Albendazole
See also Benzimidazoles
GENERAL INFORMATION
The benzimidazole antihelminthic drugs albendazole and
mebendazole (qv) are commonly used to treat soil-
transmitted helminth infections, such as gastrointestinal
roundworms, hydatid disease, neurocysticercosis, larva
migrans cutanea, and strongyloidiasis [1–3]. They bind to
nematode b tubulin and inhibit parasite microtubule poly-
merization, which causes death of adult worms after a few
days. Although both albendazole and mebendazole are
broad-spectrum antihelminthic drugs, their use differs
substantially in clinical practice. Both are effective against
ascariasis in a single dose. In hookworm infections, how-
ever, a single dose of mebendazole is associated with a low
cure rate and albendazole is more effective. Conversely, a
single dose of albendazole is not effective in many cases of
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
prolonged periods or cyclically, it is effective in echino-
coccosis, in which it is given in a dosage of 10 mg/kg/day
for 4 weeks, repeated in six cycles with 2-week rest periods
between each cycle, although even with this high dose only
about one-third of patients enjoy a complete cure, some
70% having a partial response. Albendazole is also active
against Pneumocystis jirovecii, and is effective in prophy-
laxis and treatment in immunosuppressed mice [4]. In
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
mebendazole is that mebendazole is poorly absorbed from
the gastrointestinal tract. For this reason the therapeutic
action is largely directed at intraluminal (adult) worms.
Albendazole is better absorbed, especially when it is taken
with a fatty meal. It is metabolized in the liver to a sulf-
oxide derivative, which is highly distributed to the tissues.
It is therefore used to treat disorders caused by tissue-
migrating larvae, such as visceral larva migrans caused
by Toxocara canis. Systemic adverse effects, such as
those on the liver and bone marrow, are usually rare
with benzimidazoles in the doses used to treat soil-
transmitted helminth infections. However, transient
abdominal pain, diarrhea, nausea, dizziness, and headache
can occur. Since deworming programmes in endemic
regions clearly improve child health and education as
well as reducing the burden of disease attributed to soil-
transmitted helminths, the use of these drugs is not limited
to treatment of symptomatic infections, but also for pre-
vention by mass deworming programmes of morbidity in
children living in endemic areas. Concerns about the sus-
tainability of periodic deworming with benzimidazoles
and the emergence of resistance have prompted efforts
to develop and test new control tools (such as plant cyste-
ine proteinases from various sources of latex-bearing
plants and fruits).
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DRUG STUDIES
Observational studies
Ankylostomiasis
Albendazole has been used in the treatment of human
hookworm and trichuriasis. In a mass-treatment report
from Western Australia 295 individuals in a remote rural
area were treated with albendazole 400 mg/day for 5 days
because of possible Giardia lamblia and hookworm infec-
tions [6]. The 37% prevalence of Giardia fell to 12%
between days 6 and 9, but rose again to 28% between
days 18 and 30. The effect on hookworms (Ankylostoma
duodenale) was more pronounced and more sustained
with a reduction of the pretreatment prevalence of hook-
worm infections from 76% before treatment to 0% after
3–4 weeks. The tolerability of the drug was judged to be
excellent by 89%, good by 1%, and moderately good by
1%, while 9% gave no response. Adverse effects were
reported by five individuals and consisted of mild abdom-
inal pain (n ¼ 2), mild or moderate diarrhea (n ¼ 2), mod-
erate fever (n ¼ 1), and weakness (n ¼ 1).
Ascariasis
The efficacy of 2 years of mass chemotherapy against
ascariasis has been evaluated in Iran [7]. A single dose of
albendazole 400 mg was given at 3-month intervals for 2
years to every person, except children under 2 years of age
and pregnant women. After 2 years of treatment the prev-
alences, based on 2667 post-treatment samples, had fallen
(Table 1). There were no adverse effects of mass treat-
ment with albendazole.
Echinococcosis
Hydatid disease is a common zoonosis caused by the larval
cysts of Echinococcus granulosus. Hydatid cysts most
commonly form in the liver, but can occur in any organ.
