nbk сказал(а):
Я принимал лесаксис по 2 пачки через 21 день: вечер 5 таблеток + утро 5 + вечер 4. Мой вес 90 кг. После первого курса примерно на 4-5 день началось обострение, которое длилось до начала второго курса. После первого же приема таблеток на 2 курсе все как рукой сняло. Между вторым и третьим курсом состояние было ровное. После третьего курса состояние пока нормальное. Прошло 2 недели. Собираюсь проводить диагностику.
А как же рекомендация вьетнамца: Take 3 tablets at breakfast and 3 tablets at dinner x 3,5 days? Т.е. 3,5 дня, а не 1,5 как у Вас.... + на вес 90 кг хватило бы и 4 таблеток (с небольшим запасом).
Нашел инструкцию на английском:
LESAXYS
Triclabendazol 250 mg
• Description
• Specification
LESAXYS
(Triclabendazole 250 mg tablets)
COMPOSITION:
Each tablet contents:
Triclabendazole 250 mg
Excipients: Sunset yellow, erythrosine, lactose monohydrate microcrystalline cellulose, povidone, sodium starch glycolate, poly sorbate 80, silicone dioxide, acide stearic.
MECHANISM ACTION:
Spectrum
The antiparasitic spectrum of triclabendazole is characterized by specific activity against early immature, immature and adult flukes of Fasciola hepatica and Fasciola giagantica in both domestic animals and humans. Triclabendazole is effective against flukes as early as 24 hours after infection, as well as at the pre-pathogenic (week 1 to 4 after infection), acute, subacute and chronic stage of disease.
Activity has also been demonstrated in lung fluke infections due to Paragonimus uterobilateralis in infected cotton rat and due to P.uterobilateralis, P.africanus, P.mexicanus and P.westermani in humans.
Mechanism
The exact mechanisms of action of triclabendazole and of it main active sulphoxide metabolite against trematodes have not been fully elucidated. Although this drug can be chemically considered as a benzimidazole derivative, its structural characteristics (presence of chlorine atoms and a thiomethyl group, absence of carbamate moiety) clearly differentiate it from all other benzimidazole anthelmintics. Lack of nematocidal activity also suggests that it is acting differently from all other benzimidazole anthelmintics, which irreversibly inhibit glucose uptake by susceptible worms and slowly killing them by depleting their energy sources (glycogen and adenosine triphosphate). In addition, no uncoupling activity characteristic of classic anthelmintic fasciolaicidal salicylanides has been found. The only information available at present is that triclabendazole and its active sulphoxide metabolite readily penetrate the tegument of the fluke, rapidly inhibit its motility and function. The sulphoxide metabolite was found to exert a delayed but more potent effect on parasite motility than triclabendazole itself. Thus, it is likely that the drug acts mainly through its sulphoxide metabolite, which is largely predominant in human plasma. In addition, as the drug inhibits cholchicine binding to purified liver fluke tubulin, it alters the resting membrane potential and prevents proteolytic enzyme release from mature and immature worms.
No general pharmacological studies have been undertaken in mammalian species. No effect on smooth muscle or the cardiovascular, respiratory or nervous systems were detected in the various toxicity studies.
PHARMACOKINETICS:
Extensive referenced summaries of relevant animal studies are available. In humans, pharmacokinetic investigations rely mostly on the plasma concentrations of the sulphoxide metabolite, since biotransformation of triclabendazole to its metabolite ion the systemic circulation is rapid and almost complete. Only minute amounts of unchanged compound can be detected in humans. Simultaneous determinations of triclabendazole and its sulphoxide and sulphone metabolites were performed using HPLC.
Absorption
Following oral administration of 10 mg/kg triclabendazole to fasting patients, absorption was rapid, with a median tmax for both the parent compound and the sulphoxide metabolite of 2 hours. Mean peak plasma concentrations for triclabendazole and sulphoxide metabolite were 0.34 and 15.8 mmol/L, respectively, with respective AUCs of 1.55 and 177 mmol.h/L.
Distribution
The maximum apparent volume of distribution of the sulphoxide metabolite in fed patients is about 1L/kg (assuming complete drug absorption and complete conversion of triclabendazole to the sulphoxide metabolite).
Studies in sheep suggest that the metabolites are 99% bound to albumin with only low circulating concentrations of free active compounds.
