1. Kusumi RK, Plouffe JF, Wyatt RH, Fass RJ "Central nervous sytem toxicity associated with metronidazole therapy." Ann Intern Med 93 (1980): 59-60
  2. 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
  3. 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
  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. Duffy LF, Daum F, Fisher SE, et al. "Peripheral neuropathy in Crohn's disease patients treated with metronidazole." Gastroenterology 88 (1985): 681-4
  6. Boyce EG, Cookson ET, Bond WS "Persistent metronidazole-induced peripheral neuropathy." DICP 24 (1990): 19-21
  7. 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
  8. "Product Information. Flagyl (metronidazole)." Searle (2002):

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  9. Learned-Coughlin S "Peripheral neuropathy induced by metronidazole." Ann Pharmacother 28 (1994): 536
  10. Lawford R, Sorrell TC "Amebic abscess of the spleen complicated by metronidazole-induced neurotoxicity: case report." Clin Infect Dis 19 (1994): 346-8
  11. Ahmed A, Laes DJ, Bressler EL "Reversible magnetic resonance imaging findings in metronidazole-induced encephalopathy." Neurology 45 (1995): 588-9
  12. Schreiber W, Spernal J "Metronidazole-induced psychotic disorder." Am J Psychiatry 154 (1997): 1170-1
  13. 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
  14. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):

• Ototoxicity

  Major

  Aminoglycosides can cause eighth cranial nerve damage, resulting in vestibular and/or auditory toxicities. Symptoms include dizziness, nystagmus, vertigo, ataxia, tinnitus, and varying degrees of hearing impairment. Permanent hearing loss may occur, including, rarely, total or partial irreversible bilateral deafness after the drug has been discontinued. Therapy with aminoglycosides, particularly if prolonged (> 10 days), should be administered cautiously in patients with preexisting vestibular and/or auditory impairment, since it may delay the recognition or confound the diagnosis of a drug-induced ototoxic effect. To minimize the risk of toxicity, patients should be adequately hydrated, the usual aminoglycoside dosage should not be exceeded, use with other ototoxic agents should be avoided, and peak and trough serum aminoglycoside concentrations should be periodically determined and dosage adjusted to maintain desired levels. Serial audiograms should be obtained in patients old enough to be tested, since loss of high- frequency perception usually precedes clinical hearing loss. The dosage should be reduced or therapy withdrawn promptly if signs and symptoms of toxicity develop.

  35 sources

  1. Barza M, Lauermann MW, Tally FP, Gorbach SL "Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity." Antimicrob Agents Chemother 17 (1980): 707-14
  2. Barza M, Lauermann MW, Tally FP, Gorbach SL "Prospective, randomized trial of netilmicin and amikacin, with emphasis on eighth-nerve toxicity." Antimicrob Agents Chemother 17 (1980): 707-14
  3. Bock BV, Edelstein PH, Meyer RD "Prospective comparative study of efficacy and toxicity of netilmicin and amikacin." Antimicrob Agents Chemother 17 (1980): 217-25
  4. Danhauer FJ, Fortner CL, Schimpff SC, DeJongh CA, Wesley MN, Wiernik PH "Ototoxicity and pharmacokinetically determined dosages of amikacin in granulocytopenic cancer patients." Clin Pharm 1 (1982): 539-43
  5. Uziel A "Non-genetic factors affecting hearing development." Acta Otolaryngol (Stockh) 421 (1985): 57-61
  6. Lerner SA, Schmitt BA, Seligsohn R, Matz G "Comparative study of ototoxicity and nephrotoxicity in patients randomly assigned to treatment with amikacin or gentamicin." Am J Med 80 Suppl 6 (1986): 98-104
  7. Bock BV, Edelstein PH, Meyer RD "Prospective comparative study of efficacy and toxicity of netilmicin and amikacin." Antimicrob Agents Chemother 17 (1980): 217-25
  8. Bernstein JM, Gorse GJ, Linzmayer MI, et al. "Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients." Arch Intern Med 146 (1986): 2329-34

