Amphotericin B, vials 50mg, 10ml

Composition

1 bottle contains:

Active ingredient:

amphotericin IN 50 000 UNITS;

monosubstituted sodium phosphate,

deoxycholic acid

Pharmacological action

Polyene macrocyclic antibiotic with antifungal activity. It is produced by Streptomyces nodosus. It has a fungicidal or fungistatic effect depending on the concentration in biological fluids and the sensitivity of the pathogen.

It binds to sterols (ergosterols) found in the cell membrane of a drug-sensitive fungus. As a result, the membrane permeability is disrupted and the intracellular components are released into the extracellular space and lysis of the fungus occurs.

Active against most strains of Histoplasma capsulatum, Coccidioides immitis, Paracoccidioides braziliensis, Candida spp., Blastomyces dermatidis, Rhodotorula spp., Cryptococcus neoformans, Sporothrix schenekii, Mucor mucedo, Rhizopus spp., Absidia spp., Basodiobolus ranarum, Aspergillus fumigatus.

Moderately active against some protozoa: Leishmania braziliensis, Leishmania mexicana, Naegleria fowleri.

Amphotericin B is usually resistant to: Pseudallescheria boydii, Fusarium spp.

Ineffective against bacteria, rickettsiae, viruses.

Indications

Progressive, life-threatening fungal infections caused by amphotericin B-sensitive microorganisms:

• disseminated cryptococcosis, cryptococcal meningitis;
• meningitis caused by other fungi;
• invasive and disseminated aspergillosis;
• North American blastomycosis;
• disseminated forms of candidiasis;
• the coccidioidomycosis;
• paracoccidioides;
• histoplasmosis;
• phycomyces (zygomycosis);
• chronomics;
• mold, fungal infection;
• disseminated sporotrichosis;
• hyalohyphomycosis;
• chronic mycetoma;
• infection of the abdominal cavity (including peritonitis);
• endocarditis;
• endophthalmitis;
• fungal sepsis;
• fungal urinary tract infections;
• visceral leishmaniasis (including in patients with immunodeficiency)American cutaneous-visceral leishmaniasis (not the drug of choice).

Contraindications

• hypersensitivity;
• chronic renal failure;
• lactation period.

With caution:  kidney diseases (including glomerulonephritis), amyloidosis, hepatitis, cirrhosis of the liver, anemia, agranulocytosis, diabetes mellitus, pregnancy.

Side effects

From the digestive system:  often-decreased appetite, dyspepsia, nausea, vomiting, diarrhea, gastralgia, hepatotoxicity (increased activity of “liver” enzymes, hyperbilirubinemia); infrequently – acute liver failure, hepatitis, jaundice, hemorrhagic gastroenteritis, melena.

Nervous system disorders:  often-headache, infrequently-convulsions, transient vertigo, peripheral neuropathy, encephalopathy.

From the side of the senses:  infrequently-visual impairment, diplopia; hearing loss, tinnitus.

From the side of hematopoietic organs:  often-normochromic normocytic anemia; infrequently-agranulocytosis, blood clotting disorders, leukopenia, hemolytic anemia, thrombocytopenia, eosinophilia, leukocytosis.

From the cardiovascular system:  often-low blood pressure; infrequently-arrhythmias, including ventricular fibrillation, ECG changes, increased blood pressure, shock, cardiac arrest, heart failure.

Respiratory system disorders:  often-tachypnea; infrequently-shortness of breath, allergic pneumonitis, pulmonary edema.

From the urinary system:  often-impaired renal function, including azotemia, hypokalemia, hypostenuria, renal tubular acidosis, nephrocalcinosis; infrequently-acute renal failure, oliguria, anuria, nephrogenic diabetes insipidus. Preliminary use of 0.9% sodium chloride solution reduces the risk of nephrotoxicity, while use of sodium bicarbonate reduces the risk of renal tubular necrosis.

Allergic reactions:  often – anaphylactoid reactions, bronchospasm, sneezing; infrequently-rash, especially maculopapular, pruritus, exfoliative dermatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome.

