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Mebendazole is authorised in the world under the following brand names: Bantenol, Besantin, Equivurm Plus, Lomper, MBDZ, Mebendazole (JAN/USP), Mebendazole(USAN), MEBENDAZOLE, 99%, Mebenoazole, Mebenvet, Mebex, Mebutar, Noverme, Ovitelmin, Pantelmin, Telmin, Vermicidin, Vermirax, Vermox, Vermox (TN), Verpanyl.
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Mebendazole
Mebendazole is a synthetic anthelmintic agent that is structurally related to albendazole and thiabendazole.
Uses
Mebendazole is used for the treatment of a variety of nematode (roundworm) infections, including trichuriasis (whipworm infection) caused by Trichuris trichiura, enterobiasis (pinworm infection) caused by Enterobius vermicularis, ascariasis (roundworm infection) caused by Ascaris lumbricoides, and hookworm infections caused by Ancylostoma duodenale, Necator americanus, or Ancylostoma caninum.
The drug’s broad spectrum of activity makes it useful in the treatment of mixed helminthic infections. Mebendazole has produced egg reduction percentages and/or cure rates of over 90% in patients with enterobiasis, ascariasis, or hookworm infection caused by A. duodenale or N. americanus and has produced egg reduction percentages of over 90% and cure rates of approximately 70% in patients with trichuriasis.
The efficacy of mebendazole in the treatment of helminthic infections varies in patients as a function of preexisting diarrhea, GI transit time, degree of infection, and helminth strain; cure rates are usually lower than average in patients who have massive infections and in patients with hypermotility of the GI tract.
Although other anthelmintics (e.g., praziquantel, albendazole) usually are recommended for the treatment of infections caused by cestodes (tapeworms), mebendazole has been used for the treatment of intestinal infections caused by the adult forms of certain tapeworms, including Hymenolepis nana (dwarf tapeworm), Taenia saginata (beef tapeworm), and T. solium (pork tapeworm), and for the treatment of hydatid disease caused by the larval form of Echinococcus granulosus (dog tapeworm).
Nematode (Roundworm) Infections
Ascariasis
Mebendazole is used for the treatment of ascariasis caused by Ascaris lumbricoides. Albendazole, mebendazole, or pyrantel pamoate are considered the drugs of choice for the treatment of ascariasis.
Enterobiasis
Mebendazole is used for the treatment of enterobiasis caused by Enterobius vermicularis (pinworm). Albendazole, mebendazole, or pyrantel pamoate are considered the drugs of choice for the treatment of enterobiasis.
Filariasis
Mebendazole or albendazole are considered the drugs of choice for the treatment of filariasis caused by Mansonella perstans. Mebendazole also has been used for the treatment of onchocerciasis (filariasis caused by Onchocerca volvulus), but ivermectin usually is considered the drug of choice for this infection. Other anthelmintics (usually diethylcarbamazine [available in the US from the US Centers for Disease Control and Prevention]) are recommended for the treatment of infections caused by most other filarial worms.
Hookworm Infections
Mebendazole is used for the treatment of intestinal hookworm infections caused by Ancylostoma duodenale or Necator americanus in single or mixed infections. Albendazole, mebendazole, or pyrantel pamoate are considered the drugs of choice for intestinal hookworm infections. Mebendazole has been used for the treatment of cutaneous larva migrans (creeping eruption) caused by dog and cat hookworms. However, cutaneous larva migrans usually is self-limited with spontaneous cure after several weeks or months and other drugs (albendazole, ivermectin, thiabendazole) usually are recommended if treatment is indicated. Mebendazole, albendazole, or pyrantel pamoate are considered drugs of choice for the treatment of eosinophilic enterocolitis caused by Ancylostoma caninum (dog hookworm).
