ALBENDAZOLE tablet, film coated

Albendazole by

Drug Labeling and Warnings

Albendazole by is a Prescription medication manufactured, distributed, or labeled by Northstar Rx LLC., Zydus Pharmaceuticals (USA) Inc., Cadila Healthcare Limited. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    1.1 Neurocysticercosis

    Albendazole tablets are indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium.

    1.2 Hydatid Disease

    Albendazole tablets are 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.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Dosage

    Dosing of albendazole will vary depending upon the indication. Albendazole tablets may be crushed or chewed and swallowed with a drink of water. Albendazole tablets should be taken with food [see Clinical Pharmacology (12.3)].

    Table 1 AlbendazoleDosage
    Indication
    		Patient Weight
    		Dose
    		Duration
    Hydatid Disease
    		 60 kg or greater
    		 400 mg twice daily, 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 twice daily with meals (maximum total daily dose 800 mg)
    Neurocysticercosis
    		 60 kg or greater
    		 400 mg twice daily, with meals
    		 8 to 30 days
    Less than 60 kg
    		 15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)

    2.2 Concomitant Medication to Avoid Adverse Reactions

    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 [see Warnings and Precautions (5.3)].

    2.3 Monitoring for Safety Before and During Treatment

    • Monitor blood counts at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy with albendazole in all patients [see Warnings and Precautions (5.1) ].
    • Monitor liver enzymes (transaminases) at the beginning of each 28-day cycle of therapy, and at least every 2 weeks during treatment with albendazole in all patients [see Warnings and Precautions (5.5) ]
    • Obtain a pregnancy test in females of reproductive potential prior to therapy [see Warnings and Precautions (5.2) ].
  • 3 DOSAGE FORMS AND STRENGTHS

    Albendazole tablets USP, 200 mg are white to off-white, round, film coated tablets debossed '1021' on one side and plain on the other side.

  • 4 CONTRAINDICATIONS

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

  • 5 WARNINGS AND PRECAUTIONS

    5.1 Bone Marrow Suppression

    Fatalities associated with the use of albendazole have been reported due to granulocytopenia or pancytopenia. Albendazole may cause bone marrow suppression, aplastic anemia, and agranulocytosis. Monitor blood counts 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 and patients with hepatic echinococcosis are at increased risk for bone marrow suppression and warrant more frequent monitoring of blood counts. Discontinue albendazole if clinically significant decreases in blood cell counts occur.

    5.2 Embryo-Fetal Toxicity

    Based on findings from animal reproduction studies, albendazole may cause fetal harm when administered to a pregnant woman. Embryotoxicity and skeletal malformations were reported in rats and rabbits when treated during the period of organogenesis (at oral doses approximately 0.1 to 0.6 times the recommended human dose normalized for total body surface area). Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating albendazole [see Dosage and Administration (2.3)]. Advise females of reproductive potential to use an effective method of contraception during treatment with albendazole and for 3 days after the final dose [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.3)].

    5.3 Risk of Neurologic Symptoms in Neurocysticercosis

    Patients being treated for neurocysticercosis should receive steroid and anticonvulsant therapy to prevent 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.

    5.4 Risk of Retinal Damage in Patients with Retinal Neurocysticercosis

    Cysticercosis may involve the retina. Before initiating therapy for neurocysticercosis, examine the patient for the presence of retinal lesions. If such lesions are visualized, weigh the need for anticysticeral therapy against the possibility of retinal damage resulting from inflammatory damage caused by albendazole-induced death of the parasite.

    5.5 Hepatic Effects

    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 (6)].

    Monitor liver enzymes (transaminases) 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. Perform laboratory tests frequently if albendazole treatment is restarted.

    Patients with elevated liver enzyme test results are at increased risk for hepatotoxicity and bone marrow suppression [see Warnings and Precautions (5.1)]. Discontinue therapy if liver enzymes are significantly increased or if clinically significant decreases in blood cell counts occur.

    5.6 Unmasking of Neurocysticercosis in Hydatid Patients

    Undiagnosed neurocysticercosis may be uncovered in patients treated with albendazole for other conditions. Patients with epidemiologic factors who are at risk for neurocysticercosis should be evaluated prior to initiation of therapy.

