Albendazole (3225)
[ al-ben'-da-zole ]
| Ingredients: |
Albendazole |
| Indications: |
Neurocysticercosis; Tapeworm, dog; Tapeworm, pork |
| Pregnancy Category: |
C |
| FDA Approved: |
1996- 07- 01 |
| Classes: |
Antihelmintics; Orphan Drugs; WHO Formulary |
| Brand Names: |
Abentel
-
China
;
ABZ
-
India
;
Adazol
-
Ecuador
;
Albatel
-
Thailand
;
Alben
-
Brazil
;
Albendol
-
Malaysia
;
Albenza
-
US
;
Albenzol
-
Ecuador
;
Albex
-
MIDDLEEAST
;
Albezole
-
India
;
Alfuca
-
Thailand
;
Alminth
-
India, Republic-of-yemen
;
Alzental
-
MIDDLEEAST(Except
Israel
); Singapore
;
Alzol
-
Thailand
;
Bendapar
-
Mexico
;
Bendex-400
-
South-africa
;
Borotel
-
Peru
;
Ceprazol
-
Chile, Peru
;
Champs D-Worm 6
-
Malaysia
;
Ciclopar
-
Colombia
;
Emanthal
-
India
;
Eskazole
-
Australia, Austria, England, Germany, Israel, Japan, Mexico, Netherlands
;
Fintel
-
Peru
;
Gascop
-
Mexico
;
Getzol
-
Colombia
;
Helben
-
Indonesia
;
Helmiben
-
Uruguay
;
Helmindazol
-
Peru
;
Labenda
-
Thailand
;
Loveral
-
Mexico
;
Mebenix
-
Brazil
;
Monodox
-
Colombia
;
Mycotel
-
Thailand
;
Nemozole
-
India
;
Pantex
-
Paraguay
;
Paranthil
-
South-africa
;
Rotopar
-
Ecuador
;
Rozolex
-
Costa-rica, Dominican-republic, El-salvador, Guatemala, Honduras, Nicaragua, Panama
;
Sioban
-
India
;
Vastus
-
Argentina
;
Vemizol
-
Malaysia
;
Vermin Plus
-
Mexico
;
Xadem
-
Colombia
;
Zeben
-
Thailand
;
Zela
-
Thailand
;
Zentab
-
Thailand
;
Zentel
-
AFRICA, CARIBBEAN(Except
Puerto-rico
), MIDDLEEAST(Except
Israel
); Australia, Brazil, Bulgaria, Chile, Colombia, Costa-rica, Czech-republic, Dominican-republic, Ecuador, El-salvador, France, Greece, Guatemala, Honduras, Italy, Korea, Malaysia, Mexico, Nicaragua, Panama, Peru, Philippines, Poland, Thailand, Venezuela
;
|
| DEA schedules: |
(none)
|
| Cost of therapy: |
$197.46
(
Neurocysticercosis ;
Albenza ;
200 mg ;
4 tablets/day ;
30 day supply
)
$552.90
(
Hydatid Disease ;
Albenza ;
200 mg ;
4 tablet(s)/day ;
84 (3 cyc) day supply
)
|
DESCRIPTION
|
| |
Albendazole is an orally administered broad- spectrum anthelmintic. Chemically it is methyl 5- (propyl- thio)- 2- benzimidazolecarbamate.
Its molecular formula is C12 H15 N3 O2 S.
Albendazole is a white to off- white powder. It is soluble in dimethylsulfoxide, strong acids, and strong bases. It is slightly
soluble in methanol, chloroform, ethyl acetate and acetonitrile. Albendazole is practically insoluble in water. Each white
to off- white, film- coated Albenza tablet contains 200 mg of albendazole.
Albenza inactive ingredients contain: Carnauba wax, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone,
sodium lauryl sulfate, sodium saccharin, sodium starch glycolate, and starch.
|
CLINICAL PHARMACOLOGY
|
| |
Pharmacokinetics
|
| |
Absorption and Metabolism
|
| |
Albendazole is poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. Albendazole concentrations
are negligible or undetectable in plasma as it is rapidly converted to the sulfoxide metabolite prior to reaching the systemic
circulation. The systemic anthelmintic activity has been attributed to the primary metabolite, albendazole sulfoxide. Oral
bioavailability appears to be enhanced when albendazole is coadministered with a fatty meal (estimated fat content 40 g) as
evidenced by higher (up to 5- fold on average) plasma concentrations of albendazole sulfoxide as compared to the fasted state.
