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

Active substanceIdarubicinIdarubicin

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Zavedos®

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Idarubicin

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FARM STANDART, OJSC Russia

Rubid

lyophilizate in / in

LENS-PHARM, LLC Russia

Dosage form: & nbsplyophilizate for the preparation of a solution for intravenous administration

Composition:Active substance: Idarubicin hydrochloride 5 mg

Excipients: Lactose

Description:Porous amorphous mass of red-orange color

Pharmacotherapeutic group:antitumor agent, antibiotic

ATX: & nbsp

L.01.D.B.06 Idarubicin

Pharmacodynamics:

Antitumor agent from the group of anthracycline antibiotics. Embedded in the DNA molecule, interacts with topoisomerase II and inhibits the synthesis of nucleic acids. It has a high lipophilicity and is characterized by a higher rate of penetration into the cells and less cross-resistance than doxorubicin and daunorubicin.

The main metabolite of idarubicin, idarubicinol, exhibits antitumor activity and has less pronounced cardiotoxicity than idarubicin.

Pharmacokinetics:With intravenous administration, the maximum concentration is achieved within a few minutes. The half-life after intravenous administration is 11-25 hours. Metabolization is rapid and intensive, occurs both in the liver and outside it with the formation of the main metabolite of idarubicinol, according to activity not differing from idarubicin.The half-life of idarubicinol for intravenous administration is 33-60 hours. It is excreted mainly with bile in the form of idarubicinol and kidneys (1-2% unchanged and 4.6% in the form of idarubicinol). The seizure of idarubicin by nucleated cells of blood and bone marrow in patients with leukemia is very fast and practically coincides with its appearance in blood plasma (the maximum intracellular concentration of idarubicin is reached in a few minutes after intravenous administration of the drug). Concentrations of idarubicin and idarubicinol in nucleated blood cells and bone marrow are more than 100-200 times higher than the corresponding concentrations in blood plasma.

The rate of excretion of idarubicin and idarubicinol from blood plasma and cells practically coincides (the terminal half-life of idarubicin from cells is about 15 hours, and idarubicinol is about 72 hours)

Indications:

- Acute non-lymphoblastic or myeloblastic leukemia in adults (first-line therapy for the induction of remission, as well as for relapses or resistant cases).

- Acute lymphoblastic leukemia in adults and children (second-line therapy).

- Breast cancer (with ineffective chemotherapy of the first line, not including anthracyclines).

Contraindications:

- Hypersensitivity to idarubicin and / or to other components of the drug, as well as to other anthracyclines and anthracenedions.

- Pronounced hepatic and / or renal insufficiency.

- Severe heart failure.

- Recently suffered myocardial infarction.

- Clinically significant arrhythmias.

- Myelosuppression.

- Prior therapy with maximum cumulative doses of idarubicin and / or other anthracyclines or anthracendones.

- Pregnancy and lactation.

Carefully:

Myocarditis, chicken pox, shingles, gout or urate nephrolithiasis (in the anamnesis), infections, leukopenia, thrombocytopenia, elderly age (over 60 years).

Pregnancy and lactation:

Dosing and Administration:

The drug is injected intravenously (very slowly) for 5-10 minutes. To reduce the risk of extravasation, it is recommended to administer Rubid preparation through the tube of the intravenous system (during the infusion of 0.9% sodium chloride solution).

- Acute non-lymphoblastic leukemia (OHLL)

Adults-12 mg / m2 intravenously daily for 3 days (in combination with cytarabine) or 8 mg / m2 daily for 5 days in the form of monotherapy or in combination with other antitumor drugs.

- Acute lymphoblastic leukemia (ALL)

Adults of 12 mg / m2, children 10 mg / m2 intravenously daily for 3 days in the form of monotherapy.

All these regimens should be used taking into account the hematologic status of the patient, as well as the doses of other cytotoxic drugs used in combination therapy.