Metabolism
In vivo, triclabendazole is rapidly oxidized into its sulphoxide metabolite, which is further oxidized to the sulphone metabolite. The sulphoxide form is predominant in plasma, with the parent compound and the sulphone metabolite having AUCs respectively of approximately 1% and 10% of that of the sulphoxide. The rapid biotransformation of triclabendazole in man and the previous findings in animals produced evidence of pre-systemic biotransformation including first-class metabolism of triclabendazole.
Excretion
The drug is largely excreted via the biliary tract in the faeces (90%), together with the sulphoxide and subsequently the sulphone metabolite. Less than 10% of an oral dose is excreted in the urine.
The elimination half-life of the sulphoxide metabolite form plasma is about 11 hours. Similar terminal phases of log-linear decreases in concentrations were observed for the three compounds under both fasted and fed conditions.
Influence of food
The influence of food on the pharmacokinetics of triclabendazole and its metabolites has been investigated in patients after oral administration of a 10 mg/kg dose. And increase in systemic availability probably due to improved gastrointestinal absorption, has been observed following administration of triclabendazole under fed conditions. Tmax, Cmax and AUC were more than double for both the sulphoxide and the parent compound. The pharmacokinetics of the minor sulphone metabolite were influenced by food in the same way.
To improve the systemic availability of the compound and its metabolites, administration of triclabendazole with food is therefore recommended.
INDICATION:
Triclabendazole, a benzimidazole derivative, is an anthelmintic with demonstrated activity against trematodes (flukes). It is effective in the treatment of:
Fascioliasis (“sheep liver fluke infection”) caused by Fasciola hepatica and Fasciola gigantica.
Paragonimiasis (also call: pulmonary distomiasis”, “endemic haemoptysis”, of “oriental lung fluke disease”) caused by Paragonimus westermani or other Paragonimus species.
DOSAGE & ADMINISTRATION:
Dosage of triclabendazole should be tailored to the patient’s weight. The tablets are scored and divisible into two equal halves in order to facilitate more precise dosing.
Triclabendazole should be administered orally, postprandially (see “Influence of food” under Pharmacokinetics). The tablets should be swallowed with liquid and not chewed.
Adults
10 mg/kg bodyweight as a single dose. In the event of treatment failure with a 10 mg/kg bodyweight dose, the dose can be increased to 20 mg/kg bodyweight and given in two divided doses 12-24 hours apart.
Concomitant treatment with antispasmodics has been shown to reduce pain and minimize the risk of jaundice.
The children aged 6 years and over.
Although the clinical data are limited in this population, there was no evidence of differences between adults and children in efficacy or safety. Dosage and treatment schedule should be the same as for adults. As there may be considerable disproportion between the size of the parasite and the paediatric biliary tract concomitant antispasmodic therapy should be routinely considered.
Children aged below 6 years
There is no experience with triclabendazole treatment in this population.
Elderly patients
No information is available on the relationship between age and the effects of triclabendazole in geriatric patients.
Patients with renal impairment
As no studies have been carried out in patients with renal impairment, no recommendation can be made for this population.
Patients with liver impairment
No studies have been performed in patients with liver impairment. Nevertheless, in clinical studies, a large proportion of patients had abnormal pre-treatment liver function tests (aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase, total bilirubin) which either normalized or remained stable following treatment. The most common new abnormality following treatment was an increase in serum alkaline phosphatase probably indicating functional cholestasis. In some cases increased bilirubin and/or transaminase levels accompanied the alkaline phosphatase increases. It seems likely that the liver function test abnormalities seen at baseline were due to fascioliasis, and that the predominantly cholestatic-type abnormalities observed following treatment may be the result of the expulsion of flukes through the biliary tree. This is supported by the rarity of such changes in patients treated for paragonimiasis.
Base on this data, triclabendazole should be administered with caution in patients with liver impairment not related to fascioliasis. In these patients, the treating physician should weigh the expected therapeutic benefit against the potential risks
CONTRAINDICATIONS:
Hypersensitivity to triclabendazole, other benzimidazole derivatives or any of the excipients.
For use during pregnancy and lactation see section “safety in pregnancy and breast feeding”
WARNING – PRECAUTIONS:
Mild to moderate transient increases in serum concentrations of liver enzymes (ASAT, ALAT, alkaline phosphatase) and total bilirubin have been reported in some patients receiving triclabendazole and in animals. The drug should therefore be use with caution in patients with pre-existing liver dysfunction.