  • 6 ADVERSE REACTIONS

    6.1 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.

    Table 2: Adverse Reaction Incidence 1% or Greater in Hydatid Disease andNeurocysticercosis
    Adverse Reaction
    		Hydatid Disease
    		Neurocysticercosis
    Gastrointestinal
    Abdominal Pain
    		 6
    		 0
    Nausea
    		 4
    		 6
    Vomiting
    		 4
    		 6
    General disorders and administration site conditions
    Fever
    		 1
    		 0
    Investigations
    Elevated Hepatic Enzymes
    		 16
    		 less than 1
    Nervous 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 [see Warnings and Precautions (5.1)].

    Immune System Disorders

    Hypersensitivity reactions, including rash and urticaria.

    6.2 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

  • 7 DRUG INTERACTIONS

    7.1 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.

    7.2 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 co-administration with albendazole(400 mg).

    7.3 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.

    7.4 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.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    Based on findings from animal reproduction studies, albendazole may cause fetal harm when administered to a pregnant woman. However, available human data from a small number of published case series and reports on the use of multiple-dose albendazole in the 1st trimester of pregnancy, and several published studies on single-dose albendazole use later in pregnancy, have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproductive studies, oral administration of albendazole during the period of organogenesis caused embryotoxicity and skeletal malformations in pregnant rats (at doses of 0.10 times and 0.32 times the maximum recommended human dose based on body surface area in mg/m2) and pregnant rabbits (at doses of 0.60 times the maximum recommended human dose based on body surface area in mg/m2). 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/m2) (see Data). Advise a pregnant woman of the potential risk to the fetus.

    The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. 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

    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 maximum recommended human dose based on body surface area in mg/m2, respectively) during organogenesis (gestation days 6 to 15) and in pregnant rabbits at oral doses of 30 mg/kg/day (0.60 times the maximum recommended human dose based on body surface area in mg/m2) administered during organogenesis (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.

    8.6 Lactation

    Risk Summary

    Concentrations of albendazole and the active metabolite, albendazole sulfoxide, have been reported to be low in human breast milk. There are no reports of adverse effects on the breastfed infant and no information on the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for albendazole and any potential adverse effects on the breastfed infant from albendazole or from the underlying maternal condition.

    8.3 Females and Males of Reproductive Potential

    Pregnancy Testing

    Pregnancy testing is recommended for females of reproductive potential prior to initiating albendazole.

    Contraception

    Females

    Albendazole may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with albendazole and for 3 days after the final dose.

    8.4 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.

    8.5 Geriatric Use

    In patients aged 65 and older with either hydatid disease or neurocysticercosis, there was insufficient data to determine whether the safety and effectiveness of albendazole is different from that of younger patients.

    8.7 Patients with Impaired Renal Function

    The pharmacokinetics of albendazole in patients with impaired renal function has not been studied.

    8.8 Patients with Extra-Hepatic Obstruction

    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.

  • 10 OVERDOSAGE

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

  • 11 DESCRIPTION

    Albendazole is an orally administered anthelmintic drug. 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 tablets

    Albendazole, USP is a white to faintly yellowish powder. It is freely soluble in anhydrous formic acid, very slightly soluble in ether and in methylene chloride, practically insoluble in alcohol and water.

    Each film-coated tablet contains albendazole USP, 200 mg and inactive ingredients: colloidal silicon dioxide, corn starch, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycols, povidone K-30, saccharin sodium, sodium lauryl sulfate, sodium starch glycolate type A (botanical source: potato), talc and titanium dioxide.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Albendazole is a synthetic, anthelmintic drug of the class benzimidazole [see Clinical Pharmacology (12.4)].

    12.3 Pharmacokinetics

    Absorption

    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 grams) 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 were achieved 2 hours to 5 hours after dosing and were on average 1310 ng/mL (range 460 ng/mL to 1580 ng/mL) following oral doses of albendazole (400 mg) in 6 hydatid disease patients, when administered with a fatty meal. Plasma concentrations of albendazole sulfoxide increased in a dose-proportional manner over the therapeutic dose range following ingestion of a high-fat meal (fat content 43.1 grams). The mean apparent terminal elimination half-life of albendazole sulfoxide ranged from 8 hours to 12 hours in 25 healthy 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 cerebrospinal fluid (CSF). Concentrations in plasma were 3-fold to 10-fold and 2-fold to 4-fold higher than those simultaneously determined in cyst fluid and CSF, respectively.

