VERTEN

Albendazole is an orally administered anthelmintic drug.

Chemically, it is methyl 5-(propylthio)-2-benzimidazolecarbamate.

Its molecular formula is

C 12 H 15 N 3 O 2 S. 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.

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. methyl 5-(propylthio)-2-benzimidazolecarbamate.

Albendazole is an anthelmintic drug indicated for: Treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium.

Treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus. 1.1 Neurocysticercosis Albendazole is 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 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.

Brain cysticercosis

Child under 6 years of age Female likely to be pregnant Hepatitis Male of childbearing age Hepatic impairment Malmedal failure Renal impairment Elderly Long-term high dose treatment Serum transaminases, increase (des) Trichinosis.

Albendazole is a synthetic, antihelminthic drug of the class benzimidazole. 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.

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.

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.

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 to 13 years), albendazole sulfoxide pharmacokinetics were similar to those observed in fed adults.

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.

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.

Mechanism of action

L-albendazole is an anti-helmintic pest.

It is a benzimidazole carbamate.

It acts on nematodes, cestodes and certain protozoa.

Albendazole acts on the cytoskeleton of the helminths by inhibiting the polymerization of tubulins and their incorporation into microtubules, thus blocking the absorption of glucose by parasites and causing their death.

Albendazole also has activity on

Giardia intestinalis (or duodenalis).

It exerts an irreversible action targeted on the ventral disc of trophozoite by effect on the polymerization of tubulin and giardin, causing disorganization of cytoskeleton and microrubans.

The ability to adhere to enterocytes is diminished, resulting in inhibition of growth and multiplication of the parasite.

• Liver enzymes (increase)
• Transaminases (increase)
• Alopecia (Common)
• Stevens-Johnson Syndrome
• Rash Pruritus Urticaria Polymorphic Erythema Hair damage Fever (Common)
• Cardiac aplasia
• Pancytopenia Leucopenia Agranulocytosis Hepatitis (Uncommon)
• Hypersensitivity (Uncommon)
• Feeling dizzy (Common)
• Vertigo Vomiting Nausea Abdominal pain Epigastric pain Digestive disorder
• Diarrhoea Headache (Very common).

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

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

Patients with known hypersensitivity to the benzimidazole class of compounds or any components of albendazole.

Patients 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).

Albendazole tablets should be taken with food.

Hydatid disease: 28-day cycle followed by 14-day albendazole-free interval for a total of 3 cycles.

Neurocysticercosis: 8 to 30 days.

See additional important information in the Full Prescribing Information. 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.

Table 1: Albendazole Dosage 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 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. 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.

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.

Obtain a pregnancy test in women of reproductive potential prior to therapy.

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 0115-1701-49 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F) .

Store at 20° to 25°C (68° to 77°F) .

There are limited data on use of albendazole in pregnant women to inform a drug-associated risk of major birth defects and miscarriage.

In published studies, single-dose albendazole exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes; however, this finding cannot be extrapolated to multiple-dose exposures.

In animal reproductive studies, oral administration of albendazole during gestation caused embryotoxicity and skeletal malformations in pregnant rats (at oral doses of 0.10 times and 0.32 times the recommended human dose based on body surface area in mg/m 2 ) and pregnant rabbits (at oral doses of 0.60 times the recommended human dose based on body surface area in mg/m 2 ).

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/m 2 ) .

Albendazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Albendazole should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate.

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.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and to 20%, respectively.

Cochrane review could not provide sufficient evidence of the impact of antihelminthics (including albendazole) on the pregnancy outcomes of low birthweight, perinatal mortality and preterm birth.

In a large trial of about 2507 women, albendazole use during the second or third trimester of pregnancy had no overall effect on birth weight, perinatal mortality, or congenital anomalies.

With a limited sample size and single-does exposure, another study could not rule out a two-fold increased risk of major malformations [4.7% vs. 2.2%; OR 2.2 (95% confidence interval (CI) 0.5 to 10.1); p = 0.26.

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 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 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 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 to 15.

Females and Males of Reproductive Potential Pregnancy Testing Obtain pregnancy test prior to prescribing albendazole to women of reproductive potential.

Advise women of reproductive potential to use effective birth control for the duration of albendazole therapy and for one month after end of therapy.

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.

In patients aged 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.