Albenza (Albendazole)

Albendazole is a synthetic anthelmintic from the benzimidazole group. It is structurally related to thiabendazole and mebendazole and, like mebendazole, is a benzimidazole carbamate derivative. Albendazole is metabolised in the liver to an active metabolite, albendazole sulfoxide, which is responsible for the detectable plasma concentrations of the drug; its systemic anthelmintic activity is thought to be due to this metabolite.

Although the exact way albendazole works has not been fully established, the main anthelmintic effect of benzimidazoles, including albendazole, appears to be their specific, high-affinity binding to free tubulin in parasite cells. This selectively inhibits parasite microtubule polymerisation and microtubule-dependent glucose uptake. Benzimidazole medicines bind to parasite tubulin at much lower concentrations than to mammalian tubulin; they do not inhibit glucose uptake in mammals and do not appear to affect blood glucose levels in humans.

For additional information on this drug until a more detailed monograph is developed and published, consult the manufacturer's product information. It is essential to refer to this information for full details of the usual cautions, precautions and contraindications.

Uses

Cestode (Tapeworm) Infections

Albendazole is used to treat tissue infections caused by the larval forms of certain cestodes (tapeworms), including neurocysticercosis caused by Cysticercus cellulosae, the larval form of Taenia solium (pork tapeworm). Albendazole is also used to treat hydatid disease caused by the larval form of Echinococcus granulosus (dog tapeworm). Other anthelmintics, usually praziquantel, are used to treat intestinal infections caused by adult forms of cestodes.

Neurocysticercosis

Albendazole is used to treat parenchymal neurocysticercosis resulting from active lesions caused by Cysticercus cellulosae, the larval form of Taenia solium (pork tapeworm), preferably together with corticosteroids. Symptoms commonly linked with neurocysticercosis include headaches, seizures and other central nervous system (CNS) effects, thought to result from enlarging active cysticercal lesions or oedema around individual degenerating cysts in the brain parenchyma. Important measures of response to anti-neurocysticercal treatment therefore include improvement in CNS symptoms and radiological response.

The manufacturer states that the safety and efficacy of albendazole in patients with neurocysticercosis caused by Taenia solium (T. solium) were shown by analysis of 3 sets of data, including a compilation of published reports on albendazole use in neurocysticercosis, data from compassionate use patients in the United States (US), and data from one limited clinical study. In studies of patients with susceptible neurocysticercal lesions (that is, non-enhancing cysts with no surrounding oedema on contrast-enhanced CT), albendazole reduced the number of cysts by 74-88%, and complete resolution of all active cysts occurred in 40-70% of patients.

Combining two of the data sets, the published report compilation and the US compassionate use data, the manufacturer states that about 41% of patients were cured, with no symptoms of neurocysticercosis, about 50% were considered improved, and 9% had no change. Corticosteroids are used at the same time to reduce the frequency and severity of nervous system side effects, including cerebrospinal fluid (CSF) reaction syndrome, associated with albendazole treatment for neurocysticercosis. Anticonvulsant treatment may also be needed. The use of anthelmintics, such as albendazole or praziquantel, in the treatment of cysticercosis remains controversial because efficacy has not been proven in controlled studies. Initial treatment of parenchymal disease with seizures should focus on symptom control with anticonvulsants.

Obstructive hydrocephalus is treated with surgical removal of the obstructing cyst or CSF diversion and prednisone; arachnoiditis, vasculitis or cerebral oedema is treated with corticosteroids, such as prednisone or dexamethasone, used together with albendazole or praziquantel. Even when corticosteroids are used, any cysticercocidal drug may cause irreparable damage if used to treat ocular or spinal cysts, and eye examinations should be performed before treatment to rule out intraocular cysts.

Hydatid Disease

Albendazole is used to treat cystic hydatid disease (unilocular hydatid disease) of the liver, lung and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus. Surgery is considered the treatment of choice for hydatid disease when medically feasible, but perioperative treatment with an anthelmintic medicine, such as albendazole, mebendazole or praziquantel, may be indicated in patients having surgical removal of cysts to reduce the risk of daughter cysts spreading during surgery. Ultrasound-guided percutaneous drainage plus albendazole treatment has been effective in managing hepatic hydatid cyst disease.