Maximal plasma concentrations of albendazole sulfoxide are typically achieved 2- 5 hours after dosing and are on average 1.31
μg/ ml (range 0.46- 1.58 μg/ ml) following oral doses of albendazole (400 mg) in 6 hydatid disease patients, when administered
with a fatty meal. Plasma concentrations of albendazole sulfoxide increase in a dose- proportional manner over the therapeutic
dose range following ingestion of a fatty meal (fat content 43.1 g). The mean apparent terminal elimination half- life of
albendazole sulfoxide typically ranges from 8- 12 hours in 25 normal subjects, as well as in 14 hydatid and 8 neurocysticercosis
patients.
Following 4 weeks of treatment with albendazole (200 mg three times daily), 12 patients' plasma concentrations of albendazole
sulfoxide were approximately 20% lower than those observed during the first half of the treatment period, suggesting that
albendazole may induce its own metabolism.
|
Distribution
|
| |
Albendazole sulfoxide is 70% bound to plasma protein and is widely distributed throughout the body; it has been detected in
urine, bile, liver, cyst wall, cyst fluid, cerebral spinal fluid (CSF). Concentrations in plasma were 3- to 10- fold and 2-
to 4- fold higher than those simultaneously determined in cyst fluid and CSF, respectively. Limited in vitro and clinical data suggest that albendazole sulfoxide may be eliminated from cysts at a slower rate than observed in plasma.
|
Metabolism and Excretion
|
| |
Albendazole is rapidly converted in the liver to the primary metabolite, albendazole sulfoxide, which is further metabolized
to albendazole sulfone and other primary oxidative metabolites that have been identified in human urine. Following oral administration,
albendazole has not been detected in human urine. Urinary excretion of albendazole sulfoxide is a minor elimination pathway
with less than 1% of the dose recovered in the urine. Biliary elimination presumably accounts for a portion of the elimination
as evidenced by biliary concentrations of albendazole sulfoxide similar to those achieved in plasma.
|
Special Populations
|
| |
Patients With Impaired Renal Function
|
| |
The pharmacokinetics of albendazole in patients with impaired renal function have not been studied. However, since renal elimination
of albendazole and its primary metabolite, albendazole sulfoxide, is negligible, it is unlikely that clearance of these compounds
would be altered in these patients.
|
Biliary Effects
|
| |
In patients with evidence of extrahepatic obstruction (n=5), the systemic availability of albendazole sulfoxide was increased,
as indicated by a 2- fold increase in maximum serum concentration and a 7- fold increase in area under the curve. The rate
of absorption/ conversion and elimination of albendazole sulfoxide appeared to be prolonged with mean Tmax and serum elimination half- life values of 10 hours and 31.7 hours, respectively. Plasma concentrations of parent albendazole
were measurable in only 1 of 5 patients.
|
Pediatrics
|
| |
Following single- dose administration of 200- 300 mg (approximately 10 mg/ kg) albendazole to 3 fasted and 2 fed pediatric
patients with hydatid cyst disease (age range 6- 13 years), albendazole sulfoxide pharmacokinetics were similar to those observed
in fed adults.
|
Elderly Patients
|
| |
Although no studies have investigated the effect of age on albendazole sulfoxide pharmacokinetics, data in 26 hydatid cyst
patients (up to 79 years) suggest pharmacokinetics similar to those in young healthy subjects.
|
|
|
Microbiology
|
| |
The prinicpal mode of action for albendazole is by its inhibitory effect on tublin polymerization which results in the loss
of cytoplasmic microtubules.
In the specified treatment indications albendazole appears to be active against the larval forms of the following organisms: Echinococcus granulosus and Taenia solium.
|
|
INDICATIONS AND USAGE
|
| |
Albendazole is indicated for the treatment of the following infections:
- Neurocysticercosis: Albendazole is indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms
of the pork tapeworm, Taenia solium.
