Ampholip
Ampholip: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Ampholip
ATX code: J02AA01
Active ingredient: Amphotericin B (Amphotericin B)
Manufacturer: Bharat Serums & Vaccines, Ltd. (Bharat Sirams & Waxins Limited) (India)
Description and photo update: 2019-10-07
Prices in pharmacies: from 10,400 rubles.
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Ampholip is a systemic antifungal agent.
Release form and composition
The dosage form is a concentrate for the preparation of a solution for infusion: a yellow suspension with a precipitate, it is easily homogenized when shaken (2, 10 and 20 ml in glass vials, 1 vial together with instructions for use of Ampholip is inserted into a cardboard box).
Composition of 1 ml of concentrate:
- active substance: amphotericin B - 5 mg;
- auxiliary components: dimyristoyl phosphatidylglycerol, sodium chloride, dimyristoyl phosphatidylcholine, water for injection.
Pharmacological properties
Pharmacodynamics
The drug Ampholip is a lipid-associated form of amphotericin B (AmB).
The active substance molecule consists of two phospholipids and AMB, which is a polyene macrocyclic antibacterial agent with a broad spectrum of antifungal activity produced by Streptomyces nodosus.
Phospholipids and AMB form a complex in the form of ribbon structures that have lipophilic properties.
The mechanism of action of Ampholip is due to its ability to selectively bind to sterols (ergosterols) located in the cell membrane of a fungus sensitive to AMB. This leads to disruption of membrane permeability, which contributes to the entry of intracellular components into the extracellular space.
Depending on the sensitivity of the pathogen and the concentration in biological fluids, it has a fungicidal and / or fungistatic effect.
Ampholip is active against most fungal strains that cause mycoses, including Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Sporothrix schenckii, Mucor spp.
Some protozoa, such as Leishmania mexicana and Leishmania braziliensis, are moderately sensitive to the action of the drug.
Pharmacokinetics
The pharmacokinetics of AMB with a lipid complex differs from conventional AMB.
According to research data, the maximum plasma concentration (C max) of AMB after the administration of Ampholip is lower than after the use of traditional amphotericin B in an equivalent dose.
After the administration of Ampholip, AMB is rapidly distributed in most organs and tissues, in the cerebrospinal fluid is determined in small quantities.
With an increase in the dose of the drug, the ratio of its content in the tissues in relation to the concentration in the blood increases disproportionately. This suggests that the drug is released from tissues slowly, forming a depot. It binds to plasma proteins by 90%.
AMB is characterized by a large volume of distribution and a high level of clearance from the blood, which indicates its absorption by tissues. The same characteristics of the drug explain its relatively low AUC (area under the concentration-time curve), which is consistent with the results of preclinical studies, during which high concentrations of the drug were found in the liver and spleen.
The lower nephrotoxicity of AMB, compared with traditional amphotericin B, is due to its reduced concentration in the kidneys. This is confirmed by the results of preclinical studies on dogs, which studied the toxicity of repeated use of the drug for 2-4 weeks: it was found that the nephrotic effect of Ampholip is 8-10 times lower than that of traditional amphotericin B.
Pharmacokinetics of Ampholip is characterized by non-linear dependence.
Comparison of the kinetic parameters of the drug in whole blood after administration of Ampholip at 5 mg / kg / day for 5-7 days and amphotericin B deoxycholate at 0.6 mg / kg / day for 42 days:
- maximum concentration (μg / ml): 1.7 ± 0.8 (n = 10) 1 and 1.1 ± 0.2 (n = 5) 2;
- concentration at the end of the dosing interval (μg / ml): 0.6 ± 0.3 (n = 10) 1 and 0.4 ± 0.2 (n = 5) 2;
- AUC (μg × h / ml): 14 ± 7 (n = 14) 1, 3 and 17.1 ± 5 (n = 5) 2;
- clearance (ml / h × kg): 436 ± 188.5 (n = 14) 1, 3 and 38 ± 15 (n = 5) 2;
- apparent volume of distribution (V d) (l / kg): 131 ± 57.7 (n = 8) 3 and 5 ± 2.8 (n = 5) 2;
- the final elimination half-life (T ½) (h): 173.4 ± 78 (n = 8) 3 and 91.1 ± 40.9 (n = 5) 2;
- the amount excreted in the urine within 24 hours after the last dose (% dose): 0.9 ± 0.4 (n = 8) 3 and 9.6 ± 2.5 (n = 8) 2.
1 Data obtained from studies of patients with cytologically confirmed cancer during chemotherapy or patients with neutropenia and fungal infection (suspected or confirmed). The infusion rate was 2.5 mg / kg / h.
