Amfotsil - instructions for use, dose, side effects, contraindications

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Dosage form: & nbsplyophilizate for solution for infusion

Composition:

1 bottle contains:

Active substance:

Amphotericin B 50 or 100 mg.

Excipients: sodium cholesteryl sulfate, trometamol, disodium edetate dihydrate, hydrochloric acid, lactose monohydrate, nitrogen, dimethylsulfoxide.

Description:Powder or a porous mass of light yellow color. A mixture of powder and porous mass is allowed in the vial.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

Amphotericin B

Pharmacodynamics:Amphotericin B is a macrocyclic polyene antifungal agent with a fungicidal action that is produced by the fungus Streptomyces nodosus. Amphotericin B has a high affinity for ergosterol, the main sterol of the cytoplasmic membrane of fungi and a slight affinity for cholesterol, the main sterol of the cytoplasmic membrane of mammals. The interaction of amphotericin B with ergosterol leads to a violation of the integrity of the cytoplasmic membrane, a change in its permeability, and then to damage and death of the fungal cells. The drug is active against fungi - Candida spp. (including Candida albicans), Aspergillus spp. (including Aspergillus fumigates), Coccidioides immitis, Cryptococcus neoformans and protozoans - Leishmania spp. Ineffective against bacteria, rickettsia, viruses.

Pharmacokinetics:

The main pharmacokinetic parameters are presented in the table:

Pharmacokinetic parameter, mean	Daily dose
Pharmacokinetic parameter, mean	3 mg / kg	4 mg / kg
Equilibrium volume of distribution, l / kg	3,8	4,1
Total plasma clearance, l / h / kg	0,105	0,112
Half-distribution period, min	3,5	3,5
Half-life, h	27,5	28,2
Maximum plasma concentration, μg / ml	2,6	2,9
The equilibrium area under the concentration-time curve, μg / ml hch	29	36

Special patient groups

Pharmacokinetic parameters do not depend on creatinine clearance (CK) in the range of 35-202 ml / min / 70 kg. The effect of more severe renal failure has not been studied.

Pharmacokinetic parameters with a mild degree of liver failure do not change, with more severe forms of the disease, the effect has not been studied.

Age (3-52 years) does not affect the pharmacokinetics.

Indications:

Severe systemic mycoses (mainly systemic aspergillosis and systemic candidiasis), when high toxicity or concomitant renal failure does not allow the use of amphotericin B deoxycholate. Heavy fungal infections in persons with neutropenia due to the use of cytotoxic drugs.

It is not intended for the treatment of clinically insignificant mycoses, diagnosed only on the basis of skin or serological samples.

Contraindications:Hypersensitivity to amphotericin B or any other component of the drug, lactation period.

Carefully:Glomerulonephritis, amyloidosis, hepatitis, liver cirrhosis, anemia, agranulocytosis, diabetes, pregnancy.

Pregnancy and lactation:In pregnant women, Amfocil can only be used if the potential benefit to the mother exceeds the possible risk to the fetus. If you need to use the drug Amfocil during lactation, breast-feeding should be discontinued, as there is no evidence to confirm or deny the possibility of amphotericin B penetrating into breast milk.

Dosing and Administration:

Intravenously drip.

Adults and children 3-4 mg / kg once a day.

Dissolved in sterile water for injection and diluted in 5% solution of dextrose Amfotsil is administered at a rate of 1 mg / kg / h. Before the beginning of each course of therapy, a trial dose is administered. The patient is administered 10 ml of a ready solution containing 1.6-8.3 mg of amphotericin B for 15-30 minutes. At the end of the injection, the patient is observed for 30 minutes. In patients without signs of intolerance and in the absence of infusion reactions, the administration time can be reduced to 2 hours. With severe tolerance or acute reactions, the administration time is extended.

Renal insufficiency

Nephrotoxicity of the drug Amfocil (by the degree of decrease in QC) is dose-dependent. Clear recommendations for dose adjustment are not available. Correction of the dose should be carried out according to the clinical condition of the patient.

Liver failure

Correction of the dose is not required.

