Angelmex

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

Composition:

Active substance: albendazole;

1 tablet contains 400 mg of albendazole calculated as 100% dry substance;

Excipients: microcrystalline cellulose, povidone, sodium lauryl sulfate, sodium saccharin, powdered flavoring "Orange", magnesium stearate.

Pharmaceutical form. Chewable tablets.

Main physico-chemical characteristics: biconvex, round-shaped tablets, white, nearly white, or white with a grayish tint, with a score line, having a specific odor. Marbling on the surface of tablets is permissible.

Pharmacotherapeutic group. Anthelmintic agents. 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 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 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 number 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 their condition.

Pharmacokinetics

Albendazole is poorly absorbed from the gastrointestinal tract (up to 5%). It is not detectable in unchanged form in blood plasma, as it is rapidly metabolized in the liver to its primary metabolite, albendazole sulfoxide, which also possesses anthelmintic activity. Oral bioavailability is low (approximately 30%). Concomitant administration with fatty food enhances absorption and increases the maximum plasma concentration (Cmax) by up to fivefold. The Cmax of albendazole sulfoxide is reached within 2–5 hours. Plasma protein binding is approximately 70%. Albendazole sulfoxide is widely distributed throughout the body and penetrates in significant amounts into bile, liver, cerebrospinal fluid, urine, and the walls and fluids of helminth cysts. In the liver, albendazole sulfoxide is further metabolized to albendazole sulfone (secondary metabolite) and other oxidized products. The elimination half-life (T1/2) of albendazole sulfoxide is 8–12 hours. The drug is excreted in urine as various metabolites.

In renal impairment, the clearance of albendazole and its main metabolites remains unchanged. In hepatic impairment, bioavailability of the drug increases, the Cmax of albendazole sulfoxide doubles, and the T1/2 is prolonged.

Albendazole is an inducer of microsomal enzymes of the cytochrome P450 system.

Clinical Characteristics.

Indications.

Intestinal forms of helminthiases and cutaneous larva migrans (short-term treatment with low doses): enterobiasis, ancylostomiasis and necatoriasis, hymenolepiasis, taeniasis, strongyloidiasis, ascariasis, trichuriasis, 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 surgery;
  • after surgery, if preoperative treatment was short, if dissemination of helminths 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 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 and other components of the drug, as well as to other benzimidazole derivatives.
• Women planning pregnancy. Women of childbearing potential must use effective non-hormonal contraceptive methods during treatment and for 1 month after completion of therapy with the drug.

Interaction with other medicinal products and other types of interactions.

Albendazole induces enzymes of the cytochrome P450 system.

Cimetidine, praziquantel, and dexamethasone: possible increase in plasma levels of the metabolite of albendazole responsible for systemic activity, which in turn may lead to drug overdose.

Grapefruit juice also increases plasma levels of albendazole sulfoxide.

Ritonavir, rifampicin, phenytoin, fosphenytoin, carbamazepine, and phenobarbital, primidone, levamisole: possible significant reduction in plasma concentrations of albendazole and its active metabolite albendazole sulfoxide. The clinical significance of this is unknown, but reduced efficacy of albendazole is possible, especially in the treatment of systemic helminthic infections. Efficacy of treatment should be monitored in patients, and alternative dosing regimens or therapies may be required.

Oral contraceptives, anticoagulants, oral hypoglycemic agents, theophylline: due to the potential for cytochrome P450 activity alteration, there is a theoretical risk of interaction with these drugs. Caution should be exercised when administering albendazole to patients taking these medications. Theophylline blood levels should be monitored during concomitant use. Systemic exposure increases when the drug is taken with food.

Special precautions for use.

Treatment of intestinal helminth infections and cutaneous larva migrans (short-term therapy).

To prevent inadvertent administration of the drug 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 must be used during treatment.

In patients previously treated with albendazole for other reasons, pre-existing neurocysticercosis may become apparent, particularly in areas with high prevalence of Taenia solium infection. Neurological symptoms such as seizures, increased intracranial pressure, and focal neurological signs may occur due to inflammatory reactions caused by parasite death in the brain. These symptoms may appear shortly after treatment initiation; therefore, prompt therapy with corticosteroids and anticonvulsants should be initiated immediately.

Long-term treatment of systemic helminthic infections.

Albendazole treatment may be associated with mild to moderate elevation of liver enzymes, which usually normalizes after discontinuation of therapy. Cases of hepatitis and acute liver failure of unknown etiology have been reported. Liver enzyme levels should be assessed before each treatment cycle and at least every 2 weeks during treatment. If liver enzymes rise significantly (more than twice the upper limit of normal), albendazole treatment should be discontinued. Treatment may be resumed after normalization of enzyme levels and careful assessment of benefit versus risk, but patients should be closely monitored due to the possibility of recurrence.

