Zentel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ZENTEL (ZENTEL)

Composition:

Active ingredient: albendazole;

10 ml of suspension contains 400 mg of albendazole;

Excipients: aluminum-magnesium silicate, sodium carboxymethylcellulose, glycerin, polysorbate 80, sorbitan laurate, potassium sorbate, benzoic acid, sorbic acid, anti-foaming silicone (simethicone emulsion) Q7-2587, sodium saccharin, orange flavor, vanilla flavor, passion fruit flavor, purified water.

Pharmaceutical form. Oral suspension.

Main physicochemical properties: white to creamy white suspension with an orange and vanilla odor; may contain a sediment which readily disperses upon shaking.

Pharmacotherapeutic group. Antihelminthic agents. Agents used in nematode infections. 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 form of eggs, larvae, and adult helminths. The anthelmintic action of albendazole is due to inhibition of tubulin polymerization, leading to disruption of parasite metabolism and subsequent death.

Albendazole is active against the following intestinal parasites:
Nematodes – Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Cutaneous Larva Migrans;
Cestodes – Hymenolepis nana, Taenia solium, Taenia saginata;
Trematodes – Opisthorchis viverrini, Clonorchis sinensis;
Protozoa – Giardia lamblia (intestinalis or duodenalis).

Albendazole is 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 infection with 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 was observed in a minority of patients, while the majority experienced improvement or stabilization of disease.

Pharmacokinetics.

After oral administration, albendazole is poorly absorbed (less than 5%). Systemic exposure increases when the drug is taken with fatty food, which enhances absorption by up to 5-fold. Albendazole undergoes rapid hepatic metabolism during first-pass passage. The main metabolite is albendazole sulfoxide, which is the primary active compound responsible for efficacy in tissue infections. The elimination half-life is 8.5 hours. Albendazole sulfoxide and its metabolites are excreted predominantly in bile, with only a small fraction eliminated in urine. It has been established that with prolonged administration of high doses, elimination of the drug from cysts continues for several weeks.

Elderly patients

Although pharmacokinetic studies of albendazole in elderly patients have not been conducted, data from treatment of 26 patients aged up to 79 years suggest that the pharmacokinetic profile in this age group is similar to that in young healthy volunteers.

Renal impairment

The pharmacokinetics of albendazole have not been studied in patients with renal impairment.

Hepatic impairment

The pharmacokinetics of albendazole have not been studied in patients with hepatic impairment.

Clinical characteristics.

Indications.

Intestinal helminthiases and cutaneous Larva Migrans syndrome (short-term treatment with low doses): enterobiasis, ancylostomiasis and necatoriasis, hymenolepiasis, teniasis, strongyloidiasis, ascariasis, trichocephalosis, clonorchiasis, opisthorchiasis, cutaneous Larva Migrans syndrome, 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 surgery;
• after surgery, if preoperative treatment was short, if widespread parasitic dissemination is observed, or if viable parasite forms were found during surgery;
• after percutaneous cyst drainage performed 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):

• in the presence of single or multiple cysts or granulomatous brain lesions;
• in arachnoid or intraventricular cysts;
• in 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 or to any component of the drug.

Pregnancy and breastfeeding.

Women who plan to become pregnant. Women of reproductive age should use effective non-hormonal contraceptive methods during and for 1 month after treatment with the drug.

Interaction with other medicinal products and other forms of interaction.

Albendazole induces enzymes of the cytochrome P450 system.

Medicinal products that may slightly reduce the efficacy of albendazole: anticonvulsants (e.g., phenytoin, fosphenytoin, carbamazepine, phenobarbital, primidone), levamisole, ritonavir. The effectiveness of treatment in patients should be monitored, and alternative dosing regimens or therapies may be required.

Cimetidine, praziquantel, and dexamethasone increase plasma levels of the albendazole metabolite responsible for systemic activity, which in turn may lead to an increased incidence of adverse reactions.

Grapefruit juice also increases plasma levels of albendazole sulfoxide.

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

Special precautions for use.

Treatment of intestinal helminth infections and cutaneous larva migrans

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

Treatment with albendazole may unmask pre-existing neurocysticercosis, particularly 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 an inflammatory reaction caused by the death of parasites in the brain. These symptoms may appear rapidly after treatment initiation; therefore, prompt therapy with corticosteroids and anticonvulsant agents should be initiated immediately.