The management and operative complications in 70
patients with hydatid disease aged 10–78 years have been
studied retrospectively to assess the impact of albendazole
and praziquantel compared with surgery [8]. In all, 39
patients received albendazole and praziquantel in combi-
nation and 19 received albendazole alone; none was trea-
ted with praziquantel alone. The combined use of
albendazole and praziquantel preoperatively significantly
reduced the number of cysts that contained viable proto-
scolices. During the 12-year follow-up period an initial 3
months of drug treatment (albendazole throughout and
praziquantel for 2 weeks), re-assessment, followed by
either surgery or continuation with chemotherapy was
found to be a rational treatment algorithm. In 11 patients
albendazole, given for a median of 3 months at a dose of
400 mg bd, had adverse effects: five patients developed
nausea and six had abnormal liver function tests. Therapy
was withdrawn in two patients owing to altered liver
function.
The efficacy of albendazole emulsion has been studied
in 212 patients with hydatid disease of the liver, aged 4–82
years [9]. Two regimens of albendazole were given for a

Table 1 Changes in prevalences of helminthic infections in patients treated with albendazole [5]
Number (%) of positive tests before
Helminth treatment (n ¼ 3098)
Ascaris 1198 (39%)
lumbricoides
Trichuris trichiura 22 (0.7%)
Hymenolepis nana 63 (2%)
variable period (3 months to more than 1 year); 67 adults
received albendazole 10 mg/kg/day and 145 adults
received 12.5 mg/kg/day. The overall cure rate was 75%.
In the follow-up study the recurrence rate was 10%. The
highest cure rate was observed in those who received
albendazole 12.5 mg/kg/day for 9 months. At the start of
therapy about 15% of the patients had mild pruritus, rash,
and transient gastric pain, which resolved without specific
therapy. Two patients had alopecia. There were frequent
rises in serum transaminase activities in both groups but
not to above 30–50 IU/l, except in six patients, who had
values above 200 IU/l. In two patients albendazole was
withdrawn because of vomiting. In one patient who took
12.5 mg/kg/day severe adverse effects, such as anorexia,
jaundice, anemia, edema, and hypoproteinemia, devel-
oped, necessitating withdrawal. Reintroduction of alben-
dazole 10 mg/kg/day was uneventful.
The use of albendazole and mebendazole in patients
with hydatidosis has been evaluated in 448 patients with
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,
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 degen-
erative 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 alben-
dazole 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 frequency of the usually mild
adverse effects are comparable.
Filariasis
Treatment of patients with high Loa loa microfilaremia is
sometimes complicated by an encephalopathy, suggested
to be related to a rapid killing of large number of Loa loa
microfilariae. If the Loa loa microfilarial count could be
reduced more slowly, before ivermectin is distributed,
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Albendazole 103
Number (%) of positive tests after
treatment (n ¼ 2667)
196 (7.4%)
5 (0.2%)
49 (1.8%)
ivermectin-related encephalopathy might be prevented.
In 125 patients with Loa loa microfilariasis the effect of
albendazole (800 mg/day for three consecutive days) or
multivitamin tablets on Loa loa microfilarial load and
the occurrence of encephalopathy were studied [11]. Loa
loa microfilarial loads were followed for 9 months. There
was no significant change in the overall microfilarial loads
among those treated with albendazole, although the loads
in patients with more than 8000 microfilariae/ml tended to
fall more progressively during the first 3 months of follow-
up. There were no cases of encephalopathy. The main
adverse effects reported were itching (in eight patients
taking albendazole and seven taking multivitamins),
abdominal pain (two taking albendazole), and diarrhea
(one taking albendazole, two taking multivitamins); over-
all analysis showed no significant difference in these
events between the groups. Albendazole was associated
with modest but significantly raised plasma transaminase
activities.
Neurocysticercosis
In a report on the use of albendazole 15 mg/kg/day in two
divided doses for 14 days in the treatment of persistent
neurocysticercosis [12], adverse reactions were monitored
in 43 patients with seizures and a solitary cysticercal cyst,
who had not been treated before. In all patients CT scans
confirmed the presence of a solitary cyst less than 2 cm in
diameter. Antiepileptic treatment was continued. In seven
patients dexamethasone 8 mg/day in four divided doses
was given for the first 5–7 days after the start of treatment.
