Amedrapharma.com

PRESCRIBING INFORMATION
ALBENZA®
(albendazole)
Tablets
Rχ only

DESCRIPTION
ALBENZA (albendazole) is an orally administered broad-spectrum anthelmintic. Chemically, it
is methyl 5-(propylthio)-2-benzimidazolecarbamate. Its molecular formula is C12H15N3O2S. Its
molecular weight is 265.34. It has the following chemical structure:
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 tablet contains
200 mg of albendazole.
Inactive ingredients consist of: carnauba wax, hypromellose, 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 to 5 hours after
dosing and are on average 1.31 mcg/mL (range 0.46 to 1.58 mcg/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 to 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, and 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 mg to 300 mg (approximately 10
mg/kg) albendazole to 3 fasted and 2 fed pediatric patients with hydatid cyst disease (age range 6
to 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 principal mode of action for albendazole is by its inhibitory effect on
tubulin 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
Taenia solium
INDICATIONS AND USAGE
ALBENZA is indicated for the treatment of the following infections:
Neurocysticercosis: ALBENZA 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% to 88% reduction in number of cysts; 40% to 70% of
albendazole-treated patients showed resolution of all active cysts.

Hydatid Disease: ALBENZA 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 to 90% of patients given ALBENZA 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 ALBENZA in the pre- or post-surgical setting, optimal killing of
cyst contents is achieved when 3 courses of therapy have been given.
NOTE: The efficacy of albendazole in the therapy of alveolar hydatid disease caused by
Echinococcus multilocularis has not been clearly demonstrated in clinical studies.
CONTRAINDICATIONS
ALBENZA is contraindicated in patients with known hypersensitivity to the benzimidazole class
of compounds or any components of ALBENZA.
WARNINGS
Rare fatalities associated with the use of ALBENZA have been reported due to granulocytopenia
or pancytopenia (see PRECAUTIONS). Albendazole has been shown to cause bone marrow
suppression, aplastic anemia, and agranulocytosis in patients with and without underlying
hepatic dysfunction. Blood counts should be monitored at the beginning of each 28- day cycle of
therapy, and every 2 weeks while on therapy with albendazole in all patients. Patients with liver
disease, including hepatic echinococcosis, appear to be more at risk for bone marrow suppression
leading to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia attributable to
albendazole and warrant closer monitoring of blood counts. Albendazole should be discontinued
in all patients if clinically significant decreases in blood cell counts occur.
Albendazole 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 pregnancy 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.
Pre-existing neurocysticercosis may also be uncovered in patients treated with albendazole for
other conditions. Patients may experience neurological symptoms (e.g. seizures, increased
intracranial pressure and focal signs) as a result of an inflammatory reaction caused by death of
the parasite within the brain. Symptoms may occur soon after treatment; appropriate steroid and
anticonvulsant therapy should be started immediately.
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 Patients: Patients should be advised that:
• Some people, particularly young children, may experience difficulties swallowing the tablets whole. In young children, the tablets should be crushed or chewed and swallowed with a drink of water. • 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 in all patients. Patients with liver
disease, including hepatic echinococcosis, appear to be more at risk of bone marrow suppression
and warrant closer monitoring of blood counts (see WARNINGS). Albendazole should be
discontinued in all patients if clinically significant decreases in blood cell counts occur.

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 elevations have
generally returned to normal upon discontinuation of therapy. There have also been case reports
of acute liver failure of uncertain causality and hepatitis (see ADVERSE REACTIONS).
Liver function tests (transaminases) should be performed before the start of each treatment cycle
and at least every 2 weeks during treatment. If hepatic enzymes exceed twice the upper limit of
normal, consideration should be given to discontinuing albendazole therapy based on individual
patient circumstances. Restarting albendazole treatment in patients whose hepatic enzymes have
normalized off treatment is an individual decision that should take into account the risk/benefit
of further albendazole usage. Laboratory tests should be performed frequently if albendazole
treatment is restarted.
Patients with abnormal liver function test results are at increased risk for hepatotoxicity and bone
marrow suppression (see WARNINGS). Therapy should be discontinued if liver enzymes are
significantly increased or if clinically significant decreases in blood cell counts occur.
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 ALBENZA.
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 (aminophylline 5.8 mg/kg infused over
20 minutes) were unchanged following a single oral dose of albendazole (400 mg) in 6 healthy
subjects.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term carcinogenicity
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 to 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 to 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 to 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 is uncommon, but no problems have been encountered in
those who have been treated. In neurocysticercosis, infection is more frequently encountered. In
5 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.

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 the table
below.
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.
Adverse Event Incidence ≥1% in Hydatid Disease and Neurocysticercosis
Adverse Event
Hydatid Disease
Neurocysticercosis
The following adverse events were observed at an incidence of <1%: Blood and Lymphatic System Disorders: Leukopenia. There have been rare reports of
granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia (see WARNINGS).
Patients with liver disease, including hepatic echinococcosis, appear to be more at risk of bone
marrow suppression (see WARNINGS and PRECAUTIONS).
Immune System Disorders: Hypersensitivity reactions, including rash and urticaria.

Postmarketing Adverse Reactions: In addition to adverse events reported from clinical
trials, the following events have been identified during world-wide post-approval use of
ALBENZA. Because they are reported voluntarily from a population of unknown size, estimates
of frequency cannot be made. These events have been chosen for inclusion due to a combination
of their seriousness, frequency of reporting, or potential causal connection to ALBENZA.

Blood and Lymphatic System Disorders: Aplastic anemia, bone marrow suppression,
neutropenia.

Hepatobiliary Disorders: Elevations of hepatic enzymes, hepatitis, acute liver failure.

Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson
syndrome.

Renal and Urinary Disorders: Acute renal failure.
OVERDOSAGE
Significant toxicity and mortality were shown in male and female mice at doses exceeding 5,000
mg/kg; in rats, at estimated doses between 1,300 and 2,400 mg/kg; in hamsters, at doses
exceeding 10,000 mg/kg; and in rabbits, at estimated doses between 500 and 1,250 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 ALBENZA in a patient who took at least 16 grams over
12 hours. No untoward effects were reported. In case of overdosage, symptomatic therapy and
general supportive measures are recommended.
DOSAGE AND ADMINISTRATION
Dosing of ALBENZA will vary, depending upon which of the following parasitic infections is
being treated. In young children, the tablets should be crushed or chewed and swallowed with a
drink of water.
Indication
Patient Weight
Duration
with meals (maximum total daily dose 800 mg) NOTE: When administering ALBENZA in the pre- or post-surgical setting, optimal killing of cyst contents is achieved when 3 courses of therapy have been given. 15 mg/kg/day given in divided doses twice daily 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 tablet embossed “ap” and “550”. They are supplied as follows:
Bottles of 2 NDC 52054-550-22
Bottles of 28 NDC 52054-550-28
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
ALBENZA and TILTAB are registered trademarks of GlaxoSmithKline, used with permission.
Manufactured by: GlaxoSmithKline Mississauga, Ontario L5N 6L4 Canada Distributed by: Amedra Pharmaceuticals LLC Horsham, PA 19044 LB# 799-03

Source: http://www.amedrapharma.com/docs/Albenza.pdf