Treatment of systemic helminthic infections

Albendazole treatment may be associated with mild to moderate elevations in liver enzymes, which typically normalize after discontinuation of therapy. Cases of hepatitis have been reported. Therefore, liver enzyme levels should be assessed before starting each treatment course and at least every 2 weeks during treatment. If liver enzyme levels increase significantly (more than twice the upper limit of normal), treatment with albendazole should be discontinued. Treatment may be restarted 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 at least every 2 weeks during the 28-day treatment cycle. Patients with liver disease, including hepatic echinococcosis, are more susceptible to bone marrow suppression, which may result in pancytopenia, aplastic anemia, agranulocytosis, and leukemia, necessitating careful monitoring of hematological parameters. If significant blood count reductions occur, treatment should be discontinued (see sections "Dosage and administration" and "Adverse reactions").

To prevent administration of Zentel during early pregnancy, women of childbearing potential should:

- begin treatment only after a negative pregnancy test;

- be advised to use effective contraceptive measures during treatment and for one month after discontinuation of the drug.

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

Treatment with albendazole may also unmask pre-existing neurocysticercosis, especially in areas with high prevalence of Taenia solium strains. Neurological symptoms such as seizures, increased intracranial pressure, and focal neurological signs due to inflammatory reactions from parasite death in the brain may develop. Symptoms may appear rapidly after treatment; therefore, immediate therapy with corticosteroids and anticonvulsants should be initiated.

The suspension formulation of the drug contains benzoic acid, which may cause mild irritation of the skin, eyes, and mucous membranes.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy and breastfeeding, and in women planning to become pregnant.

Ability to affect reaction speed when driving or operating machinery

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

Method of administration and dosage.

Intestinal forms and cutaneous larva migrans syndrome

Take the medication with food. Shake well before use. It is advisable to take it at the same time each day. If no improvement occurs within 3 weeks, the physician should prescribe a second course of treatment.

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.

N renal insufficiency

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

Hepatic insufficiency

Since albendazole is actively metabolized in the liver to its pharmacologically active metabolite, impaired liver function may significantly affect its pharmacokinetics. Therefore, patients with altered liver function parameters (elevated transaminase levels) at the start of albendazole therapy should be closely monitored.

Systemic helminthic infections

(prolonged treatment with high doses)

Take the drug with food.

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

Administration of high doses of the drug is not recommended in children under 6 years of age.

The dosage regimen should be individually determined by a physician depending on age, body weight, and severity of infection.

The dose for patients with body weight over 60 kg is 400 mg (10 ml of suspension) twice daily.

For patients with body weight less than 60 kg, the dose is 15 mg/kg/day, divided into two doses. The maximum daily dose is 800 mg.

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

**Usually one course of treatment is required, but further 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 insufficiency

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

Hepatic insufficiency

Since albendazole is actively metabolized in the liver to its pharmacologically active metabolite, impaired liver function may significantly affect its pharmacokinetics. Therefore, patients with abnormal liver function tests (elevated transaminase levels) should be carefully evaluated before starting albendazole treatment. Treatment should be discontinued in cases of significant elevation of transaminase levels or reduction in blood parameters to clinically significant levels (see sections "Special precautions" and "Side effects").

Children.

The drug is contraindicated for use in children under 1 year of age.

Administer to children according to the information specified in the section "Administration and dosage".

Overdose.

In case of overdose, treatment is symptomatic and based on the clinical condition.

Adverse Reactions

Adverse reactions have been classified according to their frequency of occurrence. The following frequency classification is used: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); rare (≥ 1/10,000 and < 1/1000); 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, pruritus, and urticaria.

Nervous system

Uncommon: headache and dizziness.

Gastrointestinal tract

Uncommon: abdominal 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 prone to bone marrow suppression (see sections "Method of administration and dosage" and "Special precautions").

Immune system

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

Nervous system

Very common: headache.

Common: dizziness.

Gastrointestinal tract

Common: abdominal pain, nausea, vomiting, and diarrhea. 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 of hair and moderate hair loss).

Very rare: erythema multiforme, Stevens-Johnson syndrome.

General disorders

Common: fever.

Shelf life.

2 years.

Storage conditions. Store at a temperature below 25 °C. Keep out of reach of children. Protect from direct sunlight. Shake well before use.

Packaging. 10 ml of suspension in a HDPE bottle with a polypropylene screw cap and a tamper-evident ring, placed in a cardboard box.

Prescription category. Prescription only.

Manufacturer. Aspen Bad Oldesloe GmbH, Germany.

Manufacturer's address and place of business.

Industriestrasse 32-36, Bad Oldesloe, Schleswig-Holstein, 23843, Germany.