2010/06/16

Zavedos

Composition, structure and packing Zavedos 
Hard gelatin capsules with an opaque body and cap red-orange color, with radially arranged inscription "INDARUBICIN five" on the lid, made in black ink, the contents of capsules - orange powder. 1 capsule. idarubicin hydrochloride is 5 mg. Excipients: microcrystalline cellulose, glyceryl palmitostearat. The composition of the shell capsules: gelatin, iron oxide red, titanium dioxide.

Hard gelatin capsules, c opaque cap red-orange body and opaque white, with radially arranged inscription "IDARUBICIN 10" on the lid, made in black ink; content caps - orange powder. 1 capsule. idarubicin hydrochloride 10 mg. Excipients: microcrystalline cellulose, glyceryl palmitostearat. The composition of the shell capsules: gelatin, iron oxide red, titanium dioxide.

Hard gelatin capsules, size number 2, with an opaque body and cap of white, with radially arranged inscription "IDARUBICIN 25" on the lid, made in black ink; content caps - orange powder. 1 capsule. idarubicin hydrochloride 25 mg. Excipients: microcrystalline cellulose, glyceryl palmitostearat. The composition of the shell capsules: gelatin, red iron oxide, titanium dioxide.

Lyophilisates for solution for i / v administration in the form of a porous material (powder) or tablet red-orange color. 1 vial. idarubicin hydrochloride is 5 mg. Excipients: lactose. Clinico-pharmacological group: The antitumor antibiotic.

Pharmacological action Zavedos 

The antitumor drug from the anthracycline group of antibiotics. Idarubicin, incorporating a DNA molecule, interacts with topoisomerase II and inhibits the synthesis of nucleic acids. Idarubicin has a high lipophilicity and is characterized by a higher rate of penetration into the cells as compared with doxorubicin and daunorubicin. The main metabolite of idarubicin - idarubitsinol has antitumor activity and cardiotoxicity is less pronounced than idarubicin.

Pharmacokinetics Zavedos 

Absorption

If ingestion absorption is high. Time to reach Cmax - 2-4 pm Bioavailability - 18-39%. When i / in the introduction of Cmax achieved within a few minutes.

Distribution Zavedos 

Capture idarubicin nucleated blood cells and bone marrow in leukemia patients is very fast and practically coincides with its appearance in the blood plasma. Concentrations of idarubicin and idarubitsinola in nucleated blood cells and bone marrow more than 100-200 times higher concentrations in blood plasma.

Metabolism and excretion Zavedos 

Idarubicin is rapidly metabolized to active metabolite idarubitsinola. Findings, mainly in the form idarubitsinola with bile and urine in unchanged form (1-2%) and in the form idarubitsinola (4.6%). T1 / 2 of idarubicin after oral administration is 10-35 h after i / in the introduction - 11-25 hours Idarubitsinol characterized by a longer T1 / 2 - 33-60 h with the ingestion and 41-69 hours - if i / in the introduction . Elimination rate of idarubicin and idarubitsinola from blood plasma and cells nearly identical (terminal T1 / 2 of idarubicin from cells approximately 15 hours, and idarubitsinola - about 72 h).

Statement
nelimfoblastny acute myeloid leukemia or adults (first-line therapy for induction of remission, as well as for recurrences or resistant cases);
acute lymphoblastic leukemia in adults and children (second-line therapy);
common breast cancer (in ineffectiveness of chemotherapy first line, not including anthracyclines).

Dosage regimen Zavedos 



The drug is introduced into / in the jet (very slowly) for 5-10 min. To reduce the risk of extravasation should enter Zavedos through a tube system for to / in the introduction (during infusion of 0.9% sodium chloride solution). The capsules are inside, drinking a small amount of water. Can be taken with meals. Capsule should be swallowed whole (not crack, do not dissolve, do not chew).

In acute leukemia nelimfoblastnom (ONLL) adult drug is introduced into / in to a dose of 12 mg/m2 body surface area daily for 3 days (in combination with cytarabine) or 8 mg/m2 daily for 5 days as monotherapy or in combination with other anticancer agents.

If unable to / in the introduction of idarubicin appointed interior to 30 mg/m2/sut within 3 days as monotherapy or 15-30 mg/m2 daily for 3 days in combination with other drugs of eradication.

In acute lymphoblastic leukemia adult appointed to 12 mg/m2, children - and 10 mg/m2, the drug is introduced into / in a day for 3 days as monotherapy.

When spread of breast cancer drug prescribe oral monotherapy at 45 mg/m2 for one day or 15 mg/m2/sut within 3 days every 3-4 weeks, depending on the hematological status of the patient.

