Idarubicin (Idarubicin)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceIdarubicinIdarubicin
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  • Zavedos®
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    FARM STANDART, OJSC     Russia
  • Rubid
    lyophilizate in / in 
    LENS-PHARM, LLC     Russia
    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    In 1 ml of solution contains:

    active substance: idarubicin hydrochloride 1 mg

    Excipients: glycerol - 25 mg, a solution of hydrochloric acid 0.1 M to a pH of 2.5-4.5, water for injection up to 1 ml.

    Description:Transparent red-orange liquid.
    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, loud-onset, elderly (over 60 years).
    Pregnancy and lactation:Contraindicated.
    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 the drug IDARUBICINE through the tube of the system for intravenous administration (during the infusion of 0.9% sodium chloride solution).

    - Acute non-lymphoblastic leukemia (ONLL)

    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 at 12 mg / m2, children 10 mg / m each2 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.

    - metastatic breast cancer

    In the case of monotherapy IDARUBICINE prescribe in a dose of 45 mg / m2 once or for 3 days at 15 mg / m2 1 per day; the course of treatment is repeated every 3-4 weeks, taking into account the hematological status. When using IDARUBICINE in combined chemotherapy, the drug is administered once in a dose of 35 mg / m2 per day.

    For violations of the liver or kidneys, the data on the use of the drug IDARUBICINE 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.

    Side effects:

    Classification of the incidence of adverse events (WHO): very often (≥ 1/10), often (≥ 1/100, <1/10), not often (≥ 1/1000, <1/100), rarely (≥ 1 / 10 000, <1/1000), very rarely (<1/10 000, including individual messages) or unknown (can not be estimated from the available information).

    From the cardiovascular system: often phlebitis, thrombophlebitis and thromboembolism, sinus tachycardia, tachyarrhythmias (including ventricular extrasystole and ventricular tachycardia), bradycardia, cardiomyopathies (dyspnea, pulmonary edema, hypostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, exudative pleurisy, gallop rhythm), reduction of fraction ejection of the left ventricle; very rarely - pericarditis / myocarditis, atrioventricular blockade and blockage of the legs of the bundle.

    On the part of the hematopoiesis system: very often - leukopenia, neutropenia, thrombocytopenia, anemia, infections; often - hemorrhages; not often - sepsis / septicemia, septic shock.

    On the part of the digestive system: very often - nausea, vomiting, anorexia, stomatitis, abdominal pain, diarrhea; often - increased activity of "liver" enzymes and increased serum bilirubin levels; not often - colitis (including neutropenic enterocolitis with perforation), dehydration; esophagitis; very rarely - erosion / ulcers.

    From the urinary system: very often - red color of urine within 1 - 2 days after drug administration; unknown - nephropathy due to increased formation of uric acid.

    From the skin and skin appendages: very often - alopecia, rash; often - itching, hypersensitivity of irradiated skin ("response to radiation"); not often - hyperpigmentation of skin and nails, urticaria; very rarely - peripheral erythema.

    Allergic reactions: very rarely - hot flushes to the face, anaphylaxis.

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

    Other: not often - 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, against the background or 2-3 weeks before the drug is treated IDARUBICINE radiotherapy was conducted. 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.

    A drug IDARUBICINE can 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 before and during drug therapy IDARUBICINE to carry out regular monitoring of its function (using the same evaluation technique throughout the observation period), including estimation 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. When there are signs of cardiotoxicity, drug treatment IDARUBICINE 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 intravenous administration of a 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 drug therapy IDARUBICINE, should use reliable methods of contraception.

    When working with the drug IDARUBICINE it is necessary to observe the rules for handling cytotoxic substances. 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.

    Effect on the ability to drive transp. cf. and fur:Systematic evaluation of the effect of the drug IDARUBICINE the ability to drive vehicles or work with other mechanisms was not carried out.
    Form release / dosage:
    Solution for intravenous administration in vials 5 mg / 5 ml and 10 mg / 10 ml (1 mg / ml).
    Packaging:

    To 5 ml in bottles of a glass tube or 5 ml or 10 ml in bottles of glass, sealed with rubber stoppers with aluminum caps or with caps combined of aluminum and plastic.

    For 10 bottles or 1 bottle together with instructions for use in a pack of cardboard.

    Packaging of 10 packs per film is allowed.

    Storage conditions:

    2 years.

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

    Keep out of the reach of children.

    Shelf life:In the dark place at a temperature of 2 ° C to 8 ° C. Do not freeze!
    Terms of leave from pharmacies:On prescription
    Registration number:LP-001155
    Date of registration:11.11.2011 / 18.12.2015
    Expiration Date:18.12.2020
    The owner of the registration certificate:FARM STANDART, OJSC FARM STANDART, OJSC Russia
    Manufacturer: & nbsp
    Representation: & nbspPHARMSTANDART JSC PHARMSTANDART JSC Russia
    Information update date: & nbsp22.10.2017
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