Description
Release form
Lyophilisate for solution for infusion
Packing
Bottle of 10 ml.
Pharmacological action
Polyene macrocyclic antibiotic with antifungal activity. Produced by Streptomyces nodosus. It has a fungicidal or fungistatic effect depending on the concentration in biological fluids and on the sensitivity of the pathogen. It binds to sterols (ergosterols) located in the cell membrane of a drug-sensitive fungus. As a result, the permeability of the membrane is disrupted and the intracellular components exit into the extracellular space and the lysis of the fungus.
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.
To amphotericin B, as a rule are resistant: Pseudallescheria boydii, Fusarium spp.
Ineffective against bacteria, rickettsia, viruses.
Indications
Progressive, life-threatening fungal infections caused by amphotericin susceptible In microorganisms:
disseminated cryptococcosis, cryptococcal meningitis
meningitis, caused by other fungi
disseminated aspergillosis and invasive
North American blastomycosis
form disseminated candidiasis
coccidioidomycosis
paracoccidioidomycosis
histoplasmosis, phycomycosis
(zygomycosis)
chromomycosis
musty mycosis
disseminated sporotrichosis
gialogifomikoz
mycetoma
chronic abdominal infections (including peritonitis )
endocarditis
endophthalmitis
fungal sepsis
fungal infections of the urinary tract
visceral leishmaniasis (including in the patient s with immunodeficiency), American cutaneous visceral leishmaniasis (not a drug of choice).
Contraindications
hypersensitivity
chronic renal failure
lactation.
Precautions: kidney disease (including glomerulonephritis), amyloidosis, hepatitis, cirrhosis, anemia, agranulocytosis, diabetes mellitus, pregnancy.
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 candidiasis of the oral cavity, vagina, or esophagus in patients with normal neutrophil levels in the blood.
With prolonged treatment, the likelihood of toxic effects increases.
During the treatment period, control weighing of patients, a general analysis of blood, urine, control of potassium concentration in the blood are carried out, the functional state of the kidneys, liver, ECG is determined. Patients taking potassium preparations should regularly monitor the concentration of potassium and magnesium in the plasma.
Administration of the drug to hemodialysis patients is possible only after completion of the dialysis procedure.
All procedures with the solution should be carried out with strict adherence to aseptic rules, since the drug itself and all solutions intended for its dilution do not contain preservatives or bacteriostatic agents.
When using intravenous systems previously established for other purposes, it is necessary to rinse the system with 5% dextrose solution for injection.
If anemia occurs, the drug should be discontinued.
Composition
1 vial containing IT:
Active ingredient: amphotericin B 50 000 PIECES
Excipients: monosubstituted sodium phosphate, deoxycholic acid.
Dosage and administration
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, body temperature every 30 minutes for 2-4 hours.
If good tolerance, the recommended daily dose is 0.25-0.3 mg / kg, depending on the severity of the disease.
With increased sensitivity to the drug, diseases of the cardiovascular system, kidney failure, treatment begins with low doses of 5-10 mg and, gradually increasing by 5-10 mg / day, bring to the recommended daily dose of 0.5-0.7 mg / kg .
The selection of therapeutic doses is carried out 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 of 2.5 g, duration of therapy – 9 months.
Aspergillosis: course dose – 3.6 g, treatment duration – 11 months.
Rhinocerebral phycomycosis: course dose is 3-4 g.
If therapy is interrupted for more than 7 days, it should be resumed with 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 a 5% dextrose solution for 6 hours, taking into account tolerance, 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 m2. Children are administered in minimum effective doses.
A solution with an initial concentration of 5 mg / ml is used to prepare a solution for intravenous administration. To do this, 10 ml of sterile water for injection without bacteriostatic additives is added directly to the drug vial with a sterile syringe (needle no less than No. 20). 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, the acidity of the existing dextrose solution must be checked. The pH of the dextrose solution, as a rule, exceeds 4.2, otherwise, 1-2 ml of the buffer solution should be added to it before dilution.