Toxocariasis (Visceral Larva Migrans)
Mebendazole is used for the treatment of toxocariasis (visceral larva migrans) caused by Toxocara canis or T. cati (dog and cat roundworms), and albendazole or mebendazole are considered the drugs of choice for these infections. In severe cases with cardiac, ocular, or CNS involvement, corticosteroids also may be indicated. Treatment may not be effective in ocular larva migrans; inflammation may be reduced by corticosteroid injections and surgery may be necessary for secondary damage.
Trichinosis
Mebendazole is used for the treatment of trichinosis caused by Trichinella spiralis. Although some clinicians state that albendazole and mebendazole are equally effective for the treatment of trichinosis, other clinicians consider mebendazole the drug of choice and albendazole the alternative, particularly during the tissue phase of the illness. Use of corticosteroids in addition to the anthelmintic usually is recommended, especially when symptoms are severe. Corticosteroids alleviate symptoms of the inflammatory reaction and can be lifesaving when cardiac or CNS systems are involved.
Trichuriasis
Mebendazole is used for the treatment of trichuriasis caused by Trichuris trichiura (whipworm). Mebendazole is considered a drug of choice for the treatment of trichuriasis.
Other Nematode Infections
Mebendazole used in conjunction with corticosteroids appeared to shorten the course of infection (but not the number of relapses) in several patients with eosinophilic meningitis caused by Angiostrongylus cantonensis. No drug has been shown to be effective in the treatment of this infection and some patients have worsened when treated with albendazole, mebendazole, thiabendazole, or invermectin. Mebendazole has been used in animals for the treatment of angiostrongyliasis caused by A. costaricensis or A. malaysiensis Mebendazole is considered the drug of choice and albendazole is considered an alternative for the treatment of capillariasis caused by Capillaria philippinensis. Although metronidazole generally is considered the drug of choice for the treatment of infections caused by Dracunculus medinensis (guinea worm) since it has been shown to decrease inflammation and facilitate removal of the worm, mebendazole (400-800 mg daily for 6 days) has been reported to kill the worm directly. Mebendazole is used in the treatment of infections caused by Trichostrongylus. Pyrantel pamoate is considered the drug of choice and albendazole or mebendazole are alternative for the treatment of Trichostrongylus infections. Mebendazole is considered a drug of choice for the treatment of trichuriasis caused by Trichuris trichiura (whipworm).
Cestode (Tapeworm) Infections
Mebendazole has been used in the treatment of intestinal infections caused by the adult forms of certain tapeworms, including Hymenolepis nana (dwarf tapeworm), Taenia saginata (beef tapeworm), and T. solium (pork tapeworm). However, other anthelmintics (usually praziquantel) are recommended for the treatment of intestinal infections caused by adult forms of these cestodes. Mebendazole has been effective in a limited number of patients for the treatment of hydatid disease caused by the larval form of Echinococcus granulosus (dog tapeworm). The manufacturers state that there is no evidence that mebendazole, even at high doses, is effective for the treatment of hydatid disease. Surgery is considered the treatment of choice for hydatid disease, when medically feasible, but perioperative administration of an anthelmintic drug may be indicated in patients undergoing surgical removal of cysts to minimize the risk of intraoperative dissemination of daughter cysts. Mebendazole has been used for the treatment of alveolar hydatid disease caused by E. multiocularis in a very limited number of patients; however, surgical excision of the larval mass is the recommended and only reliable treatment for these infections. Continuous albendazole or mebendazole therapy reportedly has been associated with clinical improvement in nonresectable cases.
Giardiasis
Although metronidazole generally is the drug of choice for the treatment of giardiasis caused by Giardia lamblia, mebendazole has been used for the treatment giardiasis in a limited number of adolescents and children.
Dosage and Administration
Administration
Mebendazole is administered orally. The tablets may be chewed, swallowed whole, or crushed and mixed with food. Special diets, fasting, or purgation prior to administration of the drug is not necessary. Patients should be advised of hygienic precautions needed to minimize reinfection, such as wearing shoes, washing hands with soap and cleaning under fingernails often during the day (especially before eating and after using the toilet), and washing all fruits and vegetables thoroughly before eating them.
