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  • CLASSES

    Antinematodal Agents

    DEA CLASS

    Rx

    DESCRIPTION

    Oral broad-spectrum antihelmintic antiparasitic agent (benzimidazole class)
    Used for hydatid cyst disease and neurocysticercosis; many off-label uses
    Similar to mebendazole and thiabendazole but better tolerated

    COMMON BRAND NAMES

    Albenza

    HOW SUPPLIED

    Albenza Oral Tab: 200mg

    DOSAGE & INDICATIONS

    For the treatment of hydatid cyst disease.
    Oral dosage
    Adults >= 60 kg

    400 mg PO twice daily with meals for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles.

    Adults < 60 kg

    15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles.

    Children and Adolescents

    15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 28 days followed by a 14-day drug-free period. Repeat for 2 more cycles. Published data in pediatric patients for this indication are limited, particularly in infants and young children, in whom hydatid disease is uncommon.

    For the treatment of cysticercosis or neurocysticercosis (larval form of T. solium).
    NOTE: Patients should receive steroid and anticonvulsant therapy as required. Oral or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of treatment.
    Oral dosage
    Adults >= 60 kg

    400 mg PO twice daily for 8—30 days.

    Adults < 60 kg

    15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 8—30 days.

    Children and Adolescents

    15 mg/kg/day PO given in 2 divided doses (Max: 800 mg/day) for 8—30 days. Although pediatric data are limited, the FDA-approved product label states that the efficacy of albendazole in children with neurocysticercosis appears to be similar to adults.

    For the treatment of ascariasis†, enterobiasis (pinworm infection)†, hookworm infection†, or trichuriasis†.
    Oral dosage
    Adults, Adolescents, and Children >= 2 years

    400 mg PO as a single dose. May repeat in 3 weeks.

    Children < 2 years

    200 mg PO single dose. May repeat in 3 weeks.

    For the treatment of capillariasis†.
    Oral dosage
    Adults, Adolescents, and Children >= 2 years

    200 mg PO twice daily for 10 days.

    For the secondary treatment of cutaneous larva migrans†.
    Oral dosage
    Adults

    400 mg PO once daily for 3 days.

    Children

    5 mg/kg/day PO for 3 days.

    For the secondary treatment of giardiasis†.
    Oral dosage
    Adults

    400 mg PO daily for 3 days.

    For the treatment of microsporidiosis† and for secondary microsporidiosis prophylaxis†.
    NOTE: According to the HIV treatment guidelines, initiating antiretroviral therapy (ART) before severe immunosuppression develops is key to preventing chronic microsporidiosis, as infection most commonly occurs in patients with CD4 counts < 100 cells/mm3. Other preventative measures for patients with CD4 counts < 200 cells/mm3 include: avoid untreated water sources; avoid consuming undercooked meat or seafood; limit exposure to animals known to be infected with microsporidia.
    NOTE: All patients infected with microsporidiosis should be offered ART as part of the initial treatment.
    For the treatment of microsporidiosis† including Encephalitozoon intestinalis infection.
    Oral dosage
    Adults and Adolescents

    400 mg PO twice daily to 1600 mg PO twice daily has been used. Average dosage is 800 mg PO twice daily. May take up to 2 months to see effect.

    For the treatment or secondary prophylaxis of disseminated (non-ocular) and gastrointestinal infections associated with microsporidiosis† (not including Enterocytozoon bieneusi or Vittaforma corneae) in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

     400 mg PO twice daily. The HIV guidelines recommend continuing treatment until CD4 count > 200 cells/mm3 for at least 6 months after the initiation of antiretroviral therapy.

    Infants and Children

     7.5 mg/kg (Max: 400 mg) PO twice daily until immune reconstitution after the initiation of antiretroviral therapy.

    For the treatment or secondary prophylaxis of disseminated (non-ocular) infections associated with microsporidiosis† and attributed to Trachipleistophora or Anncaliia in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

      400 mg PO twice daily in combination with itraconazole 400 mg PO once daily. The HIV guidelines recommend continuing treatment until CD4 count > 200 cells/mm3 for at least 6 months after the initiation of antiretroviral therapy.

    For treatment or secondary prophylaxis of ocular infections due to microsporidiosis† caused by microsporidia other than V. corneae in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    400 mg PO twice daily in combination with topical fumagillin bicylohexylammonium eye drops (investigational in the U.S.). According to the HIV guidelines, treatment discontinuation may be considered if signs and symptoms of the ocular infection resolve and the CD4 count is > 200 cells/mm3.

