Amphotericinum In

General characteristics. Structure:

Lyophilisate for preparation of solution for infusions in the form of the porous mass of yellow color, inodorous, or almost inodorous, is hygroscopic; let's dissolve in water and 5% glucose solution with formation of a colloid system.

Active ingredient:  1 фл. Amphotericinum In  50 000 PIECES;

Pharmacological properties:

Antifungal antibiotic of a broad spectrum of activity from group of polyenes. It is produced by an actinomyce of Streptomyces nodosus. Renders fungicidal or a fungistasis depending on concentration in biological liquids and sensitivity of the activator.
The mechanism of effect of drug is based on its ability to contact sterola (ergosterola) which are in a cellular membrane sensitive to Amphotericinum In a mushroom. Permeability of a membrane is as a result broken, and intracellular components get to extracellular space.
It is active concerning mushrooms of the sort Candida, Histoplasma capsulatum, Cryptococcus neoformans, Aspergillus, Coccidioides immitans, Blastomyces dermatitidis, Sporothtrix schenckii, Fonsecaea, and also leyshmaniye.

Pharmacokinetics. Distribution

It is distributed in most bodies and fabrics, in cerebrospinal fluid is not defined. Linkng with proteins of plasma makes 90%.

Removal

It is removed by kidneys, very slowly. 2-5% of the entered dose are removed in an active form. It can be found in urine within 7 weeks after cancellation.

Indications to use:

For parenteral and inhalation use

— GIT candidiasis, intestinal kandidonositelstvo;

— candidiasis of internals;

— the chronic granulematozny and disseminated candidiasis forms;

— coccidioidosis;

— cryptococcosis;

— histoplasmosis;

— North American zymonematosis;

— chromomycosis;

— mold mycoses;

— aspergillosis;

— sporotrichosis.

For external use

— candidiasis of skin and mucous membranes.

Route of administration and doses:

In/in introduction
Before each injection establish the exact weight of the patient and make calculation of a dose of drug.
Amphotericinum dose In is established for each patient individually at the rate of 250 PIECES/kg of body weight. Previously enter 100 PIECES/kg (for definition of individual portability). Further in the absence of side effects and if necessary the dose can be gradually increased to 1000 PIECES/kg.
The drug is administered every other day or 1-2 times a week (because of risk of cumulation).
Duration of a course of treatment depends on weight and localization of process, duration of a disease and makes not less than 4-8 weeks in order to avoid a recurrence. The general dose of Amphotericinum In on a course of treatment averages 1.5-2 million. Piece (18-20 injections).
The daily dose of Amphotericinum In for children and teenagers depends on age.

Daily doses (body weight PIECE/kg) 
Age       1-5 injection       6-10 injection     11-15 injection     16-20 injection
1-3 years                                                                 75-150 100-250 150-350 175-400
4-7 years                                                                 100-200 150-300 175-400 200-500
8-12 years                                                               125-250 175-350 200-450 225-600
13-18 years                                                             150-300 200-400 225-500 250-700

The first course of treatment consists from 20 in/in drop infusions which carry out 2 times a week.
After a monthly break it is desirable to carry out a repeated course of treatment.
At good tolerance and lack of by-effects which expressiveness at discontinuous course treatment considerably decreases both courses of treatment (30-40 infusions) are conducted within 5-6 months. At intolerance of drug daily and course doses of Amphotericinum In have to be lowered, and intervals between injections and breaks between the first and second courses – are increased.
Repeated courses of treatment begin with the smallest doses of drug, gradually raising them in the course of treatment.
Inhalation introduction
Inhalations appoint 1-2 lasting up to 15-20 min. in doses at the rate of 50 000 PIECES (10 ml) to inhalation that corresponds to a daily dose of 1000-2000 PIECES/kg of body weight of the patient.
When using the inhalers working only at a breath, the single dose is reduced to 25 000 PIECES (5 ml). Duration of a course of treatment makes 10-14 days and depends on weight and duration of a disease. If necessary appoint a repeated course after a 7-10-day break.
Rules of preparation and administration of drug
In/in kapelno drug administer during 3-6 h with a speed of 20-30 thaws/min. Solution is prepared just before use. All manipulations on preparation and introduction should be carried out, without subjecting solution to influence of bright light. As Amphotericinum solvent In it is necessary to use solution of glucose of 5% for injections. In case of a deposit in solution in/in introduction it is inadmissible.
For in/in introductions use concentration of drug of 100-125 PIECES in 1 ml of solvent. With drug add 5-10 ml of water for injections to a bottle. Then mix is shaken up before full dissolution of powder. Solution from a bottle by means of a needle is gathered in the sterile syringe and pour in a bottle from 400 ml in 5% of solution of glucose.
In the specified amount of solvent no more than 50 000 PIECES of drug have to be dissolved.
Calculation of a dose
If the body weight of the patient of 75 kg, then calculated on the basis of 250 PIECES/kg of body weight, 250 PIECES x 75 kg are necessary that makes 18 750 PIECES of Amphotericinum of Century. As in 410 ml of 5% of solution of glucose 50 000 PIECES of Amphotericinum have to contain In, the necessary dose of Amphotericinum In – 18 750 PIECES - will contain in 150 ml of solution:
18 750 PIECES x 410 ml
-------------= 150 ml
50 000 PIECES
Amphotericinum solution In for inhalations is prepared just before use by dissolution of contents of a bottle (50 000 PIECES) in 10 ml of water for injections.
For inhalations inhalers like AI, PAI-1 are recommended, but also other types can be used.