Instructions on the dissolution and dilution of the drug

Amfotsil should be dissolved in sterile water for injection. Using a sterile syringe with a needle 20 G it is necessary to quickly inject 10 ml or 20 ml of water for injection into vials containing 50 mg or 100 mg of amphotericin B, respectively. As a result, a concentrate containing 5 mg / ml of amphotericin B is formed. The vial should be gently rotated in the hands until all solids dissolve. The resulting suspension should be clear yellow without any particles or precipitate. To obtain an infusion solution concentrate should be diluted in a 5% solution of dextrose to obtain a solution with an average concentration of 0.6 mg / ml (range 0.16-0.83 mg / ml) as described below:

Amfocil Dose	The volume in which the dose should be dissolved	Volume of 5% dextrose
10-35 mg	2-7 ml	50 ml
35-70 mg	7-14 ml	100 ml
70-175 mg	14-35 ml	250 ml
175-350 mg	35-70 ml	500 ml
350-1000 mg	70-200 ml	1000 ml

The lyophilisate can not be dissolved in salt solutions or dextrose solution or diluted in salt solutions and electrolyte solutions. The use of other solutions, other than those specified in the instructions, or the presence of bacteriostatic substances (eg, benzyl alcohol) in the solutions used, can lead to the formation of sediment. When you administer the drug, you can not use filters.

Amfotsil can not be mixed with other drugs. When administered through a permanent venous catheter, it should be rinsed with a 5% dextrose solution before and after the administration of Amfocil.

Side effects:

Side effects identified during the comparative studies.

From the side of the cardiovascular system: increase or decrease in blood pressure, tachycardia.

From the digestive system: nausea, vomiting, impaired functional liver tests.

From the hematopoiesis: thrombocytopenia. On the part of the respiratory system, shortness of breath, hypoxia.

Laboratory indicators: hypercreatininaemia, hypokalemia, hypomagnesemia, hyperbilirubinemia, hanging of alkaline phosphatase activity, hyperglycemia.

Other: fever, chills, headache.

Side effects identified during the use of the drug, but the cause-and-effect relationship is not established:

System-Organ Class	≥5%	1-5%
Organism as a whole	Ascites, pain, incl. in the abdomen, back, chest, face swelling, inflammation at the injection site, lesions of the mucous membranes, sepsis	Trauma, allergic reactions, asthenia, death, hypothermia, immune disorders, infection, reactions at the injection site (including pain), pain in the neck
From the side of the cardiovascular system	Bleeding, postural hypotension	Arrhythmia, atrial fibrillation, bradycardia, chronic heart failure, cardiac arrest, phlebitis, shock, supraventricular arrhythmia, syncope, vasodilation, veno-occlusive disease of the liver, ventricular extrasystole
From the digestive system	Diarrhea, dryness of the oral mucosa, vomiting of blood, jaundice, stomatitis	Anorexia, bloody diarrhea, constipation, dyspepsia, fecal incontinence, increased activity of gamma-glutamyltranspeptidase, bleeding from the gastrointestinal tract, gingivitis, glossitis, hepatic insufficiency, melena, ulceration of the oral mucosa, candidiasis of the oral mucosa,
On the part of the organs of hematopoiesis	Anemia, blood clotting disorder, hypoprothrombinemia	Ecchymosis, decreased fibrinogen content, hypochromic anemia, leukocytosis, leukopenia, petechiae, decreased thromboplastin content
From the metabolism side	Edema, hypocalcemia, hypophosphatemia, weight gain	Acidosis, increased urea nitrogen concentration, dehydration, hyponatremia, hyperkalemia, hyperlipidemia, hypernatremia, hypervolemia, hypoglycemia, hypoproteinemia, increased lactate dehydrogenase activity, alanine aminotransferase, aspartate aminotransferase, weight loss
From the musculoskeletal system		Arthralgia, myalgia
From the nervous system	Confusion, dizziness, insomnia, drowsiness, impaired thinking, tremor	Agitation, anxiety, convulsions, depression, hallucinations, hypertension, nervousness, neuropathy, paresthesia, psychosis, speech disturbance, stupor
From the respiratory system	Apnea, bronchospasm, coughing, nosebleeds, hyperventilation, rhinitis	Hemophthisis, pulmonary edema, pharyngitis, pleural effusion, sinusitis
From the skin	Rash, incl.maculopapular, pruritus, excessive sweating	Acne, alopecia, discoloration, cutaneous nodules, ulcers, urticaria, vesulo-bullous sypic
From the sense organs	Hemorrhage in the eye	Amblyopia, deafness, tinnitus
From the genitourinary system	Hematuria	Albuminuria, dysuria, glucosuria, renal insufficiency, oliguria, incontinence, urinary retention

Overdose:

An overdose of amphotericin B can lead to cardiac arrest and respiratory depression. In case of an overdose, the administration of the drug should be stopped immediately, and such clinical parameters in the patient as a function of the kidneys, liver, heart, hematological and biochemical parameters, blood electrolytes should be carefully monitored.