    Infants and Children

     7.5 mg/kg (Max: 400 mg/dose) PO twice daily in combination with topical fumagillin (investigational in the U.S.) as lifelong therapy.

    For the treatment of strongyloidiasis† or taeniasis† (tapeworm infection†).
    Oral dosage
    Adults, Adolescents, and Children > = 2 years

    400 mg PO once daily for 3 days. May repeat course in 3 weeks.

    Children < 2 years

    200 mg PO once daily for 3 days. May repeat course in 3 weeks. 

    For the treatment of trichinosis†.
    Oral dosage
    Adults

    400 mg PO twice daily for 15 days.

    For the treatment of trichostrongyliasis†.
    Oral dosage
    Adults

    400 mg PO single dose.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    15 mg/kg/day PO or 800 mg/day PO for most indications; up to 3200 mg/day PO in HIV patients with microsporidiosis.

    Geriatric

    15 mg/kg/day PO or 800 mg/day PO for most indications.

    Adolescents

    15 mg/kg/day PO, not to exceed 800 mg/day PO.

    Children

    15 mg/kg/day PO, not to exceed 800 mg/day PO.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Patients with abnormal liver function tests prior to beginning albendazole therapy should be carefully evaluated. In patients with evidence of extrahepatic biliary obstruction, the systemic exposure of albendazole sulfoxide is increased and the elimination is prolonged.

    Renal Impairment

    The pharmacokinetics of albendazole in patients with renal impairment have not been studied; however, renal elimination of albendazole and albendazole sulfoxide is negligible and dosage adjustment in renal impairment is not expected to be necessary.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Administer with food, preferably a high-fat meal, to increase oral bioavailability.
    Albendazole tablets may be chewed or crushed.

    STORAGE

    Albenza:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Albendazole is contraindicated in any person with known hypersensitivity to albendazole, the benzimidazole class of compounds, or any product components.

    Biliary obstruction, biliary tract disease, hepatic disease, hepatitis

    Use albendazole with caution in patients with hepatic disease or biliary tract disease. Albendazole is extensively metabolized by the liver; hepatic clearance may be impaired if hepatic disease or biliary obstruction are present and may result in increased side effects. Albendazole can cause elevated liver enzymes, which usually resolves after discontinuation of therapy; however, there have been cases of acute liver failure of unknown causality and hepatitis. In addition, patients with increased liver enzymes and those with hepatic echinococcosis are at increased risk for hepatotoxicity and suppression of bone marrow. Monitor liver enzymes (transaminases) and blood counts before the start of each cycle and at least every 2 weeks during treatment. If liver enzymes exceed twice the upper limit of normal, consider discontinuing therapy based on the clinical situation. When liver enzymes return to baseline, consideration may be given to restarting albendazole. If albendazole is restarted, laboratory tests should be monitored frequently.

    Driving or operating machinery

    Central nervous system effects, including dizziness and drowsiness, are common with albendazole therapy. Patients should be advised to avoid activities that require mental alertness, such as driving or operating machinery, until they know how albendazole treatment affects them.

    Retinal cysticercosis

    Cysticercosis may rarely involve the retina. Before initiating therapy for neurocysticercosis, the patient should be examined for retinal lesions (retinal cysticercosis). The benefits of starting albendazole therapy should be weighed against the possibility of retinal damage caused by albendazole-induced changes to existing ocular lesions. Patients being treated for neurocysticercosis should receive appropriate corticosteroid therapy (e.g., dexamethasone) and anticonvulsant therapy.

    Agranulocytosis, anemia, bone marrow suppression, chemotherapy, leukopenia, neutropenia

    Albendazole may cause bone marrow suppression and should be used cautiously in any patient predisposed to leukopenia or neutropenia or other bone marrow suppression (e.g., recent chemotherapy). A complete blood cell count with differential should be performed at the start of each 28-day treatment cycle and every 2 weeks during each 28-day cycle. Albendazole may be continued if the total white blood cell count and absolute neutrophil count decrease is modest and does not progress. Rare fatalities associated with the use of albendazole have been reported due to granulocytopenia, agranulocytosis, and pancytopenia. Patients with hepatic disease, including hepatic echinococcosis, appear more likely to develop bone marrow suppression leading to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia due to albendazole. Therefore, closer monitoring of blood counts is needed in these patients. Discontinue albendazole if clinically significant decreases in blood cell counts occur.