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  9. Smith CR, Lipsky JJ, Laskin OL, et al. "Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin." N Engl J Med 302 (1980): 1106-9
  10. Tablan OC, Reyes MP, Rintelmann WF, Lerner AM "Renal and auditory toxicity of high-dose, prolonged therapy with gentamicin and tobramycin in pseudomonas endocarditis." J Infect Dis 149 (1984): 257-63
  11. Gatell JM, SanMiguel JG, Araujo V, et al. "Prospective randomized double-blind comparison of nephrotoxicity and auditory toxicity of tobramycin and netilmicin." Antimicrob Agents Chemother 26 (1984): 766-9
  12. Bernstein JM, Gorse GJ, Linzmayer I, et al. "Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients." Arch Intern Med 146 (1986): 2329-34
  13. Mathog RH, Klein WJ "Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia." N Engl J Med 280 (1969): 1223-4
  14. Ristuccia AM, Cunha BA "The aminoglycosides." Med Clin North Am 66 (1982): 303-12
  15. Gailiunas P, Dominguez-Moreno M, Lazarus JM, et al. "Vestibular toxicity of gentamicin: incidence in patients receiving long-term hemodialysis therapy." Arch Intern Med 138 (1978): 1621-4
  16. Deka RC, Ghosh P, Kacker SK "Streptomycin ototoxicity: an audiologic and vestibular study." Ear Nose Throat J 56 (1977): 218-24
  17. Esterhai JL, Bednar J, Kimmelman CP "Gentamicin-induced ototoxicity complicating treatment of chronic osteomyelitis." Clin Orthop Aug (1986): 185-6
  18. "Product Information. Amikin (amikacin)." Bristol-Myers Squibb (2002):
  19. "Product Information. Garamycin (gentamicin)." Schering-Plough Corporation (2007):
  20. "Product Information. Netromycin (netilmicin)." Schering Corporation (2002):
  21. "Product Information. Streptomycin Sulfate (streptomycin)." Pfizer U.S. Pharmaceuticals
  22. "Product Information. Nebcin (tobramycin)." Lilly, Eli and Company (2001):
  23. Gendeh BS, Said H, Gibb AG, Aziz NS, Kong N, Zahir ZM "Gentamicin ototoxicity in continuous ambulatory peritoneal dialysis." J Laryngol Otol 107 (1993): 681-5
  24. Hybels RL "Drug toxicity of the inner ear." Med Clin North Am 63 (1979): 309-19
  25. Marlowe FI "Ototoxic agents." Otolaryngol Clin North Am 11 (1978): 791-800
  26. Sheffield PA, Turner JS Jr "Ototoxic drugs: a review of clinical aspects, histopathologic changes and mechanisms of action." South Med J 64 (1971): 359-63
  27. Ballantyne J "Ototoxicity: a clinical review." Audiology 12 (1973): 325-36
  28. Ajodhia JM, Dix MR "Drug-induced deafness and its treatment." Practitioner 216 (1976): 561-70
  29. Boston Collaborative Drug Surveillance Program "Drug-induced deafness." JAMA 224 (1973): 515-6
  30. American Medical Association, Division of Drugs and Toxicology "Drug evaluations annual 1994." Chicago, IL: American Medical Association; (1994):
  31. Minor LB "Gentamicin-induced bilateral vestibular hypofunction." JAMA 279 (1998): 541-4
  32. ElBakri F, Pallett A, Smith AG, Duncombe AS "Ototoxicity induced by once-daily gentamicin." Lancet 351 (1998): 1407-8
  33. "Product Information. Mycifradin (neomycin)." Emerson Laboratories (2001):
  34. "Product Information. Zemdri (plazomicin)." Achaogen (2018):
  35. "Product Information. Arikayce (amikacin liposome)." Insmed Incorporated (2018):

• Alcoholism

  Moderate

  Nitroimidazoles (e.g., metronidazole, tinidazole, fexinidazole, secnidazole) may inhibit alcohol dehydrogenase and occasionally precipitate a disulfiram-like reaction in patients who consume alcohol while being treated. Symptoms may include abdominal cramps, nausea, vomiting, headache, flushing, rash, weakness, diarrhea, abdominal pain, dizziness, sweating, and hypotension. Patients should be instructed to avoid alcohol-containing products during nitroimidazole therapy and for at least 48 hours (fexinidazole, secnidazole) to 72 hours (metronidazole, tinidazole) 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.

  4 sources

  1. "Product Information. Flagyl (metronidazole)." Searle (2002):
  2. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
  3. "Product Information. Solosec (secnidazole)." Symbiomix Therapeutics (2017):
  4. "Product Information. Fexinidazole (fexinidazole)." sanofi-aventis (2021):

• Diseases requiring dialysis

  Moderate

  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.

  5 sources

  1. 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
  2. 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
  3. Kreeft JH, Ogilvie RI, Dufresne LR "Metronidazole kinetics in dialysis patients." Surgery 93 (1983): 149-53
  4. Lau AH, Chang CW, Sabatini S "Hemodialysis clearance of metronidazole and its metabolites." Antimicrob Agents Chemother 29 (1986): 235-8
  5. "Product Information. Flagyl (metronidazole)." Searle (2002):

• Heart Failure

  Moderate

  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.

  1 source

  1. "Product Information. Flagyl (metronidazole)." Searle (2002):

• Liver Diseases

  Moderate

  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.

  6 sources

  1. Lau AH, Evans R, Chang CW, Seligsohn R "Pharmacokinetics of metronidazole in patients with alcoholic liver disease." Antimicrob Agents Chemother 31 (1987): 1662-4
  2. Jensen JC, Gugler R "Single- and multiple-dose metronidazole kinetics." Clin Pharmacol Ther 34 (1983): 481-7
  3. Farrell G, Baird-Lambert J, Cvejic M, Buchanan N "Disposition and metabolism of metronidazole in patients with liver failure." Hepatology 4 (1984): 772-6
  4. 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
  5. Loft S, Sonne J, Dossing M, Andreasen PB "Metronidazole pharmacokinetics in patients with hepatic encephalopathy." Scand J Gastroenterol 22 (1987): 117-23
  6. "Product Information. Flagyl (metronidazole)." Searle (2002):