DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1452 with combination therapy for 4-6 years to maintain the microfilaremia
at such low levels that transmission cannot occur. The period
of therapy is estimated to correspond to the duration of fecundity of
adult worms. Albendazole is given with DEC to control LF in most
parts of the world. However, to avoid serious reactions to dying
microfilariae, the albendazole/ivermectin combination is recommended
in locations where filariasis co-exists with either onchocerciasis
or loiasis. Recently, the benefits of adding albendazole to
either DEC or ivermectin for LF control were evaluated (Addiss
et al., 2004); there currently is insufficient reliable research to confirm
or refute whether adding albendazole has an effect on LF.
Toxicity, Side Effects, Precautions, and Contraindications.
Excluding thiabendazole, the BZs have excellent safety
profiles. To date millions of children have been treated
in mass deworming chemotherapy programs. Overall,
the incidence of side effects, primarily mild GI symptoms,
occur in only 1% of treated children (Urbani and
Albonico, 2003).
The clinical utility of thiabendazole in adults is
compromised by its toxicity. Side effects frequently
encountered with therapeutic doses include anorexia,
nausea, vomiting, and dizziness.
SECTION VII
CHEMOTHERAPY OF MICROBIAL DISEASES
Less frequently, diarrhea, fatigue, drowsiness, giddiness, or
headache occur. Occasional fever, rashes, erythema multiforme,
hallucinations, sensory disturbances, and Stevens-Johnson syndrome
have been reported. Angioedema, shock, tinnitus, convulsions,
and intrahepatic cholestasis are rare complications of
therapy. Some patients excrete a metabolite that imparts an odor
to the urine much like that occurring after ingestion of asparagus.
Crystalluria without hematuria has been reported on occasion; it
promptly subsides with discontinuation of therapy. Transient
leukopenia has been noted in a few patients on thiabendazole therapy.
Because CNS side effects occur frequently, activities requiring
mental alertness should be avoided during therapy.
Thiabendazole has hepatotoxic potential and should be used with
caution in patients with hepatic disease or decreased hepatic function.
The effects of thiabendazole in pregnant women have not been
studied adequately, so it should be used in pregnancy only when the
potential benefit justifies the unknown risk.
Mebendazole does not cause significant systemic
toxicity in routine clinical use, even in the presence of
anemia and malnutrition. This probably reflects its low
systemic bioavailability. Transient symptoms of abdominal
pain, distention, and diarrhea have occurred in cases
of massive infestation and expulsion of GI worms.
Rare side effects in patients treated with high doses of
mebendazole include allergic reactions, alopecia, reversible neutropenia,
agranulocytosis, and hypospermia. Reversible elevation
of serum transaminases has been observed when the drug was given
in long courses for treatment of hydatid disease. Mebendazole treatment
has been associated with occipital seizures (Wilmshurst and
Robb, 1998). Mebendazole is a potent embryo toxin and teratogen
in laboratory animals; effects may occur in pregnant rats at single
oral doses as low as 10 mg/kg. However, there is no evidence for
teratogenicity in humans, probably due to its poor systemic
bioavailability. Although the general advice is that mebendazole
should not be given to pregnant women or to children <2 years of
age, it has been safely used after the first trimester of pregnancy for
its beneficial effect on anemia due to clearance of hookworm
(WHO, 2006). Because the soil-transmitted helminths are important
causes of maternal and child morbidity during pregnancy, the
WHO recommends its use for infected pregnant women in the second
or third trimester.
Albendazole produces few side effects when used
for short-term therapy of GI helminth infections, even
in patients with heavy worm burdens. Transient mild
GI symptoms (epigastric pain, diarrhea, nausea, and
vomiting) occur in ~1% of treated individuals.
Dizziness and headache occur on occasion. In schoolage
mass treatments, the incidence of side effects with
albendazole is very low (Horton, 2000).
Even in long-term therapy of cystic hydatid disease and neurocysticercosis,
albendazole is well tolerated by most patients. The
most common side effect is liver dysfunction, generally manifested
by an increase in serum transaminase levels; rarely jaundice may
be noted, but enzyme activities return to normal after therapy is
completed.
A pharmaco-epidemiological analysis concluded that longterm
treatment of echinococcosis or cysticercosis with high-dose
albendazole accounted for most of the adverse drug reactions attributed
to anthelmintic therapy (Bagheri et al., 2004). Therefore, liver
function tests should be monitored during protracted albendazole
therapy, and the drug is not recommended for patients with cirrhosis
(Davis et al., 1989). Especially if not pretreated with glucocorticoids,
some patients with neurocysticercosis may experience serious
neurological sequelae that depend on the location of inflamed cysts
with dying cysticerci. Other side effects during extended therapy
include GI pain, severe headaches, fever, fatigue, loss of hair,
leukopenia, and thrombocytopenia. Albendazole is teratogenic and
embryotoxic in animals, and it should not be given to pregnant
women. The safety of albendazole in children < 2 years of age has
not been established.
The BZs as a group display remarkably few clinically significant
interactions with other drugs. The most versatile member of
this family, albendazole, probably induces its own metabolism, and
plasma levels of its sulfoxide metabolites can be increased by coadministration
of glucocorticoids and possibly praziquantel. Caution
is advised when using high doses of albendazole together with general
inhibitors of hepatic CYPs. As indicated earlier, co-administration of
cimetidine can increase the bioavailability of mebendazole.
Use in Pregnancy. Because of the ongoing and anticipated widespread
use of BZs in global control programs for both STH and filarial
infections, there is a high level of interest about their use in young
children and in the second and third trimesters of pregnancy.
As indicated earlier, both albendazole and mebendazole are
embryotoxic and teratogenic in pregnant rats, and they are not generally
recommended for use in pregnancy (Bethony et al., 2006).
However, in postmarketing surveys on women who inadvertently
consumed mebendazole during the first trimester, the incidence of
spontaneous abortion and malformations did not exceed that of the