Antitumor agent from the halotestin cycle group of anthracycline antibiotics. Incorporating into the DNA molecule, idarubicin interacts with topoisomerase II and inhibits nucleic acid synthesis; It is highly lipophilic and has a higher rate of penetration into the cells and less cross-resistance in comparison with doxorubicin and daunorubicin.The main metabolite idarubicin – idarubitsinol – exhibits antitumor activity and has less severe cardiotoxicity than idarubicin.
At intake absorption – high; time to halotestin cycle maximum concentration – 2-4 hr .; bioavailability – 18-39%. When administered intravenously, the maximum concentration achieved within a few minutes. The half-life after oral administration – 10-35 hours, after intravenous administration -. 11-25 hours Idarurubitsin is rapidly metabolized to the active metabolite idarubitsinola, which is characterized by a long half-life (33-60 hours of ingestion, and 41-69 hours after intravenous injection ). It writes mainly in the bile in the form idarubitsinola and kidneys (1-2% unchanged and 4.6% in the form idarubitsinola).Capture idarubicin nucleated blood cells and bone marrow of leukemia patients is very fast and almost coincides with his appearance in the blood plasma. Idarubicin idarubitsinola concentration and in nucleated blood cells and the bone marrow is more than 100-200 times higher than corresponding concentrations in plasma.
Idarubicin and rate of excretion of idarubitsinola blood cells and plasma substantially coincides (idarubicin terminal half-life of the cell is about 15 hours, and idarubitsinola – about 72 hours).
- Acute nelimfoblastnyh or myeloid leukemia in adults (first-line therapy for induction of remission and at relapse or refractory cases).
- Acute lymphoblastic leukemia in adults and children (second-line therapy).
- Advanced breast cancer (with the ineffectiveness of halotestin cycle first-line chemotherapy not including anthracyclines).
- Hypersensitivity to idarubicin and / or other components of the drug as well as other anthracyclines and anthracenediones.
- Severe hepatic or renal insufficiency.
- Severe heart failure.
- Recent myocardial infarction.
- Clinically significant arrhythmias.
- Persistent myelosuppression.
- Prior therapy with maximum cumulative doses of idarubicin and / or other anthracyclines or anthracenediones.
- Pregnancy and lactation.
Myocarditis, chicken pox, shingles, gout or urate nephrolithiasis (in history), infection, leukopenia, thrombocytopenia, advanced age (over 60 years).
Dosing and Administration
The drug is administered intravenously (very slowly) for 5-10 minutes. Zavedos should enter through the tube system for intravenous administration To reduce the halotestin cycle risk of extravasation (during infusion of 0.9% sodium chloride solution). The capsules are taken orally, washed down with a little water. It can be taken with food. The capsule should be swallowed whole (not crack, does not dissolve, do not chew).
- Acute nonlymphoblastic leukemia (ONLL)
Adults – 12 mg / m2 intravenously every day for 3 days (in combination with cytarabine) or 8 mg / m2 daily for 5 days either alone or in combination with other anticancer agents. If not, intravenous idarubicin prescribed orally 30 mg / m2 per day for 3 days either alone, or 15 – 30 mg / m daily for 3 days in combination with other drugs protivoleykoznymi.
- Acute lymphoblastic leukemia (ALL)
Adults 12 mg / m2, children – 10 mg / m2 intravenously every day for 3 days in a monotherapy.
- Common breast cancer
drug is administered orally in the form of monotherapy calculation 45 mg / m in one day, or 15 mg / m2 per day for 3 days every 3-4 weeks depending upon hematologic status of the patient. In drug combination chemotherapy is applied in a dose of 35 mg / m for one day.
All of the circuits to be used considering hematologic status of the patient, and doses of other cytotoxic drugs used in combination therapy.
If abnormal liver or kidney function for use Zavedosa data are limited. When elevated levels of bilirubin and / or serum creatinine is recommended to use the drug in reduced doses.
When the concentration of bilirubin in the serum within 1.2-2 mg dose anthracycline% usually lower by 50% than 2 mg% – drug overturned.