Follow-up CT scans at 4–10 weeks after the start of treat-
ment showed responses in 20 patients, with complete dis-
appearance in seven patients and a reduction to 50% of
the pretreatment size in the other 13. There were adverse
effects in 15 patients, with a maximum on the fifth day
after the start of treatment. Six patients had severe head-
aches, 11 had partial seizures, and 2 had epileptic seizures
and severe postictal hemiparesis that persisted for a week
or more. Because of these serious adverse effects treat-
ment was discontinued in seven patients and dexametha-
sone was added in those patients who were not already
taking it, although its use proved questionable. Adverse
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
optimal dosage of 15 mg/kg/day divided in two doses every
12 hours for 8 days [13]. It was generally well tolerated,
although several patients had adverse reactions during the
first few days after the start of treatment, consisting of
headache, vomiting, and exacerbation of neurological
symptoms caused by an inflammatory reaction to antigens
104 Albendazole
from degenerating cysts, necessitating the concomitant
use of glucocorticoids. In very large cysticerci, or cysticerci
located in risky areas like the brainstem, these reactions
may rarely be life-threatening.
Protozoal infections
The efficacy of albendazole 800 mg bd for 14 days for per-
sistent diarrhea due to cryptosporidiosis (n ¼ 10), isosporia-
sis (n¼ 54), or microsporidiosis (n ¼ 23) has been studied in
153 HIV-positive patients [14]. Albendazole reduced the
burden of protozoal infection and promoted mucosal recov-
ery in 87 patients who had a complete clinical response. Two
patients reported nausea and vomiting. One patient devel-
oped leukopenia (1.9  109/l) after treatment and four
patients developed thrombocytopenia (51–98  109/l).
Toxocariasis
The efficacy of albendazole plus prednisolone has been
studied in five patients aged 11–72 years with ocular tox-
ocariasis [15]. All had uveitis and retinochoroidal granu-
lomas. Their symptoms had persisted for a mean of 14
months (range 3 days to 24 months). The adults were
treated with albendazole 800 mg bd for 2 weeks plus pred-
nisolone starting at 1.5 mg/kg/day tapering over 3 months.
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-
nificant hypersensitivity reactions to dying Toxocara lar-
vae. The uveitis resolved in all cases and there were no
relapses. After treatment, all the granulomas had disap-
peared, leaving heavily pigmented chorioretinal scars
without loss of vision.
Comparative studies
Ascariasis
See below under Trichuriasis
Echinococcosis
Human hydatid disease is caused by the metacestode of
Echinococcus granulosus. There are few data on the treat-
ment of pulmonary hydatid disease in children. Mebenda-
zole and albendazole have been evaluated in 82 children
with a total of 102 pulmonary hydatid cysts [16]. Mebenda-
zole was given as 50 mg/kg/day in three divided doses and
albendazole was given as 10 mg/kg/day in two divided doses
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
eight patients had raised liver enzymes, three had rash, and
one had neutropenia; all were reversible on withdrawal.
Hydatidosis
The use of albendazole and mebendazole in patients with
hydatidosis has been evaluated in 448 patients with
E. granulosis hydatid cysts who received continuous
ã 2016 Elsevier B.V. All rights reserved.
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 [10]. At the end of treat-
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
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. Headache
occurred in eight patients taking albendazole and three
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
and none, fever in three and none, dyspepsia in two and
four, and tachycardia in two and none. 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 meben-
dazole in the treatment of hydatid cysts caused by
E. granulosis and that both the intensity and frequency
of the usually mild adverse effects are comparable.
Neurocysticercosis
The treatment of subarachnoid and intraventricular neu-
rocysticercosis is controversial. In a randomized trial, 36
patients with subarachnoid and intraventricular cysticer-
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
higher albendazole sulfoxide concentrations in the
plasma. A single dose was insufficient in intraventricular
and giant cysts. Adverse effects were similar in the two
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-
mia occurred in two patients taking high-dose albendazole
and each occurred in one patient taking low-dose alben-
dazole. Six patients who took low-dose albendazole and
nine who took the high dose developed a leukocytosis or
increased alanine transaminase activities to over three
times the upper limit of normal. These laboratory abnor-
malities had disappeared by 30 days. One patient devel-
oped glucocorticoid-related hyperglycemia.
