These highlights do not include all the information needed to use ALBENZA ® safely and effectively. See full prescribing information for ALBENZA. ALBENZA ® (albendazole) tablets, for oral use ALBENZA ® (albendazole) chewable tablets, for oral use Initial U.S. Approval: 1996
Drug Labeling and Warnings
Drug Details [pdf]
ALBENZA- albendazole tablet, film coated
Department of State Health Services, Pharmacy Branch
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HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ALBENZA
® safely and effectively. See full prescribing information for ALBENZA.
ALBENZA ® (albendazole) tablets, for oral use ALBENZA ® (albendazole) chewable tablets, for oral use Initial U.S. Approval: 1996 INDICATIONS AND USAGEALBENZA is an anthelmintic drug indicated for: DOSAGE AND ADMINISTRATIONPatients weighing 60 kg or greater, 400 mg twice daily; less than 60 kg, 15 mg/kg/day in divided doses twice daily (maximum total daily dose 800 mg). ALBENZA tablets and ALBENZA chewable tablets should be taken with food. ( 2)
See additional important information in the Full Prescribing Information. ( 2) CONTRAINDICATIONSPatients with known hypersensitivity to the benzimidazole class of compounds or any components of ALBENZA. (4) WARNINGS AND PRECAUTIONS
ADVERSE REACTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Amedra Pharmaceuticals LLC at 1-888-894-6528 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS
See 17 for PATIENT COUNSELING INFORMATION. Revised: 6/2015 |
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
Dosing of ALBENZA will vary depending upon the indication. ALBENZA tablets may be crushed or chewed and swallowed with a drink of water. ALBENZA chewable tablets are also available for children and patients who may experience swallowing difficulties. ALBENZA tablets and ALBENZA chewable tablets should be taken with food [ see Clinical Pharmacology ( 12.3) ].
| 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 ALBENZA 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 ALBENZA in all patients [ see Warnings and Precautions ( 5.5) ].
- Obtain a pregnancy test in women of reproductive potential prior to therapy [ see Warnings and Precautions ( 5.2) ].
4 CONTRAINDICATIONS
ALBENZA is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds or any components of ALBENZA.
5 WARNINGS AND PRECAUTIONS
5.1 Bone Marrow Suppression
Fatalities associated with the use of ALBENZA have been reported due to granulocytopenia or pancytopenia ALBENZA 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 ALBENZA 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 ALBENZA if clinically significant decreases in blood cell counts occur.
5.2 Teratogenic Effects
ALBENZA may cause fetal harm and should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Obtain pregnancy test prior to prescribing ALBENZA to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of ALBENZA therapy and for one month after end of therapy. Immediately discontinue ALBENZA if a patient becomes pregnant and apprise the patient of the potential hazard to the fetus [ see Use in Specific Populations ( 8.1) ].
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 ALBENZA-induced death of the parasite.
5.5 Hepatic Effects
In clinical trials, treatment with ALBENZA 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 ALBENZA therapy based on individual patient circumstances. Restarting ALBENZA treatment in patients whose hepatic enzymes have normalized off treatment is an individual decision that should take into account the risk/benefit of further ALBENZA usage. Perform laboratory tests frequently if ALBENZA 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.
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 ALBENZA 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 ALBENZA.
| 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 ALBENZA. 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 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).
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
Pregnancy Category C.
There are no adequate and well-controlled studies of ALBENZA administration in pregnant women. ALBENZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
ALBENZA should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Obtain pregnancy test prior to prescribing ALBENZA to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of ALBENZA therapy and for one month after end of therapy. If a patient becomes pregnant while taking this drug, ALBENZA should be discontinued immediately. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.
ALBENZA 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.
8.3 Nursing Mothers
ALBENZA 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 ALBENZA is administered to a nursing woman.
8.4 Pediatric Use
Hydatid disease is uncommon in infants and young children. In neurocysticercosis, the efficacy of ALBENZA 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 ALBENZA is different from that of younger patients.
8.6 Patients with Impaired Renal Function
The pharmacokinetics of ALBENZA in patients with impaired renal function has not been studied.
