Axeitol Albendazole Chewable Tablets

AXEITOL

ALBENDAZOLE TABLETS

 

Composition

Each uncoated chewable tablet contains:

Albendazole USP 400mg

 

Indications

Albendazole is indicated for the treatment of the following infections:

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

Lesions considered responsive to albendazole therapy appear as non-enhancing cysts with no surrounding edema on contrast-enhanced computerized tomography. Clinical studies in patients with lesions of this type demonstrate a 74% to 88% reduction in number of cysts; 40% to 70% albendazole treated patients showed resolution of all active cysts.

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.

 

Pharmacology

Albendazole is a synthetic, benzimidazole-derivative, anthelmintic agent. The drug is structurally related to thiabendazole and mebendazole, and like mebendazole, it is a benzimidazole carbamate derivative. Albendazole is metabolized in the liver to an active metabolite, albendazole sulfoxide which accounts for detectable plasma concentrations of the drug systemic anthelmintic activity of the drug has been attributed to this metabolite. Although the exact mechanism of action of albendazole has not been fully elucidated, the principal anthelmintic effect of benzimidazoles, including albendazole, appears to be the specific, high affinity binding of the drug to free beta-tubulin in parasite cells resulting in selective inhibition of parasite microtubule polymerization and inhibition of microtubule dependent uptake of glucose. Benzimidazole drugs bind to the beta-tubulin of parasites at much lower concentrations than to mammalian beta-tubulin protein; drugs do not inhibit glucose uptake in mammals, and do not appear to have any effect on blood glucose concentrations in humans.

 

Pharmacokinetics

Absorption and Metabolism

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 co-administered with a fatty meal (estimated fat content 40 g) 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 are typically achieved 2 to 5 hours after dosing and are on an average 1.31 mcg/ml (range 0.46 to 1.58 mcg/mL), following oral doses of albendazole (400 mg) in six hydatid disease patients, when administered with a fatty meal. Plasma concentrations of albendazole sulfoxide increase in a dose-proportional manner over the therapeutic dose range following ingestion of a fatty meal. The mean apparent terminal half-life of albendazole sulfoxide typically ranges from 8 to 12 hours in twenty-five normal subjects, as well as in fourteen hydatid and eight neurocysticerosis patients. Following four weeks of treatment with albendazole (200 mg three times daily), twelve 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 cerebral spinal fluid (CSF). Concentrations in plasma were 3-to 10-fold and 2-to 4-fold higher than those simultaneously determined in cyst fluid and CSF, respectively. Limited in vitro and clinical data suggest that albendazole sulfoxide may be eliminated from cysts at a slower rate than observed in plasma.

 

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.

 

DOSAGE AND ADMINISTRATION

Dosing of Albendazole will vary, depending upon which of the following parasitic infections is being treated.

Indication Patient Weight Dose Duration
Neurocysticercosis 60 kg or greater 400 mg b.i.d., with meals 8-30 days
less than 60 kg 15 mg/kg/day given in divided doses b.i.d. with meals (maximum total daily dose 800 mg)
Hydatid Disease 60 kg or greater 400 mg b.i.d., with meals 28-day cycle followed by a
14-day albendazole-free interval, for a total of 3 cycles
less than 60kg 15mg/kg/day given in divided doses b.i.d. with meals (maximum total daily dose 800 mg)
[NOTE: When administering albendazole in the pre- or post-surgical setting, optimal killing of cyst contents is achieved when three courses of therapy have been given].

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.

