Wormstop

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT WORMSTOP

Composition:

Active substance: albendazole;

1 tablet contains 400 mg of albendazole;

Excipients: mannite (E 421), lactose monohydrate, pregelatinized starch, sodium starch glycolate (type A), crospovidone, colloidal anhydrous silicon dioxide, povidone, hydroxypropylcellulose, polysorbate 80, aspartame (E 951), microcrystalline cellulose, magnesium stearate, talc, strawberry flavor.

Pharmaceutical form. Chewable tablets.

Main physicochemical properties: white, capsule-shaped, biconvex tablets with a score line on one side.

Pharmacotherapeutic group.

Anthelmintic agents used in nematodosis. Benzimidazole derivatives. Albendazole. 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 of helminths.

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 invasion of Taenia solium, capillariasis caused by Capillaria philippinensis, and gnathostomiasis caused by Gnathostoma spinigerum.

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

Pharmacokinetics.

After oral administration, albendazole is poorly absorbed (less than 5%). Systemic exposure increases when the drug is administered with fatty food, which enhances absorption by fivefold. Albendazole is rapidly metabolized in the liver during first-pass metabolism. 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 primarily excreted via bile, with only a small fraction eliminated in urine. It has been established that with prolonged high-dose treatment, 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 obtained from treatment of 26 patients up to 79 years of age suggest that the pharmacokinetic profile in this age group is similar to that in young healthy volunteers.

Renal impairment

The pharmacokinetics of albendazole in this patient group has not been studied.

Hepatic impairment

The pharmacokinetics of albendazole in this patient group has not been studied.

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, 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 helminth infection is observed, or if viable forms were found during surgery;
• after percutaneous drainage of cysts for diagnostic or therapeutic purposes;

alveolar echinococcosis (caused by Echinococcus multilocularis):

• in inoperable cases, particularly with 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 or to any component of the drug.

Pregnancy and breastfeeding.

Women planning pregnancy. Women of reproductive age should use effective non-hormonal contraceptive methods during treatment and for one month after discontinuation of the drug.

Interaction with other medicinal products and other forms of interaction.

Albendazole induces cytochrome P450 enzyme system.

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

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

Grapefruit juice also increases plasma levels of albendazole sulfoxide.

Due to possible effects 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 inadvertent administration of Wormstop 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, particularly in areas with high prevalence of Tenia solium infection. 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, prompt initiation of appropriate therapy with corticosteroids and anticonvulsants is necessary.

Treatment of systemic helminthic infections

Albendazole therapy may be associated with mild to moderate elevations in liver enzymes, which usually return to normal after discontinuation of treatment. 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, a complete blood count should be performed at the beginning of treatment and 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 hematological abnormalities occur, treatment should be discontinued (see sections "Dosage and administration" and "Side effects").

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

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

In patients with neurocysticercosis treated with albendazole, symptoms such as seizures, increased intracranial pressure, and focal neurological signs may occur due to inflammatory reactions following parasite death. These adverse reactions should be managed with corticosteroids and anticonvulsants. To prevent increased intracranial pressure during the first week of treatment, oral or intravenous corticosteroids are recommended.

Albendazole treatment may also reveal pre-existing neurocysticercosis, especially in regions with high prevalence of Tenia solium infection. Neurological symptoms such as seizures, increased intracranial pressure, and focal neurological deficits may develop rapidly after treatment due to inflammatory reactions caused by parasite death in the brain. Prompt initiation of corticosteroid and anticonvulsant therapy is therefore required.

Since the product contains lactose, patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy and breastfeeding, as well as for treatment of women who are planning to become pregnant (see section "Contraindications").

Effect on ability to drive or operate machinery

Due to the potential side effect of dizziness, patients should refrain from driving or operating machinery during albendazole treatment.

Dosage and Administration

Intestinal infections and cutaneous larva migrans syndrome

The drug 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.

Some patients, especially children, may have difficulty swallowing the whole tablet. In such cases, the tablet may be chewed with a small amount of water or crushed before administration.

For use in adults and children aged 3 years and older.