Albendazole may cause bone marrow suppression; therefore, blood counts should be performed at the beginning of treatment and every 2 weeks during each 28-day cycle. Patients with hepatic disease, including hepatic echinococcosis, are more susceptible to myelosuppression, which may lead to pancytopenia, aplastic anemia, agranulocytosis, and leukopenia. This necessitates more careful monitoring of hematological parameters. If clinically significant decreases in blood cell counts occur, treatment should be discontinued (see sections "Dosage and administration" and "Side effects").

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

In cysticercosis, cysticercus may be located in the retinal tissue of the eye. Prior to initiating therapy, patients should be examined for retinal lesions. If such lesions are detected, the benefits of anticycercic treatment should be weighed against the potential for retinal damage due to inflammatory reactions caused by albendazole-induced parasite death.

To avoid administration of albendazole during early pregnancy, women of childbearing potential should:

• initiate treatment only after a negative pregnancy test; this test should be repeated at least once before starting the next treatment cycle;
• use effective non-hormonal contraceptive methods during treatment and for at least one month after completion of systemic helminth infection therapy with albendazole.

Systemic exposure to albendazole is increased when the drug is taken with fatty food (absorption increases up to 5-fold).

The product contains sodium saccharin, which should be taken into account in patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy or breastfeeding, and in women who are planning to become pregnant (see section "Contraindications").

Reliable contraceptive methods should be used during treatment.

Ability to affect reaction speed when driving or operating machinery.

Due to the potential for adverse reactions such as dizziness, patients should refrain from driving or operating vehicles or machinery.

Method of administration and dosage.

Intestinal infections and cutaneous larva migrans syndrome.

The drug should be taken with food. Chew or crush the tablet, swallowing it with a small amount of water. It is advisable to take it at the same time each day. If there is no recovery within three weeks, a second course of treatment should be administered.

Systemic helminthic infections (prolonged treatment with high doses).

Take the drug with food. Chew the tablet or crush it, swallowing with a small amount of water.

Administration of high doses of the drug is not recommended in children under 6 years of age. The dosage regimen should be determined individually, depending on age, body weight, and severity of infection.

For patients with body weight less than 60 kg, administer the drug at a dose of 15 mg/kg/day, divided into two doses.

For patients with body weight over 60 kg – 400 mg (1 tablet) twice daily.

Maximum daily dose – 800 mg (2 tablets).

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

** Usually one course of treatment is sufficient, but repeated courses may be required if parasitological examination 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 for treating this patient group. However, patients with signs of renal impairment should be closely monitored by a physician.

Hepatic impairment. Since albendazole is actively metabolized in the liver to 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 closely monitored by a physician. If significant elevation of transaminase levels or clinically significant decreases in blood parameters occur during treatment, therapy should be discontinued.

Children.

This medicinal formulation should not be used in children under 3 years of age.

Overdose.

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

Treatment: gastric lavage, administration of sorbents. If necessary, symptomatic and supportive therapy should be provided.

Adverse reactions.

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

Hepatobiliary system: transient increase in liver enzyme activity, hepatitis. Cases of severe liver pathology, including jaundice and hepatocellular injury, acute liver failure, which may be irreversible, have been reported during prolonged high-dose albendazole therapy.

Nervous system: headache, dizziness, vertigo, insomnia or drowsiness, confusion, disorientation, hallucinations, seizures, blurred vision, decreased visual acuity.

Cases of increased intracranial pressure and meningeal symptoms (meningism) have been reported when high doses (> 400 mg/day) are used for prolonged treatment periods (> 10 days).

Blood and lymphatic system disorders: leukopenia, neutropenia, granulocytopenia, agranulocytosis, thrombocytopenia, pancytopenia, anemia, including aplastic anemia, bone marrow depression—these are more likely in patients with liver disease, including hepatic echinococcosis.

Immune system: hypersensitivity reactions, including anaphylactic and anaphylactoid reactions, skin rashes, pruritus, urticaria.

Skin and subcutaneous tissue: hyperemia, reversible alopecia (thinning of hair, moderate hair loss), edema, dermatitis, bullous eruptions, erythema multiforme, Stevens-Johnson syndrome.

Cardiovascular system: increased blood pressure, tachycardia.

Renal and urinary system: impaired kidney function, acute renal failure, proteinuria.

Other: bone pain, sore throat, fever, asthenia, rhabdomyolysis.

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

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 carton.

Prescription category. Prescription only.

Manufacturer.

LLC "Agrofarm".

Manufacturer's address and place of business.

113-A, Centralna Street, Irpin, Kyiv region, 08200, Ukraine.