Albendazole is absorbed to a greater extent, and reaches higher plasma concentrations as its active metabolite, than mebendazole, and some clinicians consider albendazole a drug of choice for treating hydatid cyst disease caused by Echinococcus granulosus (E. granulosus). Risks associated with surgery include operative morbidity, recurrence of cysts, and anaphylaxis or spread of infection due to spillage of cyst fluid.

Preoperative treatment with albendazole may inactivate protoscolices and reduce the chance of cyst recurrence, and postoperative treatment may help prevent secondary spread of the cestode after spontaneous or operative rupture and spillage of cyst contents. The best cysticidal effect of albendazole is achieved before or after surgery when the drug is given in three 28-day treatment courses.

Some clinicians have also recommended albendazole for patients with inoperable, widespread or numerous E. granulosus cysts, or for patients with complex medical problems who are not suitable for surgery. The manufacturer states that because hydatid disease is uncommon, the safety and efficacy of albendazole in patients with hydatid disease caused by E. granulosus were demonstrated by combining accumulated clinical reports from small patient series.

Four sets of data were considered, including data from compassionate use patients in Europe, an analysis of data from published studies, data from Australian compassionate use patients (not evaluable), and data from US compassionate use patients. About 80-90% of patients receiving albendazole in three 28-day cycles had non-infectious cyst contents. About 30-31% of evaluable patients with hydatid disease who received albendazole had a clinical cure, meaning disappearance of cysts, and improvement, defined as a reduction in cyst diameter of at least 25%, was seen in about 40-42% of evaluable patients. About 24% of patients receiving albendazole had no change or were considered worse.

Although albendazole has been used to treat alveolar hydatid disease, another form of hydatid cyst disease caused by Echinococcus multilocularis, surgical excision of the larval mass is the recommended and only reliable treatment for this infection. Continuous albendazole or mebendazole treatment has reportedly been associated with clinical improvement in non-resectable cases, but the manufacturer states that the efficacy of albendazole in treating alveolar hydatid disease caused by E. multilocularis has not been demonstrated in clinical studies.

Nematode (Roundworm) Infections

Ascariasis

Albendazole is used to treat ascariasis caused by Ascaris lumbricoides. Albendazole, mebendazole or pyrantel pamoate are considered the drugs of choice for ascariasis.

Enterobiasis

Albendazole is used to treat enterobiasis caused by Enterobius vermicularis (pinworm). Albendazole, mebendazole or pyrantel pamoate are considered the drugs of choice for enterobiasis.

Filariasis

Albendazole or mebendazole are recommended as the drugs of choice for filariasis caused by Mansonella perstans. Diethylcarbamazine, which in Australia may need to be accessed through a hospital pharmacy or the Therapeutic Goods Administration's Special Access Scheme, or ivermectin, is usually recommended for infections caused by most other filarial worms.

Hookworm Infections

Albendazole is used to treat intestinal hookworm infections caused by Ancylostoma duodenale or Necator americanus, and albendazole, mebendazole or pyrantel pamoate are considered the drugs of choice for these infections. Albendazole is also used to treat cutaneous larva migrans (creeping eruption) caused by dog and cat hookworms. Although cutaneous larva migrans usually resolves on its own over several weeks or months, albendazole, ivermectin or thiabendazole are considered the drugs of choice when treatment is needed. Albendazole, mebendazole or pyrantel pamoate are also considered drugs of choice for eosinophilic enterocolitis caused by Ancylostoma caninum (dog hookworm).

Toxocariasis (Visceral Larva Migrans)

Albendazole is used to treat toxocariasis (visceral larva migrans) caused by Toxocara canis or Toxocara cati (T. cati), the 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 may also be indicated. Treatment may not be effective in ocular larva migrans; inflammation may be reduced with corticosteroid injections and surgery may be needed for secondary damage.

Trichinosis

Albendazole is used to treat trichinosis caused by Trichinella spiralis. Although some clinicians state that albendazole and mebendazole are equally effective for trichinosis, others consider mebendazole the drug of choice and albendazole an alternative. Corticosteroids are usually recommended as well as the anthelmintic, especially when symptoms are severe. Corticosteroids relieve symptoms of the inflammatory reaction and can be lifesaving when the heart or CNS is involved.