    Increased intracranial pressure, seizures

    Patients being treated for neurocystericercosis with albendazole should receive appropriate anticonvulsant and steroid therapy during therapy to prevent neurological symptoms (seizures, increased intracranial pressure, and focal signs) and cerebral hypertensive episodes, especially during the first week of anticysterceral therapy. Inflammatory reactions occur due to parasite death within the brain. For patients treated with albendazole for other indications, pre-existing neurocystericercosis may result in neurological symptoms soon after treatment is initiated; therefore, appropriate steroid and anticonvulsant therapy should started immediately.  Experts state that antiparasitic drugs are contraindicated in patients with cerebral edema (cysticercal encephalitis).

    Children, infants, neonates

    Safety and efficacy of albendazole have not been established in neonates and infants, and data are limited in children < 6 years of age. In hydatid disease, infection in infants and young children is uncommon. Neurocysticercosis infections in children are more frequently encountered and the efficacy of albendazole in children appears to be similar to adults.

    Pregnancy

    Albendazole is classified as FDA pregnancy risk category C. The FDA-labeling states that albendazole should not be used during pregnancy except in clinical situations where no acceptable alternative is available. However, the World Health Organization (WHO) supports the use of albendazole as antihelminthic therapy after the first trimester of pregnancy. Albendazole has been shown to be teratogenic in pregnant rats and rabbits; however, data suggest that bioavailability is significantly higher in rats than in humans and there are reports of successful use during human pregnancy. A report of 10 women exposed to accidental high doses of albendazole during the first trimester states that all women delivered normal infants and that some of the infants were followed for up to one year without incident. In a randomized, placebo-controlled field trial in which anthelmintic treatment was studied to control maternal anemia due to parasitic infections, 61 pregnant women were administered a single 400 mg oral dose during the second trimester with no observed adverse outcomes associated with albendazole.

    Contraception requirements, pregnancy testing, reproductive risk

    Advise female patients of the reproductive risk associated with albendazole use. Obtain pregnancy testing prior to prescribing albendazole to females of reproductive potential. Discuss contraception requirements with the patient: adequate birth control must be used during albendazole treatment and for 1 month after therapy. If a patient becomes pregnant while taking albendazole, the drug should be discontinued. If albendazole is the only acceptable treatment option, counsel the patient on the risks of continuing therapy during the pregnancy (see pregnancy precaution).

    Breast-feeding

    It is not known whether albendazole is distributed into human breast milk, but distribution of albendazole sulfoxide, the active primary metabolite, may occur. Albendazole serum concentrations are undetectable in plasma as it is rapidly converted to albendazole sulfoxide. A consultation group to the World Health Organization (WHO) suggested that a single oral dose of albendazole can be administered to breast-feeding women, but there are no recommendations for multiple doses. In single dose studies (400 mg PO), the mean peak milk concentration of albendazole sulfoxide was 351.9 mcg/L occurring at a mean of 6.9 hours and was calculated from data of 20 women. The half-life of albendazole sulfoxide in breast milk was 12.4 hours. Based on this information, it was estimated that a fully breast-fed infant would be exposed to < 0.1 mg/kg of albendazole sulfoxide over 36 hours after a single maternal dose.  Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    Severe

    hepatic failure / Delayed / 0-1.0
    renal failure (unspecified) / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known

    Moderate

    elevated hepatic enzymes / Delayed / 0-16.0
    hepatitis / Delayed / 0-1.0
    blurred vision / Early / Incidence not known

    Mild

    diarrhea / Early / Incidence not known
    drowsiness / Early / Incidence not known
    asthenia / Delayed / Incidence not known

