Composition, structure and packing
Lyophilisates for solution for infusion in the form of a porous mass of yellow, odorless or almost odorless, hygroscopic, soluble in water and 5% glucose solution with the formation of a colloidal system.
Ointment for external use only yellow, homogeneous consistency. 1 g of amphotericin B 30 000 IU.
Excipients: Vaseline oil, polysorbate 80, petroleum jelly health.
Clinico-pharmacological group: Antifungal antibiotic.
Pharmacological action
Antifungal broad-spectrum antibiotic from the group of polyenes. Produced by actinomyces Streptomyces nodosus. Has fungicidal or fungistatic action depending on the concentration in biological fluids and the sensitivity of the parasite.
The mechanism of drug action based on its ability to bind to sterols (ergosterol), located in the cell membrane is sensitive to amphotericin B of the fungus. As a result of disturbed permeability of the membrane, and intracellular components fall into the extracellular space. It is active against fungi of the genus Candida, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus, Coccidioides immitans, Blastomyces dermatitidis, Sporothtrix schenckii, Fonsecaea, and Leishmania.
Pharmacokinetics
Distribution
Distributed in most organs and tissues in the cerebrospinal fluid is not determined. Plasma protein binding is 90%.
Withdrawal
We derive the kidneys, very slowly. 2-5% of the administered dose was excreted in active form. It can be detected in urine within 7 weeks after discontinuation.
Statement
For parenteral and inhalation use - candidiasis gastrointestinal tract, intestinal kandidonositelstvo;
Candidiasis of the internal organs;
chronic granulomatous candidiasis and disseminated disease;
koktsidioidoz;
cryptococcosis;
histoplasmosis;
North American blastomycosis;
chromomycosis;
saprophytic mycosis;
aspergillosis;
sporotrichosis.
For external use - candidiasis of the skin and mucous membranes.
Dosage regimen
In / in the introduction
Before each infusion establish the exact weight of the patient and make the calculation of the dose of the drug.
The dose of amphotericin B are established for each patient individually at the rate of 250 IU / kg body weight. Previously 100 units / kg (to determine individual tolerance). Later in the absence of side effects and if necessary the dose may be gradually increased to 1000 IU / kg. The drug injected every other day or 1-2 times a week (because of the risk of cumulation).
Duration of treatment depends on the severity and localization process, the duration of disease and is at least 4-8 weeks to prevent recurrence.
The total dose of amphotericin B for treatment an average of 1.5-2 million IU (18-20 injections). Dose of amphotericin B for children and adolescents depends on age. The first course of treatment consists of 20 in / in drip infusions, which are 2 times a week. After a month's break, it is desirable to re-treatment.
With a good tolerability and absence of side effects, the severity of the discontinuous course treatment significantly reduced both the course of treatment (30-40 infusions) hold for 5-6 months.
If you are hypersensitive drug daily dose and the course amphotericin B should be reduced, and the intervals between injections and intervals between the first and second courses - increased.
Repeated courses of treatment starting with the smallest doses, gradually increasing them in the course of treatment. Inhalation Inhalation appoint 1-2 times / day for up to 15-20 min at doses at the rate of 50 000 IU (10 ml) for inhalation, which corresponds to a daily dose of 1000-2000 IU / kg of patient weight.
If you use inhalers, working only on inspiration, a single dose reduced to 25 000 IU (5 ml). The duration of treatment is 10-14 days, depending on the severity and duration of disease. If necessary, appoint a second course after the 7-10-day break.
The rules of preparation and administration of the drug
In / in introducing drug infusion for 3-6 h at a speed of 20-30 drops / min. Solution is prepared immediately before use. All the manipulations for the preparation and introduction should be carried out without subjecting the solution to bright light.
The solvent amphotericin B should be used 5% glucose solution for injection. In the case of precipitate in the solution to / inadmissible in the introduction. For iv administration of the drug concentration used 100-125 IU in 1 ml of solvent. Into a vial containing the drug is added 5-10 ml of water for injection. Then the mixture is shaken until complete dissolution of the powder. The solution from the vial with a needle dial into a sterile syringe and poured into a bottle with 400 ml of 5% glucose solution. The specified quantity of solvent should be diluted no more than 50 000 IU of the drug. Calculation of the dose if body weight 75 kg, is based on a rate of 250 IU / kg of body weight should be 250 units x 75 kg, which is 18 750 IU amphotericin B.
