Aldesleukin - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Interleukins

Included in the formulation

Proleukin

lyophilizate in / in PC

Novartis Pharma AG Switzerland

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

L.03.A.C Interleukins

Pharmacodynamics:

Aldesleykin is a recombinant human interleukin-2. It is obtained in cells Escherichia coli. This protein is not similar to the natural, it lacks glycosylation N-terminal alanine, and also at position 125, serine is replaced by cysteine.

Stimulates endogenous immune defense; activates T-lymphocytes and natural killer cells involved in the mechanisms of recognition and destruction of tumor cells. Cellular immunity, production of cytokines, including TNF-α, IL-1 and interferon-gamma, is activated. Recombinant IL-2 promotes production of antibodies by B-cells, stimulates the secretion of complement factors, and also triggers mechanisms for releasing hormones.

Pharmacokinetics:

At intravenous introduction bioavailability makes 35%, at subcutaneous - 47%. Blood plasma receives 30% of the administered dose. Eliminated by the kidneys, and the elimination is biphasic: with subcutaneous injection, the half-distribution period is 45 minutes, and the elimination half-life is 5.3 hours; when administered intravenously, the half-distribution period is 13 minutes, and the elimination half-life is 85 minutes.

Indications:

Metastatic renal cell carcinoma; melanoma (as an adjunctive therapy).

ICD-10

II.C43-C44.C43.9 Malignant melanoma of skin, unspecified

II.C64-C68.C64 Malignant neoplasm of kidney, except for renal pelvis

Contraindications:

Crohn's disease; pregnancy / lactation; violation of the function of breathing; hypersensitivity; violation of the heart (detection of the load test by thallium); the ECOG patient status is less than 2; metastasis in the central nervous system, the presence of metastases in more than one organ, the time from the diagnosis of the primary tumor is less than 24 months; the patient underwent allotransplantation of the organ; severe infections requiring antibiotic therapy; level pO₂ at rest <60 mm Hg. Art.

Carefully:

Autoimmune diseases; childhood; leukopenia; thrombocytopenia; pregnancy; concomitant therapy with corticosteroids; elevated levels of bilirubin and creatinine in serum; patients of advanced age (side effects usually develop).

Pregnancy and lactation:

Category FDA - FROM. Not recommended in pregnancy (effectiveness and safety of the drug during pregnancy is not established).At the time of treatment should stop breastfeeding (data on the excretion of the drug with breast milk and its effect on lactation there).

Dosing and Administration:

Enter intravenously or subcutaneously. Intravenous infusion: first induction cycle 5 days at a dose of 1 mg / m²/ day, then repeat the course in 2-6 days, the second cycle - after 3 weeks. In the presence of positive dynamics, up to four induction cycles are possible. If signs of toxicity occur, the infusion is interrupted until the side effects disappear, and then the dose is halved twice.

High-dose therapy - intravenous infusion for 50 or more minutes at 0.037 mcg / kg every 8 hours, in total, 14 injections are administered. Then stand the break nine days and spend 14 more introductions (up to 28 introductions).

With n / k introduction, 18 million IU are prescribed daily for 5 days, followed by a two-day break. Over the next 3 weeks, 18 million ME each on the 1st and 2nd day of each week and 9 million ME on the 3rd, 4th and 5th days of the week. After a one-week break, repeat the same 4-week cycle. In clinical trials aldesleukin injected subcutaneously to reduce toxicity, but the effectiveness of this regimen is not defined.

Side effects:

The cardiovascular system: decrease in arterial pressure, arrhythmia, angina pectoris, myocardial infarction, sinus tachycardia.

Nervous system: confusion, agitation, memory disorders, dizziness, visual impairment/ speech / motor skills, convulsions.

Gastrointestinal tract: impaired taste, nausea, vomiting, stomatitis, dyspepsia, diarrhea, gastritis, increased bilirubin / alkaline phosphatase / transaminase, hepatomegaly.

Genitourinary system: anuria, hematuria, oliguria, dysuria.

Skin: rash, itching, erythema.

Respiratory system: tachy / dyspnoea, pneumothorax, dyspnea, cough.

Hematologic disorders: anemia, eosinophilia, leukopenia, lymphocytosis, thrombocytopenia, stimulation of lymphocyte proliferation in the internal organs, bleeding.

Local reactions: bol, inflammation at the injection site, to seal the injection site, necrosis at the injection site.

Other: edema, including signs of nerve compression / vessels, fever, hyperglycemia, hypocalcemia, conjunctivitis, hypo- or hyperthyroidism, chills, hyperkalemia, weight gain, hypersensitivity reactions, anaphylaxis, diabetes.

Overdose:

In case of an overdose, there is an increase in side effects. In this case, the elimination of aldesleukin and maintenance therapy is necessary. If there is a threat of life, you need intravenous dexamethasone (reduces the effectiveness of the drug).

Interaction:

Glucocorticoids: a decrease in the effectiveness of aldesleukin and a reduction in its side effects.

It should avoid simultaneous use with drugs that have a pronounced hepatotoxic effect, since liver damage is likely.

Iodine-containing radiopaque means - the development of delayed reactions (hypersensitivity, fever, etc.).

Avoid simultaneous use with drugs that have a pronounced cardiotoxic effect and / or lower blood pressure (beta-blockers), since cardiovascular system disorders are likely.

It should be avoided simultaneous reception with drugs that have a pronounced nephrotoxic effect.

When joint use of high doses of aldesleukin and antitumor drugs, especially containing dacarbazine, cisplatin, tamoxifen and interferon-alpha, hypersensitivity reactions are noted (develop several hours after the administration of chemotherapeutic drugs and include erythema, pruritus, hypotension).

When combined with Proleukin (in / in) And interferon-alpha may be severe rhabdomyolysis and myocardial injury, including myocardial infarction, myocarditis and hypokinesia foci amplification or initial manifestations of autoimmune and inflammatory diseases, including IgA-nephropathy, okulobulbarnuyu myasthenia gravis, inflammatory arthritis, thyroiditis, bullous pemphigoid and Stevens -Johnson.

Aldesleyikin is not compatible with ganciclovir sodium salt, lorazepam, pentamidine, prochlorperazine, promethazine, bacteriostatic water for injection and saline.

Special instructions:

Treatment with aldesleukin is difficult for patients, so before starting therapy, you need to compare all the pros and cons. For the period of treatment for the patient, there should be proper care and control of important vital signs, including the work of the cardiovascular system, kidneys, liver, blood counts, monitoring of body weight, concentration of electrolytes in blood plasma, etc.

Therapy should be conducted only under the supervision of a physician of appropriate qualifications who has experience in the use of chemotherapeutic drugs. When in / in the use of the drug recommended hospitalization of the patient in a specialized hospital with an intensive care unit for the purpose of monitoring clinical and laboratory indicators. SC administration can be done by qualified personnel on an outpatient basis.

Before the introduction of a recommended premedication of NSAIDs, the infusion should be slow.

To dilute the drug, use plastic bottles. It is not recommended to filter the drug, as there is a high probability of its absorption on the filter. The diluted solution is stored at a temperature of 2-8 ° С not longer than 48 hours.

Violation of the procedure for preparing the solution (in / in and PC) and its dilution (in / in) can lead to a decrease in the biological activity of the preparation and / or the formation of a biologically inactive protein.

Patients receiving aldesleukin, do not drive a car or machinery until the adverse effects disappear completely.

Instructions

Aldesleikin (Aldesleukinum)