Albendazole is administered orally with food. Oral bioavailability of albendazole appears to be increased when the drug is administered with a fatty meal; when the drug is administered with meals containing about 40g of fat, plasma concentrations of albendazole sulfoxide are up to 5 times higher than those observed when the drug is administered to fasting patients. Albendazole may cause harm to the fetus. Therefore, women of childbearing age should begin treatment only after a negative pregnancy test, and should be cautioned against becoming pregnant while receiving albendazole or within 1 month of completing treatment with the drug. Because albendazole has been associated with mild to moderate increases of hepatic enzymes in about 16% of patients receiving the drug in clinical trials, and may cause hepatotoxicity, liver function tests should be performed prior to each course of albendazole therapy and at least every 2 weeks during treatment with the drug. If clinically important increases in liver function test results occur, albendazole should be discontinued. Leukopenia has occurred in less than 1% of patients receiving albendazole, and rarely, granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia have been reported. Blood counts should be performed at the start of, and every 2 weeks during, each 28-day treatment cycle.

Manufacturer states that if decreases in the total leukocyte count occur, treatment with albendazole may be continued if the decreases are modest and do not progress.

 

Contra-Indications

Albendazole is contra-indicated in patients with known hypersensitivity to the benzimidazole class of compounds.

 

Adverse Reactions

The adverse event profile of Albendazole differs between hydatid disease and neurocysticercosis. Adverse events occurring with a frequency of ≥1% in either disease.

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 adverse events were observed at an incidence of <1%:

Hematologic: Leukopenia. There have been rare reports of granulocytopenia, pancytopenia, agranulocytosis, orthrombocytopenia.

Dermatologic: Rash, urticaria.

Hypersensitivity: Allergic reactions.

Renal: Acute renal failure related to albendazole therapy has been observed.

 

Precautions

Patients being treated for neurocysticerosis 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 anticysticeral therapy.

Cysticercosis may, in rare cases, involve the retina. Before initiating therapy for neurocysticercosis, the patients should be examined for the presence of retinal lesions. If lesions are visualized, the need for anticysticeral therapy should be weighed against the possibility of retinal damage caused by albendazole-induced changes to the retinal lesion.

 

Pregnancy and Lactation

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

There are no adequate and well-controlled studies of albendazole administration in pregnant women. Albendazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Albendazole 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 albendazole is administered to a nursing woman.

 

Pediatric Use

Experience in children under the age of 6 years is limited. In hydatid disease, infection in infants and young children is uncommon, but no problems have been encountered in those who have been treated. In neurocysticercosis, infection is more frequently encountered. In five published studies involving pediatric patients as young as 1 year, no significant problems were encountered, and the efficacy appeared similar to the adult population.

 

Geriatric Use

Experience in patients 65 years of age or older is limited. The number of patients treated for either hydatid disease or neurocysticercosis is limited, but no problems associated with an older population have been observed.

 

Treatment of Overdosage

In case of overdosage, symptomatic therapy (e.g. Gastric lavage and activated charcoal) and general supportive measures are recommended.

 

Drug Interactions

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 eight neurocysticerosis 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 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).

Cimetidine: Albendazole sulfoxide concentrations in bile and cystic fluid were increased (about 2-fold) in hydatid cyst patients treated with cimetidine (10 mg/day/kg) (n=7) compared with albendazole (20 mg/kg/day) alone (n=12). Albendazole sulfoxide plasma concentrations were unchanged 4 hours after dosing.

Theophylline: The pharmacokinetics of theophylline (aminophylline 5.8 mg/kg infused over 20 minutes) were unchanged following a single oral dose of albendazole (400 mg) in 6 healthy subjects.

 

Storage

Store in a cool dry place. Keep out of reach of children.

 

Presentation

Pack of 20 x 1’s & 10 x l’s

Bulk pack of 100’s & 1000’s.

 

NAFDAC Reg. No: 04-8123 ()

 

Manufactured in India by

Khandelwal Laboratories Pvt. Ltd.

Survey NO.277/3/6, Demni Road, Dadra U.T. 396 191.

Regd. Office: 79/87, D. Lad Path, Mumbai -400 033.

 

Marketed by

EDEN U-K PHARMACEUTICAL LTD.

J116 Daminja Avenue Housing Estate

Fegge Onitsha, Anambra State, Nigeria.

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