Amphotericin B solution for inhalation prepared immediately before use by dissolving the contents of the vial (50,000 units) in 10 ml water for injection. For inhalation recommended dose inhalers such as AI, PAI-1, but can be used and other types.
External application
The ointment is applied to the affected skin with a thin layer 2-4 times / day. The course of treatment for candidiasis skin folds - 1-3 weeks. At intertrigo in children - 1-2 weeks. At the defeat of interdigital spaces and paronychia - 2-4 weeks. Adverse reactions to parenteral
On the part of the digestive system: nausea, vomiting, epigastric pain, decreased appetite, increase in liver enzymes.
On the part of the hemopoietic system: anemia, leukopenia, thrombocytopenia.
From the central nervous system and peripheral nervous system: headache, polyneuropathy, blurred vision, diplopia.
Since the cardiovascular system: hypotension, hypertension, arrhythmia, ECG changes.
On the part of the urinary system: renal dysfunction, including increased concentration of serum creatinine, proteinuria, azotemia, hypokalemia, acidosis. Allergic reactions: skin rash, itching, Quincke's edema, bronchospasm (inhalation use), allergic contact dermatitis (with external use).
From the water-electrolyte balance: hypokalemia.
Local reactions: with a / in the introduction - thrombophlebitis; inhalation use - a tickle in the throat, cough, runny nose.
Other: fever, chills.
For external use
In applying the ointment - a burning sensation, tingling, flushing of the skin; rarely - dry skin
Contraindications
marked disturbances of liver function;
pronounced renal dysfunction;
disease of hematopoietic system;
diabetes;
Hypersensitivity to the drug's components.
Pregnancy and lactation
Amphotericin B crosses the placenta. Adequate and strictly controlled studies safety and efficacy of the drug in pregnant women has not been conducted.
The product is only possible if the intended benefits to the mother outweighs the potential risk to the fetus. It is not known whether the allocated Amphotericin B with breast milk. Therefore, if necessary, use during lactation should decide the issue of termination of breastfeeding.
Application for violations of liver function
Contraindications disturbancies liver function.
Application for violations of renal function
Contraindications disturbancies renal function.
Cautions
In the case of anemia treatment with amphotericin B should be discontinued. In the course of treatment requires systematic monitoring of liver function, kidney, peripheral blood picture and the level of potassium in the blood plasma. With the development of pyrogenic actions when in / in the introduction of the drug prescribed antipyretic drugs, antihistamines, vitamins, ascorbic acid, NSAIDs, iron, potassium salt. Inhalation route of administration used in cases of preferential localization of mycotic processes in the lung and upper respiratory tract or the inability to / in the introduction of amphotericin B with other sites mycosis.
For a better tolerability of amphotericin B inhalation solution is recommended to add 10-15 drops of medical glycerol. Ointments should not be applied under occlusive dressings. In the absence of effects from the use of ointments Amphotericin B after 1-2 weeks is necessary to clarify the diagnosis and further treatment policy.
Overdose
Currently, cases of overdosing Amphotericin B have been reported.
Drug Interactions
With simultaneous use of amphotericin B with potentially nephrotoxic antibiotics, cyclosporine, diuretics increases the risk of nephrotoxicity.
When applied simultaneously with drugs, distressing bone marrow function, increases the risk of anemia and other hematologic disorders. Amphotericin B may cause increased effects of cardiac glycosides (especially given the shortage of potassium in the body), and nondepolarizing muscle relaxants.
At simultaneous application with flutsitozinom Amphotericin B reduces the clearance of the latter, because this may worsen the toxic effects caused flutsitozinom. Leather processing agents containing benzyl alcohol, before applying the ointment Amphotericin B can lead to precipitation of the drug.
Terms and Conditions of storage
List B. The drug should be stored in a dry place protected from light, at temperatures from 2 ° to 8 ° C. Expiration dried powder - 4 years. Expiration ointment - 2 years.
Unused storage solution for infusion is not subject. Solution for inhalation, the remainder in the vial can be used within 24 hours when stored in the refrigerator.
