Proleukin (Proleukin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAldesleikinAldesleikin
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  • Proleukin
    lyophilizate in / in PC 
    Novartis Pharma AG     Switzerland
    • Dosage form: & nbsplyophilizate for the preparation of solution for intravenous and subcutaneous administration
    Composition:

    Active substance

    Each vial with a lyophilizate for the preparation of a solution contains 22 million ME aldesleukin. After dilution in 1.2 ml of water for injection, 1 ml contains 18 million ME aldesleukin.

    Excipients

    Mannitol - 50 mg, sodium dodecyl sulfate - 130-230 mcg, monosodium phosphate monohydrate - 0.173 mg, disodium phosphate - 0.893 mg, nitrogen.

    Description:

    Amorphous lyophilized white powder.

    Pharmacotherapeutic group:Interleukins
    ATX: & nbsp

    L.03.A.C   Interleukins

    Pharmacodynamics:

    Aldesleykin is a recombinant human interleukin-2 (rIL-2), a protein with a molecular weight of about 15,600 daltons, obtained by recombinant DNA technology, using a strain E.solicontaining a modified human IL-2 gene.

    Antineoplastic, immunomodulating agent of the group of cytokines. The recombinant form of human IL-2 has a number of structural differences from natural IL-2 (not glycosylated, has no terminal alanine,in the 125th amino acid position, cysteine ​​is substituted for serine), but has a similar biological activity; stimulates the body's immune defense; activates T-lymphocytes and natural killers, involved in the mechanisms of recognition and destruction of tumor cells. Recombinant IL-2 promotes the production of antibodies by B cells, stimulates the secretion of cytokines (such as gamma interferon, tumor necrosis factor, interleukin-1, granulocyte-macrophage colony stimulating factor), stimulates complement factors, and triggers hormone release mechanisms (ACTH, cortisol ). The exact mechanism of antitumor activity in aldesleukin-mediated immunostimulation has not been fully elucidated.

    Pharmacokinetics:

    Suction and distribution

    Pharmacokinetic profile of the preparation

    Proleukin is characterized by a high concentration of the drug and blood plasma after a short intravenous (iv) injection followed by rapid distribution in the extravascular space. After subcutaneous administration, the maximum concentration in the blood plasma is reached after 2-6 hours.

    Biotransformation: metabolism and elimination

    The curve of the half-life (T1/2) In the blood serum of aldesleukin with a / in the introduction of the jet is biexponential character. T1/2 αphase is 13 minutes, T1/2 β-phases - 85 minutes. In the α-phase, about 87% of the bolus dose is excreted. The concentration of aldesleukin in the blood is proportional to the administered dose.

    When administered subcutaneously pharmacokinetics can be described using a one-compartment model, and the half-life of 5.3 hours. A longer half-life compared to on / in the introduction is explained continuing absorption of the drug from subcutaneous tissue at the injection site during the elimination phase from plasma.

    Absolute systemic bioavailability after subcutaneous administration is more than 35%.

    The drug is derived primarily by the kidneys, with a large fraction of the dose is metabolized by the kidneys, resulting in not found biologically active in urine aldesleukin. The secondary pathway is the receptor-mediated capture by target cells. This process is activated with a long course of therapy. In the periods between the courses of therapy, the clearance of IL-2 is restored to the initial values.

    The average release rate of Proleukin in patients with cancer varies from 155 to 420 ml / min.

    Immunogenicity

    In the study, 57 out of 77 (74%) patients with metastatic renal cell carcinoma and 33 out of 50 (66%) patients with metastatic melanoma who received IV treatment with various regimens of therapy showed low titres of non-neutralizing anti aldesleukin antibodies. Neutralizing antibodies in these patients were not detected. Neutralizing antibodies were detected only in 1 out of 106 (<1%) patients who received IV treatment with a drug with different regimens and dosing regimens. The clinical significance of anti-aldesleukin antibodies is unknown.

    Special patient groups

    Patients with impaired renal function

    Studies of pharmacokinetics in patients with impaired renal function. Pharmacokinetics of the drug Proleukin after iv injection of IL-2 was studied in 15 patients with oncological diseases, which showed a toxic effect of the drug on the kidneys. The creatinine clearance in such patients decreased after repeated injections of IL-2. Decrease in the clearance of creatinine ns led to a decrease in IL-2 clearance.

