Albendazole DRUG STUDIES

See also Benzimidazoles Observational studies

Ankylostomiasis
Albendazole has been used in the treatment of human
GENERAL INFORMATION hookworm and trichuriasis. In a mass-treatment report
from Western Australia 295 individuals in a remote rural
The benzimidazole antihelminthic drugs albendazole and area were treated with albendazole 400 mg/day for 5 days
mebendazole (qv) are commonly used to treat soil- because of possible Giardia lamblia and hookworm infec-
transmitted helminth infections, such as gastrointestinal tions [6]. The 37% prevalence of Giardia fell to 12%
roundworms, hydatid disease, neurocysticercosis, larva between days 6 and 9, but rose again to 28% between
migrans cutanea, and strongyloidiasis [1–3]. They bind to days 18 and 30. The effect on hookworms (Ankylostoma
nematode b tubulin and inhibit parasite microtubule poly- duodenale) was more pronounced and more sustained
merization, which causes death of adult worms after a few with a reduction of the pretreatment prevalence of hook-
days. Although both albendazole and mebendazole are worm infections from 76% before treatment to 0% after
broad-spectrum antihelminthic drugs, their use differs 3–4 weeks. The tolerability of the drug was judged to be
substantially in clinical practice. Both are effective against excellent by 89%, good by 1%, and moderately good by
ascariasis in a single dose. In hookworm infections, how- 1%, while 9% gave no response. Adverse effects were
ever, a single dose of mebendazole is associated with a low reported by five individuals and consisted of mild abdom-
cure rate and albendazole is more effective. Conversely, a inal pain (n ¼ 2), mild or moderate diarrhea (n ¼ 2), mod-
single dose of albendazole is not effective in many cases of erate fever (n ¼ 1), and weakness (n ¼ 1).
trichuriasis. For both trichuriasis and hookworm infection,
several doses of benzimidazoles are commonly needed.
Provided that an adequate concentration is attained
within the cyst, it is scolicidal. In high doses given for Ascariasis
prolonged periods or cyclically, it is effective in echino- The efficacy of 2 years of mass chemotherapy against
coccosis, in which it is given in a dosage of 10 mg/kg/day ascariasis has been evaluated in Iran [7]. A single dose of
for 4 weeks, repeated in six cycles with 2-week rest periods albendazole 400 mg was given at 3-month intervals for 2
between each cycle, although even with this high dose only years to every person, except children under 2 years of age
about one-third of patients enjoy a complete cure, some and pregnant women. After 2 years of treatment the prev-
70% having a partial response. Albendazole is also active alences, based on 2667 post-treatment samples, had fallen
against Pneumocystis jirovecii, and is effective in prophy- (Table 1). There were no adverse effects of mass treat-
laxis and treatment in immunosuppressed mice [4]. In ment with albendazole.
hydatid disease a combination of albendazole and prazi-
quantel is effective when either agent has failed when used
alone [5].
Another important difference between albendazole and Echinococcosis
mebendazole is that mebendazole is poorly absorbed from Hydatid disease is a common zoonosis caused by the larval
the gastrointestinal tract. For this reason the therapeutic cysts of Echinococcus granulosus. Hydatid cysts most
action is largely directed at intraluminal (adult) worms. commonly form in the liver, but can occur in any organ.
Albendazole is better absorbed, especially when it is taken The management and operative complications in 70
with a fatty meal. It is metabolized in the liver to a sulf- patients with hydatid disease aged 10–78 years have been
oxide derivative, which is highly distributed to the tissues. studied retrospectively to assess the impact of albendazole
It is therefore used to treat disorders caused by tissue- and praziquantel compared with surgery [8]. In all, 39
migrating larvae, such as visceral larva migrans caused patients received albendazole and praziquantel in combi-
by Toxocara canis. Systemic adverse effects, such as nation and 19 received albendazole alone; none was trea-
those on the liver and bone marrow, are usually rare ted with praziquantel alone. The combined use of
with benzimidazoles in the doses used to treat soil- albendazole and praziquantel preoperatively significantly
transmitted helminth infections. However, transient reduced the number of cysts that contained viable proto-
abdominal pain, diarrhea, nausea, dizziness, and headache scolices. During the 12-year follow-up period an initial 3
can occur. Since deworming programmes in endemic months of drug treatment (albendazole throughout and
regions clearly improve child health and education as praziquantel for 2 weeks), re-assessment, followed by
well as reducing the burden of disease attributed to soil- either surgery or continuation with chemotherapy was
transmitted helminths, the use of these drugs is not limited found to be a rational treatment algorithm. In 11 patients
to treatment of symptomatic infections, but also for pre- albendazole, given for a median of 3 months at a dose of
vention by mass deworming programmes of morbidity in 400 mg bd, had adverse effects: five patients developed
children living in endemic areas. Concerns about the sus- nausea and six had abnormal liver function tests. Therapy
tainability of periodic deworming with benzimidazoles was withdrawn in two patients owing to altered liver
and the emergence of resistance have prompted efforts function.
to develop and test new control tools (such as plant cyste- The efficacy of albendazole emulsion has been studied
ine proteinases from various sources of latex-bearing in 212 patients with hydatid disease of the liver, aged 4–82
plants and fruits). years [9]. Two regimens of albendazole were given for a

