Albendazole

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALBENDAZOLE (ALBENDAZOLE)

Composition:

Active ingredient: albendazole;

One chewable tablet contains 400 mg of albendazole;

Excipients: maize starch, microcrystalline cellulose, sodium starch glycolate, colloidal anhydrous silicon dioxide, orange flavoring, aspartame, talc, magnesium stearate.

Pharmaceutical form. Chewable tablets.

Main physico-chemical properties: tablets of almost white to grey color, flat cylindrical, with bevel.

Pharmacotherapeutic group.

Anthelmintic agents. Agents used in nematodosis. Benzimidazole derivatives. ATC code P02CA03.

Pharmacological properties.

Pharmacodynamics. Albendazole is an antiprotozoal and anthelmintic agent belonging to the benzimidazole carbamate group. The drug is effective against both intestinal and tissue parasites in the forms of eggs, larvae, and adult helminths. The anthelmintic effect of albendazole is due to inhibition of tubulin polymerization, leading to disruption of parasite metabolism and subsequent death of helminths.

Albendazole is active against the following intestinal parasites: nematodes — Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Cutaneus Larva Migrans; cestodes — Hymenolepis nana, Taenia solium, Taenia saginata; trematodes — Opisthorchis viverrini, Clonorchis sinensis; protozoa — Giardia lamblia (intestinalis or duodenalis).

Albendazole is also active against tissue parasites, including cystic and alveolar echinococcosis caused by Echinococcus granulosus and Echinococcus multilocularis, respectively. Albendazole is an effective treatment for neurocysticercosis caused by larval invasion of Taenia solium, capillariasis caused by Capillaria philippinensis, and gnathostomiasis caused by Gnathostoma spinigerum.

Albendazole destroys cysts or significantly reduces their size (by up to 80%) in patients with granulomatous echinococcosis. After treatment with albendazole, the proportion of non-viable cysts increases to 90%, compared to 10% in untreated patients. Following albendazole treatment for cysts caused by Echinococcus multilocularis, complete recovery has been observed in a minority of patients, while most experience improvement or stabilization of their condition.

Pharmacokinetics. After oral administration, the drug is poorly absorbed (up to 5%) from the gastrointestinal tract. Concomitant intake with fatty food increases absorption approximately fivefold.

Albendazole is rapidly metabolized in the liver during first-pass metabolism. The main metabolite, albendazole sulfoxide, retains about half of the pharmacological activity of the parent compound.

The elimination half-life of albendazole sulfoxide in plasma is approximately 8.5 hours. Albendazole sulfoxide and other metabolites are excreted predominantly in bile, with only a small fraction eliminated in urine. After prolonged administration of high doses, elimination of the drug from cysts may continue for several weeks.

Clinical characteristics.

Indications.

Intestinal forms of helminthiases and cutaneous Larva Migrans syndrome (short-term treatment with low doses): enterobiasis, ancylostomiasis and necatoriasis, hymenolepiasis, taeniasis, strongyloidiasis, ascariasis, trichocephalosis, clonorchiasis, opisthorchiasis, giardiasis in children.

Systemic helminthic infections (long-term treatment with high doses):

• Cystic echinococcosis (caused by Echinococcus granulosus):
  • when surgical intervention is not possible;
  • prior to surgical intervention;
  • after surgery, if preoperative treatment was short, if widespread helminthic infection is observed, or if live forms were found during surgery;
  • after percutaneous drainage of cysts for diagnostic or therapeutic purposes;
• Alveolar echinococcosis (caused by Echinococcus multilocularis):
  • in inoperable disease, particularly in cases of local or distant metastases;
  • after palliative surgical intervention;
  • after radical surgical intervention or liver transplantation;
• Neurocysticercosis (caused by larvae of Taenia solium):
  • with single or multiple cysts or granulomatous brain lesions;
  • with arachnoid or intraventricular cysts;
  • with racemose cysts;
• Capillariasis (caused by Capillaria philippinensis), gnathostomiasis (caused by Gnathostoma spinigerum and related species), trichinellosis (caused by Trichinella spiralis and T. pseudospiralis), toxocariasis (caused by Toxocara canis and related species).

Contraindications.