Dosage
Dosage in adults and children is the same. The manufacturer states that if the patient is not cured 3 weeks after mebendazole therapy, a second course of treatment is advised.
Nematode (Roundworm) Infections Ascariasis
For the treatment of ascariasis caused by Ascaris lumbricoides (including mixed helminthic infections) in adult and pediatric patients, the usual dosage of mebendazole is 100 mg twice daily for 3 consecutive days. Alternatively, some clinicians suggest that a single 500-mg dose of mebendazole can be used for the treatment of ascariasis in adults and pediatric patients.
Enterobiasis
For the treatment of enterobiasis caused by Enterobius vermicularis (pinworm) in adults and pediatric patients, the usual dose of mebendazole is 100 mg given as a single dose. In addition, some clinicians recommend that adult and pediatric patients receive a second 100-mg dose of mebendazole given 2 weeks later. The manufacturer states that if the patient is not cured within 3 weeks following the initial dose, a second dose should be administered.
Filariasis
For the treatment of filariasis caused by Mansonella perstans, some clinicians recommend that adults and pediatric patients receive mebendazole in a dosage of 100 mg twice daily for 30 days. For the treatment of onchocerciasis (filariasis caused by Onchocerca volvulus) in adults, a mebendazole dosage of 1 g twice daily for 28 days has been suggested.
Hookworm Infections
For the treatment of intestinal hookworm infections caused by Ancylostoma duodenale or Necator americanus or for eosinophilic enterocolitis caused by Ancylostoma caninum (dog hookworm), the usual dosage of mebendazole for adult and pediatric patients is 100 mg twice daily for 3 consecutive days. Alternatively, some clinicians suggest that adult and pediatric patients can receive a single 500-mg dose of mebendazole for the treatment of hookworm infections caused by A. duodenale or N. americanus.
Toxocariasis (Visceral Larva Migrans)
For the treatment of toxocariasis (visceral larva migrans) caused by dog and cat roundworms, some clinicians recommend that adults and pediatric patients receive mebendazole in a dosage of 100-200 mg twice daily for 5 days. However, optimum duration of therapy is not known and some clinicians recommend that treatment be continued for up to 20 days. A dosage of 1 g 3 times daily (50 mg/kg daily) for 21 days reportedly was curative in a least one patient with this infection.
Trichinosis
The recommended dosage of mebendazole for the treatment of trichinosis caused by Trichinella spiralis in adults and pediatric patients is 200-400 mg 3 times daily for 3 days followed by 400-500 mg 3 times for 10 days.
Trichuriasis
For the treatment of trichuriasis infections caused by Trichuris trichiura (whipworm), adults and pediatric patients should receive mebendazole in a dosage of 100 mg twice daily for 3 consecutive days. Alternatively, for the treatment of trichuriasis, some clinicians suggest that adults and pediatric patients can receive a single 500-mg dose of mebendazole. Other
Nematode Infections
For the treatment of capillariasis caused by Capillaria philippinensis, some clinicians recommend that adults and pediatric patients receive mebendazole in a dosage of 200 mg twice daily for 20 days. For the treatment of dracunculiasis caused by Dracunculus medinensis (guinea worm), a mebendazole dosage of 400-800 mg daily for 6 days reportedly has killed the worm directly. For the treatment of infections caused by Trichostrongylus, adults and pediatric patients should receive mebendazole in a dosage of 100 mg twice daily for 3 consecutive days.