Baylisascariasis

Albendazole has been used in a limited number of patients to treat baylisascariasis caused by Baylisascaris procyonis; however, no medicine has been shown to be effective for this infection. Baylisascaris procyonis (B. procyonis), a common roundworm found in the small intestine of raccoons, can cause severe or fatal encephalitis (neural larva migrans) in birds and mammals, including humans, and can also cause ocular and visceral larva migrans in humans. Since 1981, there have been at least 12 cases of severe or fatal encephalitis caused by this roundworm in the US (California (CA), Illinois (IL), Michigan (MI), Minnesota (MN), New York (NY), Oregon (OR), Pennsylvania (PA)), and 10 of these cases occurred in children aged 9 months to 6 years; cases of B. procyonis ocular larva migrans have also been reported in the US. Humans become infected by ingesting B. procyonis eggs after contact with infected raccoon faeces.

Because CNS damage may occur before symptoms develop, treatment started only after symptoms appear often does not improve the outcome. Early treatment may be more effective: if albendazole is started within 1–3 days of possible infection, it may help prevent clinical disease by killing larvae before they enter the CNS.

Immediate treatment is therefore recommended in cases of probable infection, including known exposures such as ingestion of raccoon stool or contaminated soil. Corticosteroid treatment may also be helpful, especially in ocular and CNS infections; ocular baylisascariasis has been treated successfully with laser photocoagulation to destroy the intraretinal larvae. Additional information on baylisascariasis can be obtained from Australian state and territory health departments or other Australian infectious diseases reference resources.

Other Nematode Infections

Albendazole has been used to treat capillariasis caused by Capillaria philippinensis. Mebendazole is considered the drug of choice for capillariasis, and albendazole is considered an alternative. For gnathostomiasis caused by Gnathostoma spinigerum, albendazole, ivermectin or surgical removal is recommended. For gongylonemiasis caused by Gongylonema, surgical removal or albendazole is recommended.

Albendazole is used to treat infections caused by Trichostrongylus. Pyrantel pamoate is considered the drug of choice, and albendazole or mebendazole are alternatives for Trichostrongylus infections. Albendazole is used as an alternative to mebendazole for trichuriasis caused by Trichuris trichiura (whipworm). Albendazole or pyrantel pamoate may be effective for oesophagostomiasis caused by Oesophagostomum bifurcum.

Trematode (Fluke) Infections

For infections caused by Clonorchis sinensis (Chinese liver fluke), albendazole or praziquantel are recommended as the drugs of choice. Other anthelmintics, usually praziquantel, are recommended for all other fluke infections.

Giardiasis

Although metronidazole is generally the drug of choice for giardiasis caused by Giardia lamblia, albendazole may also be effective. In paediatric patients, albendazole may be as effective as metronidazole for treating giardiasis and may cause fewer side effects.

Microsporidiosis

Albendazole has been used in the treatment of microsporidiosis. Microsporidia can cause ocular infections (Encephalitozoon hellem, Encephalitozoon cuniculi (E. cuniculi), Vittaforma corneae), intestinal infections (Enterocytozoon bieneusi, Encephalitozoon intestinalis), and disseminated infections (E. hellem, E. cuniculi, E. intestinalis, Pleistophora, Trachipleistophora, Brachiola vesicularum). Intestinal infections are most common in immunocompromised patients and are being reported increasingly in patients with human immunodeficiency virus (HIV) infection.

Some clinicians recommend albendazole together with fumagillin, which is not routinely commercially available in Australia, for ocular microsporidiosis and also consider albendazole the drug of choice for intestinal infections caused by E. intestinalis and for disseminated microsporidiosis. Although some patients with intestinal microsporidiosis caused by E. intestinalis may respond to albendazole, the organism is not eradicated in all patients and diarrhoea commonly returns after treatment is stopped. Patients with Enterocytozoon bieneusi (E. bieneusi) infections generally do not respond to albendazole.

Dosage and Administration

Administration

Albendazole is taken by mouth with food. Its oral bioavailability appears to increase when it is taken with a fatty meal; when it is given with meals containing about 40 g of fat, plasma concentrations of albendazole sulfoxide are up to 5 times higher than those seen in fasting patients.

Albendazole may harm the fetus and should be used during pregnancy only if the benefits justify the risk and only when no suitable alternative management is available. Women of childbearing age should start treatment only after a negative pregnancy test and should be advised not to become pregnant while taking albendazole or within 1 month after finishing treatment.

Because albendazole has been associated with mild to moderate increases in hepatic enzymes in about 16% of patients receiving the drug in clinical trials, and may cause hepatotoxicity, liver function tests should be performed before each course of albendazole treatment and at least every 2 weeks during treatment. If clinically important increases in liver function test results occur, albendazole should be stopped. Leukopenia has occurred in less than 1% of patients receiving albendazole, and, rarely, granulocytopenia, pancytopenia, agranulocytosis or thrombocytopenia have been reported.