Hypersensitivity to albendazole, other benzimidazole derivatives, or other components of the drug. Retinal disease. Pregnancy and breastfeeding. One menstrual cycle prior to planned pregnancy. Women of reproductive age must use effective non-hormonal contraceptive methods during treatment and for 1 month after discontinuation of the drug. Phenylketonuria.

Interaction with other medicinal products and other types of interactions.

Albendazole induces cytochrome P450 enzyme system.

Concomitant use with cimetidine, praziquantel, and dexamethasone may increase plasma levels of albendazole metabolites, potentially leading to overdose.

Medicinal products that may slightly reduce the efficacy of albendazole: anticonvulsants (e.g., phenytoin, fosphenytoin, carbamazepine, phenobarbital, primidone), levamisole, ritonavir.

Treatment efficacy should be monitored—alternative dosing regimens or therapies may become necessary.

Grapefruit juice also increases plasma levels of albendazole sulfoxide.

Due to potential effects on cytochrome P450 activity, there is a theoretical risk of interaction with the following drugs: oral contraceptives, anticoagulants, oral hypoglycemic agents, theophylline.

When albendazole is used concomitantly with theophylline, plasma levels of theophylline should be monitored.

Concomitant intake of the drug with fatty food increases absorption of albendazole from the gastrointestinal tract.

Special Warnings and Precautions.

Short-term treatment of intestinal infections and cutaneous larva migrans.

To prevent administration of albendazole during early pregnancy, women of childbearing potential should be treated only during the first week after menstruation or after a negative pregnancy test. Reliable contraception is required during treatment.

Albendazole treatment may unmask pre-existing neurocysticercosis, especially in areas with a high prevalence of Taenia solium strains. Patients may develop neurological symptoms such as seizures, increased intracranial pressure, and focal neurological signs due to inflammatory reactions caused by the death of parasites in the brain. Symptoms may appear shortly after treatment initiation; therefore, prompt therapy with corticosteroids and anticonvulsants should be initiated.

Long-term treatment of systemic helminthic infections.

Albendazole treatment may be associated with mild to moderate elevations in liver enzymes, which usually return to normal after treatment discontinuation. Therefore, liver enzyme levels should be assessed before starting each treatment course and at least every 2 weeks during therapy. If liver enzyme levels increase significantly (more than twice the upper limit of normal), albendazole treatment should be discontinued. Treatment may be resumed after normalization of enzyme levels, but the patient must be closely monitored.

Albendazole may cause bone marrow suppression; therefore, blood counts should be performed at the beginning of treatment and every 2 weeks during the 28-day cycle. Patients with hepatic disease, including hepatic echinococcosis, are more susceptible to bone marrow suppression, which may lead to pancytopenia, aplastic anemia, agranulocytosis, and leukemia, necessitating careful monitoring of hematological parameters. If significant blood count reductions occur, treatment should be stopped.

To prevent the use of albendazole during early pregnancy, women of childbearing potential must:

• initiate treatment only after a negative pregnancy test;
• use effective contraceptive methods during treatment and for at least one month after discontinuation of the drug.

In patients with neurocysticercosis treated with albendazole, symptoms (e.g., seizures, increased intracranial pressure, focal neurological signs) related to inflammatory reactions caused by parasite death may occur. These should be managed with corticosteroids and anticonvulsant therapy. To prevent increased cerebral pressure during the first week of treatment, oral or intravenous corticosteroids are recommended.

Albendazole treatment may reveal pre-existing neurocysticercosis, particularly in regions with high prevalence of Taenia solium strains. Neurological symptoms such as seizures, increased intracranial pressure, and focal neurological deficits may arise due to inflammatory reactions following parasite death in the brain. Symptoms may develop rapidly after treatment; therefore, immediate therapy with corticosteroids and anticonvulsants should be initiated.

This medicinal product contains 9.7 mg of sodium starch glycolate per tablet. Caution is advised when administering to patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

This medicinal product is contraindicated during pregnancy and breastfeeding, and in women planning to become pregnant.

Effect on ability to drive or operate machinery.

Due to the potential adverse reaction of dizziness, it is recommended that patients refrain from driving or operating machinery during albendazole treatment.

Dosage and Administration.

Intestinal infections and cutaneous Larva Migrans syndrome.

The medication should be taken with food. It is recommended to take it at the same time each day. If no improvement occurs within three weeks, a second course of treatment should be prescribed.

