Inactive ingredients: 

Alzental Film coated Tablets: Lactose monohydrate, maize starch, magnesium stearate, purified talc, sodium starch glycolate, polyplasidone XL, polyvinylpyrrolidone K25, sodium lauryl sulphate, opadry II white (Titanium dioxide, polyvinyl alcohol, talc, hypromellose, polyethylene glycol/macrogel).

Alzental Suspension: Silicon dioxide colloidal (Aerosil 200), glycerin, carboxymethylcellulose sodium, sorbic acid, methylparaben sodium, propyl paraben sodium, banana flavor concentrate, sucralose, benzoic acid, sodium benzoate, propylene glycol, purified water.

Alzental is used in the treatment of single and mixed intestinal nematode infections including ascariasis, enterobiasis, hookworm, strongyloidiasis, and trichuriasis. 

Alzental is indicated for the treatment of giardiasis.

Alzental is indicated for the treatment of capillariasis, gnathostomiasis, trichostrongyliasis. 

Alzental is indicated for the treatment of lymphatic filariasis.

Hydatid Disease (Echinococcosis): Alzental 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.

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

Dosage: 

Dosing of Alzental will vary depending upon the indication. 

Alzental tablets should not be crushed or chewed and should be swallowed with a drink of water. 

Alzental should be taken with food. 

Alzental is given orally, usually as a single dose, in the treatment of single or mixed intestinal nematode infections.

Ascariasis, Enterobiasis, Hookworm infections, or Trichuriasis: 

The Usual Dose for Adults and Children aged 2 years or Over is: 

400 mg as a single dose. In Enterobiasis, the dose may be repeated in 1-4 weeks. 

For Enterobiasis in Children of 1 to 2 years of age: 200 mg as a single dose.

Strongyloidiasis: 400 mg is given once or twice daily for 3 consecutive days; this may be repeated after 3 weeks if necessary.

Giardiasis: 400 mg daily by mouth for 5 days. 

Capillariasis: 400 mg daily for 10 days.

Gnathostomiasis: 400 mg once or twice daily for 2-3 weeks.

Trichostrongyliasis: 400 mg single dose.

Lymphatic Filariasis: A single dose of 400 mg with either a single dose of ivermectin 150-200 micrograms/kg (if there is co-endemic loiasis or onchocerciasis) or with single dose of diethylcarbamazine 6 mg/kg (if there is co-endemic loiasis or onchocerciasis). This regimen is given once each year for at least 5 years.

Hydatid Disease (Echinococcosis):

Patients weighing 60 kg or Greater: 400 mg twice daily, with meals (maximum total daily dose of 800 mg).

Patients weighing Less than 60 kg: 15 mg/kg daily given in two divided doses twice daily with meals (maximum total daily dose of 800 mg).

Duration of Treatment: 28-day cycle followed by a 14-day albendazole- free interval, for a total of 3 cycles.

Neurocysticercosis:

Patients weighing 60 kg or Greater: 400 mg twice daily, with meals, for 8-30 days.

Patients weighing Less than 60 kg: 15 mg/kg/day given in divided doses twice daily, with meals (maximum total daily dose of 800 mg).

Duration of Treatment: 8 days (for parnehcymal disease) to 1 month ( for subarachnoid disease).

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. 

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 Alzental 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 Alzental in all patients. 

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

Use in Specific Populations:

Pediatric Use: 

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. 

Geriatric Use: 

In patients aged 65 and older with either hydatid disease or neurocysticerosis, there was insufficient data to determine whether the safety and effectiveness of albendazole is different from that of younger patients. 

Patients with Impaired Renal Function: 

The pharmacokinetics of albendazole in patients with impaired renal function has not been studied.

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 albendazole were measurable in only 1 of 5 patients.

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

Bone Marrow Suppression: 

Fatalities associated with the use of albendazole have been reported due to granulocytopenia or pancytopenia. Albendazole 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 albendazole 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 albendazole, if clinically significant decreases in blood cell counts occur.

Teratogenic Effects: 

Albendazole 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 Alzental to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of Alzental therapy and for one month after end of therapy. Immediately discontinue Alzental if a patient becomes pregnant and apprise the patient of the potential hazard to the fetus.

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.

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 anticysticercal therapy against the possibility of retinal damage resulting from inflammatory damage caused by albendazole-induced death of the parasite.

Hepatic Effects: 

In clinical trials, treatment with albendazole 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.

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 Alzental therapy based on individual patient circumstances. Restarting albendazole treatment in patients whose hepatic enzymes have normalized off treatment is an individual decision that should take into account the risk/benefit of further Alzental usage. Perform laboratory tests frequently if Alzental treatment is restarted.

Patients with elevated liver enzyme test results are at increased risk for hepatotoxicity and bone marrow suppression. Discontinue therapy if liver enzymes are significantly increased or if clinically significant decreases in blood cell counts occur.

Unmasking of Neurocysticercosis in Hydatid Patients: 

Undiagnosed neurocysticercosis may be uncovered in patients treated with albendazole for other conditions. Patients with epidemiologic factors who are at risk for neurocysticercosis should be evaluated prior to initiation of therapy.

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 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). 

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: 

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.

Pregnancy: 

Category C. 

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

Alzental should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Obtain pregnancy test prior to prescribing Alzental to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of Alzental therapy and for one month after end of therapy. If a patient becomes pregnant while taking this drug, Alzental should be discontinued immediately. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus. Lactation: 

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 Alzental is administered to a nursing woman. 

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 albendazole differs between hydatid disease and neurocysticercosis. Adverse reactions occurring with a frequency of 1% or greater in either disease are described 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 albendazole. 

Adverse Reaction Incidence 1% or Greater in Hydatid Disease and Neurocysticercosis:

Gastrointestinal: 

Abdominal pain, nausea, vomiting.

General disorders and Administration site conditions:

Fever.

Investigations:

Elevated hepatic enzymes.

Nervous system disorders:

Dizziness, headache, meningeal signs, raised intracranial pressure, vertigo.

Skin and Subcutaneous tissue disorders:

Reversible Alopecia.

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.

Immune system disorders: Hypersensitivity reactions, including rash and urticaria.

Postmarketing Experience: 

The following adverse reactions have been identified during post-approval use of albendazole. 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: Blurred vision. 

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.

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

Pharmacodynamic properties:

Mechanism of Action: 

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

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

Pharmacokinetic properties:

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 co-administered 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.

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

Store in a dry place at a temperature not exceeding 30^ºC.

Alzental Film coated Tablets: Box containing 1 blister of 2 film coated tablets. 

Alzental Suspension: 1 or 49 Bottle of 20 ml.