Vormil

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

Composition:

Active substance: albendazole;

One chewable tablet contains 400 mg of albendazole;

Excipients: maize starch, microcrystalline cellulose, sodium methylparahydroxybenzoate (E 219), sodium propylparahydroxybenzoate (E 217), sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, talc, magnesium stearate, dried mixed fruit essence, aspartame (E 951), sodium lauryl sulfate.

Pharmaceutical form. Chewable tablets.

Main physicochemical properties: white or almost white, elongated, biconvex, uncoated tablets with a score line and an imprint "VORMIL".

Pharmacotherapeutic group. Antihelminthic agents. Agents used in nematode infections. Benzimidazole derivatives. ATC code P02CA03.

Pharmacological Properties

Pharmacodynamics

Albendazole is a broad-spectrum 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 effect of albendazole is due to inhibition of tubulin polymerization, leading to disruption of 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 – Hymenolepsis 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 or significantly reduces the size (by up to 80%) of cysts in patients with granulomatous echinococcosis. After treatment with albendazole, the number of non-viable cysts increases to 90%, compared to 10% in untreated patients. In patients with cysts caused by Echinococcus multilocularis, complete recovery was observed in a minority of cases after albendazole treatment, while most patients showed improvement or stabilization of their condition.

Pharmacokinetics

After oral administration, the drug is poorly absorbed (up to 5%) from the gastrointestinal tract. Concurrent intake of 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, teniasis, strongyloidiasis, ascariasis, trichocephaliasis, clonorchiasis, opisthorchiasis, giardiasis in children.

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

cystic echinococcosis (caused by Echinococcus granulosus):

• when surgical intervention is impossible;
• prior to surgical intervention;
• after surgery, if preoperative treatment was short, if widespread helminth 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):

• in 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, other benzimidazole derivatives, or any other component of the drug. Retinal disease. Women planning pregnancy. Women of reproductive age should use effective non-hormonal contraception during and for 1 month after treatment with 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 responsible for systemic activity, which in turn may lead to drug 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 in patients; alternative dosing regimens or therapies may be required.

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.

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

Systemic effect is enhanced if the drug is taken with food.

Special precautions for use.

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

To prevent administration of Vermox 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 reveal pre-existing neurocysticercosis, particularly in areas with a high prevalence of Tenia 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. These symptoms may appear rapidly after treatment initiation; therefore, appropriate therapy with corticosteroids and anticonvulsants should be started immediately.

Long-term treatment of systemic helminthic infections.

Albendazole treatment may be associated with mild to moderate increases in liver enzymes, which usually return to normal after discontinuation of therapy. Cases of hepatitis have been reported. Therefore, liver enzyme levels should be assessed before 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), 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 throughout the 28-day 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 blood parameters. If significant blood count reductions occur, treatment should be discontinued (see sections "Dosage and administration" and "Adverse reactions").

The drug may be used for deworming prior to vaccination, as well as for prophylactic treatment twice a year.

In patients with neurocysticercosis receiving 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 agents. To prevent episodes of increased cerebral pressure during the first week of treatment, oral or intravenous corticosteroids are recommended.

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

• begin treatment only after a negative pregnancy test;
• be informed about the necessity of using effective contraceptive methods during treatment and for one month after discontinuation of the drug.

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

The presence of sodium propylparaben and sodium methylparaben in the formulation may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

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

Ability to affect reaction speed when driving or operating machinery.

Given the potential adverse effect of dizziness, it is recommended to avoid driving vehicles 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 advisable 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 medication should be taken with food.

High-dose administration of the drug is not recommended for children under 6 years of age. The dosage regimen is determined individually 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 (1 tablet) twice daily. For patients with body weight less than 60 kg, the dose should be calculated at 15 mg/kg/day. This dose should be divided into two administrations. 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 hypertension during the first week 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.

Renal impairment

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

Hepatic impairment 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. If significant increases in transaminase levels or decreases in blood parameters to clinically significant levels occur, treatment should be discontinued.

Children

The drug is contraindicated for use in children under 2 years of age in this pharmaceutical form.

For children aged 1 to 2 years, Wormil oral suspension may be used if necessary.

Overdose.

Symptoms: nausea, vomiting, diarrhea, tachycardia, drowsiness, visual disturbances, visual hallucinations, speech impairment, 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.

Treatment: perform gastric lavage and administer symptomatic and supportive therapy.

Adverse Reactions

Gastrointestinal disorders: stomatitis, dry mouth, heartburn, nausea, vomiting, abdominal pain, flatulence, diarrhea, constipation, epigastric pain.

Hepatobiliary disorders: transient increase in liver enzyme activity, jaundice, hepatitis, hepatocellular disorders.

Cardiovascular system disorders: increased blood pressure, tachycardia.
Central and peripheral nervous system disorders: insomnia or somnolence, headache, dizziness, confusion, disorientation, hallucinations, seizures, decreased visual acuity.

Blood and lymphatic system disorders: leucopenia, neutropenia, thrombocytopenia, anemia, including aplastic anemia; agranulocytosis, pancytopenia. Patients with liver disease, including hepatic echinococcosis, are more susceptible to bone marrow suppression.

Skin and subcutaneous tissue disorders: skin rashes, erythema, polymorphic erythema, Stevens-Johnson syndrome, reversible alopecia (thinning and moderate hair loss), pruritus, urticaria, bullous eruption, dermatitis, swelling.

Renal and urinary system disorders: renal function impairment, acute renal failure, proteinuria.

General disorders: bone pain, throat pain, chills, weakness.

Hypersensitivity reactions are possible, including anaphylactic/anaphylactoid reactions.

Shelf life. 3 years.

Storage conditions. Store at temperatures not exceeding 25 °C in the original packaging, in a place inaccessible to children.

Packaging. 1 or 3 tablets per blister, 1 blister per pack, together with the instructions for medical use.

Prescription category.
Prescription only.

Manufacturer. Mepro Pharmaceuticals Private Limited.
Manufacturer's location and address of the place of business: Unit II, Q-Road, Phase IV, GIDC, Vadodhan, Surendranagar, Gujarat, 363 035, India.

or

Manufacturer. Xell Laboratories Pvt. Ltd., India.
Manufacturer's location and address of the place of business: E-1223, Phase-I, Ext. (Ghatal) RIICO Industrial Area, Bhiwadi, Dist. Alwar (Rajasthan), India.

Marketing Authorization Holder. Milpharm Limited.
Address of the Marketing Authorization Holder: 2nd Floor, Office Premises, 4 Charterfield House, Castle Street, Taunton, Somerset, England, TA1 4AS, United Kingdom.