    DRUG INTERACTIONS

    Amitriptyline: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Amitriptyline; Chlordiazepoxide: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Phenobarbital appears to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. It is not clear if these pharmacokinetic interactions affect the therapeutic efficacy of albendazole in the treatment of neurocysticercosis. Monitor patient clinical response closely during treatment.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Phenobarbital appears to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. It is not clear if these pharmacokinetic interactions affect the therapeutic efficacy of albendazole in the treatment of neurocysticercosis. Monitor patient clinical response closely during treatment.
    Carbamazepine: (Minor) Enzyme-inducing antiepileptic drugs, such as carbamazepine, appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
    Cimetidine: (Moderate) Cimetidine administration with albendazole has been reported to increase albendazole bioavailability. Concentrations of albendazole sulfoxide were increased in bile and cystic fluid about 2 fold in patients with hydatid cyst disease treated with cimetidine 10 mg per kg per day concomitantly with albendazole compared to administration of albendazole alone. More data are needed to elucidate the clinical consequence of this interaction.
    Clomipramine: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Clozapine: (Moderate) Albendazole induces cytochrome P450 1A. and may induce the metabolism of clozapine. Patients receiving this combination should be closely monitored when albendazole is prescribed, as albendazole may increase the clearance of clozapine. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of the clozapine, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Desipramine: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Dexamethasone: (Minor) Concomitant administration of albendazole with dexamethasone increases the plasma concentration of albendazole sulfoxide, presumably via reduction in albendazole sulfoxide clearance.
    Doxepin: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Fluoxetine; Olanzapine: (Moderate) Albendazole induces CYP1A, and although not studied, may induce the metabolism of olanzapine. Patients receiving these combinations should be closely monitored when albendazole is prescribed, as albendazole may increase the clearance of olanzapine. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Food: (Moderate) Albendazole tablets should be administered with a fatty meal to increase bioavailability and ensure therapeutic efficacy.
    Grapefruit juice: (Moderate) Grapefruit juice appears to increase the bioavailability of albendazole via reduction of CYP3A4-mediated metabolism in the intestinal mucosa. The AUC and Cmax of albendazole increased approximately 3-fold and the half-life was shortened by 46 percent when administered with grapefruit juice. The clinical consequence of the interaction is not clear, Patients should be advised to not significantly alter their intake of grapefruit juice during albendazole therapy.
    Hydantoins: (Minor) Antiepileptic drugs (AEDs) are often administered concomitantly with albendazole for the treatment of neurocysticercosis. Hydantoins appear to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. Monitor patient clinical response closely during treatment.
    Imipramine: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Mexiletine: (Moderate) Albendazole induces cytochrome P450 1A and may induce the metabolism of mexiletine. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Nortriptyline: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Olanzapine: (Moderate) Albendazole induces CYP1A, and although not studied, may induce the metabolism of olanzapine. Patients receiving these combinations should be closely monitored when albendazole is prescribed, as albendazole may increase the clearance of olanzapine. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Perphenazine; Amitriptyline: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Phenobarbital: (Minor) Phenobarbital appears to induce the oxidative metabolism of albendazole. Notably, a significant reduction in the plasma concentration of the active albendazole sulfoxide metabolite may occur. It is not clear if these pharmacokinetic interactions affect the therapeutic efficacy of albendazole in the treatment of neurocysticercosis. Monitor patient clinical response closely during treatment.
    Praziquantel: (Moderate) The serum concentration of albendazole may be increased if coadministered with praziquantel. Use albendazole cautiously in combination with praziquantel.
    Protriptyline: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Ropinirole: (Moderate) Albendazole induces CYP1A and may induce the metabolism of ropinirole. Patients receiving this combination should be closely monitored when albendazole is prescribed, as albendazole may increase the clearance of ropinirole. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of ropinirole, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Tacrine: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tacrine. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Theophylline, Aminophylline: (Moderate) Albendazole has been shown to induce the hepatic CYP1A microsomal enzymes. It is possible that the prescription of albendazole may result in an increased clearance of theophylline via induction of CYP1A enzymes. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of theophylline, leading to an increase in serum theophylline concentrations. Theophylline serum concentrations and the patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy. (Moderate) Albendazole has been shown to induce the hepatic CYP1A microsomal enzymes. It is possible that the prescription of albendazole may result in an increased clearance of aminophylline via induction of CYP1A enzymes. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of aminophylline, leading to an increase in serum aminophylline concentrations. Aminophylline serum concentrations and the patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Tricyclic antidepressants: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Trimipramine: (Moderate) Albendazole induces cytochrome P450 1A and although not studied, may induce the metabolism of tricyclic antidepressants. Albendazole may increase the clearance of the tricyclic antidepressants. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of tricyclic antidepressants, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Warfarin: (Moderate) Albendazole induces cytochrome P450 1A (CYP1A) and although not studied, may induce the metabolism of R-warfarin. Patients receiving albendazole in combination should be closely monitored when albendazole is prescribed. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of R-warfarin, leading to an increase in anticoagulant effect. The patient's clinical status and INR should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    Albendazole is classified as FDA pregnancy risk category C. The FDA-labeling states that albendazole should not be used during pregnancy except in clinical situations where no acceptable alternative is available. However, the World Health Organization (WHO) supports the use of albendazole as antihelminthic therapy after the first trimester of pregnancy. Albendazole has been shown to be teratogenic in pregnant rats and rabbits; however, data suggest that bioavailability is significantly higher in rats than in humans and there are reports of successful use during human pregnancy. A report of 10 women exposed to accidental high doses of albendazole during the first trimester states that all women delivered normal infants and that some of the infants were followed for up to one year without incident. In a randomized, placebo-controlled field trial in which anthelmintic treatment was studied to control maternal anemia due to parasitic infections, 61 pregnant women were administered a single 400 mg oral dose during the second trimester with no observed adverse outcomes associated with albendazole.