When combined chemotherapy drug used in a dose of 35 mg/m2 for one day. All of the schemes should be used to satisfy the hematological status of the patient, and doses of other cytotoxic drugs used in combination therapy.

When violations of liver and kidney function data on the use of the drug Zavedos limited. With an increased content of bilirubin and / or a serum creatinine is recommended to use the drug in decreasing doses. When the concentration of bilirubin in the blood serum within 1.2-2 mg% dose of anthracyclines is usually reduced by 50%, higher than 2 mg% - drug overturned.

Terms of preparing and implementing the solution

As a solvent for the preparation Zavedos used only water for injection. To prepare the solution of 5 mg of the drug is dissolved in 5 ml of water for injection.

Side effect
Since the cardiovascular system: phlebitis, thrombophlebitis and thromboembolism, including pulmonary embolism. A manifestation of early (acute) cardiotoxicity is a sinus tachycardia and / or ECG changes (nonspecific ST-segment changes or spikes T).

Also Tachyarrhythmias, including premature ventricular and ventricular tachycardia, bradycardia, AV-block and bundle branch block feet. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely clinically significant and do not require the abolition of therapy Zavedosom.

Late (delayed) cardiotoxicity is usually celebrated during the last courses of therapy or after several months or years after completion of therapy.

Late cardiomyopathy manifested reduced left ventricular ejection fraction and / or symptoms of congestive heart failure (dyspnea, pulmonary edema, hypostatic edema, cardiomegaly and hepatomegaly, oliguria, ascites, pleural effusion, gallop rhythm). Also, there may be subacute events (pericarditis / myocarditis). The most severe form of anthracycline-induced cardiomyopathy is a life-threatening congestive heart failure, which limits the total dose.
From the side of the hemopoietic system: leukopenia, neutropenia, thrombocytopenia and anemia. The number of neutrophils and platelets usually reaches the lowest values for 10-14 days after drug administration, restoration of the blood picture observed during the third week. Dose-dependent reversible leukopenia and neutropenia are the manifestation of toxicity, which limits the dose of the drug. Clinical manifestation of severe myelosuppression may be chills, infection, sepsis / septicemia, septic shock, hemorrhage and tissue hypoxia.
On the part of the digestive system: nausea, vomiting, anorexia, dehydration, Mucosit, stomatitis, esophagitis, abdominal pain, heartburn, erosion / ulcer gastrointestinal mucosa, diarrhea, colitis (including neutropenic enterocolitis with perforation), increase in liver enzymes and increased levels of bilirubin. Rarely on the background of the drug inside to observe the development of severe complications from the gastrointestinal tract (perforation, bleeding).
From the urinary system: a red color urine within 1-2 days after ingestion. Dermatological reactions: alopecia, rash, itching, hyperpigmentation of the skin and nails, hypersensitivity to irradiated skin ('response to irradiation), urticaria and peripheral erythema.

Allergic reactions: hot flashes to a person anaphylaxis. Local reaction: when the product enters under the skin - the formation of blisters, severe cellulitis, necrosis of the surrounding soft tissue.

Other: Hyperuricemia due to the rapid lysis of tumor cells (tumor lysis syndrome), secondary leukemia with or without preleykemicheskoy phase (most often seen with anthracyclines in combination with the DNA structure in violation of antitumor drugs) with a latent period of 1 to 3 years.

Contraindications
marked hepatic or renal insufficiency;
marked cardiac insufficiency;
recent myocardial infarction;
clinically significant arrhythmias;
persistent myelosuppression;
prior therapy with maximum cumulative doses of idarubicin and / or other anthracyclines or antratsendionov;
Pregnancy
lactation (breastfeeding);
increased sensitivity to idarubicin and / or other components of the drug, as well as to other anthracyclines and antratsendionam.

Precautions should be prescribed drug in myocarditis, chicken pox, shingles, gout, or urate nephrolithiasis (in history), infections, leukopenia, thrombocytopenia, elderly patients (over 60).

Pregnancy and lactation Zavedos 

Zavedos contraindicated in pregnancy and lactation (breastfeeding). Patients of childbearing age receiving therapy with Zavedos should use reliable methods of contraception.

Application for violations of liver function Zavedos 

When violations of liver function in patients with elevated serum creatinine Zavedosa dose necessary to reduce or repeal of drug therapy.

If the level of bilirubin in the blood serum of more than 2 mg%, Zavedos should be repealed, if the level of bilirubin is in the range 1.2-2 mg% Zavedosa dose should be reduced by 50%. Contraindications: severe renal dysfunction.