Cautions
Adverse Effects
At usual recommended dosages (i.e., 100-200 mg daily), mebendazole appears to cause minimal adverse effects. Adverse effects appear to occur more frequently when higher dosages (e.g., those used in the treatment of extraintestinal infections such as hydatid disease) are used, and may be related to effects resulting from drug-induced killing of the parasites in some cases. Transient diarrhea and abdominal pain have occurred occasionally during mebendazole treatment, but usually have been associated with massive infections and expulsion of the helminths. Nausea, vomiting, headache, tinnitus, numbness, and dizziness also have been reported occasionally during mebendazole therapy. Fever has occurred in some patients, particularly in those receiving high-dose therapy for extraintestinal infections. Myelosuppression manifested as neutropenia (including agranulocytosis) and/or thrombocytopenia also has been reported in patients receiving high-dose (e.g., 30-50 mg/kg daily) mebendazole therapy for extraintestinal infections; while the myelosuppression usually was reversible following discontinuance of the drug, death has occurred rarely. Other adverse effects reported rarely in patients receiving mebendazole include alopecia, rash, pruritus, urticaria, angioedema, flushing, hiccups, cough, weakness,drowsiness, chills, hypotension, seizures, transient abnormalities in liver function tests (e.g., increased serum concentrations of aminotransferases, alkaline phosphatase, and/or bilirubin), increased BUN, decreased hemoglobin concentration and/or hematocrit, leukopenia, thrombocytopenia, eosinophilia, hematuria, and cylindruria.Migration of roundworms through the mouth and nose also has been reported.
Precautions and Contraindications
Mebendazole is contraindicated in patients who are hypersensitive to the drug.
Pediatric Precautions
Safety of mebendazole in children younger than 2 years of age has not been established. Because of limited experience with mebendazole in children younger than 2 years of age, the drug should be used in such children only when the potential benefits justify the possible risks.
Mutagenicity and Carcinogenicity
Animal and in vitro studies have not shown mebendazole to be mutagenic. No evidence of carcinogenesis was seen in rats and mice receiving mebendazole dosages up to 40 mg/kg daily for more than 2 years.
Pregnancy, Fertitlity and Lactation
Mebendazole has been shown to be embryotoxic and teratogenic in rats when given at single oral doses as low as 10 mg/kg. Although there are no adequate and controlled studies to date in humans, the incidence of spontaneous abortion and malformation did not exceed that in the general population in a limited number of women who inadvertently received the drug during the first trimester of pregnancy; no teratogenic risk associated with mebendazole therapy was identified in 170 full-term deliveries. Mebendazole should be used during pregnancy, especially during the first trimester, only when the potential benefits justify the possible risks to the fetus. If the drug is administered during pregnancy, the patient should be informed of the potential hazard to the fetus. Reproduction studies in male and female rats using mebendazole dosages up to 40 mg/kg for 60 days and 14 days prior to gestation, respectively, have not revealed evidence of impaired fertility; however, slight maternal toxicity occurred. Since it is not known if mebendazole is distributed into milk, the drug should be used with caution in nursing women.
Drug Interactions
Anticonvulsants
Limited data suggest that both carbamazepine and phenytoin may enhance the metabolism of mebendazole, probably by inducing hepatic microsomal enzymes, resulting in decreased plasma mebendazole concentrations.This interaction is unlikely to be clinically important in patients receiving mebendazole for the management of intestinal helminth infections; however, use of carbamazepine or phenytoin may prevent an adequate therapeutic response in patients receiving the anthelmintic for the management of extraintestinal infections (e.g., hydatid disease). Pending further accumulation of data, use of alternative anticonvulsant agents (e.g., valproic acid) should be considered in patients receiving mebendazole for extraintestinal infections.
Cimetidine
Preliminary evidence suggests that cimetidine inhibits mebendazole metabolism and may result in increased plasma concentrations of the drug.
Acute Toxcicity
Overdosage of mebendazole may result in GI symptoms lasting up to a few hours. If acute overdosage of mebendazole occurs, vomiting and purging should be induced. Activated charcoal may be administered.