Preparation of solution: as a solvent for the drug is only Zavedos water for injection in an amount of 5 ml per 5 mg idarubicin.
Cardio-vascular system: phlebitis, thrombophlebitis and thromboembolism, including pulmonary embolism. A manifestation of early (acute) cardiotoxicity of idarubicin is mainly sinus halotestin cycle tachycardia and / or abnormalities on the ECG (nonspecific ST-T of the teeth)., Can also be observed tachyarrhythmia (including ventricular arrhythmias and ventricular tachycardia), a bradycardia, atrioventricular block and bundle branch block . These phenomena are rarely clinically significant, do not require discontinuation of therapy and medication is not always a predictor of later delayed cardiotoxicity. Late (delayed) cardiotoxicity usually develops during the last course of therapy or within a few months or years after completion of therapy. Late cardiomyopathy manifested decrease left ventricular ejection fraction and / or symptoms of congestive heart failure (CHF) (dyspnea, pulmonary edema, hypostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion, gallop rhythm). Also, the phenomenon can be observed subacute (pericarditis / myocarditis). The most severe form of anthracycline-induced cardiomyopathy is a life-threatening congestive heart failure, which limits the total dose of the drug.
Hematopoietic system: leukopenia, neutropenia, thrombocytopenia, anemia. The number of neutrophils and platelets usually reaches the lowest values for 10-14 day after administration, the restoration of blood picture is observed in the third week.
Dose-dependent reversible leukopenia and neutropenia are the manifestation of toxicity, which limits the dose of the drug. . The clinical manifestation of severe myelosuppression may be fever, infections, sepsis / septicemia, septic shock, hemorrhage and tissue hypoxia.
From the digestive system: nausea, vomiting, anorexia, dehydration, mucositis, stomatitis, esophagitis, abdominal pain, heartburn, erosion / ulceration, diarrhea, colitis (including neutropenic enterocolitis with perforation), increased activity of “liver” enzymes and increase in bilirubin serum. Occasionally on the background of oral Zavedosa observed the development of serious complications from the gastrointestinal tract (perforation, bleeding).
From the urinary system: red coloration of urine for 1 – 2 days after ingestion.
Skin and skin appendages: alopecia, rash, pruritus, hyperpigmentation of the skin and nails, hypersensitivity to irradiated skin ( ‘response to radiation “), urticaria, and peripheral erythema.
Allergic reactions: hot flashes to the face, anaphylaxis.
Local reactions: in contact with the drug under the skin – blistering, severe cellulitis, necrosis of the surrounding soft tissues.
Other: hyperuricemia due to rapid lysis of neoplastic cells ( “syndrome, tumor lysis”), secondary leukemia with or without preleykemicheskoy phase (often seen with anthracyclines in combination with a disruptor DNA antineoplastic agents structure) with a latent period of 1 to 3 years.
Symptoms: The symptoms of acute cardiotoxicity in the first 24 hours (late cardiotoxicity can occur several months after the overdose anthracyclines) and severe myelosuppression (within 1-2 weeks).Treatment: symptomatic.
Interaction with other medicinal products and other forms of interaction
Combination chemotherapy using Zavedosa and other drugs with similar effects can lead to additive toxic effect, particularly in relation to hemopoietic system / bone marrow and the gastrointestinal tract.
The additive myelosuppressive effects may also occur when radiation therapy was carried out against the background, or 2-3 weeks before therapy Zavedosom.
The combined use of cardiotoxic or other cardiovascular drugs (e.g., calcium channel blockers) requires careful monitoring of the heart functions during the treatment period.
Changes in liver function as a result of concomitant therapy can disrupt metabolism idarubicin and its pharmacokinetics, therapeutic efficacy and / or increase its toxicity.
In a joint application raises the risk of developing nephropathy with uricosuric drugs.
Zavedos ® should not be mixed with other drugs.
Pharmaceutical incompatible with any solutions with an alkaline pH – the destruction of idarubicin.
Do not mix with heparin – sedimentation.
