Amphotericin B liposomal (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Jodas Expoim, LLC (Russia)

Manufactured By

Jodas Expoim, Pvt. Ltd. (India)

ATC Code

J02AA01 (Amphotericin B)

Active Substance

Amphotericin B

Amphotericin B (Rec.INN registered by WHO)

Dosage Form

Amphotericin B liposomal

Lyophilisate for preparation of concentrate for preparation of dispersion for infusion 50 mg: vial

Dosage Form, Packaging, and Composition

Lyophilisate for the preparation of a concentrate for the preparation of a dispersion for infusion in the form of a powder or porous mass of yellow color; clumping is allowed.

Excipients: hydrogenated soy phosphatidylcholine – 213 mg, distearoyl phosphatidylglycerol – 84 mg, cholesterol – 52 mg, alpha-tocopherol acetate – 0.64 mg, sucrose – 900 mg, sodium succinate hexahydrate – 27 mg.

Vials of transparent colorless glass (1) – cardboard packs.
Vials of transparent colorless glass (1) complete with a filter (5 µm 1 pc.) – cardboard packs.

Clinical-Pharmacological Group

Antifungal antibiotic

Pharmacotherapeutic Group

Systemic antifungal agents; antibiotics

Pharmacological Action

Antifungal agent, an antibiotic of the polyene group. It has a fungicidal or fungistatic effect depending on the concentration in biological fluids and the sensitivity of the pathogen. The mechanism of action of amphotericin B is based on its ability to bind to sterols (ergosterols) located in the fungal cell membrane. As a result, the permeability of the membrane is disrupted, and intracellular components enter the extracellular space.

It is active against many pathogenic fungi, including Candida spp., Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus spp.

Amphotericin B is also active against Leishmania.

Pharmacokinetics

It is distributed in most organs and tissues of the body; it is not detected in the cerebrospinal fluid. Plasma protein binding is 90%. It is excreted by the kidneys, very slowly. 2-5% of the administered dose is excreted in active form. It can be detected in the urine for 7 weeks after discontinuation.

Indications

Systemic and/or deep mycoses: disseminated candidiasis, disseminated cryptococcosis and cryptococcal meningitis, invasive and disseminated aspergillosis, coccidioidomycosis, North American blastomycosis, histoplasmosis, hyalohyphomycosis, mucormycosis, chronic mycetoma.

Leishmaniasis: visceral, American cutaneous-visceral.

Fever of unknown origin (resistant to antibiotic therapy conducted for 96 hours, in patients with neutropenia and a high risk of fungal infections).

Prophylaxis of invasive fungal infections in patients with neutropenia in malignant neoplasms, as well as during transplantation of parenchymal organs and bone marrow.

ICD codes

Dosage Regimen

For IV administration, the initial dose (to determine tolerance) is 1 mg, then the dose can be increased by 5-10 mg up to the maximum daily dose. The frequency of administration is every other day or 2 times a week. For children IV – at an initial dose of 250 mcg/kg, then the dose is gradually increased by 125-250 mcg/kg up to the maximum.

For topical application, amphotericin B is applied to the affected areas of the skin 2-4 times/day.

Maximum daily doses for IV infusion for adults – 50 mg, for children – 1 mg/kg.

Adverse Reactions

From the digestive system possible – nausea, vomiting, abdominal pain, increased ALP; rarely – constipation, diarrhea, indigestion, increased activity of liver enzymes, bilirubinemia, impaired liver function, cholestatic hepatitis, liver cell damage, hepatomegaly, jaundice, pancreatitis.

From the nervous system possible headaches; rarely – asthenia, anxiety, coma, convulsions, depression, dizziness, neurosis, paresthesia, sensory disturbances, tremor.

From the hematopoietic system rarely – anemia, granulocytopenia, leukopenia, splenomegaly, thrombocytopenia.

From the water-electrolyte balance possible hypokalemia, acidosis.

From metabolism possible hypokalemia; rarely – increased urea nitrogen, increased CPK, hyperglycemia, hyperkalemia, hypernatremia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, increased LDH, shin edema.

From the cardiovascular system rarely – heart failure, extrasystole, arterial hypotension, thrombophlebitis, bradycardia, feeling of heat, arterial hypertension.

From the respiratory system rarely – bronchospasm, cough, dysphonia, dyspnea, hypoxia, respiratory failure.

Allergic reactions rarely – skin rash, itching, anaphylactoid reactions.

Dermatological reactions possible skin rash; rarely – folliculitis, erythematous rash, vesicular rash, maculopapular rash, increased sweating, urticaria.

Other possible – fever, chills, cyanosis, swelling and leg cramps.

Contraindications

Severe impairment of liver and kidney function, glomerulonephritis, amyloidosis, diseases of the hematopoietic system, diabetes mellitus, hypersensitivity to amphotericin B.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies in pregnant women have not been conducted. Amphotericin B crosses the placental barrier.

It is not known whether amphotericin B is excreted in breast milk. If it is necessary to use during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindication: severe impairment of liver function.

Use in Renal Impairment

Contraindication: severe impairment of kidney function, glomerulonephritis.

Pediatric Use

Can be used in children according to indications.

Geriatric Use

In elderly patients, it should be used taking into account the state of kidney function.

Special Precautions

During treatment, systematic monitoring of kidney function, liver function, blood composition, and blood potassium levels is necessary.

To avoid the risk of developing side effects, IV administration should be carried out slowly (over 2-6 hours).

If possible, amphotericin B should not be prescribed to patients receiving anticancer drugs. The appointment of diuretics should be avoided in patients receiving amphotericin B. If this is not possible, careful monitoring of electrolyte balance is necessary.

Drug Interactions

With simultaneous use with antimicrobial agents and immunosuppressants that have a nephrotoxic effect, cyclosporine, pentamidine (for parenteral use), an increase in the risk of nephrotoxic action is possible.

Against the background of hypokalemia caused by amphotericin B, an enhancement of the action of neuromuscular blocking agents, an increase in the toxicity of cardiac glycosides is possible; corticosteroids may enhance potassium deficiency, while their immunosuppressive effect may be especially pronounced in patients with severe fungal infection.

With simultaneous use of amphotericin B with flucytosine, a synergism of action is observed. However, the clearance of flucytosine decreases and its toxic effects are enhanced.

With simultaneous use, the renal excretion of zalcitabine decreases.

In patients with myocardial damage caused by antimony compounds, the use of amphotericin B increases the risk of arrhythmia and cardiac arrest.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.