Lyophilisates for solution for infusion in the form of a porous mass of yellow, odorless or almost odorless, hygroscopic, soluble in water and 5% glucose solution with the formation of a colloidal system.
Ointment for external use only yellow, homogeneous consistency. 1 g of amphotericin B 30 000 IU.
Excipients: Vaseline oil, polysorbate 80, petroleum jelly health.
Clinico-pharmacological group: Antifungal antibiotic.
Pharmacological action
Antifungal broad-spectrum antibiotic from the group of polyenes. Produced by actinomyces Streptomyces nodosus. Has fungicidal or fungistatic action depending on the concentration in biological fluids and the sensitivity of the parasite.
The mechanism of drug action based on its ability to bind to sterols (ergosterol), located in the cell membrane is sensitive to amphotericin B of the fungus. As a result of disturbed permeability of the membrane, and intracellular components fall into the extracellular space. It is active against fungi of the genus Candida, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus, Coccidioides immitans, Blastomyces dermatitidis, Sporothtrix schenckii, Fonsecaea, and Leishmania.
Pharmacokinetics
Distribution
Distributed in most organs and tissues in the cerebrospinal fluid is not determined. Plasma protein binding is 90%.
Withdrawal
We derive the kidneys, very slowly. 2-5% of the administered dose was excreted in active form. It can be detected in urine within 7 weeks after discontinuation.
Statement
For parenteral and inhalation use - candidiasis gastrointestinal tract, intestinal kandidonositelstvo;
Candidiasis of the internal organs;
chronic granulomatous candidiasis and disseminated disease;
koktsidioidoz;
cryptococcosis;
histoplasmosis;
North American blastomycosis;
chromomycosis;
saprophytic mycosis;
aspergillosis;
sporotrichosis.
For external use - candidiasis of the skin and mucous membranes.
Dosage regimen
In / in the introduction
Before each infusion establish the exact weight of the patient and make the calculation of the dose of the drug.
The dose of amphotericin B are established for each patient individually at the rate of 250 IU / kg body weight. Previously 100 units / kg (to determine individual tolerance). Later in the absence of side effects and if necessary the dose may be gradually increased to 1000 IU / kg. The drug injected every other day or 1-2 times a week (because of the risk of cumulation).
Duration of treatment depends on the severity and localization process, the duration of disease and is at least 4-8 weeks to prevent recurrence.
The total dose of amphotericin B for treatment an average of 1.5-2 million IU (18-20 injections). Dose of amphotericin B for children and adolescents depends on age. The first course of treatment consists of 20 in / in drip infusions, which are 2 times a week. After a month's break, it is desirable to re-treatment.
With a good tolerability and absence of side effects, the severity of the discontinuous course treatment significantly reduced both the course of treatment (30-40 infusions) hold for 5-6 months.
If you are hypersensitive drug daily dose and the course amphotericin B should be reduced, and the intervals between injections and intervals between the first and second courses - increased.
Repeated courses of treatment starting with the smallest doses, gradually increasing them in the course of treatment. Inhalation Inhalation appoint 1-2 times / day for up to 15-20 min at doses at the rate of 50 000 IU (10 ml) for inhalation, which corresponds to a daily dose of 1000-2000 IU / kg of patient weight.
If you use inhalers, working only on inspiration, a single dose reduced to 25 000 IU (5 ml). The duration of treatment is 10-14 days, depending on the severity and duration of disease. If necessary, appoint a second course after the 7-10-day break.
The rules of preparation and administration of the drug
In / in introducing drug infusion for 3-6 h at a speed of 20-30 drops / min. Solution is prepared immediately before use. All the manipulations for the preparation and introduction should be carried out without subjecting the solution to bright light.
The solvent amphotericin B should be used 5% glucose solution for injection. In the case of precipitate in the solution to / inadmissible in the introduction. For iv administration of the drug concentration used 100-125 IU in 1 ml of solvent. Into a vial containing the drug is added 5-10 ml of water for injection. Then the mixture is shaken until complete dissolution of the powder. The solution from the vial with a needle dial into a sterile syringe and poured into a bottle with 400 ml of 5% glucose solution. The specified quantity of solvent should be diluted no more than 50 000 IU of the drug. Calculation of the dose if body weight 75 kg, is based on a rate of 250 IU / kg of body weight should be 250 units x 75 kg, which is 18 750 IU amphotericin B.