Therefore, blood counts should be performed at the start of, and every 2 weeks during, each 28-day treatment cycle. The manufacturer states that if the total leukocyte count falls, treatment with albendazole may be continued if the decrease is modest and does not progress.

Dosage

Cestode (Tapeworm) Infections Neurocysticercosis

Because of its activity against the pork tapeworm (T. solium), albendazole treatment for neurocysticercosis resulting from active lesions caused by Cysticercus cellulosae, the larval form of T. solium, has been associated with adverse CNS effects, such as seizures and/or hydrocephalus, resulting from inflammatory reactions to damaged intracerebral cysts. Therefore, patients receiving albendazole for neurocysticercosis should receive appropriate corticosteroid and anticonvulsant treatment as needed. Oral or intravenous (IV) corticosteroid treatment should be considered during the first week of albendazole treatment to prevent cerebral hypertension.

Although retinal cysticercosis is rare, patients with neurocysticercosis may have retinal lesions, and destruction of cysticercal lesions by albendazole may cause retinal damage. Therefore, patients should be examined for retinal lesions and, if any are present, the need for treatment should be weighed against the possibility of retinal damage from albendazole use.

For the treatment of neurocysticercosis in adults and children 6 years of age and older and weighing 60 kg or more, the usual dosage of albendazole is 400 mg given twice daily with meals for 8-30 days. For patients weighing less than 60 kg, the usual dosage is 15 mg/kg/day, not to exceed 800 mg daily, given in 2 equally divided doses with meals for 8-30 days. Treatment courses may be repeated as needed.

Hydatid Disease

Surgery is considered the treatment of choice for hydatid disease when medically feasible, and albendazole is given either before or after surgery. When albendazole is used as adjunctive perioperative treatment for hydatid disease, the best killing effect on cyst contents is achieved by giving the drug in three 28-day treatment courses, separated by two 14-day albendazole-free intervals. For the treatment of cystic hydatid disease of the liver, lung or peritoneum caused by the larval form of the dog tapeworm, E. granulosus, in adults or children 6 years of age and older and weighing 60 kg or more, the usual dosage of albendazole is 400 mg twice daily with meals for 28 days, followed by a 14-day albendazole-free interval, for a total of 3 dosage cycles. For patients weighing less than 60 kg, the usual dosage is 15 mg/kg/day, not to exceed 800 mg daily, given in 2 equally divided doses with meals for 28 days, followed by a 14-day albendazole-free interval, for a total of 3 dosage cycles. Some clinicians recommend that adults receive 400 mg of albendazole twice daily and paediatric patients receive 15 mg/kg/day, not to exceed 800 mg daily, for 1-6 months for hydatid cyst disease.

Nematode (Roundworm) Infections Ascariasis

For ascariasis caused by Ascaris lumbricoides, adults and children should receive a single 400 mg dose of albendazole.

Enterobiasis

For enterobiasis caused by Enterobius vermicularis (pinworm), some clinicians recommend that adults and children receive an initial 400 mg dose of albendazole and a second 400 mg dose 2 weeks later.

Filariasis

For filariasis caused by Mansonella perstans, some clinicians recommend that adults and children receive albendazole 400 mg twice daily for 10 days.

Hookworm Infections

For intestinal hookworm infections caused by Ancylostoma duodenale or Necator americanus, or for eosinophilic enterocolitis caused by Ancylostoma caninum (dog hookworm), some clinicians recommend that adults and children receive a single 400 mg dose of albendazole. For cutaneous larva migrans (creeping eruption) caused by dog or cat hookworms, some clinicians recommend that adults and children receive albendazole 400 mg once daily for 3 days.

Toxocariasis (Visceral Larva Migrans)

For toxocariasis (visceral larva migrans) caused by dog and cat roundworms, some clinicians recommend that adults and children receive albendazole 400 mg twice daily for 5 days. However, the optimum duration of treatment is not known, and some clinicians recommend continuing treatment for up to 20 days.

Trichinosis

The recommended dose of albendazole for the treatment of trichinellosis caused by Trichinella spiralis in adults and children is 400 mg twice daily for 8–14 days.

