Ampholip (Ampholip)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Similar drugsTo uncover
Dosage form: & nbspconcentrate for solution for infusion
Composition:

Each ml of concentrate contains:

active substance: amphotericin B 5 mg;

Excipients: dimyristoyl phosphatidylcholine 3.4 mg dimyristoyl phosphatidylglycerol 1.5 mg sodium chloride 9.0 mg, water for injection.

Description:

Each ml of concentrate contains:

active substance: amphotericin B - 5 mg;

Excipients: dimyristoyl phosphatidylcholine 3.4 mg, dimyristoyl phosphatidylglycerol 1.5 mg, sodium chloride 9.0 mg, water for injections.

Pharmacotherapeutic group:Antifungal agent
ATX: & nbsp
  • Amphotericin B
    • Pharmacodynamics:

    Ampholytic - lipid-associated form of amphotericin B.

    The molecule of the active substance of the preparation Ampholip consists of two phospholipids and amphotericin B (AmB), which is a polyene macrocyclic antibiotic with broad-spectrum antifungal activity produced by Streptomyces nodosus. Phospholipids and amphotericin B form a complex in the form of band structures possessing lipophilic properties. The mechanism of action of amphotericin B is based on its selective ability to bind to sterols (ergosterols) located in the cell membrane of the amphotericin B sensitive fungus. As a result, the permeability of the membrane is disturbed, and intracellular components enter the extracellular space.It is active against most strains of fungi-mycosis activators including Candida spp., Cryptococcus neoformans, Aspergillus spp., Mucor spp., Sporothrix schenckii, Blastomyces dermatidis, Coccidioides immitis, Histoplasma capsulatum. Moderately active against some protozoa: Leishmania braziliensis, Leishmania mexicana.

    Pharmacokinetics:

    The pharmacokinetics of the usual amphotericin B and amphotericin B with the lipid complex are different. Studies have shown that the maximum concentration of Amphotericin B in the blood was lower after administration of Ampholip than after the administration of an equivalent amount of a traditional preparation. Amphotericin B, which is part of the molecule of the drug Ampholip, is quickly distributed into tissues. With increasing dose, the ratio of drug concentration in tissues to concentrations at blood increased disproportionately, which suggested a delayed release of the drug from the tissues and the formation of a "depot". The large volume of distribution and the high level of clearance of amphotericin B from the blood after the administration of Ampholip reflects its absorption by tissues.

    Smaller nephrotoxicity is due to a lower concentration of AmB in the kidneys. Preclinical studies of the toxicity of multiple doses (mg / kg, for 2-4 weeks)that the nephrotoxic effect of Ampholip was 8 to 10 times lower than when treated with the traditional Amphotericin B preparation, due to the lowest concentration of the drug in the kidneys.

    The relatively low AUC (area under the concentration-time curve) is associated with a rapid clearance and a large volume of Ampholip distribution, which also agrees with the results of preclinical studies in which high concentrations of the drug in the tissues (spleen, liver) were shown. The kinetics of the Ampholip is characterized by a nonlinear dependence. Pharmacokinetics of amphotericin B in whole blood after administration of drugs Ampholip and amphotericin B deoxycholate is as follows:

    Pharmacokinetic parameters of amphotericin B in whole blood in patients who were repeatedly injected with Ampholip or Amphotericin B deoxycholate

    Pharmacokinetic index

    Ampholip 5 mg / kg / day for 5-7 days Average ± SD

    AmB 0.6 mg / kg / day for 42 daysa

    Average ± SD

    Maximum concentration (μg / ml)

    1,7 ±0,8 (n=10)b

    1,1 ±0,2 (n=5)

    Concentration at the end of the interval

    dosing (μg / ml)

    0,6 ±0,3 (n=10)b

    0,4 ±0,2 (n=5)

    Area under the pharmacokinetic curve (AUC 0-24h under the FCC) (μg * h / ml)

    14,0 ±7,0 (n=14)b, c

    17,1 ±5 (n=5)

    Clearance (ml / h * kg)

    436,0 ± 188,5 (n=14)b, c

    38,0 ±15,0 (n=5)

    Apparent volume of distribution (area Vd) (l / kg)

    131,0 ±57,7 (n=8)from

    5,0 ±2,8 (n=5)

    Finite

    Elimination half-life (h)

    173,4 ± 78 (n=8)from

    91,1 ±40,9 (n=5)

    The amount excreted in the urine within 24 hours after the last dose (% dose)d

    0,9 ± 0,4 (n=8)from

    9,6 ±2,5 (n=8)

    a Data obtained in patients with American skin-visceral leishmaniasis. The infusion rate was 0.25 mg / kg / h.

    b Data were obtained in a study of patients with cytologically confirmed cancer during chemotherapy, or in patients with neutropenia and suspected or confirmed fungal infection.

    The infusion rate was 2.5 mg / kg / h.

    from The data were obtained on patients with American skin-visceral leishmaniasis. The infusion rate was 4 mg / kg / h.

    d Percentage of dose excreted within 24 hours after the last dose.

