Eraxis^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Pfizer, Inc. (USA)

Manufactured By

Pharmacia & Upjohn Company, LLC (USA)

ATC Code

J02AX06 (Anidulafungin)

Active Substance

Anidulafungin (Rec.INN registered by WHO)

Dosage Form

Eraxis®

Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution 100 mg: fl. 1 pc.

Dosage Form, Packaging, and Composition

Lyophilisate for the preparation of a concentrate for the preparation of an infusion solution in the form of a white or almost white lyophilized mass.

Excipients: fructose, mannitol, polysorbate 80, tartaric acid.

Colorless glass vials (1) – cardboard packs.

Clinical-Pharmacological Group

Antifungal drug

Pharmacotherapeutic Group

Antifungal drugs for systemic use, other antifungal drugs for systemic use

Pharmacological Action

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 species of fungi of the genus Candida and activity in areas of active growth of Aspergillus fumigatus hyphae.

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

In in vivo studies with parenteral administration, Anidulafungin demonstrated efficacy against Candida spp. fungi, as shown in models of immunocompetent and immunocompromised mice and rabbits. Anidulafungin increased survival in animals and also reduced the fungal load of organs when determined 24-96 hours after the last administration.

Pharmacokinetics

The pharmacokinetics of anidulafungin have been described in healthy volunteers, in special subgroups, and in patients treated with anidulafungin. Low interindividual variability in systemic exposure to the drug was observed (the coefficient of variation was about 25%). C_ss is rapidly achieved after using a loading dose (double the maintenance dose).

T_1/2 is 0.5-1 h, V_d is 30-50 L, which is close to the total body fluid volume. Anidulafungin is largely (>99%) bound to human plasma proteins.

At physiological temperature and pH levels, Anidulafungin undergoes slow chemical degradation to an open-ring peptide compound that has no antifungal activity. In vitro, the T_1/2 of anidulafungin under physiological conditions is approximately 24 hours. In vivo, the open-ring compound is eventually converted to peptide degradation products and is eliminated from the body mainly through biliary excretion.

The clearance of anidulafungin is about 1 L/h. In the main phase, the T_1/2 of anidulafungin is about 24 hours, which corresponds to most of the AUC profile, and the terminal T_1/2 is 40-50 hours.

In a clinical study using a single dose of radiolabeled (¹⁴C) Anidulafungin (about 88 mg) was administered to healthy subjects. Approximately 30% of the administered radioactive dose was excreted in feces over more than 9 days, of which less than 10% was unchanged. Less than 1% of the administered dose of the radioactive drug was excreted in the urine, indicating negligible renal clearance. Six days after administration, the concentration of anidulafungin decreased to values below the lower limit of quantification. Eight weeks after drug administration, negligible amounts of radioactive compounds were detected in blood, urine, and feces.

Anidulafungin has linear pharmacokinetics over a wide dose range (15-130 mg) when the drug is administered once daily.

The pharmacokinetics of anidulafungin in patients with fungal infections are similar to those in healthy individuals, based on population pharmacokinetic analysis results. When using the drug at a daily dose of 200/100 mg and an infusion rate of 1.1 mg/min, C_ss and C_min can be approximately 7 and 3 mg/L, respectively, with a mean steady-state AUC of about 110 mg×h/L.

Changes in pharmacokinetics associated with body weight had minor clinical manifestations.

Plasma concentrations of anidulafungin in healthy men and women were similar. In studies of multiple-dose administration of anidulafungin, clearance of anidulafungin was higher in male patients.

Population pharmacokinetic analysis showed that the mean clearance value differed in the group of elderly patients (≥65 years; mean clearance 1.07 L/h) from the group of younger patients (<65 years; mean value 1.22 L/h). However, the range of clearance values in these groups was similar.

In patients with class C hepatic insufficiency according to the Child-Pugh classification, a slight decrease in AUC was observed; this decrease was within the range of anidulafungin AUC levels in healthy individuals.

Renal clearance of anidulafungin is <1%.

Indications

Invasive candidiasis in adults without neutropenia.

ICD codes

Dosage Regimen

Before starting therapy, samples should be taken to determine the type of fungus. Therapy can be started before the results of these samples are obtained and adjusted accordingly after receiving the results.

Administered by intravenous drip. Should not be administered as a bolus injection.

Treatment begins with a single loading dose on day 1 – 200 mg, followed by administration of a dose of 100 mg daily.

The duration of treatment depends on the patient’s clinical response to therapy. Antifungal therapy is continued for at least 14 days after receiving laboratory results confirming the absence of the pathogen.

Adverse Reactions

From the blood coagulation system frequently – coagulopathy.

From the digestive system: frequently – hypokalemia; rarely – hyperglycemia.

From the nervous system frequently – convulsions, headache.

From the cardiovascular system frequently – hot flashes; rarely – arterial hypertension, facial redness; frequency unknown – arterial hypotension.

From the respiratory system frequency unknown – bronchospasm, dyspnea.

From the digestive system frequently – diarrhea, vomiting, nausea; rarely – pain in the upper abdomen.

From the hepatobiliary system frequently – increased ALT, ALP, AST, bilirubin in the blood, GGT; rarely – cholestasis.

From the skin frequently – rash, itching.

Allergic reactions rarely – urticaria.

From the urinary system frequently – increased serum creatinine.

Contraindications

Hypersensitivity to anidulafungin and other drugs of the echinocandin class.

Use in Pregnancy and Lactation

Anidulafungin should not be used during pregnancy.

It is not known whether Anidulafungin is excreted in human breast milk. If it is necessary to use anidulafungin during lactation, breastfeeding should be discontinued.

In experimental studies in animals, it has been shown that Anidulafungin is excreted in breast milk.

Special Precautions

The clinical efficacy of anidulafungin has been studied mainly in patients with infections caused by Candida albicans, without neutropenia. The clinical efficacy of the drug in individuals with endocarditis, osteomyelitis, or meningitis caused by Candida fungi and in patients with established infection caused by Candida krusei has not been studied.

Patients who experience increased activity of liver enzymes during treatment with anidulafungin require monitoring for the timely detection of signs of worsening liver function and for assessing the risk/benefit ratio of continuing anidulafungin therapy.

An increase in reactions associated with infusion administration has been noted with simultaneous use with anesthetics. Caution is required when using anidulafungin and anesthetic agents concomitantly.

Use in pediatrics

Anidulafungin should not be used in children.

Drug Interactions

Anidulafungin is not an inducer or inhibitor of cytochrome P450 isoenzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A). It should be noted that in vitro studies do not exclude possible interaction in vivo.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.