    Elderly patients (≥ 65 years old)

    In clinical trials of Proleukin, a small number of patients over 65 years of age participated. The therapeutic response in these patients was comparable to that in younger patients. Hc also differed in the average number of courses of therapy and the average number of doses per each course. However, due to the fact that special studies comparing the pharmacokinetics, efficacy and safety of Proleukin in elderly and young patients have not been conducted, caution should be exercised in elderly patients, since the risk of kidney and liver dysfunction increases with age . In addition, elderly patients may be more prone to developing side effects of Proleukin.

    Indications:

    Metastatic melanoma

    Metastatic Renal Cell Carcinoma

    Contraindications:

    Hypersensitivity to any of the components of the drug.

    Assessment of the general state of the scale ECOG* ≥ 2.

    The simultaneous presence of 3 risk factors associated with a lower response rate and a decrease in life expectancy: an assessment of the overall status of the scale ECOG* ≥ 1 and the presence of metastases in more than one organ, as well as a period of less than 24 months from the date of diagnosis (primary tumor) prior to the initiation of aldesleukin therapy.

    Patients with allograft of any organ.

    Decompensated diseases of the cardiovascular system, including in the anamnesis (in doubtful cases it is necessary to conduct special diagnostic tests, for example, with a load on the treadmill, scintigraphy with thallium, etc.).

    Acute infectious diseases requiring antibiotic therapy.

    Respiratory failure (oxygen partial pressure index (PaO)2) <60 mm Hg. Art. at rest).

    The presence of metastatic foci in the central nervous system (CNS) or epileptic seizures in the anamnesis, except for patients with brain metastases with a positive dynamics in the background of treatment (no deterioration in the results of computed tomography, stable neurological status).

    Oppression of bone marrow hematopoiesis: leukopenia <4000 / μL, thrombocytopenia <100,000 / μL, anemia (hematocrit <30%).

    Increase in the concentration of bilirubin and creatinine in serum.

    Simultaneous use of glucocorticosteroids.

    Autoimmune diseases.

    Pregnancy and the period of breastfeeding (safety not established).

    Age to 18 years (safety and efficacy not established).

    * ECOG (Eastern cooperative oncological group): 0 - normal activity of the patient; 1 = presence of symptoms in an outpatient patient; 2 = bed rest less than 50% of the time; 3 = bed rest more than 50% of the time, limited ability to self-service; 4 = complete inoperability, lack of ability to self-service.

    Carefully:

    Care should be taken when using Proleukin in elderly patients.

    Dosing and Administration:

    For subcutaneous and intravenous administration.

    For the treatment of metastatic kidney cell cancer, Proleukin is used in the form of continuous IV infusions or subcutaneous injections, as well as IV bolus in high doses.

    For the treatment of metastatic melanoma, Proleukin is used in the form of continuous intravenous infusions, as well as IV bolus in high doses.

    Bolus administration of high doses of Proleukin

    0.6 x 106 IU / kg (0.037 mg / kg) as a 15-minute IV infusion every 8 hours (for 5 days), no more than 14 infusions followed by a break for 5-9 days. The second cycle of infusions is carried out according to the indicated scheme, no more than 14 doses. The course of treatment consists of two cycles of IV bolus infusions for 5 days. In total, no more than 28 doses per course, depending on the tolerability of the drug.

    During clinical trials, the number of doses was limited to toxicity. For patients with metastatic renal cell carcinoma, who received the drug in accordance with this regimen during the first course of treatment, the average number of doses was 20-28 doses, for patients with metastatic melanoma - 18-28 doses.

    To assess the effectiveness of therapy should be screened 4 weeks after the end of the course of therapy, as well as immediately before the subsequent course of treatment. Repeated course of therapy with Proleukin should be performed in patients with signs of tumor regression in the absence of contraindications against the background of the previous course of therapy. The interval between therapy courses should be at least 7 weeks.

    Dosing regimen for subcutaneous administration

    18 x 106 ME subcutaneously (i / k) daily for 5 days, followed by a 2-day break.For the next 3 weeks, 18 x 106 ME PC on days 1 and 2 of each week and 9 x 106 ME at 3, 4 and 5 days of the week. After a one-week break, repeat the same 4-week cycle. The cycle of maintenance therapy (18 x 106 IU / m2 in the form of injections) should be performed in patients with positive dynamics or stabilization of the tumor process.

