Azen Albendazole USP Tablets

AZEN
Albendazole Tablets 200 mg

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory.

 

Composition

Each uncoated chewable tablet contains:

Albendazole USP 200 mg

Excipients: q.s.

Colour: Sunset Yellow Supra

Flavour: Orange Powder

 

PHARMACOLOGY

Animal and human studies have shown that Albendazole exhibits vermicidal, ovicidal and larvicidal activity. The drug is thought to exert its anthelmintic effect by blocking glucose uptake in the susceptible helminths, thereby depleting the energy level until it becomes inadequate for survival. Immobilization is followed by the death of the parasite. These events may be a consequence of the binding and subsequent inhibition of parasite tubulin polymerization by Albendazole and its metabolites, although the drug also binds to human tubulin.

Mechanism of action (If known)

As a vermicidal, albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicinesensitive site of tubulin, thus inhibiting its polymerizatIon or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their gIycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies.

Albendazole also has been shown to inhibit the enzyme fumarate reductase, which is helminth-specific. This action may be considered secondary to the effect on the microtubules due to the decreased absorption of glucose. This action occurs in the presence of reduced amounts of nicotinamide-adenine dinucleotide in reduced form (NADH), which is a coenzyme involved in many cellular oxidation-reduction reactions. Albendazole has larvicidal effects in necatoriasis and ovicidal effects in ascariasis, ancylostomiasis, and trichuriasis.

 

Relevant Pharmacokinetic Data

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 average 1.31 mcg/mL (range 0.46 to 1.58 mcg/mL) following oral doses of Albendazole (400 mg) in 6 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 (fat content 43.1 g). The mean apparent terminal elimination half-life of Albendazole Sulfoxide typically ranges from 8 to 12 hours in 25 normal subjects, as well as in 14 hydatid and 8 Neuro cysticercosis 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 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.

 

CLINICAL INFORMATION

Indications

Albendazole Tablet is indicated for the treatment of the following infections:

Neurocysticercosis

Albendazole Tablet is indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia sollun. 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% of Albendazole treated patients showed resolution of all active cysts.

Hydatid Disease

Albendazole Tablet 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. This indication is based on combined clinical studies which demonstrated non-infectious cyst contents in approximately 80-90% of patients given Albendazole for 3 cycles of therapy of 28 days each. Clinical cure (disappearance of cysts) was seen in approximately 30% of these patients, and improvement (reduction in cyst diameter of 25%) was seen in an additional 40%.

 

Contra Indications

Albendazole is contraindicated in patients with known hypersensitivity to the Benzimidazole class of compounds or any components of Albendazole.

 

Precautions

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 anticysticeral therapy.

Pre-existing neurocysticercosis may also be uncovered in patients treated with Albendazole for other conditions. Patients may experience 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. Symptoms may occur soon after treatment; appropriate steroid and anticonvulsant therapy should be started immediately. Cysticercosis may, in rare cases, involve the retina. Before initiating therapy for neurocysticercosis, the patient should be examined for the presence of retinal lesions. If such 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.

 

Warnings

Rare fatalities associated with the use of Albendazole Tablet have been reported due to granulocytopenia or pancytopenia. Albendazole has been shown to cause bone marrow suppression, aplastic anemia, and granulocytosis in patients with and without underlying hepatic dysfunction. Blood counts should be monitored 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, including hepatic echinococcosis, appear to be more at risk for bone marrow suppression leading to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia attributable to Albendazole and warrant closer monitoring of blood counts. Albendazole should be discontinued in all patients if clinically significant decreases in blood cell counts occur.

Albendazole should not be used in pregnant women except in clinical circumstances – where no alternative management is appropriate. Patients should not become pregnant for at least 1 month following cessation of Albendazole therapy. If a patient becomes pregnant while taking this drug, Albendazole should be discontinued immediately. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Adverse effects

The adverse event profile of Albendazole differs between hydatid disease and neurocysticercosis. Adverse events occurring with a frequency of > 1% in either disease are described in the table 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 events that were reported by investigators to be at least possibly or probably related to Albendazole.

Adverse Event Incidence ≥1 % in Hydatid Disease and Neurocysticercosis

Adverse Event Hydatid Disease Neurocysticercosis
Abnormal Liver Function Tests 15.6 <1.0
Abdominal Pain 6.0 0
Nausea/Vomiting 3.7 6.2
Headache 1.3 11.0
Dizziness/Vertigo 1.2 <1.0
Raised Intracranial Pressure 0 1.5
Meningeal Signs 0 1.0
Reversible Alopecia 1.6 <1.0
Fever 1.0 0

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

 

Blood and Lymphatic System Disorders

Leukopenia. There have been rare reports of granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia. Patients with liver disease, including hepatic echinococcosis, appear to be more at risk of bone marrow suppression.

 

Immune System Disorders

Hypersensitivity reactions, including rash and urticaria.

 

Drug Interaction

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.

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/kg/day) (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.

 

Dosage regimen

Average dose and dose range for adults and children
The usual recommended dose is a single dose of 400 mg of Albendazole in both adults and children above the age of 2 years.

Additional or more frequent dosage may be necessary in certain conditions.

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 5 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)
NOTE: When administering BENDAZIN in the pre- or post-surgical setting, optimal killing of cyst contents is achieved when 3 courses of therapy have been given
Neurocysticercosis 60 kg or greater 400 mg twice daily, with meals 8-30 days
less than
60 kg
15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)

 

Dosage interval

Dosing of Albendazole will vary, depending upon which of the following parasitic infections is being treated. In young children, the tablets should be crushed or chewed and swallowed with a drink of water.

 

Average duration of treatment

Not Applicable.

 

Dosage in special situations e.g. renal, hepatic and cardiac insufficiency

Not Applicable.

 

Over dosage

Brief clinical description of symptoms

Significant toxicity and mortality were shown in male and female mice at doses, exceeding 5,000 mg/kg; in rats, at estimated doses between 1,300 and 2,400 mg/kg; in hamsters, at doses exceeding 10,000 mg/kg; and in rabbits, at estimated doses between 500 and 1,250 mg/kg. In the animals, symptoms were demonstrated in a dose-response relationship and included diarrhea, vomiting, tachycardia, and respiratory distress.

Treatment of over dosage

No untoward effects were reported. In case of overdosage, symptomatic therapy and general supportive measures are recommended.

 

PHARMACEUTICAL INFORMATION

Dosage forms and strengths of different dosage forms

Each uncoated chewable tablet contains:

Albendazole USP 200 mg

Excipients: q.s.

Colour: Sunset Yellow Supra

Flavour: Orange Powder

 

Storage conditions and shelf life (expiration date)

Store below 30°C.

Protect from direct sunlight, heat and moisture.

Keep all medicines out of reach of children.

Shelf Life: 36 months

 

Package sizes

Blister pack of 2 tablets.

 

Description of the product e.g. tablet size, colour, markings etc

Orange coloured, round shape, uncoated chewable tablet.

 

Marketed by

Astranad Pharmaceuticals and Chemical Co. Ltd.

40, Oliyide Street Mushin,

Lagos. Nigeria.

 

Manufactured by

Fredun Pharmaceuticals Ltd.

14, 15, 16, Zorabian Industrial Complex,

Veoor, Palghar (E).

Dist. Thane – 401 404, INDIA.

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