2 Data obtained in a study of patients with American cutaneous-visceral leishmaniasis, the drug was administered at a rate of 0.25 mg / kg / h.
3 Data obtained from patients with American cutaneous-visceral leishmaniasis. The drug was administered at a rate of 4 mg / kg / h.
The long T ½ period is probably due to the slow redistribution of AMB from tissues. Despite the slow elimination of the drug, after repeated doses, it accumulates in the blood to a small extent. The pharmacokinetic curve increases by approximately 34% from the first day after the administration of Ampholip at a daily dose of 5 mg / kg for 7 days.
It is excreted from the body very slowly through the kidneys, in active form - 2–5% of the dose received. It can be detected in urine for 7 weeks after the end of therapy.
Indications for use
Ampholip is prescribed to treat the following fungal infections:
- systemic and deep mycoses in adults and children (including premature infants with low birth weight): disseminated forms of candidiasis, disseminated cryptococcosis, cryptococcal meningitis, meningitis caused by other fungi, intestinal candidiasis, chronic mycetoma, histoplasmidomycosis, coccinosis, chromomycosis, phycomycosis, paracoccidioidosis, disseminated sporotrichosis, North American blastomycosis, hyalogyphomycosis, chronic mycetoma, fungal mycosis, invasive and disseminated aspergillosis, fungal sepsis, endophthalmitis, endocarditis, infections of the peritoneum.
- parasitic diseases: visceral leishmaniasis in adults and children (as primary therapy, including in patients with immunodeficiency), North American visceral cutaneous blastomycosis, American visceral cutaneous leishmaniasis;
- systemic mycoses in patients with immunodeficiency (including those developed against the background of anticancer therapy) and patients with AIDS (acquired immunodeficiency syndrome);
- prevention of invasive fungal infections in adults and children, including in patients with neutropenia, which is associated with malignant neoplasms or resulted from transplantation of parenchymal organs and bone marrow.
Contraindications
Absolute:
- chronic renal failure;
- diseases of the hematopoietic system (anemia, agranulocytosis);
- lactation period;
- hypersensitivity to any component of the drug.
Ampholip is used with extreme caution in agranulocytosis, amyloidosis, glomerulonephritis, diabetes mellitus (the drug contains sucrose), liver cirrhosis, hepatitis, as well as during pregnancy.
Ampholip, instructions for use: method and dosage
The drug is administered in the form of an intravenous (IV) infusion at a rate of 2.5 mg / kg / h for 30-60 minutes, if undesirable reactions occur, the administration time is increased to 90-120 minutes. Immediately before administration, a solution is prepared from the Ampholip concentrate: diluted with a 5% dextrose solution to a final solution concentration of 1 mg / ml, for children under 16 years of age and patients with cardiovascular diseases - to a concentration of 2 mg / ml.
If the duration of the infusion is more than 2 hours, the contents of the infusion bag should be stirred every 2 hours by shaking.
Before the start of treatment (just before the introduction of the first dose), the patient is tested to determine the sensitivity reaction: Ampholip at a dose of 1 mg is injected intravenously for 15-20 minutes, for the next 3 hours, the patient's clinical condition is observed every 30 minutes, and his temperature is monitored body and blood pressure. If there are no signs of hypersensitivity, the infusion is continued. AMV can cause anaphylactoid reactions, therefore, the introduction of a test dose is carried out in the presence of emergency means (including drugs to restore respiratory function and cardiac activity). Monitoring of the concentration of creatinine and electrolytes in serum is required.
With systemic mycoses, the recommended initial daily dose is 1 mg / kg of body weight, then it is gradually increased to 3 mg / kg, and in some cases - up to 5 mg / kg. If necessary, treatment begins with a daily dose of 5 mg / kg, regardless of the patient's age. The course of treatment lasts at least 14 days.
For the prevention of invasive fungal infections in patients with neutropenia caused by chemotherapy or high doses of glucocorticosteroids, Ampholip is prescribed in a daily dose of 2 mg / kg. Treatment is carried out until the level of neutrophils reaches 0.5 x 10 9 / l.
In order to prevent invasive fungal diseases during parenchymal organ transplantation, the daily dose is 1 mg / kg. The duration of therapy is 5 days.
In visceral leishmaniasis, Ampholip is prescribed in a daily dose of 1–1.5 mg / kg for 21 days or 3 mg / kg for 10 days. After the end of the therapeutic course, it may be necessary to continue therapy at a maintenance dose or to conduct repeated courses, which is due to the risk of recurrent infection.
In patients with HIV infection complicated by disseminated cryptococcosis, the recommended daily dose is 3 mg / kg. The duration of treatment is 42 days. Due to the risk of recurrence of infection after the end of the treatment course, it may be necessary to continue therapy with a maintenance dose.