    A prolonged period of the final elimination half-life probably reflects a slow redistribution from the tissues. Although amphotericin B is excreted slowly, it accumulates very little in the blood after repeated doses. The pharmacokinetic curve of amphotericin B increases approximately 34% from the first day after the administration of lipid-associated amphotericin B at a dose of 5 mg / kg / day for 7 days.

    Indications:Fungal infections: disseminated cryptococcosis, cryptococcal meningitis; meningitis caused by other fungi, invasive and disseminated aspergillosis, North American blastomycosis, disseminated forms of candidamycosis, intestinal candidosis, coccidioidosis, paracoccidioidosis, histoplasmosis, ficomycosis, chromomycosis, moldy mycosis, disseminated sporogrhosis, hyalogomycosis, chronic mycetoma, infections of the abdominal cavity including peritonitis), endocarditis, endophthalmitis, fungal sepsis, fungal infections of the urinary tract. Visceral leishmaniasis (as a primary therapy, including in patients with immunodeficiency), American skin-visceral leishmaniasis.
    Contraindications:Hypersensitivity, chronic renal failure, lactation.
    Carefully:Glomerulonephritis, amyloidosis, hepatitis, liver cirrhosis, anemia, agranulocytosis, diabetes, pregnancy.
    Dosing and Administration:

    The drug should be administered as an intravenous infusion at a dose of 5 mg / kg / day, at a rate of 2.5 mg / kg / h. The drug Ampholip is recommended to dilute 5% solution of dextrose for injection.The solution ready for intravenous administration should have a concentration of 1 mg / ml.

    - Before using Ampholip, a test dose should be taken to determine the patient's reaction. The procedure is performed immediately before the first infusion. Since all the products of Amphotericin B may develop anaphylactoid reactions, infusion of the drug Ampholip is recommended if there are funds for restoring cardiac activity and breathing.

    Test - a dose of 1.0 mg of the drug is administered intravenously infusion, for 15-20 minutes. After stopping the infusion every 30 minutes for 3 hours observe the clinical condition of the patient, monitor blood pressure, body temperature. In the absence of signs of hypersensitivity to the components of the drug, infusion can be continued. It is necessary to monitor the concentration of creatinine and electrolytes in the blood serum.

    -In confirmed systemic fungal infections, regardless of the patient's age, therapy is usually started at a dose of 5 mg / kg per day, at least 14 days. If the infusion lasts more than 2 hours, it is recommended to mix the contents of the infusion set by shaking it every 2 hours.

    Depending on the clinical state of the patient, dosage adjustment is possible.

    The experience of using Ampholip for 1 1 months in a cumulative dose of 56.6 g did not reveal significant toxicity.

    Use in special patient groups

    Pediatric use: the drug Ampholip is prescribed in doses comparable to the doses recommended for adult patients in terms of body weight. At present, there are no data on the safety and efficacy of Amfolip in children under 1 month of age.

    Use in patients over 65 years of age: dosage adjustment when prescribing Ampolip is not required, the drug is prescribed in a dose of 5 mg / kg / day.

    Use in patients with neutropenia:

    Ampholip can be used in patients with severe neutropenia associated with neoplasms of the hematopoietic system or with the use of cytostatics and immunosuppressants.

    Use in patients with kidney disease

    The drug Ampholip can be used in patients with nephropathy, during the period of drug therapy it is recommended to monitor kidney function at least once a week.

    Patients who are on hemodialysis drug Ampholip is recommended to enter after the procedure of dialysis.

    Use in patients with liver disease

    The drug Ampholip can be used in patients with impaired liver function in an invasive fungal infection, also under conditions of immunosuppression with the "graft versus host" reaction.

    Method of solution for infusion:

    - Immediately before use, the drug should be stored for 1-2 hours at room temperature. To prepare a solution for infusion, the vial must be shaken carefully - until the precipitate disappears, take the necessary dose of the drug with a 20 ml syringe with a needle gauge of at least 18G. Needles with a syringe filled with Ampholip preparation, it is recommended to replace, on a filtering needle 5 microns. The filter needle is inserted into an infusion bag containing a 5% dextrose injection solution, the contents of the syringe are introduced into the bag. After the infusion set is shaken until the contents are completely mixed. A ready-made solution for intravenous use should have a concentration of 1 mg / ml.

    - For patients with cardiovascular diseases and patients under 16, the drug is diluted with a solution of 5% dextrose to an infusion solution concentration of 2 mg / ml.

    Precautionary measures:

    - Do not use infusion solution in the presence of any foreign particles.

    - When preparing the solution for infusion, it is recommended to strictly follow the rules of asepsis.

    Before using, use the intravenous catheter with a 5% dextrose solution or use a new dropper.

    - Do not use microbial filters.

    Do not mix with other medicinal products, with saline solutions, including 0.9% sodium chloride solution or electrolytes!