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 Albendazole 103
Table 1 Changes in prevalences of helminthic infections in patients treated with albendazole [5]

Number (%) of positive tests before Number (%) of positive tests after
Helminth treatment (n ¼ 3098) treatment (n ¼ 2667)

Ascaris 1198 (39%) 196 (7.4%)

lumbricoides
Trichuris trichiura 22 (0.7%) 5 (0.2%)
Hymenolepis nana 63 (2%) 49 (1.8%)

variable period (3 months to more than 1 year); 67 adults ivermectin-related encephalopathy might be prevented.
received albendazole 10 mg/kg/day and 145 adults In 125 patients with Loa loa microfilariasis the effect of
received 12.5 mg/kg/day. The overall cure rate was 75%. albendazole (800 mg/day for three consecutive days) or
In the follow-up study the recurrence rate was 10%. The multivitamin tablets on Loa loa microfilarial load and
highest cure rate was observed in those who received the occurrence of encephalopathy were studied [11]. Loa
albendazole 12.5 mg/kg/day for 9 months. At the start of loa microfilarial loads were followed for 9 months. There
therapy about 15% of the patients had mild pruritus, rash, was no significant change in the overall microfilarial loads
and transient gastric pain, which resolved without specific among those treated with albendazole, although the loads
therapy. Two patients had alopecia. There were frequent in patients with more than 8000 microfilariae/ml tended to
rises in serum transaminase activities in both groups but fall more progressively during the first 3 months of follow-
not to above 30–50 IU/l, except in six patients, who had up. There were no cases of encephalopathy. The main
values above 200 IU/l. In two patients albendazole was adverse effects reported were itching (in eight patients
withdrawn because of vomiting. In one patient who took taking albendazole and seven taking multivitamins),
12.5 mg/kg/day severe adverse effects, such as anorexia, abdominal pain (two taking albendazole), and diarrhea
jaundice, anemia, edema, and hypoproteinemia, devel- (one taking albendazole, two taking multivitamins); over-
oped, necessitating withdrawal. Reintroduction of alben- all analysis showed no significant difference in these
dazole 10 mg/kg/day was uneventful. events between the groups. Albendazole was associated
The use of albendazole and mebendazole in patients with modest but significantly raised plasma transaminase
with hydatidosis has been evaluated in 448 patients with activities.
E. granulosis hydatid cysts who received continuous treat-
ment 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 [10]. At the end of treatment, Neurocysticercosis
82% of the cysts treated with albendazole and 56% of the In a report on the use of albendazole 15 mg/kg/day in two
cysts treated with mebendazole showed degenerative divided doses for 14 days in the treatment of persistent
changes. During long-term follow-up 25% of these cysts neurocysticercosis [12], adverse reactions were monitored
showed relapse, which took place within 2 years in 78% of in 43 patients with seizures and a solitary cysticercal cyst,
cases. Further treatment with albendazole induced degen- who had not been treated before. In all patients CT scans
erative changes in over 90% of the relapsed cysts, without confirmed the presence of a solitary cyst less than 2 cm in
induction of more frequent or more severe adverse effects, diameter. Antiepileptic treatment was continued. In seven
as observed during the first treatment period. Adverse patients dexamethasone 8 mg/day in four divided doses
effects during the first treatment period consisted of raised was given for the first 5–7 days after the start of treatment.
transaminases with albendazole (67 of 323 patients) and Follow-up CT scans at 4–10 weeks after the start of treat-
mebendazole (16 of 125 patients), and abdominal pain in ment showed responses in 20 patients, with complete dis-
12% and 11% respectively. With both drugs, occasional appearance in seven patients and a reduction to 50% of
patients experienced headache, abdominal distension, the pretreatment size in the other 13. There were adverse
vertigo, urticaria, jaundice, thrombocytopenia, fever, or effects in 15 patients, with a maximum on the fifth day
dyspepsia, but most of these are known manifestations of after the start of treatment. Six patients had severe head-
Echinococcus infection. Six of 323 patients taking alben- aches, 11 had partial seizures, and 2 had epileptic seizures
dazole withdrew because of adverse effects compared with and severe postictal hemiparesis that persisted for a week
eight of 125 patients taking mebendazole. It appears that or more. Because of these serious adverse effects treat-
albendazole is more effective than mebendazole in the ment was discontinued in seven patients and dexametha-
treatment of hydatid cysts caused by E. granulosis and sone was added in those patients who were not already
that both the intensity and frequency of the usually mild taking it, although its use proved questionable. Adverse
adverse effects are comparable. effects were seen in three of seven patients who took
prophylactic steroid therapy and in 12 of 36 patients who
did not.
Albendazole was effective in neurocysticercosis in an
Filariasis optimal dosage of 15 mg/kg/day divided in two doses every
Treatment of patients with high Loa loa microfilaremia is 12 hours for 8 days [13]. It was generally well tolerated,
sometimes complicated by an encephalopathy, suggested although several patients had adverse reactions during the
to be related to a rapid killing of large number of Loa loa first few days after the start of treatment, consisting of
microfilariae. If the Loa loa microfilarial count could be headache, vomiting, and exacerbation of neurological
reduced more slowly, before ivermectin is distributed, symptoms caused by an inflammatory reaction to antigens