Treatment of an overdose of amphotericin B should be symptomatic. There is no specific antidote. It is not removed during hemodialysis.

Interaction:

Pharmaceutically incompatible with other medicinal products. With simultaneous use with antitumor agents, nephrotoxicity and the risk of bronchospasm and lowering blood pressure increase.

When used simultaneously with glucocorticosteroids and corticotropin, the risk of hypokalemia increases, which can predispose to the development of heart disorders.

When used simultaneously with cyclosporine or tacrolimus, the nephrotoxicity of Amfocil is lower than with amphotericin B deoxycholate.

With simultaneous use with cardiac glycosides, the risk of developing hypokalemia increases, which can increase their toxicity. The concentration of potassium in the blood is monitored.

Increases the toxicity of flucytosine; Care should be taken. It is an antagonist of antifungal agents - azole derivatives (ketoconazole, miconazole, clotrimazole, fluconazole, itraconazole, etc.) Caution should be exercised when using simultaneously with nephrotoxic agents (aminoglycosides, pentamidine) because of the risk of aggravation of nephrotoxicity.

Hypokalemia, which develops amphotericin B, can enhance the effects of nondepolarizing muscle relaxants. It is required to monitor the concentration of potassium in the blood.

Special instructions:

The first dose of Amfocil should be administered under close supervision of medical personnel.

Acute post-fusion reactions (including fever, chills, hypoxia, lowering blood pressure, nausea, or tachypnea) may occur within 1-3 hours after the onset of infusion. These reactions take place more severely with the administration of the first dose and subsequently weaken. Introduction of blockers H₁-gistaminovyh receptors and glucocorticosteroids prevent or weaken such reactions.

Rapid intravenous administration of the drug is prohibited.

Despite the lower nephrotoxicity compared to amphotericin B in deoxycholate, dozolimitating nephrotoxicity with the administration of Amfocil is not excluded.

During the course, treatment should monitor the liver and kidney function, the content of serum electrolytes, conduct a general blood test with counting the leukocyte formula and control prothrombin time.

With prolonged treatment, the likelihood of toxic effects increases.

During the period of treatment, we control the patients, the general blood test, urine, control the potassium concentration in the blood, determine the functional state of the kidneys, liver, and electrocardiograms.Patients taking potassium supplements should regularly monitor the levels of potassium and magnesium in the plasma.

The administration of the drug to patients on hemodialysis is possible only after the completion of the dialysis procedure.

Back pain, which occurs periodically with intravenous administration, occurs after discontinuation of the infusion and usually does not occur again after a decrease in the rate of administration.

When anemia occurs, use of Amfocil should be discontinued.

Effect on the ability to drive transp. cf. and fur:During the use of Amfocil, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:Lyophilizate for the preparation of a solution for infusions 50 mg, 100 mg.

Packaging:50 mg of active substance per bottle (class 1 Hearth.Pharm) in volume of 20 ml, 100 mg of active substance per bottle (class 1 Hearth.Pharm) in volume of 50 ml, transparent glass, sealed with a gray stopper of butyl rubber, crimped with aluminum ring with safety plastic cover.1 bottle with instructions for use in a cardboard box.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C. After reconstitution with water, the solution is suitable for use for 24 hours at a temperature of 2-8 ° C. After diluting with 5% glucose, the solution is suitable for use for 24 hours at a temperature of 2-8 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006577/10

Date of registration:09.07.2010

Expiration Date:Unlimited

The owner of the registration certificate:Torrex Chiesi Pharma GmbHTorrex Chiesi Pharma GmbH Austria

Manufacturer: & nbsp

BEN VENUE Laboratories, Inc. USA

Representation: & nbspChiesi Pharmaceuticals Ltd.Chiesi Pharmaceuticals Ltd.

Information update date: & nbsp24.08.2017

Illustrated instructions

Instructions

Amfotsil (Amphocil)