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NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
Last Update:September 18, 2021.
Mebendazole is an anthelmintic agent used commonly for roundworm (pinworm and hookworm) infections, trichinosis, capillariasis and toxocariasis and other parasitic worm infections. Mebendazole when given for prolonged periods in high doses has been associated with elevations in serum enzyme levels, and rare instances of acute, clinically apparent liver injury have been linked to its use.
Mebendazole (me ben' da zole) is a benzimidazole anthelmintic similar in structure and mechanism of action to thiabendazole and albendazole. The benzimidazoles act by selective binding to beta-tubulin of parasitic worms, causing their immobilization and death. Mebendazole and albendazole share similar anthelmintic activity, mebendazole generally being preferred for treatment of pinworm and roundworm infections, and albendazole (because it is better absorbed) for systemic parasitic infections such as echinococcosis and cysticercosis. Mebendazole was approved for use in the United States in 1974 and is indicated for therapy of common parasitic worm infections. Mebendazole is available generically and under the brand names Emverm and Vermox in 100 mg and 500 mg chewable tablets. The usual dose is 100 or 500 mg once (pinworm) or varying doses for 3 days (whipworm, hookworm and roundworm infections), or varying doses for longer periods, depending upon the indication. Side effects with single dose regimens are uncommon, but can include gastrointestinal upset, fever, headache, nausea, vomiting and diarrhea. With more extended therapy, gastrointestinal symptoms are the most frequent side effects and rare but potentially severe adverse effects include neutropenia, hypersensitivity reactions, hepatitis, angioedema, Stevens Johnson syndrome and toxic epidermal necrolysis.
Mebendazole when given in typical doses has not been associated with serum enzyme elevations, although the duration of therapy is usually short and monitoring for enzyme elevations has rarely been reported. With high dose therapy (which is now rarely used with the availability of albendazole), elevations in serum aminotransferase levels (2 to 10 times normal) can occur, but are usually well tolerated. There have been rare reports of acute liver injury due to mebenazole, particularly when it is given repeatedly or in higher doses. The onset is usually with fever and malaise within days of starting or restarting therapy. The pattern of serum enzyme elevations is typically hepatocellular, and jaundice is uncommon. The abnormalities usually resolve rapidly with stopping therapy. Signs of hypersensitivity (rash, fever and eosinophilia) are typical and liver biopsy may show granulomas.
Likelihood score: D (possible cause of clinically apparent liver injury with extended therapy).
Mebendazole acts by binding tubulin in parasitic worms, which it does with greater avidity than the tubulin in mammalian cells, but some of the toxicity of the benzimidazoles may be related to this tubulin-binding activity. In most instances of clinically apparent liver injury, hypersensitivity appears to be the cause.
Mebendazole is usually well tolerated and the liver injury reported with its use has been mild and self-limited in course. Patients with hypersensitivity and acute liver injury attributed to mebendazole should avoid repeat exposure. It is unknown whether there is cross sensitivity with other benzimidazoles (such as albendazole), but there probably is and switching to another class of anthelmintic agents is appropriate if therapy is still needed.
Drug Class:Anthelmintic Agents
A 52 year old Belgian man was treated with mebendazole (100 mg twice daily) for 3 days for suspected ascariasis. Fourteen days later the course was repeated, but within 2 days of restarting mebendazole he developed fever (39oC), diarrhea, poor appetite and fatigue. Because of the fever, he was given a 5 day course of cefuroxime, but remained febrile and symptomatic and was then found to have elevations in serum aminotransferase levels, with normal serum bilirubin and alkaline phosphatase (Table). He had eosinophilia (18%: absolute count 2,286/μL). Tests for hepatitis A, B and C were negative. He had low levels of antinuclear antibody (ANA: 1:40) and smooth muscle antibody (SMA: 1:160), but total globulin levels were normal. Ultrasound of the abdomen was negative. Stools were negative for ova and parasites. A liver biopsy showed multiple granulomas with multinucleate cells and active inflammation. There were no ova or helminths visualized and special stains for mycobacteria were negative. He improved rapidly without further therapy and 3 months later serum enzymes were normal.
| Medication: | Mebendazole (100 mg twice daily) for ~5 days |
|---|---|
| Pattern: | Hepatocellular (R=9.7) |
| Severity: | 1+ (enzyme elevations without jaundice) |
| Latency: | 26 days after initial course, 2 days of second course |
| Recovery: | Within 3 months |
| Other medications: | Cefuroxime (after onset of symptoms) |
| Days After Starting | Days After Stopping | ALT (U/L) | Alk P (U/L) | Bilirubin* (mg/dL) | Other |
|---|---|---|---|---|---|
| 0 | Mebendazole (100 mg twice daily for 3 days) | ||||
| 14 | Mebendazole (100 mg twice daily for 2 days) | ||||
| 16 | 0 | Fever and rash | |||
| 26 | 10 | 466 | 170 | 1.0 | Eosinophilia |
| 28 | 12 | 540 | Liver biopsy | ||
| 100 | 90 | Normal | Normal | Normal | No symptoms |
| Normal Values | <48 | <60 | <1.2 | ||
Acute hepatocellular injury arose concurrent with symptoms and signs of hypersensitivity (rash and fever) within days of starting a second course of mebendazole. This pattern is typical of immunoallergic hepatitis and usually resolves rapidly, but can be severe if there is reexposure. The ANA and SMA titers may have been stimulated by the acute injury; in the absence of hyperglobulinemia were not compatible with autoimmune hepatitis. The granulomas found on liver biopsy reflect the generalized hypersensitivity and similar granulomas are likely to be found in other organs (lymph nodes, spleen).
REPRESENTATIVE TRADE NAMES
Mebendazole – Generic, Vermox®
DRUG CLASS
Anthelmintic Agents
Product labeling at DailyMed, National Library of Medicine, NIH
| DRUG | CAS REGISTRY NUMBER | MOLECULAR FORMULA | STRUCTURE |
|---|---|---|---|
| Mebendazole | 31431-39-7 | C16-H13-N3-O3 |
References updated: 18 September 2021
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