The following buffer solution is recommended: sodium hydrogen phosphate (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 min at a pressure of 1 atm and 121 ° C.
Side effects
From the digestive system: often – loss of appetite, dyspepsia, nausea, vomiting, diarrhea, gastralgia, hepatotoxicity (increased activity of liver enzymes, hyperbilirubinemia) infrequently – acute liver failure, hepatitis, jaundice, hemorrhagic gastroenteritis, melena.
From the nervous system: often – headache, infrequently – cramps, transient vertigo, peripheral neuropathy, encephalopathy.
On the part of the sensory organs: infrequently – visual impairment, diplopia, hearing loss, tinnitus.
From the hemopoietic organs: often – normochromic normocytic anemia infrequently – agranulocytosis, blood clotting disorder, leukopenia, hemolytic anemia, thrombocytopenia, eosinophilia, leukocytosis.
From the cardiovascular system: often – lowering blood pressure infrequently – arrhythmias, including ventricular fibrillation, changes in the ECG, increased blood pressure, shock, cardiac arrest, heart failure.
From the respiratory system: 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. The preliminary introduction of a 0.9% solution of sodium nitrate reduces the risk of nephrotoxicity, the introduction of sodium bicarbonate – 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: often – fever, weight loss, myalgia, arthralgia, general weakness.
Laboratory indicators: hypokalemia, hyperkalemia, hypomagnesemia, hypocalcemia, hypercreatininemia.
Drug Interactions
Pharmaceutically 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.
Synergism – with nitrofurans.
Increases the effect and toxicity of anticoagulants, theophylline and sulfonylurea, flucytosine (lengthens 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 (increase toxicity).
Inducers of microsomal liver enzymes (including phenytoin, rifampicin, barbiturates, carbamazepine) accelerate liver metabolism (decrease in effect).
Enhances the toxic effect of cardiac glycosides (especially against the background of an initial deficiency of potassium in the body) and curariform muscle relaxants.
Glucocorticosteroids, carbonic anhydrase inhibitors, adrenocorticotropic hormones increase the risk of hypokalemia.
You can not prescribe simultaneously with nephrotoxic drugs (aminoglycosides, cyclosporine, pentamidine and others) – the risk of developing renal dysfunction increases.
Antitumor drugs, radiation therapy, and drugs that inhibit bone marrow hematopoiesis increase the risk of anemia and other hematological disorders.
Antitumor drugs increase nephrotoxicity, bronchospasm, and lower blood pressure.
Glucocorticosteroids and corticotropin increase hypokalemia, which can lead to the development of arrhythmias. If necessary, the simultaneous administration of these drugs should monitor the electrolyte composition of the blood and ECG.
Amphotericin B may increase cardiac glycoside toxicity (due to hypokalemia).
Concomitant administration with imidazoles (including fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole) may lead to the development of resistance to amphotericin B. Combined treatment with imidazoles with amphotericin B should be prescribed with caution.
Do not use concomitantly with nephrotoxic drugs (aminoglycosides, cyclosporine, pentamidine and others) – the risk of developing renal dysfunction increases.
Extends the muscle relaxant effect of depolarizing muscle relaxants.
Leukocyte mass should be administered at a significant interval after administration of amphotericin B (risk of complications from the respiratory system).
Overdose
Symptoms: cardiac arrest and breathing.
Treatment: symptomatic. It is necessary to monitor cardiac and respiratory activity, liver and kidney function, patterns of peripheral blood and electrolyte levels and prescribe maintenance therapy. Not removed by hemodialysis.
The patient should be stabilized before resuming treatment.
Storage Conditions
List B. In a dry, dark place at 2 to 10 ° C. Store in places out of reach of children.
Term hodnosty
4 years
Pharmacy conditions
In retseptu
Dosage form
infusion solution
Prescription
For children prescribed by a doctor, For adults, Pregnant as prescribed by a doctor
Indications
Indications
Vaginal candidiasis
Sintez AKOMP, Russia