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104 Albendazole

from degenerating cysts, necessitating the concomitant treatment with albendazole 10–12 mg/kg/day for 3–6
use of glucocorticoids. In very large cysticerci, or cysticerci months daily orally in a total dose of (323 patients) twice
located in risky areas like the brainstem, these reactions or mebendazole 50 mg/kg/day [10]. At the end of treat-
may rarely be life-threatening. ment, 82% of the cysts treated with albendazole and 56%
of the cysts treated with mebendazole showed degenera-
tive changes. During long-term follow-up 25% of these
Protozoal infections cysts showed relapse, which took place within 2 years in
78% of cases. Further treatment with albendazole induced
The efficacy of albendazole 800 mg bd for 14 days for per-
degenerative changes in over 90% of the relapsed cysts,
sistent diarrhea due to cryptosporidiosis (n ¼ 10), isosporia-
without induction of more frequent or more severe
sis (n¼ 54), or microsporidiosis (n ¼ 23) has been studied in
adverse effects, as observed during the first treatment
153 HIV-positive patients [14]. Albendazole reduced the
period. Adverse effects during the first treatment period
burden of protozoal infection and promoted mucosal recov-
consisted of raised transaminases with albendazole (67 of
ery in 87 patients who had a complete clinical response. Two
323 patients) and mebendazole (16 of 125 patients), and
patients reported nausea and vomiting. One patient devel-
abdominal pain in 12% and 11% respectively. Headache
oped leukopenia (1.9  109/l) after treatment and four
occurred in eight patients taking albendazole and three
patients developed thrombocytopenia (51–98  109/l).
taking mebendazole, abdominal distension in seven and
five patients, vertigo in five and one, urticaria in five and
three, jaundice in one and one, thrombocytopenia in two
Toxocariasis and none, fever in three and none, dyspepsia in two and
The efficacy of albendazole plus prednisolone has been four, and tachycardia in two and none. Six of 323 patients
studied in five patients aged 11–72 years with ocular tox- taking albendazole withdrew because of adverse effects
ocariasis [15]. All had uveitis and retinochoroidal granu- compared with eight of 125 patients taking mebendazole.
lomas. Their symptoms had persisted for a mean of 14 It appears that albendazole is more effective than meben-
months (range 3 days to 24 months). The adults were dazole in the treatment of hydatid cysts caused by
treated with albendazole 800 mg bd for 2 weeks plus pred- E. granulosis and that both the intensity and frequency
nisolone starting at 1.5 mg/kg/day tapering over 3 months. of the usually mild adverse effects are comparable.
The children were treated with 400 mg bd for 2 weeks plus
prednisolone 1.0 mg/kg/day. All tolerated the therapy well
without adverse effects. In particular, there were no sig-
Neurocysticercosis
nificant hypersensitivity reactions to dying Toxocara lar-
vae. The uveitis resolved in all cases and there were no The treatment of subarachnoid and intraventricular neu-
relapses. After treatment, all the granulomas had disap- rocysticercosis is controversial. In a randomized trial, 36
patients with subarachnoid and intraventricular cysticer-
peared, leaving heavily pigmented chorioretinal scars
without loss of vision. cosis were assigned to albendazole 15 mg/kg/day (n ¼ 16)
or 30 mg/kg/day (n ¼ 20) plus dexamethasone for 8 days
[17]. The results were in favor of the higher dose, with
larger cyst reduction on MRI scans at 90 and 180 days and
Comparative studies higher albendazole sulfoxide concentrations in the
plasma. A single dose was insufficient in intraventricular
Ascariasis
and giant cysts. Adverse effects were similar in the two
See below under Trichuriasis groups. Three patients in each group had new headaches
or an increase in headaches, one in each group had sei-
zures, and one had focal paresthesia. Rash and hyperther-
Echinococcosis mia occurred in two patients taking high-dose albendazole
Human hydatid disease is caused by the metacestode of and each occurred in one patient taking low-dose alben-
Echinococcus granulosus. There are few data on the treat- dazole. Six patients who took low-dose albendazole and
ment of pulmonary hydatid disease in children. Mebenda- nine who took the high dose developed a leukocytosis or
zole and albendazole have been evaluated in 82 children increased alanine transaminase activities to over three
with a total of 102 pulmonary hydatid cysts [16]. Mebenda- times the upper limit of normal. These laboratory abnor-
zole was given as 50 mg/kg/day in three divided doses and malities had disappeared by 30 days. One patient devel-
albendazole was given as 10 mg/kg/day in two divided doses oped glucocorticoid-related hyperglycemia.
continuously or in cycles consisting of 4 weeks of treatment
alternating with 2-week drug-free intervals. The duration of
treatment was 1–36 months. While taking benzimidazoles Pediculosis capitis
eight patients had raised liver enzymes, three had rash, and
Pediculosis capitis, caused by head lice, is one of the most
one had neutropenia; all were reversible on withdrawal.
common human ectoparasitic infections, infesting school-
children of all socioeconomic groups. In 150 children, the
usefulness of albendazole was studied in the treatment of
Hydatidosis pediculosis capitis in combination with 1% permethrin or
The use of albendazole and mebendazole in patients with alone [18]. Group 1 (n ¼ 30) took a single dose of alben-
hydatidosis has been evaluated in 448 patients with dazole 400 mg; group 2 (n ¼ 30) took albendazole 400 mg
E. granulosis hydatid cysts who received continuous for 3 days; group 3 (n ¼ 30) used permethrin 1%; group 4

