Method of action:
Medically reviewed by Oliinyk Elizabeth Ivanovna, PharmD. Last updated on 2020-03-12
Attention! Information on this page is intended only for medical professionals! Information is collected in open sources and may contain significant errors! Be careful and double-check all the information on this page!
Top 20 medicines with the same components:
EskazoleZA is indicated for the treatment of parenchymal neurocysticercosis due to active lesions caused by larval forms of the pork tapeworm, Taenia solium.
EskazoleZA is indicated for the treatment of cystic hydatid disease of the liver, lung, and peritoneum, caused by the larval form of the dog tapeworm, Echinococcus granulosus.
Dosing of EskazoleZA will vary depending upon the indication. EskazoleZA tablets may be crushed or chewed and swallowed with a drink of water. EskazoleZA tablets should be taken with food.
Table 1: EskazoleZA Dosage
|Hydatid Disease||60 kg or greater||400 mg twice daily, with meals||28-day cycle followed by a 14-day Eskazoledazole-free interval, for a total of 3 cycles|
|Less than 60 kg||15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)|
|Neurocysticercosis||60 kg or greater||400 mg twice daily, with meals||8 to 30 days|
|Less than 60 kg||15 mg/kg/day given in divided doses twice daily with meals (maximum total daily dose 800 mg)|
Concomitant Medication To Avoid Adverse Reactions
Patients being treated for neurocysticercosis should receive appropriate steroid and anticonvulsant therapy as required. Oral or intravenous corticosteroids should be considered to prevent cerebral hypertensive episodes during the first week of treatment.
Monitoring For Safety Before And During Treatment
- Monitor blood counts at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy with EskazoleZA in all patients.
- Monitor liver enzymes (transaminases) at the beginning of each 28-day cycle of therapy, and at least every 2 weeks during treatment with EskazoleZA in all patients.
- Obtain a pregnancy test in women of reproductive potential prior to therapy.
EskazoleZA is contraindicated in patients with known hypersensitivity to the benzimidazole class of compounds or any components of EskazoleZA.
Included as part of the PRECAUTIONS section.
Bone Marrow Suppression
Fatalities associated with the use of EskazoleZA have been reported due to granulocytopenia or pancytopenia EskazoleZA may cause bone marrow suppression, aplastic anemia, and agranulocytosis. Monitor blood counts at the beginning of each 28-day cycle of therapy, and every 2 weeks while on therapy with EskazoleZA in all patients. Patients with liver disease and patients with hepatic echinococcosis are at increased risk for bone marrow suppression and warrant more frequent monitoring of blood counts. Discontinue EskazoleZA if clinically significant decreases in blood cell counts occur.
EskazoleZA may cause fetal harm and should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Obtain pregnancy test prior to prescribing EskazoleZA to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of EskazoleZA therapy and for one month after end of therapy. Immediately discontinue EskazoleZA if a patient becomes pregnant and apprise the patient of the potential hazard to the fetus.
Risk Of Neurologic Symptoms In Neurocysticercosis
Patients being treated for neurocysticercosis should receive steroid and anticonvulsant therapy to prevent neurological symptoms (e.g. seizures, increased intracranial pressure and focal signs) as a result of an inflammatory reaction caused by death of the parasite within the brain.
Risk Of Retinal Damage In Patients With Retinal Neurocysticercosis
Cysticercosis may involve the retina. Before initiating therapy for neurocysticercosis, examine the patient for the presence of retinal lesions. If such lesions are visualized, weigh the need for anticysticeral therapy against the possibility of retinal damage resulting from inflammatory damage caused by EskazoleZA-induced death of the parasite.
In clinical trials, treatment with EskazoleZA has been associated with mild to moderate elevations of hepatic enzymes in approximately 16% of patients. These elevations have generally returned to normal upon discontinuation of therapy. There have also been case reports of acute liver failure of uncertain causality and hepatitis.