The tablet may be chewed or crushed and taken with a small amount of water.

Systemic helminthic infections (long-term treatment with high doses).

The medicinal product should be taken with food.

For use in adults and children aged 6 years and older.

The administration of high-dose therapy is not recommended in children under 6 years of age. The dosing regimen should be determined individually, depending on age, body weight, and severity of infection.

The dose for patients with body weight over 60 kg is 400 mg (1 tablet) twice daily. For patients with body weight less than 60 kg, the dose is 15 mg/kg/day, divided into two doses. Maximum daily dose — 800 mg.

• When treating patients with neurocysticercosis, appropriate corticosteroid and anticonvulsant therapy should be prescribed. Oral and intravenous corticosteroids are recommended to prevent the development of cerebral hyperpressure during the first week of treatment.

Typically, a single course of treatment is required, but additional courses may be necessary if parasitological test results remain positive.

Elderly patients

Experience with the use of the drug in elderly patients is limited. Dose adjustment is not required; however, albendazole should be used with caution in elderly patients with impaired liver function.

Renal impairment

Since albendazole is excreted in very small amounts via the kidneys, dose adjustment is not required in this patient group. However, patients with signs of renal impairment should be closely monitored.

Hepatic impairment

Since albendazole is extensively metabolized in the liver into a pharmacologically active metabolite, impaired liver function may significantly affect its pharmacokinetics. Therefore, patients with abnormal liver function tests (elevated transaminase levels) at the start of albendazole therapy should be carefully evaluated. If there is a significant increase in transaminase levels or clinically relevant changes in blood parameters, treatment should be discontinued.

Children

The drug is contraindicated for the treatment of children under 3 years of age in this pharmaceutical form. For children aged 2 to 3 years, another pharmaceutical form is recommended – oral suspension.

Overdose

Symptoms: nausea, vomiting, diarrhea, tachycardia, drowsiness, visual disturbances, visual hallucinations, speech disorders, dizziness, loss of consciousness, hepatomegaly, elevated transaminase levels, jaundice; respiratory distress, brown-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces proportional to the administered dose of the drug.

Treatment: gastric lavage should be performed, and symptomatic and supportive therapy should be administered.

Side effects.

Adverse reactions have been classified according to their frequency of occurrence.

The following frequency classification of adverse reactions is used: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); and very rare (< 1/10,000).

Adverse effects occurring during short-term treatment of intestinal infections and cutaneous larva migrans syndrome.

Immune system.

Rare: hypersensitivity reactions, including rash, itching, and urticaria.

Nervous system.

Uncommon: headache and dizziness.

Gastrointestinal tract.

Uncommon: gastrointestinal symptoms from the upper gastrointestinal tract (e.g., epigastric pain, nausea, vomiting) and diarrhea.

Hepatobiliary system.

Rare: increased levels of liver enzymes.

Skin and subcutaneous tissue.

Very rare: erythema multiforme, Stevens-Johnson syndrome.

Adverse effects occurring during long-term treatment of systemic helminthic infections.

Blood and lymphatic system.

Uncommon: leukopenia.

Very rare: pancytopenia, aplastic anemia, agranulocytosis.

Patients with liver disease, including hepatic echinococcosis, are more susceptible to bone marrow suppression.

Immune system.

Uncommon: hypersensitivity reactions, including rash, itching, and urticaria.

Nervous system.

Very common: headache.

Common: dizziness.

Gastrointestinal tract.

Common: gastrointestinal disturbances (abdominal pain, nausea, vomiting). These events are associated with albendazole treatment in patients with echinococcosis.

Hepatobiliary system.

Very common: mild to moderate elevation of liver enzyme levels.

Uncommon: hepatitis.

Skin and subcutaneous tissue.

Common: reversible alopecia (thinning and moderate hair loss).

Very rare: erythema multiforme, Stevens-Johnson syndrome.

General disorders.

Common: fever.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 ºC.

Keep out of reach of children.

Packaging.

3 tablets in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer/Applicant.

TOV "Ternopharm".

Manufacturer's location and address of business activity / Applicant's location.

4 Fabrychna Street, Ternopil, Ukraine, 46010.

Tel./fax: (0352) 521-444, www.ternopharm.com.ua