Pediculosis capitis
Pediculosis capitis, caused by head lice, is one of the most
common human ectoparasitic infections, infesting school-
children of all socioeconomic groups. In 150 children, the
usefulness of albendazole was studied in the treatment of
pediculosis capitis in combination with 1% permethrin or
alone [18]. Group 1 (n ¼ 30) took a single dose of alben-
dazole 400 mg; group 2 (n ¼ 30) took albendazole 400 mg
for 3 days; group 3 (n ¼ 30) used permethrin 1%; group 4

(n ¼ 30) used permethrin 1% and took a single dose of
albendazole 400 mg; and group 5 (n ¼ 30) used permethrin
1% and took albendazole 400 mg for 3 days. Those who
took albendazole also took a dose of albendazole 400 mg 1
week later. The success rates after 2 weeks were 62%,
67%, 80%, 85%, and 82% respectively. There were no
significant differences among the five groups. The results
suggested that albendazole is effective against pediculosis
capitis and that there is no synergistic effect between
albendazole and 1% permethrin. Adverse effects were
not reported in this study.
Trichuriasis
In a randomized trial in Mexico [19] 622 children with
Trichuris were randomized to either albendazole 400 mg/
day for 3 days, one dose of albendazole 400 mg, or one
dose of pyrantel 11 mg/kg. The aim was to study efficacy
and the effects on growth. After three courses at 1 year the
level of infection with Trichuris was reduced by 99% in the
3-day albendazole treatment group, by 87% in the single-
dose albendazole treatment group, and by 67% in the
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
courses of albendazole. This was only found in the patients
with lower pretreatment Trichuris stool egg counts. These
findings suggest that although elimination of Trichuris
may promote growth in children, albendazole in a dose
of 1200 mg/kg every 4 months may have an independent
negative effect on growth. In an accompanying commen-
tary [20] it was concluded that the suggestion that rela-
tively high doses of albendazole may affect growth
deserves study, but that this possible effect must be
weighed against the negative effect of prolonged helmin-
thic infestation on children’s health, growth, and cognitive
function. However, it is unlikely that high-dose treatment
will be standard in mass-treatment campaigns, and these
results should not deter the use of single-dose albendazole
in mass-treatment programs in high-risk populations.
In 110 children with ascariasis or trichuriasis the efficacy
of a single dose of albendazole 400 mg has been compared
with that of nitazoxanide 100 mg bd for 3 days in children
aged 1–3 years and 200 mg bd for 3 days in children aged
4–11 years [21]. Nitazoxanide cured 89 and 89% of the
cases of ascariasis and trichuriasis respectively. Albenda-
zole cured 91 and 58% of the cases of ascariasis and trichur-
iasis respectively. Abdominal pain (n¼ 9), nausea (n ¼ 1),
diarrhea (n¼ 2), and headache (n ¼ 1) were reported as
mild adverse effects in 105 patients who took nitazoxanide,
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.
Placebo-controlled studies
Albendazole has been used in the treatment and prophy-
laxis of microsporidiosis in patients with AIDS. In a small,
double-blind, placebo-controlled trial from France [22]
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Albendazole 105
the efficacy and safety of treatment with albendazole
was studied in four patients treated with albendazole
400 mg bd for 3 weeks and in four patients treated with
placebo. Microsporidia were cleared in all patients given
albendazole but in none of those given placebo. After-
wards all eight patients were again randomized to receive
either maintenance treatment with albendazole 400 mg bd
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 took no maintenance therapy
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-
aminase activities, and one had thrombocytopenia. How-
ever, half the patients were also taking anti-HIV triple
therapy, which makes it difficult to assess these abnormal-
ities. The authors concluded that the adverse effects were
not serious and did not hinder maintenance therapy. The
tentative conclusion derived from these findings is that
albendazole may be useful in the treatment of microspor-
idiosis, which in patients with AIDS often leads to debil-
itating chronic diarrhea and is difficult to treat.