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 Albendazole 105

(n ¼ 30) used permethrin 1% and took a single dose of the efficacy and safety of treatment with albendazole
albendazole 400 mg; and group 5 (n ¼ 30) used permethrin was studied in four patients treated with albendazole
1% and took albendazole 400 mg for 3 days. Those who 400 mg bd for 3 weeks and in four patients treated with
took albendazole also took a dose of albendazole 400 mg 1 placebo. Microsporidia were cleared in all patients given
week later. The success rates after 2 weeks were 62%, albendazole but in none of those given placebo. After-
67%, 80%, 85%, and 82% respectively. There were no wards all eight patients were again randomized to receive
significant differences among the five groups. The results either maintenance treatment with albendazole 400 mg bd
suggested that albendazole is effective against pediculosis or no treatment for the next 12 months; none of the three
capitis and that there is no synergistic effect between patients taking maintenance treatment had a recurrence,
albendazole and 1% permethrin. Adverse effects were while three of the five who took no maintenance therapy
not reported in this study. developed a recurrence. During the double-blind part of
the trial there were no serious adverse effects in the
patients who took albendazole, although two complained
of headache, one of abdominal pain, one had raised trans-
Trichuriasis aminase activities, and one had thrombocytopenia. How-
In a randomized trial in Mexico [19] 622 children with ever, half the patients were also taking anti-HIV triple
Trichuris were randomized to either albendazole 400 mg/ therapy, which makes it difficult to assess these abnormal-
day for 3 days, one dose of albendazole 400 mg, or one ities. The authors concluded that the adverse effects were
dose of pyrantel 11 mg/kg. The aim was to study efficacy not serious and did not hinder maintenance therapy. The
and the effects on growth. After three courses at 1 year the tentative conclusion derived from these findings is that
level of infection with Trichuris was reduced by 99% in the albendazole may be useful in the treatment of microspor-
3-day albendazole treatment group, by 87% in the single- idiosis, which in patients with AIDS often leads to debil-
dose albendazole treatment group, and by 67% in the itating chronic diarrhea and is difficult to treat.
pyrantel group. There were no significant differences in
the increases in height, weight, or arm circumference, but
contrary to expectations there was a lower increase in the
thickness of the triceps skin fold in those given 3-day Use in non-infective conditions
courses of albendazole. This was only found in the patients
with lower pretreatment Trichuris stool egg counts. These The efficacy of albendazole has been evaluated in a few
findings suggest that although elimination of Trichuris patients with either hepatocellular carcinoma (n ¼ 1) or
may promote growth in children, albendazole in a dose colorectal cancer and hepatic metastases refractory to
of 1200 mg/kg every 4 months may have an independent other forms of treatment (n ¼ 8) [23]. Apart from hemato-
negative effect on growth. In an accompanying commen- logical and biochemical indices, the tumor markers carci-
tary [20] it was concluded that the suggestion that rela- noembryonic antigen (CEA) and alpha-fetoprotein (AFP)
tively high doses of albendazole may affect growth were measured to monitor treatment efficacy. One other
deserves study, but that this possible effect must be patient with a neuroendocrine cancer and a mesothelioma
weighed against the negative effect of prolonged helmin- was treated on a compassionate basis and only monitored
thic infestation on children’s health, growth, and cognitive for adverse effects. Albendazole was given orally in a dose
function. However, it is unlikely that high-dose treatment of 10 mg/kg/day in two divided doses for 28 days. Alben-
will be standard in mass-treatment campaigns, and these dazole reduced CEA in two patients and in the other five
results should not deter the use of single-dose albendazole patients with measurable tumor markers, serum CEA or
in mass-treatment programs in high-risk populations. AFP was stabilized in three. In the seven patients who
In 110 children with ascariasis or trichuriasis the efficacy completed this pilot study, albendazole was well tolerated
of a single dose of albendazole 400 mg has been compared and there were no significant changes in any hematologi-
with that of nitazoxanide 100 mg bd for 3 days in children cal, kidney, or liver function tests. However, three patients
aged 1–3 years and 200 mg bd for 3 days in children aged were withdrawn because of severe neutropenia, which
4–11 years [21]. Nitazoxanide cured 89 and 89% of the resulted in the death of one. Neutropenia was more fre-
cases of ascariasis and trichuriasis respectively. Albenda- quent than is usually experienced in the treatment of hyda-
zole cured 91 and 58% of the cases of ascariasis and trichur- tid disease. The authors speculated that this may relate to
iasis respectively. Abdominal pain (n¼ 9), nausea (n ¼ 1), reduced metabolism in patients with liver cancer or liver
diarrhea (n¼ 2), and headache (n ¼ 1) were reported as metastases, leading to the passage of unmetabolized drug
mild adverse effects in 105 patients who took nitazoxanide, into the circulation.
and abdominal pain (n¼ 1), nausea (n ¼ 1), and vomiting
(n ¼ 1) were reported as adverse effects in 54 patients who
took albendazole. All the adverse events were mild and
transient and drug withdrawal was not necessary. General adverse effects and adverse
reactions
As with other antihelminthic drugs, the general adverse
effects of albendazole can reflect the destruction of the
Placebo-controlled studies
parasite rather than a direct action of the drug; pyrexia is
Albendazole has been used in the treatment and prophy- likely to be seen, even in the absence of other problems.
laxis of microsporidiosis in patients with AIDS. In a small, Albendazole was well tolerated in 30-day courses of
double-blind, placebo-controlled trial from France [22] 10–14 mg/kg/day separated by 2-week intervals.