    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.

    Specific Populations

    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.

    Geriatrics

    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.

    12.4 Microbiology

    Mechanism of Action

    Albendazole binds to the colchicine-sensitive site of β-tubulin inhibiting their polymerization into microtubules. The decrease in microtubules in the intestinal cells of the parasites decreases their absorptive function, especially the uptake of glucose by the adult and larval forms of the parasites, and also depletes glycogen storage. Insufficient glucose results in insufficient energy for the production of adenosine trisphosphate (ATP) and the parasite eventually dies.

    Mechanism of Resistance

    Parasitic resistance to albendazole is caused by changes in amino acids that result in changes in the β-tubulin protein. This causes reduced binding of the drug to β-tubulin.

    In the specified treatment indications, albendazole appears to be active against the larval forms of the following organisms:

    Echinococcus granulosus

    Taenia solium

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long-term carcinogenicity studies were conducted in mice and rats.

    No evidence of increased incidence of tumors was found in the mice or rats at up to 400 mg/kg/day or 20 mg/kg/day respectively (2 times and 0.2 times the recommended human dose on a body surface area basis).

    In genotoxicity tests, albendazole was found negative in an Ames Salmonella/Microsome Plate mutation assay, 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).

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    16.1 How Supplied

    Albendazole Tablets USP, 200 mg are white to off-white, round, film coated tablets debossed '1021' on one side and plain on the other side and are supplied as:

    NDC: 16714-907-01 in bottle of 2 tablets (1 x 2 unit-dose blister pack) with child-resistant closure

    16.2 Storage and Handling

    Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

  • 17 PATIENT COUNSELING INFORMATION

    Patients should be advised that:

    • Some people, particularly children, may experience difficulties swallowing the albendazole tablets whole.
    • Take albendazole tablets with food.
    • Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females to inform their prescriber of a known or suspected pregnancy [see Warnings and Precautions (5.2), Use in Specific Populations (8.1)] .
    • Advise females of reproductive potential to use effective contraception during treatment with albendazole and for 3 days after the final dose [see Use in Specific Populations (8.3)] .
    • During albendazole therapy, monitor blood counts and liver enzymes every 2 weeks because of the possibility of harm to the liver or bone marrow [see Warnings and Precautions (5.5)] .
  • SPL UNCLASSIFIED SECTION

    Manufactured for:

    Northstar Rx LLC

    Memphis, TN 38141.

    Manufactured by:

    Cadila Healthcare Ltd.

    Ahmedabad, India.

    Rev.: 07/19

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

    NDC: 16714-907-01

    Albendazole Tablets USP, 200 mg

    Bottle of 2 tablets (1 x 2 unit-dose blister pack) with child-resistant closure

    Rx only

    Northstar

    Albendazole tablets
  • INGREDIENTS AND APPEARANCE
    ALBENDAZOLE 
    albendazole tablet, film coated
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 16714-907
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ALBENDAZOLE (UNII: F4216019LN) (ALBENDAZOLE - UNII:F4216019LN) ALBENDAZOLE200 mg
    Inactive Ingredients
    Ingredient NameStrength
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    HYPROMELLOSES (UNII: 3NXW29V3WO)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)  
    POVIDONE K30 (UNII: U725QWY32X)  
    SACCHARIN SODIUM (UNII: SB8ZUX40TY)  
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
    SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    TALC (UNII: 7SEV7J4R1U)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    Product Characteristics
    ColorWHITE (WHITE TO OFF WHITE) Scoreno score
    ShapeROUND (ROUND) Size12mm
    FlavorImprint Code 1021
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 16714-907-011 in 1 BOTTLE04/19/2019
    12 in 1 BLISTER PACK; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20897904/19/2019
    Labeler - Northstar Rx LLC. (830546433)
    Registrant - Zydus Pharmaceuticals (USA) Inc. (156861945)
    Establishment
    NameAddressID/FEIBusiness Operations
    Cadila Healthcare Limited863362789ANALYSIS(16714-907) , MANUFACTURE(16714-907)
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