- Lesions considered responsive to albendazole therapy appear as nonenhancing cysts with no surrounding edema on contrast- enhanced
computerized tomography. Clinical studies in patients with lesions of this type demonstrate a 74- 88% reduction in number
of cysts; 40- 70% of albendazole- treated patients showed resolution of all active cysts.
- Hydatid Disease: Albendazole is indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval
form of the dog tapeworm, Echinococcus granulosus.
- This indication is based on combined clinical studies which demonstrated non- infectious cyst contents in approximately 80-
90% of patients given albendazole for 3 cycles of therapy of 28 days each (see DOSAGE AND ADMINISTRATION ). Clinical cure (disappearance of cysts) was seen in approximately 30% of these patients, and improvement (reduction in cyst
diameter of ≥25%) was seen in an additional 40%.
- NOTE: When medically feasible, surgery is considered the treatment of choice for hydatid disease. When administering albendazole
in the pre- or post- surgical setting, optimal killing of cyst contents is achieved when three courses of therapy have been
given.
- NOTE: The efficacy of albendazole in the therapy of alveolar hydatid disease caused by Echinococcus multiocularis has not been clearly demonstrated in clinical studies.
|
CONTRAINDICATIONS
|
| |
Albendazole is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds or any components
of albendazole tablets.
|
WARNINGS
|
| |
Rare fatalities associated with the use of albendazole have been reported due to granulocytopenia or pancytopenia. (See PRECAUTIONS .) Blood counts should be monitored at the beginning of each 28 day cycle of therapy, and every 2 weeks while on therapy with
albendazole. Albendazole may be continued if the total white blood cell count and absolute neutrophil count decrease appear
modest and do not progress.
Albandazole should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate.
Patients should not become pregnant for at least 1 month following cessation of albendazole therapy. If a patient becomes
pregnant while taking this drug, albendazole should be discontinued immediately. If pregancy occurs while taking this drug,
the patient should be apprised of the potential hazard to the fetus.
|
PRECAUTIONS
|
| |
General
|
| |
Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. Oral
or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of anticysticeral
therapy.
Cysticercosis may, in rare cases, involve the retina. Before initiating therapy for neurocysticercosis, the patient should
be examined for the presence of retinal lesions. If such lesions are visualized, the need for anticysticeral therapy should
be weighed against the possibility of retinal damage caused by albendazole- induced changes to the retinal lesion.
|
Information for the Patient
|
| |
Patients should be advised that:
| • |
Albendazole may cause fetal harm, therefore, women of childbearing age should begin treatment after a negative pregnancy test.
|
| • |
Women of childbearing age should be cautioned against becoming pregnant while on albendazole or within 1 month of completing
treatment.
|
| • |
During albendazole therapy, because of the possibility of harm to the liver or bone marrow, routine (every 2 weeks) monitoring
of blood counts and liver function tests should take place.
|
| • |
Albendazole should be taken with food.
|
|
Laboratory Tests
|
| |
- White Blood Cell Count: Albendazole has been shown to cause occasional (less than 1% of treated patients) reversible reductions in total white blood
cell count. Rarely, more significant reductions may be encountered including granulocytopenia, agranulocytosis, or pancytopenia.
Blood counts should be performed at the start of each 28 day treatment cycle and every 2 weeks during each 28 day cycle. Albedazole
may be continued if the total white blood cell count decrease appears modest and does not progress.
- Liver Function: In clinical trials, treatment with albendazole has been associated with mild to moderate elevations of hepatic enzymes in
approximately 16% of patients. These have returned to normal upon discontinuation of therapy. Liver function tests (transaminases)
should be performed before the start of each treatment cycle and at least every 2 weeks during treatment. If enzymes are significantly
increased, albendazole therapy should be discontinued. Therapy can be reinstituted when liver enzymes have returned to pretreatment
levels, but laboratory tests should be performed frequently during repeat therapy.
- Patients with abnormal liver function test results prior to commencing albendazole therapy should be carefully evaluated,
since the drug is metabolized by the liver and has been associated with hepatoxicity in a few patients.