The dose of Ampholip can be adjusted depending on the patient's clinical condition.
Method of preparation of solution for infusion:
- Keep the preparation at room temperature for 1–2 hours.
- Shake the bottle thoroughly to stir the sediment.
- Take the required dose using a 20 ml syringe with a needle of at least 18G.
- Replace the needle on the spitz with a 5 µm filter needle.
- Insert the needle into the infusion bag containing 5% dextrose solution and inject the concentrate.
- Shake the bag to mix the contents.
When preparing the infusion solution, aseptic rules should be followed. Do not use the solution if it contains any foreign particles. The use of microbial filters is prohibited.
Ampholip is recommended to be administered through a new dropper. When using an IV system previously installed for other purposes, the intravenous catheter must be flushed with a 5% dextrose solution.
It is forbidden to mix Ampholip with other drugs and saline solutions, including electrolytes and 0.9% sodium chloride solution.
Side effects
Against the background of antifungal therapy, the following side effects may occur:
- hematopoietic organs: often - normocytic normochromic anemia; infrequently - hemolytic anemia, blood clotting disorder, leukocytosis, thrombocytopenia, leukopenia, eosinophilia, agranulocytosis;
- urinary system: often - impaired renal function, including azotemia, hypostenuria, hypokalemia, nephrocalcinosis, renal tubular acidosis; infrequently - anuria, oliguria, acute renal failure, nephrogenic diabetes insipidus (the risk of nephrotoxicity decreases with the preliminary administration of a 0.9% sodium chloride solution, renal tubular necrosis with the administration of sodium bicarbonate);
- digestive system: often - diarrhea, nausea, decreased appetite, vomiting, gastralgia, dyspepsia, hepatotoxicity (hyperbilirubinemia, increased activity of liver enzymes); infrequently - melena, hemorrhagic gastroenteritis, jaundice, hepatitis, acute liver failure;
- respiratory system: often - tachypnea; infrequently - allergic pneumonitis, shortness of breath, pulmonary edema;
- cardiovascular system: often - lowering blood pressure; infrequently - increased blood pressure, arrhythmias (including ventricular fibrillation), changes in the electrocardiogram, heart failure, shock, cardiac arrest;
- sense organs: infrequently - tinnitus, hearing loss, diplopia, visual impairment;
- central nervous system: often - headache; infrequently - transient vertigo, peripheral neuropathy, convulsions, epileptic seizures, polyneuropathy, encephalopathy;
- allergic reactions: often - sneezing, bronchospasm, anaphylactoid-type reactions; infrequently - pruritus, rash (most often normochromic normocytic anemia), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis;
- laboratory parameters: hypomagnesemia, hyperkalemia, hypokalemia;
- local reactions: thrombophlebitis at the injection site, chemical burn;
- others: often - general weakness, weight loss, fever, arthralgia, myalgia.
Overdose
An overdose of Ampholip can cause respiratory and cardiac arrest.
Treatment is symptomatic. During the period of therapy, it is required to monitor the functions of respiration, heart, kidneys and liver, the picture of peripheral blood, the content of electrolytes in the blood. Supportive therapy is prescribed. Resuming the use of Ampholip is possible only after complete stabilization of the patient's condition.
Hemodialysis is ineffective.
special instructions
Ampholip is indicated for the treatment of predominantly progressive and life-threatening fungal infections. It should not be used for the treatment of superficial (non-invasive) mycoses.
Ampholip and the solutions used for its dilution do not contain preservatives and bacteriostatic agents; therefore, the preparation should be diluted with strict adherence to aseptic rules.
During the period of treatment, it is necessary to regularly (at least 1 time per week) carry out laboratory monitoring of the function of the hematopoietic system, kidneys and liver. Ampholip should be prescribed with extreme caution to patients receiving nephrotoxic drugs.
With prolonged treatment, the risk of developing toxic effects increases, therefore, it is necessary to periodically do a control weighing of patients, conduct a general analysis of urine and blood, as well as monitor the condition of the liver and kidneys, electrocardiogram indicators and the level of potassium in the blood. In patients receiving potassium supplements, it is necessary to regularly monitor the plasma levels of magnesium and potassium.
With intravenous administration of Ampholip, back pain may appear. It resolves when the infusion is discontinued and usually does not recur when the rate of subsequent infusions is reduced.
If anemia develops, the drug is discontinued.
No significant changes in the blood coagulation system were observed against the background of antifungal therapy. Nevertheless, the possibility of hemolysis cannot be completely ruled out.
Influence on the ability to drive vehicles and complex mechanisms
Treatment with the drug can be accompanied by side effects that affect the patient's reaction rate and ability to concentrate.
