Albendazole Drug Information

Neurocysticercosis Albendazole is indicated for the treatment of parenchymal neurocysticercosis due to

active lesions caused by larval forms of the pork tapeworm, Taenia solium.

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction profile of albendazole differs between hydatid disease and neurocysticercosis. Adverse reactions occurring with a frequency of 1% or greater in either disease are described in Table 2 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 adverse reactions that were reported to be at least possibly or probably related to albendazole. T able 2: Adverse Reaction Incidence 1% or Greater in Hydatid Disease and Neurocysticercosis A dverse Reaction H ydatid Disease N eurocysticercosis G astrointestinal Abdominal Pain 6 0 Nausea 4 6 Vomiting 4 6 G eneral disorders and administration site conditions Fever 1 0 Investigations Elevated Hepatic Enzymes 16 less than 1 N ervous system disorders Dizziness 1 less than 1 Headache 1 11 Meningeal Signs 0 1 Raised Intracranial Pressure 0 2 Vertigo 1 less than 1 Skin and subcutaneous tissue disorders Reversible Alopecia 2 less than 1 The following adverse events were observed at an incidence of less than 1%: Blood and Lymphatic System Disorders: There have been reports of leukopenia, granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia . Immune System Disorders: Hypersensitivity reactions, including rash and urticaria.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of albendazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders: Aplastic anemia, bone marrow suppression, neutropenia.

Eye Disorders: Vision blurred. Gastrointestinal Disorders: Diarrhea. General System Disorders: Asthenia.

Hepatobiliary Disorders: Elevations of hepatic enzymes, hepatitis, acute liver failure. Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis. Nervous System Disorders: Somnolence, convulsion.

Renal and Urinary Disorders: Acute renal failure. Skin and Subcutaneous Tissue Disorders: Erythema multiforme, Stevens-Johnson syndrome.

Dexamethasone Steady-state trough concentrations of albendazole sulfoxide were about 56% higher when

8 mg dexamethasone was co-administered 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 T max and mean plasma elimination half-life of albendazole sulfoxide were unchanged. The pharmacokinetics of praziquantel were unchanged following co-administration 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 Following a single dose of albendazole (400 mg), the pharmacokinetics of

theophylline (aminophylline 5.8 mg/kg infused over 20 minutes) were unchanged. Albendazole induces cytochrome P450 1A in human hepatoma cells; therefore, it is recommended that plasma concentrations of theophylline be monitored during and after treatment.

Pregnancy Risk Summary There are limited data on use of albendazole in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In published studies, single-dose albendazole exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes; however, this finding cannot be extrapolated to multiple-dose exposures ( see Data ). In animal reproductive studies, oral administration of albendazole during gestation caused embryotoxicity and skeletal malformations in pregnant rats (at oral doses of 0.10 times and 0.32 times the recommended human dose based on body surface area in mg/m 2 ) and pregnant rabbits (at oral doses of 0.60 times the recommended human dose based on body surface area in mg/m 2 ). Albendazole was also associated with maternal toxicity in rabbits (at doses of 0.60 times the recommended human dose based on body surface area in mg/m 2 ) ( see Data ). Albendazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Albendazole should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate.

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. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data A Cochrane review could not provide sufficient evidence of the impact of antihelminthics (including albendazole) on the pregnancy outcomes of low birthweight, perinatal mortality and preterm birth. In a large trial of about 2507 women, albendazole use during the second or third trimester of pregnancy had no overall effect on birth weight, perinatal mortality, or congenital anomalies.

With a limited sample size and single-does exposure, another study could not rule out a two-fold increased risk of major malformations. Animal Data 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/m 2, 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/m 2 ) 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/m 2 ), administered during gestation days 6 to 15.

Pediatric Use Hydatid disease is uncommon in infants and young children. In neurocysticercosis, the efficacy of albendazole in children appears to be similar to that in adults.

Albendazole is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds or any components of albendazole. Patients with known hypersensitivity to the benzimidazole class of compounds or any components of albendazole.

In case of overdosage, symptomatic therapy and general supportive measures are recommended.