Mechanism of Action
Although the exact mechanism of anthelmintic activity of mebendazole has not been fully elucidated, the drug appears to cause selective and irreversible inhibition of the uptake of glucose and other low molecular weight nutrients in susceptible helminths; inhibition of glucose uptake appears to result in endogenous depletion of glycogen stores in the helminth. Mebendazole does not inhibit glucose uptake in mammals. Mebendazole appears to cause degenerative changes in the intestine of nematodes and in the absorptive cells of cestodes. The principal anthelmintic effect of the drug appears to be degeneration of cytoplasmic microtubules within these intestinal and absorptive cells. Microtubular deterioration results in inhibition of organelle movement and interferes with the absorptive and secretory function. As a result of excessive accumulation of intracellular transport secretory granules, hydrolytic and proteolytic enzymes are released and cause cellular autolysis. This irreversible damage leads to death of the parasite. Mebendazole has no effect on blood glucose concentrations in humans, and examination of the intestine and other organs of treated animals has shown an intact microtubular system and normal subcellular organelles. The presence of food in the digestive tract of the definitive host does not affect the action of the drug during treatment of intestinal helminthic infections. Spectrum Mebendazole is active against certain nematodes (roundworms) pathogenic to humans, including Ancylostoma duodenale (hookworm), Angiostrongylus cantonensis, Ascaris lumbricoides (roundworm), Capillaria philippinensis (Philippine threadworm), Enterobius vermicularis (pinworm), Gnathostoma spinigerum, Necator americanus (hookworm), Strongyloides stercoralis (threadworm), Trichinella spiralis (pork worm), and Trichuris trichiura (whipworm); however, the drug’s activity against S. stercoralis is variable and is usually less than that against other nematodes. Mebendazole has been reported to be filaricidal against Mansonella perstans and Onchocerca volvulus. Mebendazole has also been shown to be active against certain cestodes (tapeworms), including Hymenolepis nana (dwarf tapeworm), Taenia saginata (beef tapeworm), T. solium (pork tapeworm), and Echinococcus granulosus (hydatid cyst).
Pharmacokinetics
Absorption
Mebendazole appears to be minimally absorbed from the GI tract following oral administration. Limited data indicate that about 2-10% of an oral dose is absorbed. Peak plasma concentrations of mebendazole occur approximately 0.5-7 hours after oral administration of the drug and exhibit wide interpatient variation. Following oral administration of multiple doses of mebendazole (40 mg/kg daily) to 2 adults with hydatid cysts, mean peak plasma concentrations of about 0.08 mcg/mL occurred at 0.5-2 hours. Following oral administration of a single 10-mg/kg dose of mebendazole to patients with hydatid cysts in another study, peak plasma concentrations of about 0.02-0. mcg/mL occurred at 1.5-7. hours. Following oral administration of multiple doses of mebendazole (100 mg 2 times daily for 3 days) to several children, peak plasma mebendazole concentrations did not exceed 0.03 mcg/mL and peak plasma concentrations of the 2-amino metabolite of the drug (the major metabolite) did not exceed 0.09 mcg/mL.
Distribution
Mebendazole is highly bound to plasma proteins. It is not known if mebendazole is distributed into milk.
Elimination
The elimination half-life of mebendazole has been reported to be about 2.8-9 hours. Although the exact metabolic fate of mebendazole has not been fully determined, the drug is metabolized via decarboxylation to 2-amino-5(6)-benzimidazolyl phenylketone; this metabolite does not have anthelmintic activity. Approximately 2-10% of an oral dose of mebendazole is excreted in urine within 24-48 hours of administration, principally as unchanged drug and the 2-amino metabolite. The metabolic fate and rate of excretion of unabsorbed mebendazole have not been determined.
Chemistry and Stability
Chemistry
Mebendazole is a synthetic, benzimidazole-derivative anthelmintic agent. The drug is structurally related to albendazole and thiabendazole. Mebendazole occurs as a white to slightly yellow powder and is practically insoluble in water and in alcohol.
Stability
Commercially available mebendazole chewable tablets should be stored at 15-25°C107 in well-closed containers and have an expiration date of 3 years following the date of manufacture.
Preparations
Mebendazole Oral Tablets, chewable 100 mg Mebendazole Tablets, Copley Vermox®, Janssen AHFS DRUG INFORMATION® (2004)
| Dosage forms of Mebendazole: | |||
|---|---|---|---|
| Vermox 100 mg Chewable Tablet | Mebendazole powder | Mebendazole 100 mg tablet chew | Mebendazole 100 mg Chew Tabs |
Organs and Systems
Liver
All benzimidazoles can cause mild and reversible rises in transaminases, but even in high doses withdrawal is justified in only a few patients.
