Anidulafungin (Lyophilisate) Instructions for Use

ATC Code

J02AX06 (Anidulafungin)

Active Substance

Anidulafungin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antifungal drug

Pharmacotherapeutic Group

Systemic antifungal agents; other systemic antifungal agents

Pharmacological Action

Anidulafungin 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 species of fungi of the genus Candida and activity at the sites of active growth of Aspergillus fumigatus hyphal cells.

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 in 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%). Steady-state concentration (C_ss) is rapidly achieved after using a loading dose (double the maintenance dose).

The half-life (T_1/2) is 0.5-1 hour, and the volume of distribution (V_d) is 30-50 L, which is close to the total body fluid volume. Anidulafungin is highly bound (>99%) to human plasma proteins.

At physiological temperature and pH levels, Anidulafungin undergoes slow chemical degradation to a ring-opened peptide compound that lacks antifungal activity. In vitro, the T_1/2 of anidulafungin under physiological conditions is approximately 24 hours. In vivo, the ring-opened compound is subsequently converted to peptide degradation products and is eliminated from the body mainly through biliary excretion.

The clearance of anidulafungin is about 1 L/h. The major phase T_1/2 of anidulafungin is about 24 hours, which corresponds to the majority 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) 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 radioactive drug dose was excreted in 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 exhibits linear pharmacokinetics over a wide dose range (15-130 mg) when administered once daily.

The pharmacokinetics of anidulafungin in patients with fungal infections are similar to those in healthy subjects, based on population pharmacokinetic analyses. 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 was higher in male patients.

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

In patients with Child-Pugh class C hepatic impairment, a small 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

Lyophilisate

Samples should be taken to identify the fungal species before starting therapy. Treatment can be initiated before the results of these samples are obtained and adjusted accordingly after receiving the results.

It is administered by intravenous drip infusion. It should not be administered as a bolus injection.

Treatment is started 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 obtaining laboratory results confirming the absence of the pathogen.

Adverse Reactions

From the blood coagulation system: Common – coagulopathy.

From the digestive system: Common – hypokalemia; Rare – hyperglycemia.

From the nervous system: Common – convulsions, headache.

From the cardiovascular system: Common – flushing; Rare – arterial hypertension, facial redness; Frequency unknown – arterial hypotension.

From the respiratory system: Frequency unknown – bronchospasm, dyspnea.

From the digestive system: Common – diarrhea, vomiting, nausea; Rare – pain in the upper abdomen.

From the hepatobiliary system: Common – increased ALT, ALP, AST, blood bilirubin, GGT; Rare – cholestasis.

From the skin: Common – rash, itching.

Allergic reactions: Rare – urticaria.

From the urinary system: Common – 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 primarily 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 liver enzyme activity during treatment with anidulafungin require monitoring for timely detection of signs of worsening liver function and for assessing the risk/benefit ratio of continuing anidulafungin therapy.

An increase in infusion-related reactions has been observed with concomitant use of anesthetics. Caution is advised 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 under in vivo conditions.

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.