ALBENDAZOLE (Page 3 of 3)

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 tablet USP, 200 mg are available as white to off-white, circular, bicovex, bevel-edged, film coated tablet debossed with “C237” on one side and plain on other side.

Bottles of 2 Tablets NDC 69097-237-72

Bottles of 28 Tablets NDC 69097-237-73

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 tablets and for 3 days after the final dose [see Use in Specific Populations (8.3) ].
  • During albendazole tablets 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) ].

Manufactured by:

Cipla Ltd. Indore SEZ,

Pithampur, India

Manufactured for:

Cipla USA, Inc.

1560 Sawgrass Corporate Parkway,

Suite 130, Sunrise, FL 33323

Revised: 7/2019

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Rx Only

NDC 69097-237-72

Albendazole Tablets, USP 200 mg

Each Film coated tablets contain Albendaozle USP, 200 mg

2 Tablets

Cipla

container-labels-2s
(click image for full-size original)
ALBENDAZOLE albendazole tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:69097-237
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ALBENDAZOLE (ALBENDAZOLE) ALBENDAZOLE 200 mg
Inactive Ingredients
Ingredient Name Strength
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
MICROCRYSTALLINE CELLULOSE
POVIDONE
SODIUM LAURYL SULFATE
SACCHARIN SODIUM
STARCH, CORN
POLYVINYL ALCOHOL, UNSPECIFIED
TALC
TITANIUM DIOXIDE
POLYETHYLENE GLYCOL 4000
Product Characteristics
Color WHITE (white to off-white) Score no score
Shape ROUND (circular, bicovex, bevel-edged, film coated tablet) Size 11mm
Flavor Imprint Code C237
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:69097-237-72 2 TABLET in 1 BOTTLE None
2 NDC:69097-237-73 28 TABLET in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA210434 09/24/2018
Labeler — Cipla USA Inc. (078719707)
Registrant — Cipla USA Inc. (078719707)
Establishment
Name Address ID/FEI Operations
Cipla Limited- Indore 918596409 ANALYSIS (69097-237), MANUFACTURE (69097-237), LABEL (69097-237), PACK (69097-237)
Establishment
Name Address ID/FEI Operations
Cipla Kurkumbh 917066446 API MANUFACTURE (69097-237)

Revised: 07/2019 Cipla USA Inc.

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