Local reactions:  thrombophlebitis at the injection site, chemical burn.

Other services:  often – fever, weight loss, myalgia, arthralgia, general weakness.

Laboratory parameters:  hypokalemia, hyperkalemia, hypomagnesemia, hypocalcemia, hypercreatininemia.

Interaction

Pharmacologically incompatible with heparin,0.9% sodium chloride solution and other solutions containing electrolytes.

The presence of bacteriostatic additives (including benzyl alcohol) can lead to precipitation of the drug.

Synergy – with nitrofurans.

Increases the effect and toxicity of anticoagulants, theophylline and sulfonylureas, flucitosine (extends the half-life); reduces the effect of ethinyl estradiol – the risk of breakthrough bleeding.

Inhibitors of microsomal liver enzymes (including cimetidine, non-narcotic analgesics, antidepressants) slow down the metabolic rate, increase the concentration in the blood serum (increased toxicity).

Inducers of microsomal liver enzymes (including phenytoin, rifampicin, barbiturates, carbamazepine) accelerate liver metabolism (reducing the effect).

Increases the toxic effect of cardiac glycosides (especially against the background of the initial potassium deficiency in the body) and curare-like muscle relaxants.

Glucocorticosteroids, carbonic anhydrase inhibitors, and adrenocorticotropic hormones increase the risk of hypokalemia.

It should not be prescribed simultaneously with nephrotoxic drugs (aminoglycosides, cyclosporine, pentamidine, etc. ) – the risk of developing impaired renal function increases.

Antitumor medications, radiation therapy, and medications that inhibit bone marrow hematopoiesis increase the risk of anemia and other hematological disorders.

Antitumor drugs increase nephrotoxicity, bronchospasm, and lowering of blood pressure.

Glucocorticosteroids and corticotropin increase hypokalemia, which can lead to the development of arrhythmias. If it is necessary to simultaneously prescribe these drugs, the blood electrolyte composition and ECG should be monitored.

Amphotericin B may increase the toxicity of cardiac glycosides (due to hypokalemia).

Concomitant use with imidazoles (including fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole) may lead to the development of resistance to amphotericin B. Combined treatment with imidazoles and amphotericin B should be prescribed with caution.

It should not be prescribed simultaneously with nephrotoxic drugs (aminoglycosides, cyclosporine, pentamidine, etc. ) – the risk of developing impaired renal function increases.

Prolongs the muscle-relaxing effect of depolarizing muscle relaxants.

Leukocyte mass should be administered at a significant interval after use of amphotericin B (risk of respiratory complications).

How to take, course of use and dosage

Intravenous drip for 2-4 hours, the recommended concentration is 0.1 mg / ml. A test dose of 1 mg (base) is diluted in 20 ml of a 5% dextrose solution and administered intravenously for at least 20-30 minutes under the control of blood pressure, pulse, and body temperature every 30 minutes for 2-4 hours.

If well tolerated, the recommended daily dose is 0.25-0.3 mg / kg, depending on the severity of the disease.

In case of hypersensitivity to the drug, diseases of the cardiovascular system, or renal insufficiency, treatment begins with low doses of 5-10 mg and, gradually increasing by 5-10 mg / day, is adjusted to the recommended daily dose of 0.5-0.7 mg/kg.

Therapeutic doses are selected individually, depending on the type and severity of the infection. When using the drug every other day, the dose should not exceed 1.5 mg / kg (to avoid the development of cardiopulmonary insufficiency). The maximum daily dose is 1.5 mg / kg.

Sporotrichosis: course dose 2.5 g, duration of therapy-9 months.

Aspergillosis:  the course dose is 3.6 g, the duration of treatment is 11 months.

Rhinocerebral phycomycosis:  the course dose is 3-4 g.

If therapy is interrupted for more than 7 days, it should be resumed from the lowest dose (0.25 mg/kg), gradually increasing to the desired level.