When violations of the liver or kidney function data on the use of the drug Rubid are limited. If the content of bilirubin or creatinine is high in the blood serum, it is recommended to use the drug in reduced doses.

With bilirubin in the blood serum within 1.2-2 mg%, the dose of anthracyclines is usually reduced by 50%, above 2 mg% - the drug is canceled.

Preparation of the solution: As a solvent for the Rubid preparation, only water for injections in an amount of 5 ml for every 5 mg of idarubicin.

Side effects:

From the cardiovascular system: phlebitis, thrombophlebitis and thromboembolism, including pulmonary embolism. The manifestation of early (acute) cardiotoxicity of Rubid's preparation is mainly sinus tachycardia and / or anomalies on the ECG (nonspecific changes in ST-T teeth). There may also be tachyarrhythmias (including ventricular extrasystole and ventricular tachycardia), bradycardia, atrioventricular blockade, and blockade of the bundle of the bundle.These phenomena are rarely clinically significant, do not require the abolition of Rubid therapy, and are not always a predictor of later delayed cardiotoxicity. Late (delayed) cardiotoxicity usually develops during the last course of therapy, or several months or years after completion of therapy. Late cardiomyopathy is manifested by a decrease in the left ventricular ejection fraction and / or symptoms of congestive heart failure (CHF) (dyspnea, pulmonary edema, hypostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, exudative pleurisy, gallop rhythm). Also subacute phenomena (pericarditis / myocarditis) can be noted. The most severe form of anthracycline-induced cardiomyopathy is the life-threatening CHF, which is a toxicity that limits the total dose of the drug. On the part of the hematopoiesis system: leukopenia, neutropenia, thrombocytopenia, anemia. The number of neutrophils and platelets usually reaches the lowest values by 10-14 days after the administration of the drug, the restoration of the blood picture is observed during the third week.The inhibition of bone marrow function (dose-limiting toxicity) is dose-dependent and is usually reversible.

Clinical manifestations of severe myelosuppression may include chills, infections, sepsis / septicemia, septic shock, hemorrhage and tissue hypoxia.

On the part of the digestive system: nausea, vomiting, anorexia, dehydration, stomatitis, esophagitis, abdominal pain, heartburn, erosion / ulcers, diarrhea, colitis (including neutropenic enterocolitis with perforation), increased activity of "liver" enzymes and increased serum bilirubin levels.

From the urinary system: Nephropathy due to increased uric acid formation is a red color of urine within 1 to 2 days after drug administration.

From the skin and skin appendages: alopecia, rash, itching, hyperpigmentation of the skin and nails, hypersensitivity of irradiated skin ("response to radiation"), hives and peripheral erythema.

Allergic reactions: hot flushes to the face, anaphylaxis.

Local reactions: when the product gets under the skin - blistering, heavy cellulite, necrosis of surrounding soft tissues.

Other: immunosuppression, hyperuricemia due to rapid lysis of tumor cells ("tumor lysis syndrome"), secondary leukemia with or without preleukemic phase (most often observed with anthracyclines in combination with DNA-breaking antitumor agents) with a latent period of 1 to 3 years .

Overdose:

Symptoms: manifestations of acute cardiotoxicity in the first 24 hours (late cardiotoxicity may occur several months after anthracycline overdose) and severe myelosuppression (within 1-2 weeks).

Treatment: symptomatic, if necessary - blood transfusion, platelet mass, administration of antibiotics. Dialysis is ineffective.

Interaction:

Drugs with cardiotoxic and myelotoxic effects mutually enhance the side effect.

Additive myelosuppressive effect can also be observed if radiation therapy was carried out against the background or 2-3 weeks prior to rubid therapy.

Joint use with other cardiovascular drugs (eg, calcium channel blockers) requires careful monitoring of heart function throughout the treatment period.

Hepatotoxic drugs can lead to a disruption in the metabolism of the drug, its pharmacokinetics and therapeutic efficacy and / or toxicity.

