Interaction between
Metronidazole
and
Busulfan
Major
Others
Basic Information
| ID | DDInter1202 and DDInter255 |
| Interaction | Coadministration with metronidazole may significantly increase the plasma concentrations of busulfan. The mechanism of interaction has not been described. |
| Management | Due to the potential for severe toxicity and mortality associated with elevated busulfan plasma levels, concomitant use with metronidazole should be avoided. However, if concomitant therapy is necessary, close monitoring for signs of busulfan toxicity is recommended. |
| References | [1] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [2] "Product Information. Busulfex (busulfan)." ESP Pharma Inc, Edison, NJ. [3] Gulbis AM, Culotta KS, Jones RB, Andersson BS "Busulfan and metronidazole: an often forgotten but significant drug interaction." Ann Pharmacother 45 (2011): e39 [4] Nilsson C, Aschan J, Hentschke P, Ringden O, Ljungman P, Hassan M "The effect of metronidazole on busulfan pharmacokinetics in patients undergoing hematopoietic stem cell transplantation." Bone Marrow Transplant 31 (2003): 429-435 [5] Albert KS, Welch RD, DeSante KA, DiSanto AR "Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidiarrheal mixture." J Pharm Sci 68 (1979): 586-8 [6] Ericsson CD, Feldman S, Pickering LK, Cleary TG "Influence of subsalicylate bismuth on absorption of doxycycline." JAMA 247 (1982): 2266-7 [7] "Product Information. Seysara (sarecycline)." Allergan Inc, Irvine, CA. [8] "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc., Boston, MA. [9] Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15 [10] Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000 [11] Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8 [12] Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80 [13] Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4 [14] "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc, West Orange, NJ. [15] Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7 [16] Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3 [17] "Product Information. Flagyl (metronidazole)." Searle, Skokie, IL. [18] "Product Information. Achromycin (tetracycline)." Lederle Laboratories, Wayne, NJ. [19] "Product Information. Declomycin (demeclocycline)." Lederle Laboratories, Wayne, NJ. |
| Alternative for Metronidazole |
A02B
|
| Alternative for Busulfan |
L01A
|
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.