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106 Albendazole

Its adverse effects are similar to those of mebendazole has led some to suggest that glucocorticoids should be
and are possibly more common because of better and given preventively when using albendazole in neurocysti-
more reliable absorption. cercosis [30]; however, dexamethasone can interact with
The direct adverse effects of albendazole are few and albendazole, increasing its plasma concentrations [31],
usually minor, and consist of gastrointestinal upsets, diz- and it is not clear whether this might produce new
ziness, rash, and alopecia, which usually do not require problems.
drug withdrawal. Early pyrexia and neutropenia can also Encephalopathy is an adverse event related to the treat-
occur. Cyst rupture can also occur, as with mebendazole. ment of Loa loa with diethylcarbamazine or ivermectin,
About 15% of patients treated with albendazole at and it has also been related to albendazole [13].
higher doses develop raised serum transaminases, neces-  A 55-year-old woman from Cameroon took oral albendazole
sitating careful monitoring and sometimes withdrawal of 200 mg bd for a symptomatic Loa loa infection with microfilar-
treatment after prolonged use. Careful monitoring of emia of 152 microfilariae/ml and a Mansonella perstans infec-
leukocyte and platelet counts is also indicated. The pos- tion of 133 microfilariae/ml. Three days after the start of
sibility of teratogenicity and embryotoxicity from animal therapy she developed an encephalopathy. Albendazole was
studies suggests that the drug should be avoided in withdrawn and she recovered without any specific treatment
pregnancy. within the next 16 hours. On day 4, the Loa loa microfilarial
count was 29 microfilariae/ml.

