Kansidas lyophilisate 50mg, vial 1pc

Composition

1 bottle contains:

Active ingredient:

caspofungin 50 mg;

Auxiliary substances:

sucrose,

mannitol,

glacial acetic acid,

sodium hydroxide.

Pharmacological action

Cancidas is an antifungal drug for systemic use. It is a semi-synthetic lipopeptide compound (echinocandin) synthesized from the fermentation product of Glarea lozoyensis. Caspofungin inhibits the synthesis of β – (1,3)-D – glucan, an essential component of the cell wall of many rhifomycetes and yeasts.

In vitro caspofungin is active against various pathogenic fungi of the genus Aspergillus (including Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus nidulans, Aspergillus terreus and Aspergillus candidus) and Candida (including Candida albicans, Candida dubliniensis, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lipolytica, Candida lusitaniae, Candida parapsilosis, Candida rugosa and Candida tropicalis).

In vivo, caspofungin activity was detected when parenterally administered to animals with normal and reduced immunity, infected with Aspergillus and Candida. The use of caspofungin in these cases increases the life expectancy of infected animals (Aspergillus and Candida) and the eradication of pathogenic fungi (Candida) in the affected organs. Caspofungin is also active in immunodeficient animals infected with Candida glabrata, Candida krusei, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, which achieve the eradication of pathogenic fungi (Candida) in the affected organs. Caspofungin is highly active in the prevention and treatment of pulmonary aspergillosis, which was revealed in a study on models of fatal lung infections in vivo.

Caspofungin is active against strains of Candida fungi that are resistant to fluconazole, amphotericin B or flucytosine, which have a different mechanism of action.

In some patients, Candida fungi with reduced sensitivity to caspofungin are isolated during treatment with the drug. Determination of the minimum inhibitory concentration (MPC) for caspofungin is not performed, since there is no correlation between MPC and clinical efficacy of the drug. There is no evidence of drug resistance in patients with invasive aspergillosis.

Standardized methods for determining sensitivity to beta-(1,3)-D-glucan synthesis inhibitors have not been developed, and the results of in vitro sensitivity studies may not correlate with clinical data.

Pharmacokinetics

Distribution

After a single intravenous infusion for 1 h, the plasma concentration of caspofungin decreases in a multiphase manner. Immediately after the infusion, a short alpha phase occurs, followed by a beta phase with T 1/2 from 9 to 11 hours, which is the main characteristic of the profile and has a clear logarithmic-linear relationship between 6 and 48 hours after the infusion. During this period, the concentration of the drug in the plasma decreases significantly. There is also an additional γ-phase with a T 1/2 of 40 to 50 hours. The predominant mechanism affecting plasma clearance is distribution rather than excretion or biotransformation. Caspofungin binds intensively to proteins (approximately 97%) with minimal penetration into red blood cells. Approximately 92% of the 3H tag is detected in tissues 36-48 hours after use of a single dose of 70 mg of 3H-labeled caspofungin acetate. During the first 30 hours after use, caspofungin excretion and biotransformation are insignificant.

Metabolism

Caspofungin is slowly metabolized by hydrolysis and N-acetylation and undergoes spontaneous chemical degradation to an open-ring peptide compound. At a later time (5 or more days after use of a single dose of labeled 3H caspofungin acetate), a low level (less than 7 pmol/mg of protein or 1.3% or less of the administered dose) of covalent binding of the radioactive label is observed in plasma, which may be due to the formation of two reactive intermediates of chemical destruction of caspofungin. Additional metabolism involves hydrolysis to constituent amino acids and their derivatives, including dihydroxyhomothyrosine and N-acetyl-dihydroxyhomothyrosine. These two tyrosine derivatives are found only in the urine, which indicates their rapid renal clearance.

Deduction

About 75% of the drug is excreted from the body (pharmacokinetic study with radioactively labeled caspofungin): 41% – in the urine and 34% – in the feces. Plasma concentrations of the tag and caspofungin during the first 24-48 hours after dose use do not differ, after which the drug level decreases faster, and a decrease in its concentration below the quantitative level is observed 6-8 days after dose use, and the radioactive tag – after 22.3 weeks. A small amount of caspofungin is excreted unchanged in the urine (approximately 1.4% of the dose). The renal clearance of the initial drug is low and is approximately 0.15 ml / min

. Pharmacokinetics in special clinical cases

The plasma concentration of caspofungin in healthy men and women on day 1 after use of a single dose of 70 mg is the same. After 13 daily injections of 50 mg, the plasma concentration of caspofungin in some women is approximately 20% higher than in men.

The content of caspofungin in plasma in healthy men and elderly women (65 years and older), compared with healthy young men, slightly increased by 28% (AUC). In elderly patients with invasive candidiasis or during empirical therapy, the same moderate changes in the concentration of the drug in plasma were observed, as in the group of healthy elderly patients in relation to healthy young patients. Correction of the dosage regimen for elderly (65 years and older) patients is not required.

The plasma concentration of caspofungin in patients with mild hepatic insufficiency (5-6 points on the Child-Pugh scale) after a single dose of 70 mg increases by approximately 55% (AUC), compared with healthy volunteers. use of the drug to these patients for 14 days (70 mg on day 1, followed by daily use of 50 mg) is accompanied by a moderate increase in its plasma concentration and amounts to 19-25% (AUC) on days 7 and 14, compared with healthy volunteers.

Five long-term clinical trials were conducted with the study of Cancidas in patients under 18 years of age, including pharmacokinetic studies (initially in adolescents (12-17 years) and children (2-11 years), then in young children (3-23 months), and in newborns and children of the first three months of life).