Application during pregnancy and lactation
Amphotericin B crosses the placental barrier. Adequate and strictly controlled studies on its use during pregnancy have not been conducted. Ampholip is used only in the presence of absolute indications, if the benefits of treatment for the woman outweighs the potential risks to the fetus.
It is not known whether the drug is excreted in breast milk, therefore its appointment during lactation is contraindicated. If therapy is necessary, breastfeeding should be discontinued.
Pediatric use
Ampholip is used in pediatrics according to indications, but so far there is no data confirming the safety and efficacy of the drug in newborns under 1 month of age.
Doses for children are comparable to those for adults based on body weight.
With impaired renal function
It is contraindicated to use Ampholip in chronic renal failure.
Ampholip is allowed to be prescribed to patients with nephropathy, however, during treatment, it is recommended to monitor the state of renal function at least once a week.
Patients receiving hemodialysis, the introduction of the drug should be carried out only after the dialysis procedure.
For violations of liver function
Ampholip is approved for use in patients with impaired hepatic function and concomitant invasive fungal infection, as well as in patients with immunosuppression states with a graft versus host reaction.
Use in the elderly
The dose of Ampholip for elderly patients is not adjusted.
Drug interactions
Ampholip is pharmaceutically incompatible with heparin and solutions containing electrolytes, including 0.9% sodium chloride solution. The presence of bacteriostatic additives (including benzyl alcohol) can cause the drug to precipitate (turbidity, precipitation).
Possible interaction reactions with the simultaneous use of other drugs:
- nitrofurans: synergistic action is noted;
- curariform muscle relaxants: their toxic effect is enhanced;
- theophylline, anticoagulants, sulfonylureas, flucytosine: their effects are enhanced, including toxic ones;
- ethinyl estradiol: its effect decreases, which is accompanied by the risk of developing breakthrough bleeding;
- inducers of microsomal liver enzymes (for example, phenytoin, carbamazepine, barbiturates, rifampicin): the metabolism of amphotericin B in the liver is accelerated and its effect is reduced;
- inhibitors of microsomal liver enzymes (for example, cimetidine, antidepressants, non-narcotic analgesics): the metabolic rate of amphotericin B slows down, its concentration in the blood serum increases and, as a result, toxicity increases
- nephrotoxic drugs (including aminoglycosides, pentamidine, cyclosporine): the risk of developing impaired renal function increases (contraindicated combination);
- imidazoles (including ketoconazole, itraconazole, miconazole, fluconazole, clotrimazole): development of the body's resistance to the action of amphotericin B is possible (special care should be taken);
- cardiac glycosides: their toxic effect increases, especially in patients with an initial deficiency of potassium ions in the body;
- depolarizing muscle relaxants: their muscle relaxant effect is lengthened;
- adrenocorticotropic hormone, carbonic anhydrase inhibitors, glucocorticosteroids: the risk of occurrence or increase of hypokalemia increases, which can cause the development of arrhythmias (with their simultaneous use, the electrocardiogram indices and the electrolyte composition of the blood should be monitored);
- drugs that inhibit bone marrow hematopoiesis, antineoplastic drugs, radiation therapy: the risk of anemia and other hematological disorders increases (it is necessary to monitor the electrocardiogram and electrolyte composition of the blood);
- anticancer drugs: side effects such as lowering blood pressure, bronchospasm, and nephrotoxicity are enhanced.
Analogs
Ampholip analogs are: Amphotericin B, Amphocyl, Biflurin, Vikand, Vfend, Griseofulvin, Nystatin, Pimafucin, etc.
Terms and conditions of storage
Ampholip belongs to List B drugs. Keep out of the reach of children, protected from light at a temperature of 2-8 ° C. Avoid freezing.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Ampholip
According to reviews, Ampholip is an effective antifungal agent that is used for severe systemic mycoses. The drug is generally well tolerated; it is allowed to use it to treat children.
Disorders of the digestive system are the most frequently mentioned side effects. The cost of Ampholip is generally considered high.
Price for Ampholip in pharmacies
The price of Ampholip depends on the volume of the concentrate for the preparation of the solution for infusion (5 mg / ml) in the bottle, the region of sale and the pharmacy chain selling the drug. The approximate cost of 1 bottle with a volume of 2 ml is 2,400–3650 rubles, with a volume of 10 ml - 8,000–11,150 rubles, with a volume of 20 ml - 12,900–17,600 rubles.
Ampholip: prices in online pharmacies
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Drug name Price Pharmacy |
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Ampholip 5 mg / ml concentrate for preparation of solution for infusion 20 ml 1 pc. RUB 10,400 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