Baylisascariasis

To help prevent clinical disease by killing larvae before they enter the CNS, albendazole should be started as early as possible, ideally within 1–3 days of possible infection, at a dose of 25–50 mg/kg/day for 10 days. If infection is considered likely, treatment should begin immediately and should not be delayed until symptoms appear.

Other Nematode Infections

For capillariasis caused by Capillaria philippinensis, some clinicians recommend albendazole 400 mg once daily for 10 days for adults and children. Adults and children with gnathostomiasis caused by Gnathostoma spinigerum should receive albendazole 400 mg twice daily for 21 days, and adults and children with gongylonemiasis caused by Gongylonema should receive 10 mg/kg/day for 3 days.

For infections caused by Trichostrongylus, adults and children should receive a single 400 mg dose of albendazole. Adults and children with trichuriasis caused by Trichuris trichiura (whipworm) should receive albendazole 400 mg once daily for 3 days. Trematode (Fluke) Infections For infections caused by Clonorchis sinensis (Chinese liver fluke), some clinicians recommend albendazole 10 mg/kg/day for 7 days for adults and children.

Giardiasis

For giardiasis caused by Giardia lamblia in adults and children, albendazole has been given at a dose of 400 mg daily for 5 days. Microsporidiosis For ocular or disseminated microsporidiosis, some clinicians recommend albendazole 400 mg twice daily for adults. For intestinal microsporidiosis caused by Encephalitozoon intestinalis, some clinicians recommend albendazole 400 mg twice daily for 21 days for adults.

Albendazole Side Effects

Albendazole, a benzimidazole derivative closely related to mebendazole, is used to treat helminth infections such as gastrointestinal roundworm infections, hydatid disease, neurocysticercosis, cutaneous larva migrans and strongyloidiasis. Provided an adequate concentration is reached within the cyst, it is scolicidal. In high doses given for prolonged periods or in cycles, it is effective in echinococcosis, in which it is given at 10 mg/kg/day for 4 weeks, repeated in six cycles with 2-week rest periods between each cycle, although even at this high dose only about one-third of patients achieve a complete cure, while around 70% have a partial response. Albendazole is also active against Pneumocystis jiroveci and is effective for prophylaxis and treatment in immunosuppressed mice. In hydatid disease, a combination of albendazole and praziquantel is effective when either medicine has failed when used alone.

Albendazole: Observational and Comparative studies

Placebo-controlled studies

Albendazole has been used in the treatment and prophylaxis of microsporidiosis in patients with acquired immunodeficiency syndrome (AIDS). In a small double-blind, placebo-controlled trial from France, the efficacy and safety of albendazole were studied in four patients treated with albendazole 400 mg twice daily for 3 weeks and in four patients given placebo. Microsporidia were cleared in all patients given albendazole, but in none of those given placebo. Afterwards, all eight patients were again randomised to receive either maintenance treatment with albendazole 400 mg twice daily or no treatment for the next 12 months; none of the three patients taking maintenance treatment had a recurrence, while three of the five who had no maintenance therapy developed a recurrence. During the double-blind part of the trial there were no serious side effects in the patients who took albendazole, although two complained of headache, one of abdominal pain, one had raised transaminase activities, and one had thrombocytopenia. However, half the patients were also taking anti-HIV triple therapy, which makes it difficult to assess these abnormalities. The authors concluded that the side effects were not serious and did not interfere with maintenance therapy. The tentative conclusion from these findings is that albendazole may be useful in the treatment of microsporidiosis, which in patients with AIDS often leads to debilitating chronic diarrhoea and is difficult to treat.

Use in non-infective conditions

The efficacy of albendazole has been evaluated in a small number of patients with either hepatocellular carcinoma or colorectal cancer with hepatic metastases that were refractory to other forms of treatment. Apart from haematological and biochemical indices, the tumour markers carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) were measured to monitor treatment efficacy. One other patient with a neuroendocrine cancer and mesothelioma was treated on a compassionate basis and monitored only for side effects. Albendazole was given by mouth at 10 mg/kg/day in two divided doses for 28 days. Albendazole reduced CEA in two patients and, in the other five patients with measurable tumour markers, serum CEA or AFP was stabilised in three. In the seven patients who completed this pilot study, albendazole was well tolerated and there were no significant changes in any haematological, kidney, or liver function tests. However, three patients were withdrawn because of severe neutropenia, which resulted in the death of one. Neutropenia was more frequent than is usually seen in the treatment of hydatid disease. The authors speculated that this may relate to reduced metabolism in patients with liver cancer or liver metastases, leading to unmetabolised drug entering the circulation.