- Theophylline: Although single doses of albendazole have been shown not to inhibit theophylline metabolism (see DRUG INTERACTIONS ), albendazole does induce cytochrome P450 1A in human hepatoma cells. Therefore, it is recommended that plasma concentrations
of theophylline be monitored during and after treatment with albendazole.
|
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
Long- term carcinogeicity studies were conducted in mice and rats. In the mouse study, albendazole was administered in the
diet at doses of 25, 100, and 400 mg/ kg/ day (0.1, 0.5, and 2 times the recommended human dose based on body surface area
in mg/ m2, respectively) for 108 weeks. In the rat study, albendazole was administered in the diet at doses of 3.5, 7, and 20 mg/ kg/
day (0.04, 0.08, and 0.21 times the recommended human dose based on body surface area in mg/ m2, respectively) for 117 weeks. There was no evidence of increased incidence of tumors in the treated mice and rats when compared
to the control group.
In genotoxicity tests, albendazole was found negative in an Ames Salmonella/ Microsome Plate mutation assay with and without
metabolic activation or with and without pre- incubation, cell- mediated Chinese Hamster Ovary chromosomal aberration test
and in vivo mouse micronucleus test. In the in vitro BALB/ 3T3 cells transformation assay, albendazole produced weak activity in the presence of metabolic activation while no
activity was found in the absence of metabolic activation.
Albendazole did not adversely affect male or female fertility in the rat at an oral dose of 30 mg/ kg/ day (0.32 times the
recommended human dose based on body surface area in mg/ m2).
|
Pregnancy, Teratogenic Effects, Pregnancy Category C
|
| |
Albendazole has been shown to be teratogenic (to cause embryotoxicity and skeletal malformations) in pregnant rats and rabbits.
The teratogenic response in the rat was shown at oral doses of 10 and 30 mg/ kg/ day (0.10 times and 0.32 times the recommended
human dose based on body surface area in mg/ m2, respectively) during gestation days 6- 15 and in pregnant rabbits at oral doses of 30 mg/ kg/ day (0.60 times the recommended
human dose based on body surface area in mg/ m2) administered during gestation days 7- 19. In the rabbit study, maternal toxicity (33% mortality) was noted at 30 mg/ kg/
day. In mice, no teratogenic effects were observed at oral doses up to 30 mg/ kg/ day (0.16 times the recommended human dose
based on body surface area in mg/ m2), administered during gestation days 6- 15.
There are no adequate and well- controlled studies of albendazole administration in pregnant women. Albendazole should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS .)
|
Nursing Mothers
|
| |
Albendazole is excreted in animal milk. It is not known whether it is excreted in human milk. Because many drugs are excreted
in human milk, caution should be exercised when albendazole is administered to a nursing woman.
|
Pediatric Use
|
| |
Experience in children under the age of 6 years is limited. In hydatid disease, infection in infants and young children in
uncommon, but no problems have been encountered in those who have been treated. In neurocysticercosis, infection is more frequently
encountered. In five published studies involving pediatric patients as young as 1 year, no significant problems were encountered,
and the efficacy appeared similar to the adult population.
|
Geriatric Use
|
| |
Experience in patients 65 years of age or older is limited. The number of patients treated for either hydatid disease or neurocysticercosis
is limited, but no problems associated with an older population have been observed.
|
|
DRUG INTERACTIONS
|
| |
- Dexamethasone: Steady- state trough concentrations of albendazole sulfoxide were about 56% higher when 8 mg dexamethasone was coadministered
with each dose of albendazole (15 mg/ kg/ day) in 8 neurocysticercosis patients.
- Praziquantel: In the fed state, praziquantel (40 mg/ kg) increased mean maximum plasma concentration and area under the curve of albendazole
sulfoxide by about 50% in healthy subjects (n=10) compared with a separate group of subjects (n=6) given albendazole alone.
Mean Tmax and mean plasma elimination half- life of albendazole sulfoxide were unchanged. The pharmacokinetics of praziquantel were
unchanged following coadministration with albendazole (400 mg).