    Dosing regime with continuous in / in injection

    18 x 10 IU / m2 in the form of a 24-hour continuous intravenous infusion for 5 days, followed by a 2-6 day break. Within the next 5 days, the drug is administered according to a similar scheme followed by a 3-week break. Together, this represents one induction therapy cycle. After the 3-week break, a second induction therapy cycle is performed. Supporting cycles (18 x 106 IU / m2 in the form of a 24-hour IV infusion for 5 days) with 4-week intervals is recommended in patients with positive dynamics or stabilization of the tumor process (a total of up to 4 cycles).

    Correction of the dosing regimen (SC and IV)

    If the drug is intolerant, reduce its dose or stop treatment until the disappearance of toxic effects.

    Patients with impaired renal function

    No studies have been conducted to assess the pharmacokinetics, safety and tolerability of the drug in patients with impaired renal function. Patients with impaired renal function should be under constant supervision. Metabolism and excretion of other drugs may change with their simultaneous use with Proleukin.

    Patients with impaired hepatic function

    No studies have been conducted to evaluate the pharmacokinetics, efficacy and tolerability of the drug in patients with impaired hepatic function. The use of the drug Proleukin can lead to a transient increase in the activity of "liver" transaminases, an increase in the concentration of bilirubin, creatinine and uric acid in the blood plasma. Patients with impaired liver function should be under constant supervision.

    Application in elderly patients (> 65 no)

    No clinical studies have been conducted to evaluate the efficacy and tolerability of Proleukin in elderly patients. It is recommended to use with caution the drug Proleukin in elderly patients, since the likelihood of developing violations of kidney and liver function increases with age.

    Children and adolescents (under 18 years of age)

    Safety and efficacy of Proleukin in the treatment of children and adolescents is finally established.

    Preparation of the drug solution

    The contents of the vial are dissolved in 1.2 ml of water for injection, while water should be directed to the wall of the vial to avoid pricing. The contents of the vial should be mixed gently, carrying out circular movements with a vial, until the lyophilizate is completely dissolved.

    Do not shake the bottle.

    The resulting solution is a colorless transparent liquid with a pH of 7.5 (ranging from 7.2 to 7.8). The drug is ready for administration or can be further diluted to prepare an infusion solution.

    The prepared solution (obtained by dissolving the contents of the vial into 1.2 ml of water for injection) is stable for 48 hours when stored in a refrigerating chamber and at room temperature (2 ° C to 30 ° C). Due to the fact that the product contains preservatives. it is recommended to use the solution immediately after preparation.

    To prepare an infusion solution, the daily dose of the prepared drug Proleukin is diluted in 500 ml of a 5% dextrose solution containing 0.1% human albumin.The resulting solution is injected infusion for 24 hours.

    The addition of human albumin, which is necessary to preserve the biological activity of the drug, to the solution of dextrose should be carried out before adding a solution of the drug Proleukin.

    Before the introduction, the prepared solution should be brought to room temperature and visually inspected for the absence of mechanical inclusions and discoloration. The solution may have a yellowish gauze.

    The prepared solution is intended for single use only (does not contain preservatives). Any unused solution or opened bottle should be disposed of in accordance with the requirements for the handling of biologically hazardous preparations.

    For intravenous administration of the drug Proleukin, do not use infusion systems with built-in filters.

    Preparation of a bolus length solution

    The required dose of Proleukin solution, prepared with sterile water for injection, is diluted in 50 ml of 5% sterile dextrose solution. The resulting solution should be injected 15 minutes after preparation.

    Contraindicated in the use of bacteriostatic water for injection or 0.9% sodium chloride solution for the preparation or dilution of the finished solution of the drug Proleukin in connection with increased aggregation. Prolatekin should not be administered through a common system with other drugs.

    Side effects:

    The frequency and severity of the adverse events (AEs) of the Proleukin drug depend on the dose and dosage regimen. It should be noted that most AEs are reversible and disappear after 1-2 days of interruption in treatment. The incidence of deaths associated with treatment in patients with metastatic renal cell carcinoma who received monotherapy with Proleukin was 4% (11 of 255). With subcutaneous administration of the drug, the mortality from side effects of therapy with Proleukin was less than 1%. The incidence of deaths associated with treatment in patients with metastatic melanoma who received Proleukin monotherapy was 2% (6 of 270).