Features of use:

In case of development of anemia treatment by Amphotericinum In should be stopped.

In the course of treatment systematic control of function of a liver, kidneys, pictures of peripheral blood and level of potassium in a blood plasma is necessary.

At development of the pyrogenic action at in administration of drug appoint febrifugal drugs, antihistaminic drugs, group B vitamins, ascorbic acid, NPVS, iron preparations, potassium salts.

The inhalation way of introduction is used in cases of preferential localization of mycotic processes in lungs and upper parts of respiratory tracts or impossibility in/in introductions of Amphotericinum In at other localizations of mycoses. For the best portability of Amphotericinum In for inhalation it is recommended to add 10-15 drops of medical glycerin to solution.

Side effects:

For parenteral use
From the alimentary system: nausea, vomiting, pains in epigastriums, a loss of appetite, increase in activity of liver enzymes.
From system of a hemopoiesis: anemia, leukopenia, thrombocytopenia.
From TsNS and peripheral nervous system: headache, polyneuropathy, sight illegibility, diplopia.
From cardiovascular system: arterial hypotension, arterial hypertension, arrhythmia, changes of an ECG.
From an urinary system: a renal failure, including increase in concentration of creatinine in blood serum, a proteinuria, an azotemia, a hypopotassemia, acidosis.
Allergic reactions: skin rash, an itch, a Quincke's edema, a bronchospasm (at inhalation use), allergic contact dermatitis (at external use).
From water and electrolytic balance: hypopotassemia.
Local reactions: at in introduction - thrombophlebitis; at inhalation use - irritation in a throat, cough, cold.
Others: fervescence, fever.
For external use
At ointment use - a burning sensation, prickings, a dermahemia; seldom - a xeroderma.

Interaction with other medicines:

At simultaneous use of Amphotericinum In with potentially nefrotoksichny antibiotics, cyclosporine, diuretics the risk of development of nephrotoxic action increases.

At simultaneous use with the medicines oppressing function of marrow the risk of development of anemia and other hematologic disturbances increases.

Amphotericinum of B can cause strengthening of effects of cardiac glycosides (especially against the background of deficit of potassium in an organism) and not depolarizing muscle relaxants.

At simultaneous use with flutsitoziny Amphotericinum In reduces clearance of the last thereof the toxic effects caused flutsitoziny can amplify.

Processing of skin the means containing benzyl alcohol before ointment imposing In can lead Amphotericinum to drug precipitation.

Contraindications:

— the expressed abnormal liver functions;

— the expressed renal failures;

— diseases of the hemopoietic system;

— diabetes mellitus;

— hypersensitivity to drug components.

 

Use of the drug AMPHOTERICINUM In at pregnancy and feeding by a breast
Amphotericinum In gets through a placenta. Adequate and strictly controlled researches of safety and efficiency of use of drug for pregnant women were not conducted. Use of drug is possible only if the estimated advantage for mother exceeds potential risk for a fruit.

It is unknown whether Amphotericinum In with breast milk is allocated. Therefore in need of use in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

 

Use at abnormal liver functions
It is contraindicated at the expressed abnormal liver functions.

 

Use at renal failures
It is contraindicated at the expressed renal failures.

 

Use for children
The daily dose of Amphotericinum In for children and teenagers depends on age.

Daily doses (body weight PIECE/kg)    
Age       1-5 injection       6-10 injection     11-15 injection      16-20 injection
1-3 years                                                                   75-150 100-250 150-350 175-400
4-7 years                                                                   100-200 150-300 175-400 200-500
8-12 years                                                                 125-250 175-350 200-450 225-600
13-18 years                                                               150-300 200-400 225-500 250-700

The first course of treatment consists from 20 in/in drop infusions which carry out 2 times a week.

Overdose:

Now about cases of overdose of the drug Amphotericinum In it was not reported.

Storage conditions:

List B. Drug should be stored in the dry, protected from light place, at a temperature from 2 to 8 °C. A period of validity of the lyophilized powder - 4 years. Unused solution for infusions is not subject to storage. The solution for inhalations which remained in a bottle can be used during 24 h at storage in the refrigerator.

Issue conditions:

According to the recipe

Packaging:

Bottles of 10 ml (1) - packs cardboard.