General adverse effects

As with other antihelminthic drugs, the general side effects of albendazole can reflect destruction of the parasite rather than a direct effect of the drug; fever is likely to occur, even in the absence of other problems. Albendazole was well tolerated in 30-day courses of 10-14 mg/kg/day separated by 2-week intervals.

Its side effects are similar to those of mebendazole and may be more common because absorption is better and more reliable.

The direct side effects of albendazole are few and usually minor, and include gastrointestinal upset, dizziness, rash, and alopecia, which usually do not require the medicine to be stopped. Early fever and neutropenia can also occur. Cyst rupture can also occur, as with mebendazole. About 15% of patients treated with higher doses of albendazole develop raised serum transaminases, so careful monitoring is needed and treatment sometimes has to be stopped after prolonged use. Careful monitoring of leukocyte and platelet counts is also indicated. The possibility of teratogenicity and embryotoxicity shown in animal studies suggests that the drug should be avoided in pregnancy.

Second-Generation Effects Teratogenicity

It has been emphasised that albendazole is teratogenic in animals and should not be used in pregnancy.

Drug-Drug Interactions

Antiepileptic drugs

The pharmacological interactions of the antiepileptic drugs phenytoin, carbamazepine, and phenobarbital with albendazole have been studied in 32 adults with active intraparenchymatous neurocysticercosis:

• nine patients took phenytoin 3-4 mg/kg/day;
• nine patients took carbamazepine 10-20 mg/kg/day;
• five patients took phenobarbital 1.5-4.5 mg/kg/day;
• nine patients took no antiepileptic drugs.

All were treated with albendazole 7.5 mg/kg every 12 hours for 8 consecutive days. Phenytoin, carbamazepine, and phenobarbital all induced the oxidative metabolism of albendazole to a similar extent in a non-enantioselective manner. As a result, there was a significant reduction in the plasma concentration of the active metabolite of albendazole, albendazole sulfoxide.

Cimetidine

The poor intestinal absorption of albendazole, which may be increased by a fatty meal, contributes to difficulty in predicting its therapeutic response in echinococcosis. The effect of taking cimetidine at the same time on the systemic availability of albendazole has been studied in six healthy men. After an overnight fast, a single oral dose of albendazole (10 mg/kg) was given on an empty stomach with water, a fatty meal, grapefruit juice, or grapefruit juice plus cimetidine. The systemic availability of albendazole was reduced by cimetidine. There were no adverse events. These results are consistent with presystemic metabolism of albendazole by cytochrome P450 3A4 (CYP3A4).

Albendazole: Organs and Systems

Nervous system

When used to treat neurocysticercosis, albendazole (like praziquantel) can cause a CSF syndrome characterised by fever, headache, meningism, and worsening of some or many of the neurological signs of the disease; this is thought to be due to a local reaction to dying and dead larvae and can be reduced by prednisone.

Since neurocysticercosis is a neurological infection, it is not surprising that treatment with any drug can make some neurological reactions to the drug, or to the death of the parasite, particularly marked. For example, with a dose of 1.5 mg/kg continued for some time in cases of neurocysticercosis, most patients initially develop intolerance in the form of headache, vomiting, fever, and occasionally diplopia and meningeal irritation. Even shorter and less intensive treatment has produced similar effects. However, all of these symptoms are probably due to the death of the parasite, and if therapy is continued they usually disappear within a few days. Nevertheless, they can be alarming and require treatment. Data from large studies mention somnolence and even transient hemiparesis as occasional side effects.

Very rarely, in neurocysticercosis, the reaction of the nervous system to the death of the parasite is extremely violent. In one case, cerebral oedema resulted in permanent neurological damage, while other patients have developed hydrocephalus or acute intracranial hypertension requiring treatment, for example with glucocorticoids or mannitol.

Albendazole has sometimes worsened extrapyramidal disorders or triggered seizures in patients with previous epileptic symptoms. The risk of intracranial hypertension has led some to suggest that glucocorticoids should be given preventively when using albendazole in neurocysticercosis; however, dexamethasone can interact with albendazole, increasing its plasma concentrations, and it is not clear whether this might cause new problems.

Encephalopathy is an adverse event related to treatment of Loa loa (L. loa) with diethylcarbamazine or ivermectin, and it has also been linked to albendazole.