Use in non-infective conditions
The efficacy of albendazole has been evaluated in a few
patients with either hepatocellular carcinoma (n ¼ 1) or
colorectal cancer and hepatic metastases refractory to
other forms of treatment (n ¼ 8) [23]. Apart from hemato-
logical and biochemical indices, the tumor markers carci-
noembryonic antigen (CEA) and alpha-fetoprotein (AFP)
were measured to monitor treatment efficacy. One other
patient with a neuroendocrine cancer and a mesothelioma
was treated on a compassionate basis and only monitored
for adverse effects. Albendazole was given orally in a dose
of 10 mg/kg/day in two divided doses for 28 days. Alben-
dazole reduced CEA in two patients and in the other five
patients with measurable tumor markers, serum CEA or
AFP was stabilized in three. In the seven patients who
completed this pilot study, albendazole was well tolerated
and there were no significant changes in any hematologi-
cal, kidney, or liver function tests. However, three patients
were withdrawn because of severe neutropenia, which
resulted in the death of one. Neutropenia was more fre-
quent than is usually experienced in the treatment of hyda-
tid disease. The authors speculated that this may relate to
reduced metabolism in patients with liver cancer or liver
metastases, leading to the passage of unmetabolized drug
into the circulation.
General adverse effects and adverse
reactions
As with other antihelminthic drugs, the general adverse
effects of albendazole can reflect the destruction of the
parasite rather than a direct action of the drug; pyrexia is
likely to be seen, 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.
106 Albendazole
Its adverse effects are similar to those of mebendazole
and are possibly more common because of better and
more reliable absorption.
The direct adverse effects of albendazole are few and
usually minor, and consist of gastrointestinal upsets, diz-
ziness, rash, and alopecia, which usually do not require
drug withdrawal. Early pyrexia and neutropenia can also
occur. Cyst rupture can also occur, as with mebendazole.
About 15% of patients treated with albendazole at
higher doses develop raised serum transaminases, neces-
sitating careful monitoring and sometimes withdrawal of
treatment after prolonged use. Careful monitoring of
leukocyte and platelet counts is also indicated. The pos-
sibility of teratogenicity and embryotoxicity from animal
studies suggests that the drug should be avoided in
pregnancy.
ORGANS AND SYSTEMS
Nervous system
Used in the treatment of neurocysticercosis, albendazole
(like praziquantel) can cause a CSF syndrome character-
ized by fever, headaches, meningism, and exacerbation of
some or many of the neurological signs of the disease; it is
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
the neurological reactions to that drug (or to the death of
the parasite) are particularly pronounced. For example,
with a dose of 1.5 mg/kg continued for some time in cases
of neurocysticercosis, a majority of patients initially
develop intolerance in the form of headache, vomiting,
fever, and occasionally diplopia and meningeal irritation
[26]. Even shorter and less intensive treatment has pro-
duced 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. Nev-
ertheless, they can be alarming and demand treatment.
Data from large studies mention somnolence and even
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,
relieved only by diuretic treatment, took albendazole 800 mg/
day for 3 weeks [27]. After 2 days she reported increased
headache plus vertigo, nausea, and vomiting. Analysis of the
cerebrospinal fluid showed increased white cell pleocytosis.
Her headache improved after the addition of a glucocorticoid
and 3 months after withdrawal of albendazole her headache
had not recurred.
Very rarely, in cases of neurocysticercosis, the reaction of
the nervous system to the death of the parasite is
extremely violent. In one case cerebral edema resulted in
permanent neurological damage [28], while other patients
have suffered hydrocephalus or acute intracranial hyper-
tension requiring treatment, for example with glucocorti-
coids or mannitol [29].
Albendazole has sometimes aggravated extrapyramidal
disorders or precipitated seizures in patients with prior
epileptic symptoms. The risk of intracranial hypertension
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has led some to suggest that glucocorticoids should be
given preventively when using albendazole in neurocysti-
cercosis [30]; however, dexamethasone can interact with
albendazole, increasing its plasma concentrations [31],
and it is not clear whether this might produce new
problems.