    The adverse events (AEs) detected in clinical trials are grouped according to the classification of organs and organ systems MedDRAare listed in order of decreasing frequency of occurrence.

    To estimate the frequency of occurrence, the following criteria were used: "very often" (≥1 / 10); "often" (≥1 / 100, <1/10); "infrequently" (≥1 / 1000, <1/100); "rarely" (≥1 / 10,000, <1/1000); "very rarely" (≥1 / 10000), including individual messages. Since in postmarketing period, reports of AEs are received voluntarily from a population of undetermined size, it is not possible to reliably estimate the frequency of their occurrence, and for this reason, "frequency is unknown". Within each group allocated according to frequency of occurrence, AEs are distributed in order of decreasing their clinical significance.

    Infectious and parasitic diseases: often - respiratory infections, sepsis.

    Violations from the blood and lymphatic system: very often - leukopenia, anemia, thrombocytopenia; often - disorders of the blood coagulation system, eosinophilia; infrequently - neutropenia; rarely - agranulocytosis, febrile neutropenia; frequency unknown - disseminated intravascular coagulation syndrome, aplastic anemia, hemolytic anemia.

    Immune system disorders: infrequently - hypersensitivity reactions; frequency unknown - anaphylactic reactions.

    Disorders from the endocrine system: very often - hypothyroidism; often hyperthyroidism.

    Disorders from the metabolism and nutrition: very often - anorexia; often - acidosis, hyperglycemia, hypercalcemia, hypocalcemia, hyperkalemia, dehydration; infrequently - hypoglycemia; rarely - diabetes.

    Disorders of the psyche: very often - anxiety, confusion, depression, insomnia; often - irritability, agitation, hallucinations.

    Impaired nervous system: very often - dizziness, headache, paresthesia, drowsiness; often - neuropathy, syncope, speech disturbance, loss of taste sensations, lethargy; infrequently - coma, convulsions, paralysis, myasthenia gravis; frequency unknown - intracranial hemorrhage, cerebral hemorrhage, leukoencephalopathy.

    Disorders from the side of the organ of vision: often - conjunctivitis; infrequently - the pathology of the optic nerve, including neuritis.

    Heart Disease: very often - sinus tachycardia, arrhythmia; often - cyanosis, transient changes in the electrocardiogram (ECG), myocardial ischemia, palpitations, cardio-vascular disorders, including heart failure; infrequently - myocarditis, cardiomyopathy,cardiac arrest, effusion to the pericardial cavity; rarely - ventricular hypokinesia; frequency unknown - cardiac tamponade.

    Vascular disorders: very often - lowering blood pressure; often - inflammation of the veins, increased blood pressure; infrequently - thrombosis, thrombophlebitis, hemorrhage.

    Disturbances from the respiratory system, chest and mediastinal organs: very often - shortness of breath, cough; often - pulmonary edema, effusion to the pleural cavity, hypoxia, hemoptysis, epistaxis, nasal congestion, rhinitis; frequency unknown - adult respiratory distress syndrome, pulmonary embolism.

    Disorders from the gastrointestinal tract: very often - nausea with / without vomiting, diarrhea, stomatitis; often - dysphagia, dyspepsia, constipation, gastrointestinal bleeding, including bleeding from the rectum, vomiting of blood, ascites, cheilitis, gastritis; infrequently - pancreatitis, intestinal obstruction, perforation of the gastrointestinal tract, including necrosis / gangrene; frequency unknown - exacerbation of Crohn's disease.

    Disorders from the liver and bile ducts: often - increased activity of "hepatic" transaminases, increased alkaline phosphatase and lactate dehydrogenase activity in blood plasma, hyperbilirubinemia, hepatomegaly or hepatosplenomegaly; rarely - liver failure (fatal); frequency unknown - cholecystitis.

    Disturbances from the skin and subcutaneous tissues: very often erythema and / or rash, exfoliative dermatitis, prurigo, increased sweating; often - hives, alopecia; the frequency is unknown - vitiligo, Quincke's edema, vesicle-bullous rash, Stevens-Johnson syndrome.