A 55-year-old woman from Cameroon took oral albendazole 200 mg twice daily for a symptomatic L. loa infection with microfilaraemia of 152 microfilariae/ml and a Mansonella perstans infection of 133 microfilariae/ml. Three days after starting treatment she developed encephalopathy. Albendazole was stopped and she recovered without any specific treatment within the next 16 hours. On day 4, the L. loa microfilarial count was 29 microfilariae/ml.

The clinical presentation, the interval after starting treatment, the course of the episode, and the results of cerebrospinal fluid analysis and electroencephalography in this case were similar to those seen in cases of encephalopathy following treatment of L. loa with ivermectin or diethylcarbamazine. However, pretreatment filaraemia was relatively low and L. loa microfilariae were not detectable in the cerebrospinal fluid. This suggests that pre-existing conditions might increase susceptibility to encephalopathy.

Sensory systems

Allergic conjunctivitis was seen in cases of industrial occupational skin reactions to albendazole.

Hematologic

There have been various reports of bone marrow depression. In one study, two of 20 patients had a reversible fall in leukocyte count. Pancytopenia, reversible on withdrawal, has been documented in an elderly woman. Even with high doses, neutropenia occurs in under 1% of cases. In older literature, an occasional haematological death was reported.

Megakaryocytic thrombocytopenia attributed to albendazole has been reported.

A 25-year-old woman who had been taking albendazole 13 mg/kg/day for 5 months for hepatic and pulmonary echinococcosis developed fatigue, bleeding gums and prolonged menstrual bleeding. She had ecchymoses and petechiae on her legs, marked thrombocytopenia (10 × 10⁹/L), mild iron-deficiency anaemia and a normal leukocyte count. No antiplatelet antibodies were detected. Bone marrow aspiration showed an absence of megakaryocytes, with normal granulocytes and mild erythroid hyperplasia. Cytogenetic analysis of the bone marrow showed a normal karyotype and immunophenotype. Albendazole was discontinued and oral iron was prescribed. At follow-up 2 months later, all laboratory abnormalities had resolved.

Gastrointestinal

With a single oral dose of albendazole 400 mg, there is usually little more in the way of side effects than mild gastrointestinal disturbances, notably epigastric pain or dry mouth, occurring in only about 6% of patients in some large series; a few patients have abdominal pain. With higher doses, irritation of the central nervous system can lead to nausea and vomiting.

Diarrhoea occurs in a few patients taking albendazole and is usually mild. However, a typical case of pseudomembranous colitis has been documented, although the patient also had AIDS and intestinal microsporidiosis and had taken a number of other drugs; the complication responded to vancomycin.

Liver

Even with single low doses, a transient increase in transaminase activities has been repeatedly reported, generally affecting up to 13-20% of patients taking albendazole. At higher doses, some evidence of moderate hepatitis has been claimed to be present in almost all patients, but in one series using high doses of albendazole or mebendazole for echinococcosis only 17% had a generally slight increase in serum transaminases, and a fair number of these had pre-existing liver disorders. Like various other side effects, the increase in transaminases may be due to breakdown of liver cysts; it is almost always reversible and is usually not a reason to stop treatment; it does not become more marked during long-term treatment. Very occasionally, a person develops jaundice or some other sign of hepatitis.

Skin

A generalised rash has sometimes been seen in patients taking albendazole, and skin complications, including urticaria and contact dermatitis, are a potential problem in employees in the pharmaceutical industry if they have heavy exposure to the drug.

A 38-year-old woman with cough, eosinophilia, and pulmonary infiltrates due to visceral larva migrans from Toxocara canis infection took albendazole 600 mg for 8 weeks and developed slight transient skin eruptions.

Stevens-Johnson syndrome was reported in a man who took albendazole 400 mg/day for toxocariasis.

Hair

There are various well-documented reports of reversible alopecia in patients taking albendazole, which in one study occurred in 2% of cases and in another study in one case out of 20.

• Severe alopecia has been described in a child aged almost 3 years who took albendazole 400 mg/day for 3 days; 2 months later alopecia developed and resolved within 1 month.
• When one woman took 400 mg twice daily for 10 months for hydatid disease, she lost much of her hair; no other likely cause could be identified, and her hair growth recovered when the drug was stopped.

Oddly, however, a fair proportion of patients, when specifically asked, seem to report that their hair growth actually improved during treatment.

Musculoskeletal

Myalgia and arthralgia can occur in patients taking albendazole. However, these symptoms are often features of the condition being treated.