In recent years, there has been an increase in invasive yeast infections, the most common causative agents of which are Candida spp. and Aspergillus ssp. One of the causes of high mortality is the resistance of pathogens to drugs, which requires the search for new antifungal agents.

Caspofungin is the first drug in a new group of antifungal agents - echinocandins, whose mechanism of action is associated with blocking the synthesis of beta-1,3-D-glucan, a component of the cell wall of fungi.

Activity spectrum: has fungicidal activity against Candida spp., including strains resistant to azoles and amphotericin B, it acts fungistically on Aspergillus spp., As well as some rare mycelial fungi (Acremonium spp., Bipolaris spp., Etc.). Active against vegetative forms Pneumocystis carinii.

Pharmacokinetics: it is applied only parenterally, because oral bioavailability of at most 1%. High concentrations are observed in plasma, lungs, liver, spleen and intestines. 97% linked to albumin.

Excretion: 35% of a single dose is excreted in the feces, 41% in the urine. About 1.4% is excreted unchanged in the urine. The half-life of 9-13 hours, which allows you to use the drug 1 time per day.

The pharmacokinetics of caspofungin do not differ in healthy volunteers and in individuals with an initial stage of chronic renal failure (chronic renal failure) (creatinine clearance 50 to 80 ml / min). With a GFR of less than 50 ml / min, the plasma concentration of caspofungin increases. However, in people who received 50 mg of drug per day, GFR did not have a significant effect on the level of caspofungin in the plasma, it is not necessary to modify the dose in case of insufficiency kidney. Caspofungin does not pass through the dialysis membranes, therefore, it does not require a dose change in dialysis patients.

There is no need to change the dose at the initial stage of liver failure (5-6 points according to Child-Pugh). It is recommended to reduce the dose in case of moderate to severe hepatic insufficiency (7-9 points according to Child-Pugh) to 35 mg / day. There are no data on the use of the drug in severe hepatic impairment (more than 9 points in Child-Pugh).

There is no need to change the dose of caspofungin depending on the patient's gender, race and age.

Drug interactions: is not an inducer of hepatic microsomal enzymes. With simultaneous use with tacrolimus, it reduces its concentration in the plasma. With simultaneous use with cyclosporine, a transient increase in ALT, AST, an increase in the area under the pharmacokinetic curve of caspofungin is possible. The inducers of microsomal enzymes in the liver reduce the concentration of caspofungin (the dose should be increased to 70 mg / day). In combination with amphotericin B, no antagonism towards antifungal activity was observed.

Adverse Drug Reactions: Has a good safety profile. The most common side effects are fever, phlebitis, diarrhea, nausea, vomiting, increased ALT and AST (not more than 5% of patients).

For caspofungin, no mutagenic effect has been revealed, a negative effect on the reproductive function. It is embryotoxic (in animal studies, a violation of bone ossification processes is shown). Penetrates through the placental barrier. Caspofungin should only be prescribed to pregnant women if the potential benefit exceeds the potential risk (class C medication). Caution should be exercised with breastfeeding women, as in animal studies, caspofungin has been excreted in breast milk.

Dosage methods: do not mix with other drugs in the same infusion system, do not use solutions containing dextrose.

Candidiasis infection: 70 mg the first day, then 50 mg per day. The duration of treatment is determined by the dynamics of the clinical and microbiological picture. Candidiasis esophagitis: 50 mg daily. Invasive aspergillosis: 70 mg the first day, then 50 mg per day. The drug is administered intravenously for 1 hour.

Liposomal amphotericin B - is one of the modern dosage forms of amphotericin B polyene with improved tolerance. It is obtained by encapsulating amphotericin B in liposomes (fatty vesicles formed when phospholipids are dispersed in water), which guarantees the release of the active substance only on contact with fungal cells and is intact compared to normal tissues.

The mechanism of action: due to the binding of the drug to the ergosterol of the fungal membrane, which leads to a violation of its integrity, loss of cytoplasm and cell death.

Activity spectrum: active against Candida spp. (strains often resistant to C. lusitaniae), Aspergillus spp. (A.terreus can be resistant), C.neoformans, pathogens of zygomycosis (Mucor spp., Rhizopus spp., etc.), Fusarium spp., Sporothrix schenckii, pathogens of endemic yeast infections (B. dermatitidis, H.capsulatum , C.immitis, P.brasiliensis) and some other fungi.

Pharmacokinetics: creates higher maximum blood concentrations than amphotericin B. It practically does not penetrate the renal tissue (therefore less nephrotoxic). It has more pronounced cumulative properties. The half-life is on average 4 to 6 days, with prolonged use, an increase up to 49 days is possible.

Adverse reactions: compared to a standard medication less often causes anemia, fever, chills, hypotension, less nephrotoxic. There are insufficient data on the mutagenic carcinogenic effects of liposomal amphotericin B. Animal studies have not shown the teratogenic effect of liposomal amphotericin B. The drug can be used in pregnant women (class B), children, should be used with caution in nursing mothers and people of over 65.

Indications: severe forms of systemic mycosis (invasive candidiasis, aspergillosis, cryptococcosis, sporotrichosis, zygomycosis, trichosporosis, fusariosis, pheogyphomycosis, endemic mycoses (blastomycosis, coccidioidiosis, paracoccidiosis disease, vesicular disease) with the ineffectiveness of the standard drug, with its nephrotoxicity or the expressed IV infusion responses that are not stopped by premedication.

Drug interactions: a sufficient number of studies assessing the interaction of liposomal amphotericin B with other drugs have not been conducted. It is likely that drugs that interact with amphotericin B can also interact with its liposomal form. Thus, combinations with glucocorticoids and cardiac glycosides can cause hypokalemia. With simultaneous use with flucytosine, an increase in its toxicity is possible. Amphotericin B (standard and liposomal) is incompatible with 0.9% sodium chloride solution and other solutions containing electrolytes. When using intravenous administration systems, established for the introduction of other drugs, it is necessary to flush the system with a 5% glucose solution.

Dosage: administered by intravenous infusion over 2 hours. The solution for infusion should only be prepared with 5% glucose. The infusion time can be reduced to 30 minutes with good tolerance to the drug. The dose is calculated per kg of body weight, depending on the type of yeast infection (1 to 5 mg / kg per day).

Given the growing number of invasive mycoses and the simultaneous increase in the resistance of their pathogens, the creation of new antimycotics is becoming increasingly important. The introduction of caspofungin in practice is the answer to this problem, and the creation of a new lipososmal form of amphotericin B is a step towards solving the problem of the high toxicity of certain antifungal agents.