Monitor liver enzymes (transaminases) before the start of each treatment cycle and at least every 2 weeks during treatment. If hepatic enzymes exceed twice the upper limit of normal, consideration should be given to discontinuing EskazoleZA therapy based on individual patient circumstances. Restarting EskazoleZA treatment in patients whose hepatic enzymes have normalized off treatment is an individual decision that should take into account the risk/benefit of further EskazoleZA usage. Perform laboratory tests frequently if EskazoleZA treatment is restarted.
Patients with elevated liver enzyme test results are at increased risk for hepatotoxicity and bone marrow suppression. Discontinue therapy if liver enzymes are significantly increased or if clinically significant decreases in blood cell counts occur.
Unmasking Of Neurocysticercosis In Hydatid Patients
Undiagnosed neurocysticercosis may be uncovered in patients treated with EskazoleZA for other conditions. Patients with epidemiologic factors who are at risk for neurocysticercosis should be evaluated prior to initiation of therapy.
Use In Specific Populations
Pregnancy Category C.
There are no adequate and well-controlled studies of EskazoleZA administration in pregnant women. EskazoleZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
EskazoleZA should not be used in pregnant women except in clinical circumstances where no alternative management is appropriate. Obtain pregnancy test prior to prescribing EskazoleZA to women of reproductive potential. Advise women of reproductive potential to use effective birth control for the duration of EskazoleZA therapy and for one month after end of therapy. If a patient becomes pregnant while taking this drug, EskazoleZA should be discontinued immediately. If pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.
EskazoleZA has been shown to be teratogenic (to cause embryotoxicity and skeletal malformations) in pregnant rats and rabbits. The teratogenic response in the rat was shown at oral doses of 10 and 30 mg/kg/day (0.10 times and 0.32 times the recommended human dose based on body surface area in mg/m², respectively) during gestation days 6 to 15 and in pregnant rabbits at oral doses of 30 mg/kg/day (0.60 times the recommended human dose based on body surface area in mg/m²) administered during gestation days 7 to 19. In the rabbit study, maternal toxicity (33% mortality) was noted at 30 mg/kg/day. In mice, no teratogenic effects were observed at oral doses up to 30 mg/kg/day (0.16 times the recommended human dose based on body surface area in mg/m²), administered during gestation days 6 to 15.
EskazoleZA is excreted in animal milk. It is not known whether it is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when EskazoleZA is administered to a nursing woman.
Hydatid disease is uncommon in infants and young children. In neurocysticercosis, the efficacy of EskazoleZA in children appears to be similar to that in adults.
In patients aged 65 and older with either hydatid disease or neurocysticercosis, there was insufficient data to determine whether the safety and effectiveness of EskazoleZA is different from that of younger patients.
Patients With Impaired Renal Function
The pharmacokinetics of EskazoleZA in patients with impaired renal function has not been studied.
Patients With Extra-Hepatic Obstruction
In patients with evidence of extrahepatic obstruction (n = 5), the systemic availability of Eskazoledazole sulfoxide was increased, as indicated by a 2-fold increase in maximum serum concentration and a 7-fold increase in area under the curve. The rate of absorption/conversion and elimination of Eskazoledazole sulfoxide appeared to be prolonged with mean Tmax and serum elimination half-life values of 10 hours and 31.7 hours, respectively. Plasma concentrations of parent EskazoleZA were measurable in only 1 of 5 patients.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The adverse reaction profile of EskazoleZA differs between hydatid disease and neurocysticercosis. Adverse reactions occurring with a frequency of 1% or greater in either disease are described in Table 2 below.
These symptoms were usually mild and resolved without treatment. Treatment discontinuations were predominantly due to leukopenia (0.7%) or hepatic abnormalities (3.8% in hydatid disease). The following incidence reflects adverse reactions that were reported to be at least possibly or probably related to EskazoleZA.