No data available for patients with renal impairment, and no treatment recommendations can be made for this population/.
Triclabendazole should be use with caution in patients with glucose-6-phosphate dehydrogenase deficiency due to the possibility of inducing haemolysis.
Keep out of reach of children.
DRUG INTERACTIONS:
Class interactions (other benzimidazoles)
Thiabendazole may compete with other drugs (e.g. theophylline) for sites of metabolism in the liver and thereby increase serum concentrations of such drugs to potentially toxic levels. When thiabendazole and a xanthine derivative are used concomitantly, it may be necessary to monitor serum concentrations of the xanthine derivative and/ or reduce it dosage.
Interactions with other drugs used to treat fascioliasis of paragonimiasis
No specific drug interactions studies have been conducted with triclabendazole. However, animal studies with triclabendazole in combination with other anthelmintics such as fenbendazole or levamisole have shown no evidence of synergistic toxicity.
Safety in Pregnancy and breast feeding:
Pregnancy
Studies in rat and rabbits have not revealed evidence of harm to the fetus, although birth weight was lower in the offspring of animals given doses of 100 and 100 mg/kg bodyweight/ day, which are equivalent to 10 to 20 times the recommended therapeutic dose in humans for the more usual treatment.
Other benzimidazole derivatives, such as mebendazole, oxfendazole, flubendazole and albendazole, have been show to be embryotoxic and teratogenic in some species of laboratory animals. This difference in embryotoxicity and teratogenicity potential could be related to the different mode of action of triclabendazole as compared to other benzimidazole anthelmintics.
Nevertheless, in the absence of appropriate controlled studies in pregnant women, triclabendazole should be used in pregnancy only when the potential benefits outweigh the possible risks.
Lactation
Transfer of radioactive substance(s) into the rat embyro/fetal compartments was investigated following single peroral administration of 14C-labelled triclabendazole at a dose 10 mg/kg. Excretion into the milk of lactating rats was not specifically investigated. However, as a result of uptake of radioactivity into the mammary glands, triclabendazole may well be excreted with the milk in lactating animals. Published data indicate that in goats, approximately 1% of an oral dose is excreted in the milk.
Since no information on drug concentrations in milk is available for humans, triclabendazole should be avoided during lactation. Nevertheless, if lactation must be continued, it should be suspended during treatment and for the following 72 hours.
Effects on ability to drive and use machines:
Patients should be warned that dizziness may occur, in which case they should not drive, operate potentially dangerous machinery, or engage in other activities that may become hazardous.
ADVERSE REACTIONS:
Frequency estimates: Very common ≥ 10%, common≥ 1%, to ≤10%; uncommon ≥ 0.1% to ≤ 1%; rare ≥ 0.01% to ≤ 0.1%; very rare ≤ 0.01%.
It should keep in mind that some adverse events associated with triclabendazole treatment may be secondary to the parasitic infection being treated, to dying parasites and/or to expulsion of dead parasites from the hepatobiliary system rather than to the drug itself. Such effects may be more frequent and/or severe in patients with a heavy worm burden.
Body as a whole
Very common: sweating
Common: weakness, chest pain, fever
Digestive system
Very common: abdorminal/epigastric pain
Common: anorexia, diarrhoea, nausea, vomiting
Liver/biliary system
Common: icterus/jaundice, biliary colic
Nervous system
Common: dizziness/vertigo, headache
Uncommon: drowsiness
Skin
Common: Urticaria
Uncommon: pruritus
Musculo-skeletal system
Uncommon: back pain
Respiratory system
Common: dypsnoea, cough
Renal/metabolic disorders
Uncommon: borderline and reversible elevations of serum creatinine.
Please inform your doctor of all undesirable effects upon drug administration.
OVERDOSE:
No specific information is available either on clinical signs and symptoms of on the treatment of overdose with triclabendazole.
AVAILABILITY: blister pack of 1’s, box of 7 tablets.
STORAGE CONDITION: Store at temperature not exceeding 30oC. Do not expose to direct sunlight.
QUALITY SPECIFICATION: As per In-House
SHELF-LIFE: 36 months from manufacturing date.