For children:  intravenously, initially 0.25 mg / kg (base) per day in 5% dextrose solution for 6 hours; taking into account tolerability, the dose is gradually increased (usually by 0.125 – 0.25 mg / kg every day or every other day) to a maximum dose of 1 mg/kg or 30 mg per 1 m%^%2. It is administered to children in the minimum effective doses.

To prepare the solution for intravenous use, a solution with an initial concentration of 5 mg/ml is used. To do this, use a sterile syringe (needle no less than No. 20) to inject 10 ml of sterile water for injection without bacteriostatic additives directly into the drug bottle. The contents of the vial are shaken until a clear colloidal solution is formed. To obtain a solution with a concentration of 0.1 mg/ml, it is diluted with a 5% dextrose solution with a pH of at least 4.2 in a ratio of 1: 50. Before dilution, it is necessary to check the acidity of the available dextrose solution. The pH of the dextrose solution usually exceeds 4.2, otherwise 1-2 ml of buffer solution should be added to it before dilution.

The following buffer solution is recommended: sodium hydrophosphate (anhydrous) -1.59 g, sodium dihydrogen phosphate (anhydrous) – 0.96 g, water for injection-up to 100 ml.

Before adding dextrose to the solution, the buffer solution is sterilized by filtration through a bacterial ceramic or membrane filter or by autoclaving for 30 minutes at a pressure of 1 atm and 121 °C.

Overdose

Symptoms: cardiac and respiratory arrest.

Treatment: symptomatic. It is necessary to monitor cardiac and respiratory activity, liver and kidney function, peripheral blood picture and electrolyte content, and prescribe maintenance therapy. It is not removed during hemodialysis.

Before resuming treatment, the patient’s condition should be stabilized.

Functional features

After a single intravenous injection, an effective concentration (dose-dependent) is created in the blood, which persists for 24 hours. After intravenous use of 1-5 mg / day, the maximum plasma concentration (cmax) is 0.5 – 2 mcg/ml. Binding to plasma proteins is more than 90%.

It is distributed in the lungs, liver, spleen, kidneys, adrenal glands, muscles and other tissues. Concentrations in pleural effusion, peritoneal fluid, synovial fluids, and aqueous humor reach approximately 2/3 of the plasma concentration; in cerebrospinal fluid, it is usually not detected. The apparent volume of distribution in adults is 4 l / kg, in children-0.4-8.3 l / kg, in newborns-1.5-9.4 l/kg.

It is metabolized (pathways unknown). In the bile and urine, about 98% is present as metabolites. It is excreted slowly by the kidneys, with an initial half-life of 24 hours in adults,5.5 – 40.3 hours in children, and 18.8 – 62.5 hours in newborns; the final half-life is 15 days. Despite its slow elimination, it accumulates weakly. It is practically not excreted during hemodialysis. After withdrawal, it is detected in the body for several more weeks.

Special instructions

Amphotericin B should be used primarily for the treatment of progressive and life-threatening fungal infections. It should not be used to treat non-invasive (superficial) mycoses such as oral, vaginal, or esophageal candidiasis in patients with normal blood neutrophil counts.

With prolonged treatment, the likelihood of toxic effects increases.

During the treatment period, control weighing of patients, general analysis of blood and urine, monitoring of the concentration of potassium in the blood, determine the functional state of the kidneys, liver, ECG. Patients taking potassium supplements should regularly monitor their plasma potassium and magnesium concentrations.

use of the drug to patients undergoing hemodialysis is possible only after completion of the dialysis procedure.

All procedures with the solution should be carried out in strict compliance with the rules of asepsis, since the drug itself and all solutions intended for its dilution do not contain preservatives or bacteriostatic agents.

When using systems for intravenous use that were previously installed for other purposes, it is necessary to flush the system with a 5% dextrose solution for injection.

If anemia occurs, the drug should be discontinued.

Storage conditions

List B. Store in a dry place protected from light at a temperature of 2 to 10°C. Keep out of reach of children.

Shelf life

4 years

Active ingredient

Amphotericin B

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults, Children as prescribed by a doctor, Pregnant women as prescribed by a doctor

Indications

Vaginal Candidiasis