Granulomatous hepatitis with eosinophilia has been attributed with mebendazole.
A 52-year-old man with ascariasis took two 3-day cycles of mebendazole 100 mg bd with a 2-week interval. Within 48 hours of the second course he developed fever (39°C), diarrhea, anorexia, and prostration. Ten days later he had tender hepatomegaly. His liver function tests were abnormal (aspartate transaminase 466 IU/1, alanine transaminase 458 IU/1). The serum alkaline phosphatase and bilirubin were normal and the gamma-glutamyl transferase mildly raised. The white blood cell count was 12.7 x 109/1 with 18% eosi-nophils.
Coagulation was normal. Tests for Hepatitis A, B, and C, cytomegalovirus, and Epstein-Barr virus were all negative. Serum ACE was not raised. Antimitochondrial antibodies were negative but anti-nuclear antibodies and antibodies against smooth muscle were positive. Extensive tests to exclude other causes of granulomatous hepatitis were all negative. A liver biopsy showed multiple granulomata consisting of epithelioid cells, multinucleated giant cells, plasma cells, and lymphocytes.
There was slight fibrosis around the granulomata. There was no evidence of cholestasis. No helminthic ova were found. Ziehl-Nielsen and periodic acid Schiff stains were both negative. After 2 days the fever had subsided without treatment and he felt better. The serum transaminases returned to normal over the next 10 weeks and the eosinophilia disappeared.
Liver damage has been described after treatment with most benzimidazoles, but it is usually cholestatic. The liver damage described in this case was granulomatous. Liver damage after mebendazole in the low dose used in this case is rare, probably because of its poor absorption.
It is more frequent, although still rare, in the higher doses used in the treatment of human echinococcosis.
Urinary tract
Glomerulonephritis has been observed in five patients from Kenya.
Skin
Two cases of exfoliative dermatitis occurred in a total of 131 patients treated. In one Indian case, a fixed drug eruption was attributed to the drug and other forms of rash have been seen.
An outbreak of Stevens-Johnson syndrome has been reported in 52 Filipino overseas contract workers (aged 20-30 years, 50 women) working in China who used mebendazole for helminthic prophylaxis. All took mebendazole at least once after the appearance of rashes and fever. Three women eventually died, primarily due to septicemia.
Side effects
Mebendazole, a benzimidazole, is poorly absorbed from the gut, although it dependably enters cyst fluid; it is therefore most useful for treating intestinal infections and cyst-forming infestations. It is essentially an antihelminthic drug, being effective against hookworm, ascariasis, enterobiasis, and trichuriasis. Mebendazole is effective against enteric Strongyloides but since it is not absorbed it is ineffective against tissue forms. However, it is also effective against Giardia lamblia, while Trichomonas vaginalis is susceptible in vitro. Mebendazole does not interfere with the normal intestinal flora.
Mebendazole has been assessed in a range of doses and durations of treatment. The most usual dose is 100 mg bd for 3 days; absorption is minimal, but there is considerable variation in plasma concentrations; the half-life is 2-9 hours. Much higher doses, up to 60 mg/ kg/day, have been used in inoperable cases of cystic echinococcosis infestation, and then unwanted effects are more common.
Flubendazole is an analogue of mebendazole used in intestinal helminthiasis and hydatid disease. In trials of two-dose oral treatment for intestinal helminthiasis, reactions were mild and uncommon. They consisted of nausea, abdominal pain, dyspepsia, and sleepiness. Subsequent field experience has not suggested that flubendazole differs appreciably from other members of the class as regards adverse effects.