When combined with uricosuric drugs, the risk of developing nephropathy increases.

Rubid preparation should not be mixed with other drugs.

Pharmaceutically incompatible with any solutions with alkaline pH - destruction of idarubicin. Do not mix with heparin - precipitate formation.

Special instructions:

The drug should be used only under the supervision of a doctor who has experience in carrying out cytotoxic chemotherapy.

Before starting treatment, patients should completely recover from signs of acute toxicity as a result of previous therapy with cytotoxic drugs, such as stomatitis, neutropenia, thrombocytopenia and generalized infections.

- Before and during each cycle of therapy, a blood test with a formula count must be performed.

- To reduce the risk of severe toxic cardiac damage, it is recommended to monitor its function regularly (using the same evaluation technique throughout the follow-up period) before and during Rubid's therapy.including an assessment of the left ventricular ejection fraction from echocardiography or multichannel radioisotope angiography, and ECG monitoring. Monitoring of cardiac function should be particularly rigorous in patients with risk factors, as well as in patients receiving high cumulative doses of anthracyclines. If signs of cardiotoxicity are found, treatment with Rubid should be stopped immediately. Risk factors for cardiotoxicity include cardiovascular diseases in the active or latent phase, previous or concomitant radiotherapy of the mediastinum or pericardial region, previous therapy with other anthracyclines or anthracenedions, simultaneous use of other drugs that suppress the contractile ability of the heart. However, cardiotoxicity due to the use of the drug can develop at lower cumulative doses and regardless of the presence or absence of risk factors for the development of cardiotoxicity. It is assumed that the toxicity of idarubicin and other anthracyclines and anthracendones is additive.

- Limit cumulative doses for intravenous use of the drug has not yet been established. There have been reports of cases of cardiomyopathy as a result of drug treatment in about 5% of patients with an intravenous cumulative dose of 150-290 mg / m2.

- Since violations of the liver and / or kidneys can affect the distribution of idarubicin, before and during treatment, it is necessary to monitor liver and kidney function (with determination of bilirubin and serum levels of creatinine).

- In connection with the possible development of hyperuricemia, patients during therapy are recommended to determine the level of uric acid in the blood, the content of potassium, calcium, phosphate and creatinine in the blood serum. Hydration, alkalinization of urine and prevention with allopurinol allow to minimize the risk of complications associated with tumor lysis syndrome.

- After insertion into veins of small diameter or after repeated injection into the same vein, phlebosclerosis may develop. The risk of phlebitis / thrombophlebitis at the injection site can be reduced by strictly following the recommendations for the administration of the drug.

- When the first signs of extravasation appear (burning or pain at the injection site), the infusion should be stopped immediately and then resumed infusion into another vein until the full dose is given.

- Men and women receiving Rubid therapy should use reliable contraceptive methods.

- When working with the drug Rubid, the rules for handling cytotoxic substances must be observed. The surface contaminated with the drug is recommended to be treated with dilute sodium hypochlorite solution (containing 1% chlorine). If the product gets on the skin, immediately wash the skin with plenty of soap and water or a solution of sodium bicarbonate; if caught in the eye - pull back the eyelids and rinse the eye (eye) with plenty of water for at least 15 minutes.

Form release / dosage:Lyophilizate for the preparation of a solution for intravenous administration in vials of 5 mg.

Packaging:1 bottle with instructions for use in a cardboard pack. For 25 and 35 bottles with an equal number of instructions for use in a box of cardboard (for hospitals).

Storage conditions:

List B.

Store in a dry place, protected from light and out of reach of children, at a temperature not exceeding 25 ° C. It is recommended that the preparation be used immediately after the first opening and then reconstituted with a solvent.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N003818 / 01

Date of registration:05.02.2010

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

LENS-PHARM, LLC Russia

Information update date: & nbsp10.11.2014

Illustrated instructions

Instructions

Rubid (Rubide)