The clinical presentation, the interval after starting treat-

ment, the evolution of the episode, and the results of
ORGANS AND SYSTEMS cerebral spinal fluid analysis and electroencephalography
in this case were similar to those seen in cases of enceph-
Nervous system alopathy following treatment of Loa loa with ivermectin
or diethylcarbamazine. However, pretreatment filaremia
Used in the treatment of neurocysticercosis, albendazole
was relatively low and Loa loa microfilariae were not
(like praziquantel) can cause a CSF syndrome character-
detectable in the cerebral spinal fluid. Thus, pre-existing
ized by fever, headaches, meningism, and exacerbation of
conditions might increase the susceptibility to
some or many of the neurological signs of the disease; it is
encephalopathy.
thought to be due to a local reaction to dying and dead
larvae and can be attenuated by prednisone [24,25].
Since neurocysticercosis is a neurological infection, it is
not surprising that when treating it with any drug some of Sensory systems
the neurological reactions to that drug (or to the death of
the parasite) are particularly pronounced. For example, An allergic conjunctivitis was seen in cases of industrial
with a dose of 1.5 mg/kg continued for some time in cases occupational skin reactions to albendazole [32].
of neurocysticercosis, a majority of patients initially Eye pain has been attributed to albendazole in a patient
develop intolerance in the form of headache, vomiting, with ocular cysticercosis [33].
fever, and occasionally diplopia and meningeal irritation  A 19-year-old Nepalese housewife with horizontal diplopia due
[26]. Even shorter and less intensive treatment has pro- to orbital cysticercosis was given albendazole 15 mg/kg/day for
duced similar effects. However, all of these symptoms are 8 days. After 3 days she developed nausea, vomiting, and dis-
probably due to the death of the parasite, and if therapy is tressing nocturnal left eye pain. She was reluctant to continue
continued they usually disappear within a few days. Nev- taking albendazole and her symptoms settled after a short
ertheless, they can be alarming and demand treatment. course of oral analgesia. Later ocular examinations did not
Data from large studies mention somnolence and even show any residual orbital cyst.
transient hemiparesis as incidental adverse effects.
 A 35-year-old Chinese woman with a 26-year history of persis-
tent headache as the dominant symptom of neurocysticercosis, Hematologic
relieved only by diuretic treatment, took albendazole 800 mg/
There have been various reports of bone marrow depres-
day for 3 weeks [27]. After 2 days she reported increased
headache plus vertigo, nausea, and vomiting. Analysis of the
sion. In one study [34] two of 20 patients had a reversible
cerebrospinal fluid showed increased white cell pleocytosis. drop in leukocyte count. Pancytopenia, reversible on with-
Her headache improved after the addition of a glucocorticoid drawal, has been documented in an elderly woman [35].
and 3 months after withdrawal of albendazole her headache Even with high doses neutropenia occurs in under 1% of
had not recurred. cases. In the older literature an occasional hematological
death was reported.
Very rarely, in cases of neurocysticercosis, the reaction of
the nervous system to the death of the parasite is  A 68-year-old man with a large cystic lung mass due to echino-
extremely violent. In one case cerebral edema resulted in coccosis was given albendazole and 2 weeks later developed
permanent neurological damage [28], while other patients septic shock with severe pancytopenia [36]. He died after 10
days with no marrow recovery. Autopsy was consistent with
have suffered hydrocephalus or acute intracranial hyper-
albendazole-induced pancytopenia.
tension requiring treatment, for example with glucocorti-
coids or mannitol [29]. The clearance of albendazole sulfoxide is impaired in liver
Albendazole has sometimes aggravated extrapyramidal disease, which was relevant in this case. The authors sug-
disorders or precipitated seizures in patients with prior gested that frequent serial monitoring of blood counts is
epileptic symptoms. The risk of intracranial hypertension warranted in patients with liver disease.