    Disturbances from the musculoskeletal and connective tissue: often - myalgia, arthralgia; infrequently - myopathy, myositis.

    Disorders from the kidneys and urinary tract: very often - oliguria, an increase in the concentration of creatinine and urea in the blood plasma; often - hematuria, kidney failure, anuria.

    General disorders and disorders at the site of administration: very often - reactions in place administration *, pain at the injection site, fever with / without chills, malaise, fatigue and weakness, pain, swelling, weight gain; often - inflammation of the mucous membranes, decrease in body weight; infrequently - hypothermia; rarely - necrosis at the injection site.

    * - The incidence of pain, inflammation and other reactions at the site of administration decreases with intravenous administration.

    Syndrome of increased permeability of capillaries

    Heart rhythm disturbances (supraventricular and ventricular arrhythmia), stress angina, myocardial infarction, respiratory failure, gastrointestinal bleeding or ischemia, renal failure, edema and mental status disorders may be associated with capillary hypertension syndrome. The frequency of development and severity of the syndrome of increased permeability of capillaries is lower with subcutaneous administration compared with prolonged intravenous administration of the drug Proleukin.

    Severe manifestations of eosinophilia

    During treatment, most patients develop lymphocytopenia and eosinophilia, followed by, within 24-48 hours, the development of lymphocytosis. These changes may be related to the mechanism of the antitumor effect of Proleukin. There have been cases of the development of severe eosinophilia, accompanied by eosinophilic infiltration of cardiac and pulmonary tissue. Cerebrovascular

    There are cases of development of cerebrovascular disease, both isolated and combined with other undesirable phenomena. There are reports of skin and leukocytoclastic vasculitis. In some cases, these conditions are amenable to glucocorticosteroid therapy.

    Bacterial infections

    Bacterial infections or worsening of their course, including septicemia, bacterial endocarditis, septic thrombophlebitis, peritonitis and pneumonia occur more frequently on the background of intravenous administration.

    Leukoencephalopathy

    There are isolated literature data on leukoencephalopathy associated with the use of interleukin-2, mainly in patients treated with the drug for other indications. The role of interleukin-2 in the development of leukoencephalopathy remains unclear. Nevertheless, opportunistic infections, simultaneous use of several interferons, a large number of chemotherapy courses and other factors can predispose to the development of leukoencephalopathy.

    Overdose:

    Side effects of the drug Proleukin are dose-dependent, so if the recommended dose is exceeded, we should expect a more pronounced manifestation of them.After discontinuing therapy with Proleukin, the side effects regress, the persistent manifestations require symptomatic treatment. Dangerous for life toxic effects can be reduced by intravenous administration of dexamethasone, which, however, may lead to a decrease in the effectiveness of therapy with Proleukin.

    Interaction:

    The following combinations are not recommended

    Antineoplastic agents

    With the simultaneous use of the drug Proleukin with cisplatin, vinblastine, dacarbazine, the development of a fatal complication - tumor lysis syndrome - has been reported, so the simultaneous use of these drugs with Proleukin is not recommended. In patients receiving the combined regimens of high doses of Proleukin and antitumor drugs, in particular dacarbazine, cisplatin, tamoxifen and interferon alfa, hypersensitivity reactions were noted that were manifested by erythema, pruritus, and blood pressure lowering and developed several hours after chemotherapy. In some patients, these reactions required drug treatment.

    Glucocorticosteroids

    The simultaneous use of the drug Proleukin with glucocorticosteroids can lead to a decrease in the effectiveness of the drug Proleukin, so this combination should be avoided. However, for life indications, you can combine Proleukin with dexamethasone if the toxicity does not exceed an acceptable level.

    Radiopaque means

    The use of radiopaque agents after a course of therapy with Proleukin may lead to the re-emergence of toxic phenomena noted during the use of the drug. More often, similar conditions are observed within 2 pedl after the last dose of the drug, but it is possible to develop them within a few months after the end of therapy. Avoid the use of radiopaque substances within 2 weeks after using Proleukin.