8.7 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 T max and serum elimination half-life values of 10 hours and 31.7 hours, respectively. Plasma concentrations of parent ALBENZA were measurable in only 1 of 5 patients.
10 OVERDOSAGE
In case of overdosage, symptomatic therapy and general supportive measures are recommended.
11 DESCRIPTION
ALBENZA (albendazole) is an orally administered anthelmintic drug. Chemically, it is methyl 5-(propylthio)-2-benzimidazolecarbamate. Its molecular formula is C
12H
15N
3O
2S. Its molecular weight is 265.34. It has the following chemical structure:
Albendazole is a white to yellowish powder. It is freely soluble in anhydrous formic acid and very slightly soluble in ether and in methylene chloride. Albendazole is practically insoluble in alcohol and in water.
Tablets
Each white to off-white, circular, biconvex, bevel-edged film coated, TILTAB tablet is debossed with “ap” and “550” and 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.
Chewable Tablets
Each round, mottled pink, concave chewable tablet is debossed with “ap” above “551” and contains 200 mg of albendazole.
Inactive ingredients consist of: lactose monohydrate, microcrystalline cellulose, D-mannitol, sodium starch glycolate, povidone, N-C Wild Berry Type Flavor, magnesium stearate, crospovidone, polyvinyl acetate, sucralose, colloidal silicone dioxide, sodium lauryl sulfate, D&C Red #30/Helendon Pink Aluminum Lake.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
ALBENZA (albendazole) is a synthetic, antihelminthic 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.
In a study conducted in 113 fed and 117 fasted healthy subjects, ALBENZA chewable tablets were bioequivalent to ALBENZA tablets following single 400 mg oral doses of albendazole. In this study, the average time to reach the maximal plasma concentrations of albendazole sulfoxide was 4.5 hours (range 2 to 10 hours) with a fatty meal (fat content 60 grams) and at 3 hours (range 1 to 5 hours) in the fasted state. Following administration of ALBENZA chewable tablets, average maximal plasma concentrations of albendazole sulfoxide were 804 ng/mL (range 202 to 2244 ng/mL) and 218 ng/mL (range 54 to 592 ng/mL) in the fed and fasted states, respectively. The apparent elimination half-life of albendazole sulfoxide was comparable between ALBENZA chewable tablets and ALBENZA tablets when both were given either under fed or fasted conditions.
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) ALBENZA 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
ALBENZA 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/m 2).
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Tablets
Each white to off-white, circular, biconvex, bevel-edged film coated, TILTAB tablet is debossed with “ap” and “550” and contains 200 mg of albendazole.
Bottles of 2 Tablets NDC: 52054-550-22
Bottles of 28 Tablets NDC: 52054-550-28
Chewable Tablets
Each round, mottled pink, concave chewable tablet is debossed with “ap” above “551” and contains 200 mg of albendazole.
2 Tablets in 1 Blister Pack (configured as a Wallet Card) NDC: 52054-551-22
6 Tablets in 1 Blister Pack; 2 Blister Packs in 1 Carton NDC: 52054-551-12
17 PATIENT COUNSELING INFORMATION
Patients should be advised that:
- Some people, particularly children, may experience difficulties swallowing the ALBENZA tablets whole. ALBENZA chewable tablet is available for children and patients who may be unable to swallow a tablet.
- Take ALBENZA with food.
- ALBENZA may cause fetal harm, therefore, obtain a pregnancy test in women of reproductive potential prior to initiating therapy.
- Advise women of reproductive potential to use effective birth control while on ALBENZA and for one month after completing treatment.
- During ALBENZA therapy, monitor blood counts and liver enzymes every 2 weeks because of the possibility of harm to the liver or bone marrow.
ALBENZA and TILTAB are registered trademarks of GlaxoSmithKline, used with permission.
Distributed by:
Amedra Pharmaceuticals LLC
Horsham, PA 19044
LB# 799-04
| ALBENZA
albendazole tablet, film coated |
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| Labeler - Department of State Health Services, Pharmacy Branch (781992540) |
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