There is an interaction between Mebendazole and Metronidazole. Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. So all the resources ( Product information leaflet, FDA website, Stockley’s interaction) says to avoid concomitant use of mebendazole and metronidazole.

A case control study was conducted in an attempt to identify risk factors associated with an outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis that occurred amongst Filipino workers in Taiwan. The risk of developing this serious condition was significantly higher in workers who had taken both metronidazole and mebendazole sometime in the preceding 6 weeks (odds ratio of 9.5). In addition, there was an increase in risk with higher doses of metronidazole.However, Stevens-Johnson syndrome/toxic epidermal necrolysis is a serious condition, and therefore, the manufacturer of mebendazole states that the concurrent use of mebendazole and metronidazole should be avoided .

Have you seen this article?

Article Outbreak of Stevens-Johnson Syndrome/Toxic Epidermal Necroly...

thanks Donna

yes have seen it, but how much is it reliable and to what extent it’s applicable in clinical practice?

Hi Ayman,

For a better clarification on the interaction between Metronidazole and Mebendazole and the clinical significance of this I would recommend you run an interaction check on Medscape Interaction Checker or any other reliable platform.

Medscape in particular will offer in-depth information on the category of the interaction, the population most affected where applicable and the clinical strategy for minimizing or avoiding the interaction.

If mebendazole taken orally their interaction with metronidazol will be very lettil beacause mebendazole is poorly absorbed into the bloodstream.

There is an interaction between Mebendazole and Metronidazole. Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. So all the resources ( Product information leaflet, FDA website, Stockley’s interaction) says to avoid concomitant use of mebendazole and metronidazole.

A case control study was conducted in an attempt to identify risk factors associated with an outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis that occurred amongst Filipino workers in Taiwan. The risk of developing this serious condition was significantly higher in workers who had taken both metronidazole and mebendazole sometime in the preceding 6 weeks (odds ratio of 9.5). In addition, there was an increase in risk with higher doses of metronidazole.However, Stevens-Johnson syndrome/toxic epidermal necrolysis is a serious condition, and therefore, the manufacturer of mebendazole states that the concurrent use of mebendazole and metronidazole should be avoided .

Title MetroNIDAZOLE (Systemic) / Mebendazole

Risk Rating X: Avoid combination

Summary Mebendazole may enhance the adverse/toxic effect of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased. Severity Major Reliability Rating Fair

Patient Management Avoid the combination of mebendazole and metronidazole due to the potential increased risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.

Discussion A case control study of 46 patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and matched controls (2 per case) reported greater use of combined mebendazole and metronidazole among cases than controls (76% vs 25%), with a corresponding odds ratio (OR) (95% confidence interval) associated with the use of the combination of 9.5 (3.9 to 23.9).1 Use of either drug alone was not associated with an increased risk of SJS/TEN, although reports of SJS/TEN with each drug alone have been reported previously.2,3,4 Metronidazole doses of 2,000 mg per day or greater were associated with an increased occurrence of SJS/TEN (OR 18.9 [3.6 to 112.8]) compared with doses of 1,000 mg or less per day. The opposite dose relationship was observed for mebendazole, with higher doses (2,000 mg per day or greater) associated with a lower odds for SJS/TEN (OR 0.1 [0.03 to 0.6]) compared with lower doses (1,000 mg per day or less). The authors of the report suspected that the inverse dose relationship was due to the use of lower mebendazole doses in combination with higher dose metronidazole.1

Due to this report, the mebendazole Canadian product monograph recommends avoidance of the combination of mebendazole and metronidazole.5

Whether the metronidazole (or mebendazole) dose or the combined use of metronidazole and mebendazole is primarily responsible for the cases of SJS/TEN evaluated in this study is uncertain, as is the precise mechanism by which dose or a drug interaction would cause SJS/TEN.