- Cimetidine: Albendazole sulfoxide concentrations in bile and cystic fluid were increased (about 2- fold) in hydatid cyst patients treated
with cimetidine (10 mg/ kg/ day) (n=7) compared with albendazole (20 mg/ kg/ day) alone (n=12). Albendazole sulfoxide plasma
concentrations were unchanged 4 hours after dosing.
- Theophylline: The pharmacokinetics of theophylline (amino- phylline 5.8 mg/ kg infused over 20 minutes) were unchanged following a single
oral dose of albendazole (400 mg) in 6 healthy subjects.
|
ADVERSE REACTIONS
|
| |
The adverse event profile of albendazole differs between hydatid disease and neurocysticercosis. Adverse events occurring
with a frequency of ≥1% in either disease are described in TABLE 1 .
These symptoms were usually mild and resolved without treatment. Treatment discontinuations were predominantly due to leukopenia
(0.7%) or hepatic abnormalities (3.8% in hydatid disease). The following incidence reflects events that were reported by investigators
to be at least possibly or probably related to albendazole.
| TABLE 1
Adverse Event Incidence ≥1% in Hydatid Disease and Neurocysticercosis
|
| Adverse Event |
Hydatid Disease |
Neurocysticercosis |
| Abnormal liver function tests |
15.6% |
<1.0% |
| Abdominal pain |
6.0% |
0% |
| Nausea/ vomiting |
3.7% |
6.2% |
| Headache |
1.3% |
11.0% |
| Dizziness/ vertigo |
1.2% |
<1.0% |
| Raised intracranial pressure |
0% |
1.5% |
| Meningeal signs |
0% |
1.0% |
| Reversible alopecia |
1.6% |
<1.0% |
| Fever |
1.0% |
0% |
|
The following adverse events were observed at an incidence of <1%:
- Hematologic: Leukopenia. There have been rare reports of granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia (see WARNINGS ).
- Dermatologic: Rash, urticaria.
- Hypersensitivity: Allergic reactions.
- Renal: Acute renal failure related to albendazole therapy has been observed.
|
OVERDOSAGE
|
| |
Significant toxicity and mortality were shown in male and female mice at doses exceeding 5000 mg/ kg; in rats, at estimated
doses between 1300 and 2400 mg/ kg; in hamsters, at doses exceeding 10, 000 mg/ kg; and in rabbits, at estimated doses between
500 and 1250 mg/ kg. In the animals, symptoms were demonstrated in a dose- response relationship and included diarrhea, vomiting,
tachycardia, and respiratory distress.
One overdosage has been reported with albendazole in a patient who took at least 16 g over 12 hours. No untoward effects were
reported. In case of overdosage, symptomatic therapy ( e.g., gastric lavage and activated charcoal) and general supportive measures are recommended.
|
DOSAGE AND ADMINISTRATION
|
| |
Dosing of albendazole will vary, depending upon which parasitic infections is being treated. (See TABLE 2.)
| TABLE 2
|
| |
Patient Weight |
Dose |
Duration |
| Hydatid Disease
|
| |
60 kg or greater |
400 mg bid, with meals |
28 day cycle followed by a 14 day albendazole- free interval, for a total of 3 cycles |
| |
Less than 60 kg |
15 mg/ kg/ day given in divided doses bid with meals (maximum total daily dose 800 mg) |
|
| |
NOTE: When administering albendazole in the pre- or post- surgical setting, optimal killing of cyst contents is achieved when
three courses of therapy have been given.
|
| Neurocysticercosis
|
| |
60 kg or greater |
400 mg bid, with meals |
8- 30 days |
| |
Less than 60 kg |
15 mg/ kg/ day given in divided doses bid with meals (maximum total daily dose 800 mg) |
|
|
Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. Oral
or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of treatment.
|
HOW SUPPLIED
|
| |
Albenza is supplied as 200 mg, white to off- white, circular, biconvex, bevel- edged, film- coated Tiltab tablets.
Storage: Store between 20- 25°C (68- 77°F).
|
PRODUCT IDENTIFICATION
|
| |
None Available |
PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| tablet - oral - 200 mg -
|
| 112.0's |
$167.16 |
Albenza
GlaxoSmithKline
|
00007550040 |
|
|