Table 2: Adverse Reaction Incidence 1% or Greater in Hydatid Disease and Neurocysticercosis
|Adverse Reaction||Hydatid Disease||Neurocysticercosis|
|General disorders and administration site conditions|
|Elevated Hepatic Enzymes||16||less than 1|
|Nervous system disorders|
|Dizziness||1||less than 1|
|Raised Intracranial Pressure||0||2|
|Vertigo||1||less than 1|
|Skin and subcutaneous tissue disorders|
|Reversible Alopecia||2||less than 1|
The following adverse events were observed at an incidence of less than 1%:
Blood and Lymphatic System Disorders : There have been reports of leukopenia, granulocytopenia, pancytopenia, agranulocytosis, or thrombocytopenia.
Immune System Disorders : Hypersensitivity reactions, including rash and urticaria.
The following adverse reactions have been identified during post-approval use of EskazoleZA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders : Aplastic anemia, bone marrow suppression, neutropenia.
Eye Disorders : Vision blurred.
Gastrointestinal Disorders : Diarrhea.
General System Disorders : Asthenia.
Hepatobiliary Disorders : Elevations of hepatic enzymes, hepatitis, acute liver failure.
Musculoskeletal and Connective Tissue Disorders : Rhabdomyolysis.
Nervous System Disorders : Somnolence, convulsion.
Renal and Urinary Disorders : Acute renal failure.
Skin and Subcutaneous Tissue Disorders : Erythema multiforme, Stevens-Johnson syndrome.
In case of overdosage, symptomatic therapy and general supportive measures are recommended.
Eskazoledazole is poorly absorbed from the gastrointestinal tract due to its low aqueous solubility. Eskazoledazole concentrations are negligible or undetectable in plasma as it is rapidly converted to the sulfoxide metabolite prior to reaching the systemic circulation. The systemic anthelmintic activity has been attributed to the primary metabolite, Eskazoledazole sulfoxide. Oral bioavailability appears to be enhanced when Eskazoledazole is coadministered with a fatty meal (estimated fat content 40 grams) as evidenced by higher (up to 5-fold on average) plasma concentrations of Eskazoledazole sulfoxide as compared to the fasted state.
Maximal plasma concentrations of Eskazoledazole sulfoxide were achieved 2 hours to 5 hours after dosing and were on average 1310 ng/mL (range 460 ng/mL to 1580 ng/mL) following oral doses of Eskazoledazole (400 mg) in 6 hydatid disease patients, when administered with a fatty meal. Plasma concentrations of Eskazoledazole sulfoxide increased in a dose-proportional manner over the therapeutic dose range following ingestion of a high-fat meal (fat content 43.1 grams). The mean apparent terminal elimination half-life of Eskazoledazole sulfoxide ranged from 8 hours to 12 hours in 25 healthy subjects, as well as in 14 hydatid and 8 neurocysticercosis patients.
Following 4 weeks of treatment with Eskazoledazole (200 mg three times daily), 12 patients' plasma concentrations of Eskazoledazole sulfoxide were approximately 20% lower than those observed during the first half of the treatment period, suggesting that Eskazoledazole may induce its own metabolism.
Eskazoledazole sulfoxide is 70% bound to plasma protein and is widely distributed throughout the body; it has been detected in urine, bile, liver, cyst wall, cyst fluid, and cerebrospinal fluid (CSF).
Concentrations in plasma were 3-fold to 10-fold and 2-fold to 4-fold higher than those simultaneously determined in cyst fluid and CSF, respectively.
Metabolism And Excretion
Eskazoledazole is rapidly converted in the liver to the primary metabolite, Eskazoledazole sulfoxide, which is further metabolized to Eskazoledazole sulfone and other primary oxidative metabolites that have been identified in human urine. Following oral administration, Eskazoledazole has not been detected in human urine. Urinary excretion of Eskazoledazole sulfoxide is a minor elimination pathway with less than 1% of the dose recovered in the urine. Biliary elimination presumably accounts for a portion of the elimination as evidenced by biliary concentrations of Eskazoledazole sulfoxide similar to those achieved in plasma.
However, we will provide data for each active ingredient