Footnotes

1. Chen KT, Twu SJ, Chang HJ, Lin RS. Outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with mebendazole and metronidazole use among Filipino laborers in Taiwan. Am J Public Health. 2003;93(3):489-492. [PubMed 12604501]

2. Mazumdar G, Shome K. Stevens-Johnson syndrome following use of metronidazole in a dental patient. Indian J Pharmacol. 2014;46(1):121-122. [PubMed 24550598]

3. Piskin G, Mekkes JR. Stevens-Johnson syndrome from metronidazole. Contact Dermatitis. 2006;55(3):192-193. [16918620]

4. Ajonuma LC, Chika LC. Outbreak of Stevens-Johnson syndrome among Filipino overseas contract workers using mebendazole for helminthiasis prophylaxis. Trop Doct. 2000;30(1):57. [PubMed 10842543]

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'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo

A) A drug etiology for SJS/TEN is easy to postulate but difficult to prove. Because no reliable skin or laboratory tests are available, skillful collection of patient histories remains the best tool for identifying a particular drug as the trigger of SJS/TEN. Although rechallenge tests would provide convincing evidence, such testing is not feasible for ethical reasons.

Several cases of SJS/TEN associated with use of thiabendazole or metronidazole have been reported. Mebendazole and metronidazole are generally safe if 1 of the agents is used in a low dosage.

B) FDA also have been reported that Metronidazole and Serious Skin Reactions: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. Then avoid concomitant use of mebendazole and metronidazole .

C) Dermatologists use a variety of systemic drugs, some of which can cause severe adverse reactions and even fatalities. Drug-induced anaphylaxis and toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS) represent severe immediate and delayed-type adverse drug reactions (ADRs), respectively. Occurrence of such reactions after topical drug application has been reported seems to be extremely rare.

D) A patient with chronic liver disease was treated with large doses of mebendazole for a hepatic hydatid cyst. Eighteen days after beginning treatment he developed marrow aplasia which reverted to normal after the drug was stopped. Patients treated with large doses of mebendazole should have their blood counts monitored during treatment.

References

1. Chen KT, Twu SJ, Chang HJ, Lin RS. Outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with mebendazole and metronidazole use among Filipino laborers in Taiwan. Am J Public Health. 2003 Mar;93(3):489-92.

2. Ajonuma LC, Chika LC. Outbreak of Stevens-Johnson syndrome among Filipino overseas contract workers using mebendazole for helminthiasis prophylaxis. Trop Doct. 2000 Jan;30(1):57.

3. Dewerdt S, Machet L, Jan-Lamy V, Lorette G, Therizol-Ferly M, Vaillant L. Stevens-Johnson syndrome after albendazole. Acta Derm Venereol. 1997 Sep;77(5):411.

4. Robinson HM, Samorodin CS. Thiabendazole-induced toxic epidermal necrolysis. Arch Dermatol. 1976 Dec;112(12):1757-60.

5. Orion E, Matz H, Wolf R. The life-threatening complications of dermatologic therapies. Clin Dermatol. 2005 Mar-Apr;23(2):182-92.

6. Sachs B, Fischer-Barth W, Erdmann S, Merk HF, Seebeck J. Anaphylaxis and toxic epidermal necrolysis or Stevens-Johnson syndrome after nonmucosal topical drug application: fact or fiction? Allergy. 2007 Aug;62(8):877-83.

7. Pharmaceutical Society of Australia "APPGuide online. Australian prescription products guide online. Available from: URL: http://www.appco.com.au/appguide/default.asp." ([2006])

8. Canadian Pharmacists Association "e-CPS. Available from: URL: http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink."

9. Schmutz JL, Barbaud A, Tréchot P. Anaphylactic reaction to metronidazole. Ann Dermatol Venereol. 2009 Oct;136(10):759. doi: 10.1016/j.annder.2009.03.003. Epub 2009 Apr 8.

10. Speare R, Skerratt LF, Berger L, Johnson PM. Toxic effects of mebendazole at high dose on the haematology of red-legged pademelons (Thylogale stigmatica). Aust Vet J. 2004 May;82(5):300-3.

11. Fernández-Bañares F, González-Huix F, Xiol X, Catalá I, Miró J, López N, Casais L. Marrow aplasia during high dose mebendazole treatment. Am J Trop Med Hyg. 1986 Mar;35(2):350-1.