    Advise female patients of the reproductive risk associated with albendazole use. Obtain pregnancy testing prior to prescribing albendazole to females of reproductive potential. Discuss contraception requirements with the patient: adequate birth control must be used during albendazole treatment and for 1 month after therapy. If a patient becomes pregnant while taking albendazole, the drug should be discontinued. If albendazole is the only acceptable treatment option, counsel the patient on the risks of continuing therapy during the pregnancy (see pregnancy precaution).

    MECHANISM OF ACTION

    Mechanism of Action: Benzimidazole antihelmintic agents inhibit the polymerization of tubulin and the microtubule-dependent uptake of glucose by binding free ß-tubulin. Albendazole selectively damages cytoplasmic microtubules in the absorptive and intestinal cells of nematodes but not of the host. This microtubular deterioration is irreversible and leads to disruption of absorptive and secretory functions of the cells, which are essential to the organism's survival. This disruption results in accumulation of secretory substances in the Golgi apparatus, decreased glucose uptake, and depleted endogenous glycogen stores in the helminth. Due to diminished energy production the parasite is immobilized and eventually dies. Albendazole is larvicidal in necatoriasis and ovicidal in ascariasis, ancylostomiasis, and trichuriasis. Resistance to albendazole has been documented in animals and is due to loss of affinity to tubulin binding sites.In general, the following organisms are susceptible to albendazole: Echinococcus granulosus (dog tapeworm), Taenia saginata (beef tapeworm), Taenia solium (pork tapeworm), Trichinella spiralis (pork worm), Trichuris trichiura (whipworm), Enterobius vermicularis (pinworm), Strongyloides stercoralis (threadworm), Ascaris lumbricoides (roundworm), Ancylostoma duodenale (hookworm), and Necator americanus (hookworm).

    PHARMACOKINETICS

    Albendazole is administered orally. In the treatment of hydatid disease, tissue concentrations of albendazole sulfoxide > 500 ng/mL are required for therapeutic efficacy. Albendazole sulfoxide is 70% protein bound and has a half life of approximately 8—12 hours. Concentrations in plasma are approximately 3-fold to 10-fold and 2-fold to 4-fold higher than those seen in cyst fluid and CSF, respectively. Albendazole is extensively metabolized by the liver to albendazole sulfoxide, the primary active metabolite.The primary elimination route is the bile. Renal elimination is negligible (< 1%).
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP1A
    Albendazole induces cytochrome P450 1A enzymes and may induce its own metabolism. After 4 weeks of treatment with albendazole (200 mg 3 times daily), plasma concentrations were 20% lower than those observed in the first half of the treatment period in 12 patients.

    Oral Route

    The chewable tablets have been shown to be bioequivalent to the oral tablets. After oral administration, albendazole is poorly absorbed from the GI tract. To increase bioavailability, it is recommended to give albendazole with a high-fat meal; the absorption of albendazole increases between 5 to 6.5-fold compared to when given with a non-fatty meal. Grapefruit juice also increases albendazole's oral bioavailability. After oral administration, peak plasma concentrations are reached at approximately 4.5 hours (range, 2—10 hours) when given with a fatty meal compared with 3 hours (range, 1—5 hours) in the fasted state. After administration of albendazole (400 mg) regular tablets with a fatty meal, peak plasma concentrations of albendazole sulfoxide were on average 1310 ng/mL (range, 460—1580 ng/mL) in 6 patients with hydatid disease. Concentrations of albendazole sulfoxide appear to increase in a dose-proportional manner over the therapeutic range after administration with a high-fat meal. Average peak plasma concentrations of albendazole sulfoxide after administration of a 400-mg dose of chewable tablets were 804 ng/mL (range, 202—2244 ng/mL) and 218 ng/mL (range, 54—592 ng/mL) in the fed and fasted states, respectively. In the treatment of hydatid disease, tissue concentrations of albendazole sulfoxide > 500 ng/mL are required for therapeutic efficacy.