Encephalopathy is an adverse event related to the treat-
ment of Loa loa with diethylcarbamazine or ivermectin,
and it has also been related to albendazole [13].
 A 55-year-old woman from Cameroon took oral albendazole
200 mg bd for a symptomatic Loa loa infection with microfilar-
emia of 152 microfilariae/ml and a Mansonella perstans infec-
tion of 133 microfilariae/ml. Three days after the start of
therapy she developed an encephalopathy. Albendazole was
withdrawn and she recovered without any specific treatment
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
cerebral spinal fluid analysis and electroencephalography
in this case were similar to those seen in cases of enceph-
alopathy following treatment of Loa loa with ivermectin
or diethylcarbamazine. However, pretreatment filaremia
was relatively low and Loa loa microfilariae were not
detectable in the cerebral spinal fluid. Thus, pre-existing
conditions might increase the susceptibility to
encephalopathy.
Sensory systems
An allergic conjunctivitis was seen in cases of industrial
occupational skin reactions to albendazole [32].
Eye pain has been attributed to albendazole in a patient
with ocular cysticercosis [33].
 A 19-year-old Nepalese housewife with horizontal diplopia due
to orbital cysticercosis was given albendazole 15 mg/kg/day for
8 days. After 3 days she developed nausea, vomiting, and dis-
tressing nocturnal left eye pain. She was reluctant to continue
taking albendazole and her symptoms settled after a short
course of oral analgesia. Later ocular examinations did not
show any residual orbital cyst.
Hematologic
There have been various reports of bone marrow depres-
sion. In one study [34] two of 20 patients had a reversible
drop in leukocyte count. Pancytopenia, reversible on with-
drawal, has been documented in an elderly woman [35].
Even with high doses neutropenia occurs in under 1% of
cases. In the older literature an occasional hematological
death was reported.
 A 68-year-old man with a large cystic lung mass due to echino-
coccosis was given albendazole and 2 weeks later developed
septic shock with severe pancytopenia [36]. He died after 10
days with no marrow recovery. Autopsy was consistent with
albendazole-induced pancytopenia.
The clearance of albendazole sulfoxide is impaired in liver
disease, which was relevant in this case. The authors sug-
gested that frequent serial monitoring of blood counts is
warranted in patients with liver disease.

Megakaryocytic thrombocytopenia has been attributed
to albendazole [37].
 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 over her legs,
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
hyperplasia. A cytogenetic study of the bone marrow showed
normal karyotype and immunophenotype. The albendazole
was withdrawn and oral iron given. 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 adverse effects than mild
gastrointestinal disturbances (notably epigastric pain or
dry mouth), occurring only in 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.
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
had taken a number of other drugs; the complication
responded to vancomycin [38].
Liver
Even in single low doses a transient increase in transam-
inase activities has been repeatedly reported, generally
affecting up to 13–20% of patients taking albendazole
[24,39]. At the higher doses some evidence of moderate
hepatitis has been claimed to be present in almost all
patients, but in one series with high doses of albendazole
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-
nases may be attributable to the breakdown of liver
cysts; it is almost always reversible and is usually not a
reason for withdrawal; it does not become more marked
during long-term treatment. A very occasional individual
develops jaundice [41] or some other manifestation of
hepatitis [42].
 In a 17-year-old man severe jaundice, anemia, and edema
occurred 20 days after starting albendazole emulsion 12.5 mg/
kg/day [43]. After recovery albendazole was re-instituted in a
dose of 10 mg/kg/day for 6 months without problems.
Skin
A generalized rash has sometimes been seen in patients
taking albendazole [44], and skin complications (including
urticaria and contact dermatitis) are a potential problem
in employees in the pharmaceutical industry if they
undergo heavy exposure to the drug [32].
ã 2016 Elsevier B.V. All rights reserved.
Albendazole 107
 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 [45].
Stevens–Johnson syndrome was reported in a man who
took albendazole 400 mg/day for toxocariasis [46].
Hair
There are various well-documented reports of reversible
alopecia in patients taking albendazole [40,47] which in
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
child who took albendazole 400 mg/d for 3 days; 2 months
later alopecia developed and resolved within 1 month [48].