Zavedos ® should only be used under the supervision of a doctor who has experience of cytotoxic chemotherapy.
Before treatment, patients should Zavedosom fully recover from the acute signs of toxicity due to previous therapy with cytotoxic drugs, such as stomatitis, neutropenia, thrombocytopenia, and generalized infections. Prior to and during each cycle of therapy is necessary to carry out a blood test to count leukocyte formula.
To reduce the risk of severe toxic lesions of the heart is recommended prior to and during therapy Zavedosom regular monitoring of its functions (using the same assessment methodology throughout the whole observation period), including the assessment of left ventricular ejection fraction by echocardiography or multichannel radionuclide angiography and ECG monitoring. Monitoring of cardiac function must be particularly strict in patients with risk factors, and in patients receiving high cumulative doses of anthracyclines. If you find signs of cardiotoxicity Zavedosom treatment should be discontinued immediately. Risk factors for development of cardiac toxicity include cardiovascular disease in the active or latent phase, prior or concomitant radiotherapy of the mediastinum or pericardial area, previous therapy with other anthracyclines or anthracenediones, the simultaneous use of other drugs that suppress the contractile ability of the heart. However, cardiotoxicity due to the use halotestin cycle of the drug may occur at lower cumulative doses and regardless of the presence or absence of risk factors for cardiotoxicity. It is assumed that the toxicity of idarubicin and other anthracyclines and anthracenediones is additive.
Limiting cumulative doses by intravenous and oral administration Zavedosa ® has not yet been established. It reported cases of cardiomyopathy resulting from treatment with about 5% of patients with a cumulative intravenous dose of 150-290 mg / m2. Available data on the oral administration Zavedosa a total cumulative dose of 400 mg / m2 suggest a low probability of cardiotoxicity.
As the disruption of the liver and / or kidneys can affect the distribution of idarubicin, before and during treatment is necessary to monitor liver and kidney function (with the definition of bilirubin and serum creatinine).
Before the appointment Zavedosa capsules in patients with gastrointestinal disease with increased risk of bleeding and / or perforation, the physician must weigh the anticipated benefits of the drug and the risk of complications.
Patients taking Zavedos ® inside, must be monitored carefully as possible the development of gastrointestinal bleeding and severe mucosal damage.
In connection with the possible development of hyperuricemia in patients during therapy is recommended to determine the level of uric acid, potassium, calcium, phosphate, and serum creatinine. Hydration, urine alkalinisation, and prophylaxis with allopurinol minimize the risk of complications associated with tumor lysis syndrome.
After the introduction of the small-diameter vein or after re-injection into the same vein fleboskleroz may develop. The risk of phlebitis / thrombophlebitis at the injection site can be reduced by strict adherence to the recommendations on the introduction of the drug.
At the first signs of extravasation (burning or pain at the injection site) the infusion should be stopped immediately, and then resume the infusion into another vein until a full dose.
Men and women receiving therapy with Zavedos should use reliable methods of contraception.
When working with the preparation Zavedos ® is necessary to observe the rules of treatment with cytotoxic agents. Contaminated drug is recommended to treat the surface with a dilute solution of sodium hypochlorite solution (containing 1% available chlorine). If the product enters the skin – immediately produce copious water washing the skin halotestin cycle with soap and water or sodium bicarbonate; Eye contact – pull eyelids and produce rinsing eye (s) with plenty of water for at least 15 minutes.
Valium for drug of a solution for intravenous injection in vials of 5 mg. 1 bottle with instruction on use in carton box. Capsules of 5 mg, 10 mg or 25 mg. 1 capsule in a bottle of dark glass. 1 bottle with instruction on use in carton box.
Valium for drug of a solution for intravenous administration: at a temperature no higher than 25 ° C out of reach of children. It is recommended to use the drug after the first opening, followed by reduction of the solvent.
Capsules: at a temperature no higher than 25 ° C out of reach of children.
- Valium for drug of a solution for intravenous injection – 3 years.
- Capsules – 3 years
Do not use after the expiration date printed on the package.