    Combinations that require caution

    Preparations with hepatotoxic, nephrotoxic, myelotoxic or cardiotoxic action

    The simultaneous use of drugs that have hepatotoxic, nephrotoxic, myelotoxic or cardiotoxic effects, with Proleukin can enhance the toxic effects of the latter.It is necessary to use these drugs with care with Proleukin with regular monitoring of the functions of these systems and organs.

    Preparations, affecting the central nervous system

    The drug Proleukin can influence the function of the central nervous system, and, thus, disrupt the therapeutic response to psychotropic drugs.

    Antihypertensive drugs

    Antihypertensive drugs, including beta-blockers, increase the hypotensive effect of Proleukin. The simultaneous use of Proleukin with antihypertensive drugs requires regular monitoring of blood pressure.

    Incompatibility

    Violation of the procedure for preparing the solution and its dilution can lead to a decrease in the biological activity of the preparation and / or the formation of a biologically inactive protein. Hc should use bacteriostatic water for injection or 0.9% solution of sodium chloride to prepare the drug solution (these solutions promote the aggregation of the substance).

    Do not mix Proleukin with other medicinal substances.

    Special instructions:

    Syndrome of increased permeability of capillaries

    One of the undesirable phenomena of the drug is the syndrome of increased capillary permeability, characterized by a decrease in the vascular tone, the release of plasma proteins of blood and fluid into the extravascular space. The syndrome of increased vascular permeability is accompanied by a decrease in arterial pressure, tachycardia and a decrease in organ perfusion, in some cases with a fatal outcome. The incidence and severity of this complication is less after subcutaneous administration of the drug than after intravenous infusion.

    The syndrome develops in the next few hours after the beginning of therapy with Proleukin, a clinically pronounced hypotension is reported to develop 2 to 12 hours after drug administration. It is necessary to monitor the parameters of the function of the cardiovascular and respiratory systems, especially in patients receiving Proleukin IV. In some patients, it is possible to resolve arterial hypotension without appropriate treatment. Under other conditions, intravenous infusion solutions are indicated. In other cases, the introduction of low doses of catecholamines is indicated to normalize blood pressure and to ensure normal perfusion of internal organs.Long-term use of catecholamines or use in higher doses can lead to heart rhythm disturbances.

    Before / in the management of infusion solutions should be evaluated the ratio of the expected benefit of increasing the volume of intravascular fluid and the risk of secondary pulmonary edema, ascites, effusion into the pleural cavity and pericardial cavity on the background of increased capillary permeability. If the treatment is ineffective, therapy with Proleukin should be stopped.

    Serous exudate

    The drug Proleukin stimulates the secretory processes of serous membranes, contributing to an increase in the volume of effusion in the serous cavities. In this regard, before the beginning of therapy with Proleukin, measures should be taken to prevent conditions accompanied by an increase in the amount of effusion in the serous cavities, especially that localization, an increase in the amount of effusion in which may lead to inadequate function of vital organs (eg, pericardial effusion or in the pleural cavity).

    Autoimmune diseases

    Against the background of the use of the drug Proleukin, the course of autoimmune diseases can progress,leading to complications that are life-threatening. There were reports of cases of exacerbation of Crohn's disease on the background of treatment with Proleukin. Thyroid function and other potentially important autoimmune diseases of the organs should be closely monitored, since not all patients with IL-2-associated autoimmune disorders have signs of previous autoimmune disorders.

    Effects on the central nervous system

    With the development of a lethargic state or drowsiness, the use of Proleukin should be discontinued, since continuation of therapy can provoke the development of deep coma.

    Proleukin therapy may increase the severity of clinical symptoms in patients with undiagnosed or treated metastatic process in the CNS. Therefore, before starting therapy with Proleukin, all patients are recommended to conduct a full-fledged examination in order to detect metastases in the CNS and adequate treatment before treatment with Proleukin.

    In the course of therapy with Proleukin, patients may experience changes in their mental status, manifested by irritability, confusion, or depression.These changes are reversible, however, they can persist for several days after drug discontinuation. Proleukin is able to change the patient's response to psychotropic medications.

    Impaired liver and kidney function

    The use of Proleukin is accompanied by a reversible increase in the activity of "liver" transaminases, an increase in the concentration of bilirubin, urea and creatinine in the blood serum. The drug Proleukin has an effect on renal and hepatic metabolism, as well as excretion of concurrently used drugs. Caution should be exercised when using simultaneously with other medicines that are capable of providing nephro- or hepatotoxic effects. It is necessary to closely monitor the condition of patients with impaired renal or hepatic function.