 When one woman took 400 mg bd 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 [49].
Oddly, however, a fair proportion of patients when spe-
cifically questioned seem to remark that their hair growth
has actually improved during treatment [34].
Musculoskeletal
Myalgia and arthralgia can occur in patients taking alben-
dazole [50]. However, these symptoms are often features
of the disease being treated.
SECOND-GENERATION EFFECTS
Teratogenicity
It has been emphasized that albendazole is teratogenic in
animals and should not be used in pregnancy [51].
SUSCEPTIBILITY FACTORS
Age
The pharmacokinetics of albendazole/albendazole sulfox-
ide and praziquantel have been investigated in 20 Thai
school-age children with Giardia intestinalis infections
[52]. They were randomized to a single oral dose of alben-
dazole (400 mg) with or without a single oral dose of
praziquantel (20 mg/kg). There was no significant phar-
macokinetic interaction and no adverse effects.
DRUG ADMINISTRATION
Drug formulations
In a randomized crossover study [53] in 10 healthy volun-
teers (ages 18–41 years, weights 55–110 kg, body mass
index 19–34 kg/m2, four men) the systemic availability of
108 Albendazole
the commercially available tablet of albendazole was com-
pared with three newer formulations:
1. an oral suspension in arachis oil and the surfactant
polysorbate 80 (aimed at increasing lipid solubility);
2. an oral solution incorporated into hydroxypropyl-b-
cyclodextrin (aimed at increasing water solubility);
3. a macrogol suppository (aimed at avoiding intestinal
degradation of albendazole).
Compared with the results with the tablet, the systemic
availability was significantly increased by the oil-
surfactant suspension (4.3-fold) and the cyclodextrin
solution (9.7-fold). Rectal administration of albendazole-
containing macrogol suppositories failed. Seven subjects
had diarrhea 4–6 hours after the administration of the
solution with hydroxypropyl-b-cyclodextrin.
DRUG–DRUG INTERACTIONS
Antiepileptic drugs
See also Glucocorticoids; Grapefruit (under Citrus
paradisi in Rutaceae); Levamisole
The pharmacological interactions of the antiepileptic
drugs phenytoin, carbamazepine, and phenobarbital with
albendazole have been studied in 32 adults with active
intraparenchymatous neurocysticercosis [54]:

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 on 8 consecutive days. Phenytoin, carbamazepine,
and phenobarbital all induced the oxidative metabolism of
albendazole to a similar extent in a non-enantioselective
manner. In consequence, 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 enhanced by a fatty meal, contributes to difficulties in
predicting its therapeutic response in echinococcosis. The
effect of cimetidine co-administration on the systemic
availability of albendazole has been studied in six healthy
men [55]. After an overnight fast, a single oral dose of
albendazole (10 mg/kg) was administered 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 presys-
temic metabolism of albendazole by CYP3A4.
HIV protease inhibitors
 A 40-year-old man with HIV infection, taking HAART, devel-
oped alveolar echinococcosis [56]. He was given albendazole
400 mg bd. Within 2 weeks he developed pancytopenia. Zido-
vudine, lamivudine, nelfinavir, and pyrimethamine/sulfameth-
oxazole were withdrawn. Full recovery of the bone marrow
occurred within 10 weeks. HAART was changed to stavudine,
ã 2016 Elsevier B.V. All rights reserved.
abacavir, and lopinavir/ritonavir. Instead of albendazole, he
was given mebendazole. Since a pharmacokinetic interaction
between albendazole and the HIV protease inhibitors was sus-
pected to have contributed to the development of pancytope-
nia, mebendazole plasma concentrations were carefully
monitored. Therapeutic mebendazole plasma concentrations
were reached after 6 weeks at a dose of 150 mg bd instead of
the usual dosage of 500–1500 mg bd.
These data suggest that there may be a significant pharma-
cokinetic interaction between benzimidazoles and
CYP3A4 inhibitors like protease inhibitors. This may result
in significantly increased serum benzimidazole concentra-
tions, when benzimidazole doses are not adjusted under
concomitant treatment with HIV protease inhibitors.
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