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 Albendazole 107

Megakaryocytic thrombocytopenia has been attributed  A 38-year-old woman with cough, eosinophilia, and pulmonary
to albendazole [37]. infiltrates due to visceral larva migrans from Toxocara canis
infection took albendazole 600 mg for 8 weeks and developed
 A 25-year-old woman who had been taking albendazole 13 mg/
slight transient skin eruptions [45].
kg/day for 5 months for hepatic and pulmonary echinococcosis
developed fatigue, bleeding gums, and prolonged menstrual Stevens–Johnson syndrome was reported in a man who
bleeding. She had ecchymoses and petechiae over her legs, took albendazole 400 mg/day for toxocariasis [46].
marked thrombocytopenia (10  109/l), a mild iron deficiency
anemia, and a normal leukocyte count. There was no antiplate-
let immunoglobulin. A bone marrow aspiration showed absent
megakaryocytes with normal granulocytes and mild erythroid Hair
hyperplasia. A cytogenetic study of the bone marrow showed
normal karyotype and immunophenotype. The albendazole There are various well-documented reports of reversible
was withdrawn and oral iron given. At follow-up 2 months alopecia in patients taking albendazole [40,47] which in
later all laboratory abnormalities had resolved. one study occurred in 2% of cases [24] and in another
study in one case out of 20 [34].
 Severe alopecia has been described in an almost 3-year-old
Gastrointestinal child who took albendazole 400 mg/d for 3 days; 2 months
later alopecia developed and resolved within 1 month [48].
With a single oral dose of albendazole 400 mg, there is  When one woman took 400 mg bd for 10 months for hydatid
usually little more in the way of adverse effects than mild disease, she lost much of her hair; no other likely cause could be
gastrointestinal disturbances (notably epigastric pain or identified, and her hair growth recovered when the drug was
dry mouth), occurring only in about 6% of patients in stopped [49].
some large series; a few patients have abdominal pain.
Oddly, however, a fair proportion of patients when spe-
With higher doses, irritation of the central nervous system
cifically questioned seem to remark that their hair growth
can lead to nausea and vomiting.
has actually improved during treatment [34].
Diarrhea occurs in a few patients taking albendazole
and is usually mild. However, a typical case of pseudo-
membranous colitis has been documented, although the
patient also had AIDS and intestinal microsporidiosis and Musculoskeletal
had taken a number of other drugs; the complication
responded to vancomycin [38]. Myalgia and arthralgia can occur in patients taking alben-
dazole [50]. However, these symptoms are often features
of the disease being treated.
Liver
Even in single low doses a transient increase in transam-
inase activities has been repeatedly reported, generally SECOND-GENERATION EFFECTS
affecting up to 13–20% of patients taking albendazole
[24,39]. At the higher doses some evidence of moderate Teratogenicity
hepatitis has been claimed to be present in almost all It has been emphasized that albendazole is teratogenic in
patients, but in one series with high doses of albendazole animals and should not be used in pregnancy [51].
or mebendazole for echinococcosis only 17% had a (gen-