    Side effects:

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

    From the nervous system: often - headache; infrequently - convulsions, transient vertego, peripheral neuropathy, encephalopathy. Polyneuropathy, epileptic seizures.

    From the sense organs: infrequent - impaired vision, diplopia; loss of hearing, tinnitus.

    On the part of the organs of hematopoiesis: often - normochromic normocytic anemia; infrequently - agranulocytosis, clotting disorder, leukopenia, hemolytic anemia, thrombocytopenia, eoenophilia, leukocytosis.

    From the side of the cardiovascular system: often - lowering blood pressure; infrequent - arrhythmias, including ventricular fibrillation, changes in the electrocardiogram, 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, incl. azotemia, hypokalemia, hypostenuria, renal tubular acidosis, nephrocalcinosis; infrequently - acute renal failure, ol and huria, anuria, nephrogenic diabetes insipidus. Preliminary introduction of 0.9% sodium chloride solution reduces the risk of nephrotoxicity, the introduction of sodium bicarbonate - the risk of renal tubular necrosis.

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

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

    Other: often - fever, weight loss, myalgia, arthralgnia, general weakness.

    Laboratory indicators: hypokalemia, hyperkalemia, hypomagnesemia.

    Overdose:

    Symptoms: cardiac arrest and respiration.

    Treatment: symptomatic. It is necessary to monitor cardiac and respiratory activity, liver and kidney function, peripheral blood and electrolyte content, and prescribe maintenance therapy. It is not removed during hemodialysis. Before the resumption of treatment, the patient's condition should be stabilized.

    Interaction: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. Synergy with nitrofurans. Increases the effect and toxicity of anticoagulants, theophyllium and preparations of sulfonylurea, flucytosine (prolongs T1 / 2); reduces the effect of ethinyl estradiol - the risk of bleeding "breakthrough". Inhibitors of microsomal liver enzymes (incl. cimetidine, non-narcotic analgesics, antidepressants) slow down metabolic rate, increase serum concentration (increase in toxicity).Inductors of microsomal liver enzymes (incl. phenytoin, rifampicin, barbiturates, carbamazepine) accelerate metabolism in the liver (decreased effect). Increases the toxic effect of cardiac glycosides (especially against the background of the initial deficiency of potassium ions in the body) and curare like muscle relaxants. Glucocorticosteroids, inhibitors of carbonic anhydrase, adrenocorticotropic hormone increase the risk of hypokalemia. It is impossible to prescribe concomitantly with nephrotoxic drugs (am and notes and goats, ciclosporin, pentamidine and others) - the risk of kidney dysfunction is increasing. Antineoplastic drugs, radiation therapy and drugs that depress bone marrow hematopoies increase the risk of anemia and other hematological disorders. Antitumor drugs increase nephrotoxicity, bronchospasm and lower blood pressure. Glucocorticosteroids and corticotropin strengthen hypokalemia, which can lead to the development of arrhythmias. If it is necessary to prescribe these medicines at the same time, electrolyte blood composition and an electrocardiogram should be monitored.Amphotericin B may increase the toxicity of cardiac glycosides (due to hypokalemia). Simultaneous 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 administered with caution. It is not possible to appoint simultaneously with nephrotoxic drugs (aminoglycosides, ciclosporin, pentamidine, etc.) - the risk of kidney dysfunction is increasing. Lengthens the muscle relaxant effect of depolarizing muscle relaxants.
    Special instructions:

    With prolonged treatment, the likelihood of toxic effects increases. During the period of treatment, the patients should be weighed, the general blood test, urine, potassium level in the blood, determine the functional state of the kidneys, liver, and electrocardiograms. Patients taking potassium supplements should regularly monitor the level 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.

    All procedures with the solution should be carried out with strict adherence to the rules of aseptic, 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, the system should be rinsed with 5% glucose solution for injection. When anemia occurs, the drug should be discontinued.

    Amphotericin B should be used primarily for the treatment of progressive and life-threatening fungal infections. It should not be used for the treatment of non-invasive (superficial) mycoses.

    Form release / dosage:Concentrate for the preparation of solution for infusions 5 mg / ml.
    Packaging:In glass bottles of 2 ml, 10 ml, 20 ml. Each vial is in a cardboard box with a nested instruction for medical use.
    Storage conditions:

    In the dark place at a temperature of 2 to 8 ° C. Do not freeze. Keep out of the reach of children.

    List B.

    Shelf life:3 years.Do not use after the expiry date, packaging.
    Terms of leave from pharmacies:On prescription
    Registration number:П N015503 / 01
    Date of registration:09.12.2009 / 26.11.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:Bharat Searms & Waxings LimitedBharat Searms & Waxings Limited India
    Manufacturer: & nbsp
    Representation: & nbspFirm EUROSERVICE, CJSCFirm EUROSERVICE, CJSCRussia
    Information update date: & nbsp24.08.2017
    Illustrated instructions
      Instructions
      Up