Comparative studies
Echinococcosis
The use of albendazole and mebendazole in patients with hydatidosis has been evaluated in 448 patients with Echinococcus granulosis hydatid cysts who received continuous treatment with albendazole 10-12 mg/kg/day for 3-6 months daily orally in a total dose of (323 patients) twice or mebendazole 50 mg/kg/day. At the end of treatment, 82% of the cysts treated with albendazole and 56% of the cysts treated with mebendazole showed degenerative changes. During long-term follow-up 25% of these cysts showed relapse, which took place within 2 years in 78% of cases. Further treatment with albendazole induced degenerative changes in over 90% of the relapsed cysts, without induction of more frequent or more severe adverse effects, as observed during the first treatment period. Adverse effects during the first treatment period consisted of raised transaminases with albendazole (67 of 323 patients) and mebendazole (16 of 125 patients), and abdominal pain in 12 and 11% respectively. With both drugs, occasional patients experienced headache, abdominal distension, vertigo, urticaria, jaundice, thrombocytopenia, fever, or dyspepsia, but most of these are known manifestations of echinococcus infection. Six of 323 patients taking albendazole withdrew because of adverse effects compared with eight of 125 patients taking mebendazole. It appears that albendazole is more effective than mebendazole in the treatment of hydatid cysts caused by E. granulosis and that both the intensity and the frequency of the usually mild adverse effects are comparable.
In 78 patients with hydatid disease there was a low recurrence rate of hydatid disease (below 3%) after a postoperative prophylactic course of mebendazole 20 mg/kg/day in three divided doses for 3 months. The only adverse effect of mebendazole was excessive loss of hair in two women. The unusual low recurrence rate of hydatid disease after treatment with mebendazole in this study was subsequently questioned and attributed to meticulously careful surgical procedures, with avoidance of spillage of hydatid fluid and complete removal of parasitic components.
General adverse effects
With normal doses (100 mg bd for 3 days) very slight headache, dizziness, and nausea or diarrhea are common; in principle allergy can occur. Mild and reversible rises in transaminases can occur and need to be followed, but even in high doses withdrawal is justified in only a few patients. Neutropenia has been noted and can be severe and persistent. High doses (up to 50-60 mg/kg) can also cause alopecia and cough. Mebendazole has been associated with extra-intestinal migration of Ascaris in heavily infected patients. Apart from the poor therapeutic response obtained in some 25% of cases, drug toxicity (especially at high prolonged dosage) has led to withdrawal in a small proportion of patients. Adverse effects severe enough to lead to withdrawal have included worsening of pre-existing hyperlipidemia (type IV), progressive uremia, and a marked rise in liver enzymes. One individual developed a rash accompanied by a striking rise in serum transaminases, which recurred on subsequent re-exposure. Experience in the treatment of Echinococcus multilocularis infection is similar. One patient with fatal agranulocytosis also had severe, probably unrelated, liver disease. Some 3-4% develop fever, which can be persistent and accompanied by respiratory symptoms and eosinophilia. Other adverse effects include pain over the site of the cyst, allergic reactions, alopecia, glomerulonephritis, and rashes.
Various authors have reported spontaneous rupture of hydatid cysts with mebendazole, and this is probably more frequent than in untreated individuals. Pleural and peritoneal cysts are more likely to rupture.
Evidence of teratogenicity in rats has not been accompanied by reports that it causes harm in human pregnancy, but the WHO recommends avoidance during the first trimester. It is not known if mebendazole enters the breast milk; no adverse effects have been reported but the issue has not been specifically studied.
Mebendazole: Organs and Systems
Susceptibility Factors
Age
Children aged under 2 years who are infected with helminths are currently excluded from treatment with mebendazole and other antihelminthic drugs on the basis of the manufacturer’s instructions. In a double-blind, randomized trial in Tanzania 212 children aged under 2 years were given a total of 653 antihelminthic treatments (317 mebendazole 500 mg; 336 placebo). There were no significant differences in adverse events in the two groups. In the light of the potential nutritional benefit achieved by regular deworming in this age group, the policy that excludes children aged under 2 years from treatment should probably be reconsidered.
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Therapeutic classes of Mebendazole:
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