Infection	Age	Dosing duration
Enterobiasis, ancylostomiasis, necatoriasis, ascariasis, trichuriasis	Adults and children aged 3 years and older*	400 mg once daily (1 tablet) as a single dose
Strongyloidiasis, taeniasis, hymenolepiasis	Adults and children aged 3 years and older	400 mg once daily (1 tablet) for 3 days For hymenolepiasis, a repeat course is recommended between day 10 and day 21 after the previous course.
Clonorchiasis, opisthorchiasis	Adults and children aged 3 years and older	400 mg (1 tablet) twice daily for 3 days
Cutaneous larva migrans Larva Migrans	Adults and children aged 3 years and older	400 mg (1 tablet) once daily for 1–3 days
Giardiasis	Children aged 3 to 12 years only*	400 mg (1 tablet) once daily for 5 days

* For children aged 2 to 3 years, another dosage form of the drug should be used – oral suspension.

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 urine in very small amounts, 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 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) should be closely monitored at the beginning of albendazole treatment.

Systemic helminthic infections

(long-term treatment with high doses)

The drug should be taken with food.

It is administered to 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 determined individually by the physician depending on age, body weight, and severity of infection.

The dose for patients with a 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.

Infection	Duration of treatment
Cystic echinococcosis	28 days. The 28-day cycle may be repeated (up to three times in total) after a 14-day break.
Inoperable and multiple cysts	Up to three 28-day cycles for treatment of hepatic, pulmonary, and peritoneal cysts. Longer treatment may be required for cysts in other locations (in bones or brain).
Before surgery	Two 28-day cycles are recommended before surgery. If surgery must be performed before completing these cycles, treatment should be continued as long as possible prior to surgery.
After surgery After percutaneous drainage of cysts	If a short course of treatment (less than 14 days) was administered before surgery or if emergency surgery was performed, two 28-day treatment cycles, separated by a 14-day drug-free interval, should be given after surgery. Similarly, if viable cysts are found or if there was dissemination of parasites, two full treatment cycles should be administered.
Alveolar echinococcosis	28 days. A second 28-day course is repeated after a two-week drug-free interval. Treatment may be extended over several months or years.
Neurocysticercosis**	Treatment duration ranges from 7 to 30 days. A second course may be repeated after a two-week drug-free interval.
Cysts in parenchyma and granulomas	Usual treatment duration is from 7 days (minimum) to 28 days.
Arachnoid and intraventricular cysts	The usual treatment course is 28 days.
Racemose cysts	The usual treatment course is 28 days, but may last longer. Duration of treatment is determined based on clinical and radiological response.

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

Infection	Duration of intake
Capillariasis	400 mg once daily for 10 days***
Gnathostomiasis	400 mg once daily for 10–20 days***
Trichinellosis, toxocariasis	400 mg twice daily for 5–10 days***

***Usually, 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 by the kidneys in very small amounts, dose adjustment is not required in patients with renal impairment. Nevertheless, such patients with signs of renal insufficiency should be closely monitored.

Hepatic impairment

Since albendazole is extensively 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) at the start of albendazole treatment should be carefully evaluated. Treatment should be discontinued in case of significant elevation in transaminase levels or drop in blood counts to clinically significant levels (see sections "Special precautions" and "Adverse reactions").

Children

The drug is contraindicated for use in children under 3 years of age. For treatment of children aged 2 to 3 years, an alternative dosage form – oral suspension – is recommended.

Administer to children according to the information specified in the section "Dosage and administration".

Overdose.

Symptoms may include, depending on the dose ingested: diarrhea, nausea, vomiting, tachycardia, and elevated transaminase levels. In case of overdose, treatment is symptomatic and based on the clinical condition.

Adverse Reactions

Adverse effects have been classified according to their frequency of occurrence. The following classification of adverse event frequencies is used: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); 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 susceptible to bone marrow suppression.

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.

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 in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

3 tablets in a blister pack.

1 blister pack in a cardboard box.

Prescription status

Prescription only.

Manufacturer

BAFNA PHARMACEUTICALS Limited

BAFNA PHARMACEUTICALS LimiTeD

Manufacturer's address and place of business

No. 147, Madhavaram, Red Hills Road, Grantlion Village, Vadakarai, Chennai, 600 052, India

No. 147, MADHAVARAM, RED HILLS ROAD, GRANTLYON VILLAGE, VADAKARAI, CHENNAI, 600 052, INDIA

Marketing Authorization Holder

M. Biotek Ltd

M. Biotech ltd

Address of the Marketing Authorization Holder

Gladstone House, 77–79 High Street, Egham TW20 9HY, Surrey, United Kingdom