erally slight) increase in serum transaminases, and a fair
number of these had pre-existent liver disorders [40]. Like
various other adverse effects, the increase in transami- SUSCEPTIBILITY FACTORS
nases may be attributable to the breakdown of liver
cysts; it is almost always reversible and is usually not a Age
reason for withdrawal; it does not become more marked
during long-term treatment. A very occasional individual The pharmacokinetics of albendazole/albendazole sulfox-
develops jaundice [41] or some other manifestation of ide and praziquantel have been investigated in 20 Thai
hepatitis [42]. school-age children with Giardia intestinalis infections
[52]. They were randomized to a single oral dose of alben-
 In a 17-year-old man severe jaundice, anemia, and edema
dazole (400 mg) with or without a single oral dose of
occurred 20 days after starting albendazole emulsion 12.5 mg/ praziquantel (20 mg/kg). There was no significant phar-
kg/day [43]. After recovery albendazole was re-instituted in a
macokinetic interaction and no adverse effects.
dose of 10 mg/kg/day for 6 months without problems.

Skin DRUG ADMINISTRATION

A generalized rash has sometimes been seen in patients Drug formulations
taking albendazole [44], and skin complications (including
urticaria and contact dermatitis) are a potential problem In a randomized crossover study [53] in 10 healthy volun-
in employees in the pharmaceutical industry if they teers (ages 18–41 years, weights 55–110 kg, body mass
undergo heavy exposure to the drug [32]. index 19–34 kg/m2, four men) the systemic availability of

ã 2016 Elsevier B.V. All rights reserved.

108 Albendazole

the commercially available tablet of albendazole was com- abacavir, and lopinavir/ritonavir. Instead of albendazole, he
pared with three newer formulations: was given mebendazole. Since a pharmacokinetic interaction
between albendazole and the HIV protease inhibitors was sus-
1. an oral suspension in arachis oil and the surfactant pected to have contributed to the development of pancytope-
polysorbate 80 (aimed at increasing lipid solubility); nia, mebendazole plasma concentrations were carefully
2. an oral solution incorporated into hydroxypropyl-b- monitored. Therapeutic mebendazole plasma concentrations
cyclodextrin (aimed at increasing water solubility); were reached after 6 weeks at a dose of 150 mg bd instead of
3. a macrogol suppository (aimed at avoiding intestinal the usual dosage of 500–1500 mg bd.
degradation of albendazole). These data suggest that there may be a significant pharma-
Compared with the results with the tablet, the systemic cokinetic interaction between benzimidazoles and
availability was significantly increased by the oil- CYP3A4 inhibitors like protease inhibitors. This may result
surfactant suspension (4.3-fold) and the cyclodextrin in significantly increased serum benzimidazole concentra-
solution (9.7-fold). Rectal administration of albendazole- tions, when benzimidazole doses are not adjusted under
containing macrogol suppositories failed. Seven subjects concomitant treatment with HIV protease inhibitors.
had diarrhea 4–6 hours after the administration of the
solution with hydroxypropyl-b-cyclodextrin.
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ã 2016 Elsevier B.V. All rights reserved.