    Infections

    The use of the drug Proleukin may lead to an increase in the frequency and / or severity of the bacterial infection process, including septicemia, bacterial endocarditis, septic thrombophlebitis, peritonitis, pneumonia.

    Such complications often occur against the background of intravenous administration of the drug.An increase in the frequency and severity of cases of development of infectious processes at the site of localization of the intravenous catheter in patients receiving Proleukin IV was reported. Use preventive antibacterial therapy in patients with a central intravenous catheter.

    With the exception of several cases of urinary tract infection caused by Escherichia coli, The main pathogens causing infectious complications were in most cases Staphylococcus aureus or Staphylococcus epidermidis.

    Subcutaneous administration of the drug is often accompanied by reactions at the injection site, until the development of necrosis. This effect can be reduced by changing the injection site. It is necessary to conduct adequate therapy of bacterial infection before starting treatment with the drug.

    Change in glucose metabolism

    There is a possibility of developing a violation of glucose metabolism during therapy with Proleukin. It is necessary to monitor the concentration of blood glucose, especially in patients with diabetes mellitus.

    Drugs that reduce the severity of the side effects of Proleukin

    In most patients, with the use of Proleukin in therapeutic doses, fever and undesirable effects from the gastrointestinal tract develop.It is possible to simultaneously use paracetamol to lower the temperature of the green. It is possible to take anti-emetic and antidiarrheal drugs to stop certain unwanted effects from the gastrointestinal tract. Simultaneous use of antihistamines drugs itchy skin in some patients.

    Laboratory and clinical studies

    In addition to routine tests, patients with renal cell carcinoma or metastatic melanoma before starting therapy with Proleukin and then following a certain periodicity, the following studies are recommended:

    - a general blood test, including the determination of the leukocyte formula (including the differential count of the number of blood cells), considering the ability of the Proleukin drug to cause anemia and thrombocytopenia;

    - biochemical blood analysis, including control of water-electrolyte balance, blood electrolyte content, blood glucose concentration, renal and hepatic functional tests, especially in patients with liver function or night before the beginning of treatment;

    - Before the start of therapy, it is recommended to perform an X-ray examination of the thoracic organs,electrocardiography (ECG) and special diagnostic tests, for example, with a load on the treadmill, etc. (but indications), determination of the gas composition of the arterial blood.

    If any changes are detected, including signs of myocardial ischemia, further examination is necessary to exclude a pronounced coronary pathology. Patients receiving high doses of the Proleukin IV drug should perform a special diagnostic test with thallium to assess myocardial perfusion. Before starting treatment with Proleukin, you should make sure that your lungs function normally (FEV1> 2L or 75% of the norm in terms of height and age). Patients receiving I / O need regular monitoring of the circulatory system, including blood pressure and pulse measurement, as well as examination of other organs and systems, including assessment of mental status and diuresis. It should be more frequent in patients with low blood pressure. Hypovolemia should be assessed by measuring central venous pressure.Assessment of the functional state of the lungs, including pulse oximetry and the determination of the gas composition of arterial blood, is mandatory in patients with wheezing or rapid breathing, as well as with complaints of dyspnea.

    Effect on the ability to drive transp. cf. and fur:

    Proleukin may affect the central nervous system, causing hallucinations, drowsiness, fainting, seizures. In the period of treatment should be abandoned the management of vehicles and mechanisms.

    Form release / dosage:

    Lyophilizate for the preparation of a solution for subcutaneous and intravenous administration of 18 million IU / ml in a vial.

    Packaging:

    Lyophilizate for the preparation of a solution for subcutaneous and intravenous administration of 18 million IU / ml in a vial.

    For 1 bottle with instructions but for use in a cardboard bundle.

    Storage conditions:

    At a temperature of 2 ° C to 8 ° C.

    Do not freeze.

    Keep out of the reach of children!

    Shelf life:

    24 months.

    Do not use after the expiration date indicated.

    Terms of leave from pharmacies:On prescription
    Registration number:П N016117 / 01
    Date of registration:05.10.2009
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp19.08.2015
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