Application for violations of renal function Zavedos 

When violations of renal function in patients with elevated serum creatinine Zavedosa dose necessary to reduce or repeal of drug therapy. Contraindications: severe liver problems.

Cautions Zavedos 

Zavedos should be used only under the supervision of a physician who has experience with cytotoxic chemotherapy. Before using the product Zavedos should ensure that no patient has signs of acute toxicity (stomatitis, neutropenia, thrombocytopenia, generalized infection), resulting from previous therapy with cytotoxic drugs.

Prior to and during each cycle of therapy should involve careful control of the picture of peripheral blood leukocyte counts in the counting.

To reduce the risk of severe cardiac toxicity is recommended before and during therapy Zavedosom conduct regular monitoring of its functions (using the same method of evaluation during the entire period of observation), including assessment of left ventricular ejection fraction by echocardiography or radionuclide angiography, multi-channel as well as ECG monitoring. Monitoring of cardiac function should be particularly careful in patients with risk factors, as well as in patients receiving high cumulative doses of anthracyclines.

If you find signs of cardiotoxicity Zavedosom treatment should be stopped immediately. Risk factors of cardiotoxicity include cardiovascular disease in active or latent phase, prior or concomitant radiation therapy of the mediastinum or pericardial area, previous therapy or other anthracycline antratsendionami, the simultaneous use of other drugs that suppress the contractile ability of the heart.

However, due to cardiotoxicity of the drug may develop 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 antratsendionov is additive. Limit cumulative doses Zavedosa with in / introduction and ingestion has been found.

Reported cases of cardiomyopathy in about 5% of patients with a / in the introduction of a cumulative dose equal to 150-290 mg/m2. The available data on patients who received Zavedos inside a total cumulative dose of 400 mg/m2 suggest a low probability of developing cardiotoxicity of. Since the disruption of the liver and / or kidneys may 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 caps Zavedosa patients with increased risk of bleeding and / or perforation of the gastrointestinal tract, should assess the relationship alleged benefits of the drug and the risk of complications.

Patients receiving Zavedos inside, should be under close supervision, as may the development of gastro-intestinal bleeding and severe damage to the mucous membrane of the digestive tract. In connection with the possible development of hyperuricemia during therapy is recommended to determine the level of uric acid, potassium, calcium, phosphate and creatinine in serum. Carrying out preventive measures (hydration, alkalization of urine, receiving allopurinol) to minimize risk for complications associated with tumor lysis syndrome.

After the introduction into the veins of small diameter, or after repeated injections in the same vein can develop fleboskleroz. The risk of phlebitis / thrombophlebitis at the injection site can be reduced with strict adherence to the recommendations for the introduction of the drug. When the first signs of extravasation (burning or pain at the injection site) infusion should be stopped immediately, and then resume the infusion into another vein before the full dose. When working with the drug Zavedos must observe the rules of treatment with cytotoxic agents.

If you accidentally hit product to the skin immediately wash it with plenty of water with soap or a solution of sodium bicarbonate, with a random product enters eyes - flush eyes with plenty of water for at least 15 minutes. Contaminated surface preparation recommend treating with a dilute solution of sodium hypochlorite (containing 1% chlorine).

Overdose

Symptoms: signs of acute cardiotoxicity in the first 24 h (late cardiotoxicity may occur several months after the overdose anthracycline) and severe myelosuppression (1-2 weeks). Treatment: perform symptomatically.

Drug Interactions Zavedos 

Combination chemotherapy with Zavedosa and other drugs of similar effect may result in additive toxic effects, particularly with regard to system blood / bone marrow and gastrointestinal tract. Mielosupressivny additive effect may also occur if the background or for 2-3 weeks before therapy was carried Zavedosom radiotherapy.

Combined use of other cardiotoxic or cardiovascular drugs (eg, calcium channel blockers), requires a careful monitoring of cardiac function during the entire period of treatment. Change of liver function resulting from concomitant therapy can disrupt the metabolism of idarubicin and its pharmacokinetics, therapeutic efficacy and / or increase its toxicity. In a joint application with urikozuricheskimi drugs increases the risk of developing nephropathy.

Pharmaceutical interaction. Zavedos not be mixed with other drugs.

Pharmaceutical incompatible with any solutions with alkaline values pH - is the destruction of idarubicin. The drug should not be mixed with heparin due to the possible formation of sediment.

Terms and Conditions of storage Zavedos 

List B. The drug should be stored out of reach of children at or above 25 ° C. Lyophilisates recommended for use immediately after the first autopsy with subsequent recovery of the solvent. Shelf life - 3 years.