Amphotericin B solution for inhalation prepared immediately before use by dissolving the contents of the vial (50,000 units) in 10 ml water for injection. For inhalation recommended dose inhalers such as AI, PAI-1, but can be used and other types.
External application
The ointment is applied to the affected skin with a thin layer 2-4 times / day. The course of treatment for candidiasis skin folds - 1-3 weeks. At intertrigo in children - 1-2 weeks. At the defeat of interdigital spaces and paronychia - 2-4 weeks. Adverse reactions to parenteral
On the part of the digestive system: nausea, vomiting, epigastric pain, decreased appetite, increase in liver enzymes.
On the part of the hemopoietic system: anemia, leukopenia, thrombocytopenia.
From the central nervous system and peripheral nervous system: headache, polyneuropathy, blurred vision, diplopia.
Since the cardiovascular system: hypotension, hypertension, arrhythmia, ECG changes.
On the part of the urinary system: renal dysfunction, including increased concentration of serum creatinine, proteinuria, azotemia, hypokalemia, acidosis. Allergic reactions: skin rash, itching, Quincke's edema, bronchospasm (inhalation use), allergic contact dermatitis (with external use).
From the water-electrolyte balance: hypokalemia.
Local reactions: with a / in the introduction - thrombophlebitis; inhalation use - a tickle in the throat, cough, runny nose.
Other: fever, chills.
For external use
In applying the ointment - a burning sensation, tingling, flushing of the skin; rarely - dry skin
Contraindications
marked disturbances of liver function;
pronounced renal dysfunction;
disease of hematopoietic system;
diabetes;
Hypersensitivity to the drug's components.
Pregnancy and lactation
Amphotericin B crosses the placenta. Adequate and strictly controlled studies safety and efficacy of the drug in pregnant women has not been conducted.
The product is only possible if the intended benefits to the mother outweighs the potential risk to the fetus. It is not known whether the allocated Amphotericin B with breast milk. Therefore, if necessary, use during lactation should decide the issue of termination of breastfeeding.
Application for violations of liver function
Contraindications disturbancies liver function.
Application for violations of renal function
Contraindications disturbancies renal function.
Cautions
In the case of anemia treatment with amphotericin B should be discontinued. In the course of treatment requires systematic monitoring of liver function, kidney, peripheral blood picture and the level of potassium in the blood plasma. With the development of pyrogenic actions when in / in the introduction of the drug prescribed antipyretic drugs, antihistamines, vitamins, ascorbic acid, NSAIDs, iron, potassium salt. Inhalation route of administration used in cases of preferential localization of mycotic processes in the lung and upper respiratory tract or the inability to / in the introduction of amphotericin B with other sites mycosis.
For a better tolerability of amphotericin B inhalation solution is recommended to add 10-15 drops of medical glycerol. Ointments should not be applied under occlusive dressings. In the absence of effects from the use of ointments Amphotericin B after 1-2 weeks is necessary to clarify the diagnosis and further treatment policy.
Overdose
Currently, cases of overdosing Amphotericin B have been reported.
Drug Interactions
With simultaneous use of amphotericin B with potentially nephrotoxic antibiotics, cyclosporine, diuretics increases the risk of nephrotoxicity.
When applied simultaneously with drugs, distressing bone marrow function, increases the risk of anemia and other hematologic disorders. Amphotericin B may cause increased effects of cardiac glycosides (especially given the shortage of potassium in the body), and nondepolarizing muscle relaxants.
At simultaneous application with flutsitozinom Amphotericin B reduces the clearance of the latter, because this may worsen the toxic effects caused flutsitozinom. Leather processing agents containing benzyl alcohol, before applying the ointment Amphotericin B can lead to precipitation of the drug.
Terms and Conditions of storage
List B. The drug should be stored in a dry place protected from light, at temperatures from 2 ° to 8 ° C. Expiration dried powder - 4 years. Expiration ointment - 2 years.
Unused storage solution for infusion is not subject. Solution for inhalation, the remainder in the vial can be used within 24 hours when stored in the refrigerator.
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