In adolescents (12-17 years) treated with caspofungin at a dose of 50 mg / m2 (maximum daily dose-70 mg), the plasma concentration ( AUC0-24 h) generally corresponded to the concentration in adults taking caspofungin at a dose of 50 mg/day. All adolescents received caspofungin above 50 mg, and 6 out of 8 patients received the maximum daily dose of 70 mg. The concentration of caspofungin in the blood plasma of these patients was lower compared to the concentration in adults who received the drug at a daily dose of 70 mg, exactly the dose that was most often prescribed to adolescents.

In children aged 2-11 years who received caspofungin at a dose of 50 mg / m2 per day (maximum daily dose of 70 mg), its plasma concentration (AUC0-24) was comparable to that of adult patients who received caspofungin at a dose of 50 mg/day. On the first day of use, the drug concentration in blood plasma (AUC0-24) was slightly higher in children compared to adults (by 37% at the compared doses of 50 mg / m2 and 50 mg 1 time / day). However, it should be emphasized that the plasma concentration (AUC0-24) in children on the first day was still lower than in adults with long-term treatment.

In children aged 3-23 months who were prescribed caspofungin at a daily dose of 50 mg / m2 (the maximum dose is 70 mg), the concentration of caspofungin in blood plasma with prolonged use was comparable to the concentration in adults who were prescribed a dose of the drug 50 mg/day. As in older children, children in this age group who received caspofungin at a dose of 50 mg / m2, the concentration of the drug in blood plasma was higher on the first day of treatment compared to adults who received a standard dose of caspofungin 50 mg. The pharmacokinetic parameters of caspofungin at a dose of 50 mg / m2 in children of the younger age group (3-23 months) and older group (2-11 years) with the same dosage regimen were comparable.

In newborns and children under 3 months of age who received caspofungin at a dose of 25 mg/m2, the peak concentration of caspofungin (From 1 h) and its threshold concentration (From 24 h) after repeated use corresponded to similar indicators in adults who received the drug at a dose of 50 mg / day. On the first day, the peak concentration from 1 h was comparable to adults, and the threshold concentration From 24 h was moderately increased in newborns and infants compared to the corresponding indicators in adults. Determination of the drug concentration in blood plasma (AUC0-24) was not performed in this study due to the complexity of sampling. It should be noted that the efficacy and safety of Cancidas have not been studied in prospective, adequate clinical trials in newborns and children under 3 months of age.

Indications

Empirical therapy in patients with febrile neutropenia with suspected fungal infection, invasive candidiasis (including candidaemia) in patients with and without neutropenia, invasive aspergillosis (in patients who are refractory to other therapy or intolerant to it), esophageal candidiasis, oropharyngeal candidiasis.

Contraindications

Hypersensitivity.

Side effects

From the body as a whole: often – fever, headache, chills.

From the digestive system: often – nausea, diarrhea, vomiting, abdominal pain, increased serum activity of ACT, ALT, ALP, direct and total bilirubin.

From the hematopoietic system: often-anemia.

From the cardiovascular system: often – tachycardia, phlebitis / thrombophlebitis, peripheral edema, venous post-infusion complications, hot flashes.

Respiratory system disorders: often-shortness of breath.

Skin and subcutaneous fat disorders: rash, itching (including at the injection site), increased sweating.

From the side of laboratory parameters: often – hypoalbuminemia, hypoproteinemia, hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia, leukopenia, neutropenia, thrombocytopenia, eosinophilia, decreased hemoglobin and hematocrit, increased partial thromboplastin and prothrombin time, proteinuria, leukocyturia, microhematuria, increased serum creatinine concentration; infrequently – hypercalcemia.

There are isolated reports of rare cases of liver dysfunction and allergic reactions such as rash, facial swelling, itching, feeling hot or bronchospasm, and anaphylaxis. In the post-marketing period, rare cases of liver dysfunction, as well as peripheral edema and hypercalcemia were detected. In patients with invasive aspergillosis – pulmonary edema, respiratory distress syndrome in adults, infiltrates on the X-ray.

Interaction

Do not mix with other solutions (including those containing dextrose). Compatible with 0.9% NaCl, Ringer Lactate solution. Efavirenz, nelfinavir, nevirapine, rifampicin, dexamethasone, phenytoin, or carbamazepine, when administered concomitantly, lead to a decrease in the concentration of caspofungin in plasma. It does not affect the pharmacokinetics of itraconazole, amphotericin B, rifampicin or active metabolites of mycophenolate mofetil. Reduces the concentration of tacrolimus. Cyclosporine increases AUC by 35%. Rifampin can both accelerate and slow the elimination of caspofungin.

How to take, course of use and dosage

Intravenous drip, for at least 1 hour.

Esophageal and oropharyngeal cadidosis: 50 mg once a day.

Aspergillosis: on the first day, a single daily loading dose of 70 mg is administered. In the following days, the daily dose is 50 mg once a day, if necessary, the dose can be increased to 70 mg once a day.

The duration of treatment depends on the severity of the underlying disease, recovery from immunosuppression, and the patient’s clinical response.

Special instructions

Use with caution in patients receiving cyclosporine, as well as in patients with moderate hepatic insufficiency (from 7 to 9 points on the Child-Pugh scale). There is no clinical experience of using the drug in patients with severe hepatic insufficiency (more than 9 points on the Child-Pugh scale).

Use in pediatrics

It is not recommended for use in children and adolescents under 18 years of age.

Storage conditions

At a temperature of 2-8 °C

Shelf life

2 years

Active ingredient

Caspofungin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution