Eraxis, lyophilizate 100 mg

Eraxis is an antifungal agent, a semi-synthetic echinocandin, a lipopeptide synthesized by fermentation of Aspergillus nidulans products. Anidulafungin selectively inhibits 1,3-β-D glucan synthase, an important fungal cell enzyme that is absent in mammalian cells. This leads to disruption of the formation of 1,3-β-D-glucan, the main component of the fungal cell wall. Anidulafungin has fungicidal activity against various fungi of the genus Сandida and activity in the areas of active cell growth of hyphae of the fungus Aspergillus fumigatus.

Anidulafungin is active in vitro against Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis.

In in vivo studies with parenteral administration, anidulafungin showed efficacy against Candida spp. fungi, as shown in models of immunocompetent and immunocompromised mice and rabbits. Anidulafungin increased survival in animals and also reduced organ burden with Candida spp. fungi when determined between 24 and 96 hours after the last administration.

Indications

Invasive candidiasis, including candidemia; esophageal candidiasis.

Active ingredient

Anidulafungin

Composition

1 bottle of lyophilizate for the preparation of solution for infusion contains:
active substance: anidulafungin 100 mg

How to take, the dosage

Before therapy, material should be obtained for culture and other laboratory tests (including histological examination) to isolate and identify the pathogen. Treatment can be started before the laboratory results are available. However, after receiving these results, antifungal therapy must be adjusted.

The drug Eraxis is administered intravenously. The infusion rate should not exceed 1.1 mg/min, which is equivalent to 1.4 ml/min for a dose of 100 mg.

The minimum duration of infusion is 90 minutes.

Invasive candidiasis, including candidemia

Eraxis is administered once in a dose of 200 mg in the first day, then in a dose of 100 mg/day. The duration of treatment depends on the clinical response of the patient. Antifungal therapy should be continued for at least 14 days after disappearance of infection symptoms and eradication of the pathogen.

Esophageal candidiasis

In the first day Eraxis is administered once in a dose of 100 mg, then in a dose of 50 mg/day. Duration of treatment depends on clinical response of a patient and makes at least 14 days, and not less than 7 days after disappearance of infection symptoms. If there is a risk of recurrence of esophageal candidiasis in patients with HIV infection, the need for antifungal antifungal therapy after treatment with anidulafungin should be determined.

Instructions for preparation of infusion solution

Eraxis is available in single-use vials.

The Eraxis drug should be reconstituted with water for injection and then diluted only with 0.9% sodium chloride solution for infusion or 5% glucose solution for infusion.

WARNING: Compatibility of reconstituted Anidulafungin with other IV drugs and solutions is unknown.

Reconstitution

Aseptically, 30 ml of water for injection is added to the vial to produce a solution containing anidulafungin at a concentration of approximately 3.33 mg/ml.

The solution should be colorless and clear and should contain no visible particles.

If visible particles and/or visible staining are detected, the solution should be destroyed.

The reconstituted solution should be used within 1 hour.

Dilution and infusion

In aseptic conditions, the reconstituted solution is transferred from the vial to an infusion bag (or vial) containing 0.9% sodium chloride solution for infusion or 5% glucose solution for infusion to achieve the desired concentration of anidulafungin. The table below shows the required volumes of solution and solvent as well as the infusion rate and minimum duration of infusion.

The ready-to-use infusion solution should be used within 24 hours.

If the infusion solution is not used immediately after preparation, it should be stored at 2 to 8°C.

Preparing solution for infusion

^A 0.9% sodium chloride solution for infusion or 5% glucose solution for infusion

^B The concentration of the infusion solution is approximately 0.77 mg/ml

Hepatic function impairment

In patients with mild, moderate and severe hepatic impairment (Child-Pugh grades A, B and C), no dose adjustment of Eraxis is required.

In patients with any degree of renal impairment, including those receiving hemodialysis, no dose adjustment of Eraxis is required. The drug can be used regardless of the time of hemodialysis.

Patient Special Groups

Dose adjustment of Eraxis is not required in adult patients depending on their age, sex, weight, race and presence of HIV infection.

Performance in children and adolescents

The experience with Eraxis in children is limited. Use in children under 18 years of age is recommended when the potential benefit of use exceeds the possible risk.

Interaction

Preclinical in vitro and in vivo trials and clinical studies have shown that anidulafungin is not a clinically important substrate, inducer or, inhibitor of cytochrome P450 isoenzymes. Drug interactions have been studied only in adult patients. Anidulafungin showed insignificant renal clearance (

. In vitro studies have shown that anidulafungin is not metabolized by human cytochrome P450 or by isolated human hepatocytes, and that at clinically relevant concentrations, anidulafungin only slightly inhibits the activity of human cytochrome P450 isoenzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A).

No clinically significant drug interactions have been observed with the following drugs when co-administered with anidulafungin.

Cyclosporine (cytochrome CYP3A4 isoenzyme substrate)

When anidulafungin is administered to healthy volunteers at a dose of 100 mg/day after a saturation dose of 200 mg/day or in combination with cyclosporine at a dose of 1.25 mg/kg orally 2 times/day, cyclosporine had only a minor effect on the equilibrium C_max of anidulafungin, but the AUC was increased by 22%. An in vitro study showed that anidulafungin had no effect on cyclosporine metabolism. The adverse events observed were consistent with those described in other studies where only anidulafungin was studied. No dose adjustment is required for either drug when used together.

Voriconazole (inhibitor and substrate of cytochrome isoenzymes CYP2C19, CYP2C9, CYP3A4)

In the study, 17 healthy volunteers received anidulafungin at a dose of 100 mg/day after a saturation dose of 200 mg; voriconazole 200 mg 2 times/day orally after a saturation dose of 400 mg 2 times the first day; then both drugs. The equilibrium C_max and AUC varied insignificantly when the drugs were used together. No dose adjustment is required for either drug when used together.

Tacrolimus (cytochrome CYP3A4 isoenzyme substrate)

In the study, 35 healthy volunteers took tacrolimus once orally at a dose of 5 mg, then received anidulafungin at a dose of 100 mg/day after a shock dose of 200 mg; then both drugs were given. The equilibrium C_max and AUC of anidulafungin and tacrolimus changed little when the drugs were used together. No dose adjustment is required for either drug when used together.

Liposomal amphotericin B

The pharmacokinetics of anidulafungin were studied in 27 patients receiving anidulafungin at a dose of 100 mg/day who were also administered liposomal amphotericin B at a dose of up to 5 mg/kg/day. Population pharmacokinetic analysis showed that the combined administration of liposomal amphotericin B had little effect on the pharmacokinetics of anidulafungin. No dose adjustment of anidulafungin was necessary.

Rifampicin (potent cytochrome P450 inducer)

The pharmacokinetics of anidulafungin were studied in 27 patients receiving anidulafungin at a dose of 50 mg/day or 75 mg/day who were also administered rifampicin at a dose up to 600 mg/day. Combined administration of rifampicin had little effect on the pharmacokinetics of anidulafungin. No dose adjustment of anidulafungin is required.

Special Instructions

Eraxis infusion-related adverse events occur less frequently if the infusion rate is less than 1.1 mg/min, so the infusion rate should not exceed the recommended rate.

The reconstituted solution

If the reconstituted solution is not used immediately, it should be stored at 2 to 8°C for 1 h. Do not freeze. The chemical and physical stability of the reconstituted solution is 1 h at 5°C.

The infusion solution

The infusion solution should be stored at 2 to 8°C and should be used within 24 h. Do not freeze. The chemical and physical stability of the infusion solution is 24 h at 5°C.

Microbiologically, the infusion solution should be used immediately.

Pharmaceutical Incompatibilities

The Eraxis solution should not be mixed or co-administered with other drugs or electrolytes except 0.9% sodium chloride solution for infusion (9 mg/ml) or 5% glucose solution for infusion (50 mg/ml).

Influence on driving and operating ability

There are no data on the effect of anidulafungin on the ability to drive and operate machinery.

Contraindications

Hypersensitivity to anidulafungin or other components of Eraxis; hypersensitivity to other drugs of the echinocandin class (e.g., Caspofungin).

With caution

Action on the liver

Laboratory signs of hepatic function impairment were observed in healthy individuals and patients taking anidulafungin. Significant liver function abnormalities were observed in patients with serious diseases who received concomitant therapy with other drugs along with anidulafungin. Individual cases of severe liver failure, hepatitis or exacerbation of liver failure have been described, but no association of these disorders with anidulafungin administration has been established. Patients who develop liver failure during therapy with anidulafungin should be closely monitored, and the decision to continue therapy with anidulafungin should be made after risk-benefit assessment.

Side effects

According to data from clinical studies, adverse events observed with Eraxis have been mild to moderate and have rarely resulted in drug withdrawal.

Infusion-related adverse events have included rash, urticaria, hot flashes, pruritus, dyspnea, and hypotension. These events can be minimized by administering anidulafungin intravenously at a rate not exceeding 1.1 mg/min.

The following adverse events associated with taking the drug have been classified according to frequency: frequent (≥1/100,

Infections: infrequent – fungemia, Clostridium difficile-associated candidiasis, colitis, oral candidiasis.

Metabolic disorders: frequent – hyperkalemia, hypokalemia, hypomagnesemia; infrequent – hyperglycemia, hypercalcemia, hypernatriemia.

Cardiovascular system disorders: frequent – flushing of the skin; infrequent – atrial fibrillation, sinus arrhythmia, ventricular extrasystole, right bundle branch block; thrombosis, hypertension, fever.

Gastrointestinal disorders: frequent – diarrhea, increased bilirubin, increased gamma-glutamyltransferase, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase; infrequent – pain in upper abdomen, vomiting, involuntary defecation, nausea, constipation, cholestasis.

Hematopoietic system and lymphatic system disorders: frequent – thrombocytopenia, coagulopathy; infrequent – thrombocytosis.

Nervous system disorders: frequent – seizures, headache.

Musculoskeletal and connective tissue disorders: infrequent – back pain.

Skin and subcutaneous tissue disorders: frequent – rash, urticaria; infrequent – itching, generalized urticaria.

An organ of vision: infrequent – pain in the eyes, visual disturbances, blurred vision.

General and local reactions: infrequent – pain at the site of infusion.

Laboratory measures: frequent – decreased platelet count, increased serum creatinine level, prolonged QT interval on ECG; infrequent – decreased serum magnesium and potassium levels, increased platelet count, increased serum urea level.

The following adverse events (all of them infrequent, ≥1/1000,

The safety report based on the full clinical trial (Phase II and III, 669 patients) described

Overdose

In case of anidulafungin overdose, symptomatic therapy should be used. No clinically significant adverse events were observed when anidulafungin was accidentally administered in a single dose of 400 mg as a saturation dose.

When anidulafungin was administered to 10 healthy volunteers at a saturation dose of 260 mg followed by dosing of 130 mg/day, the drug was well tolerated. No dose-dependent toxicity was detected. Three of 10 subjects had transient asymptomatic increases in transaminase levels (less than 3 times the normal range).

Anidulafungin is not excreted by hemodialysis.

Pregnancy use

Reproductive toxicity of anidulafungin has not been identified in experimental studies. The possible risk to humans is unknown. There are no controlled studies on the use of anidulafungin in pregnant women.

Therefore, anidulafungin should only be used in pregnancy if the expected benefit to the mother clearly outweighs the potential risk to the fetus.

Anidulafungin has been shown in experimental models to be excreted with milk. It is not known whether anidulafungin is excreted with breast milk in women. The decision to continue/discontinue therapy with anidulafungin should be based on the benefits of breastfeeding for the child and the benefits of therapy with anidulafungin for the mother.