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.
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 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.
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.
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.
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.
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.
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).
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.
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 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).
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.
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.
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.