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

Active substanceIdarubicinIdarubicin

Similar drugsTo uncover

Zavedos®

capsules inwards

Idarubicin

solution in / in

FARM STANDART, OJSC Russia

Rubid

lyophilizate in / in

LENS-PHARM, LLC Russia

Dosage form: & nbspcapsules

Composition:

Each 5 mg capsule contains:

active substance: idarubicin hydrochloride - 5 mg;

Excipients: cellulose microcrystalline 93.0 mg, glyceryl palmitostearate 2.0 mg.

Each 10 mg capsule contains:

active substance: idarubicin hydrochloride 10 mg;

Excipients: cellulose microcrystalline 88.0 mg, glyceryl palmitostearate 2.0 mg.

Each 25 mg capsule contains:

active substance: idarubicin hydrochloride 25 mg;

Excipients: cellulose microcrystalline 122.0 mg, glyceryl palmitostearate 3.0 mg.

Capsule composition:

Housing: iron dye red oxide (E172) 1.5% (-) titanium dioxide (E171) 0.5% / 2.0% / 2.0%, gelatin to 100%

Cover: iron dye red oxide (E172) 1.5% / 1.5% / -, titanium dioxide (E171) 0.5% / 0.5% / 2.0%, gelatin to 100%

Ink: shellac 24-27%, iron dye oxide black 24-28%, propylene glycol 3-7%, ammonia solution concentrated 1-2%, potassium hydroxide 0.05-0.1%

Description:

Dosage of 5 mg: hard gelatin capsules No. 4 with opaque, red-orange body and lid, and a radially placed inscription with black ink "IDARUBICIN 5" on the lid.The contents of the capsule are orange powder.

Dosage of 10 mg: hard gelatin capsules No. 4, with an opaque white body and a red orange lid and a radially placed black ink inscription IDARUBICIN 10 on the lid. The contents of the capsule are orange powder.

Dosage of 25 mg: hard gelatin capsules No. 2, with an opaque, white body and a lid and a radially placed inscription in black ink "IDARUBICIN 25m on the lid." The contents of the capsule are orange powder.

Pharmacotherapeutic group:Antitumor agent, antibiotic

ATX: & nbsp

L.01.D.B.06 Idarubicin

Pharmacodynamics:

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

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

Pharmacokinetics:

At intake absorption - high; Time to reach maximum concentration (TC_max) - 2-4 hours; bioavailability is 18-39%. Half-life after oral administration - 10-35 hours. Idarubicin is rapidly metabolized to the active metabolite idarubicinol, which is characterized by a longer half-life (33-60 hours). It is excreted mainly through the intestine in the form of idarubicinol and kidneys (1-2% unchanged and 4.6% in the form of idarubicinol).

Capture of idarubicin by nucleated cells of blood and bone marrow in patients with leukemia occurs very quickly and practically coincides with its appearance in blood plasma. Concentrations of idarubicin and idarubicinol in nucleated blood cells and bone marrow are more than 200 times higher than the corresponding concentrations in blood plasma.

The rate of excretion of idarubicin and idarubicinol from plasma of blood and cells practically coincides.

Liver or kidney failure

The pharmacokinetics of idarubicin in patients with hepatic impairment have not been fully studied. It is expected that in patients with impaired liver function of moderate and severe severity, there may be a change in the parameters of the metabolism of idarubicin, and a higher concentration in the blood plasma may also be observed.Also, there may be a change in metabolism against a background of renal insufficiency (see the sections "Dosing and Administration" and "Special instructions").

Pharmacokinetics in children

In children who received idarubicin inside at doses from 30 to 50 mg / m²for three days, the average terminal half-life was 9.2 hours (range 6.4-25.5 h). There is a significant accumulation of idarubicinol after 3 days of therapy.

Indications:

- Acute non-lymphoblastic or myeloblastic leukemia in adults (for induction of remission in previously untreated patients, as well as in relapses or resistant cases), in cases when parenteral administration of the drug is impossible (for medical, psychological or social reasons).

- Common 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 or renal insufficiency.

- Severe heart failure.

- Recently suffered myocardial infarction.

- Clinically significant arrhythmias.

- Persistent 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:

There are no adequate, well-controlled studies of the use of idarubicin in pregnant women. The use of idarubicin is contraindicated during pregnancy. In this regard, women of reproductive age and men should use reliable contraceptive methods during treatment with idarubicin.

A woman should be warned about the potential harm that can be caused to the fetus during therapy.

It is not known whether idarubicin in breast milk. It is recommended to stop breastfeeding during therapy.

Dosing and Administration:

Capsules are taken orally, with a small amount of water. Capsules should be swallowed whole (do not bite, do not dissolve, do not chew). Can be taken while eating.

- Acute non-lymphoblastic leukemia (OHLL)

Idarubicin is administered internally at 30 mg / m²per day for 3 days in the form of monotherapy or 15 - 30 mg / m² daily for 3 days in combination with other antitumor drugs.

- Common Breast Cancer

The drug is administered orally in the form of monotherapy at a rate of 45 mg / m² per day, or 15 mg / m per day for 3 days every 3-4 weeks, depending on the patient's hematologic status. With combined chemotherapy, the drug is used at a dose of 35 mg / m² per day.

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.

Impaired liver or kidney function

There are limited data on the use of Zavedos® in cases of impaired liver or kidney function. With an increased concentration of bilirubin and / or creatinine in the blood serum, it is recommended to use the drug in reduced doses. At a concentration of 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:

From the cardiovascular system: shock, phlebitis, thrombophlebitis and thromboembolism, including thromboembolism of the pulmonary artery. The manifestation of early (acute) cardiotoxicity of idarubicin 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 withdrawal of drug therapy and are not always a predictor of 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 cardiomyopathy caused by anthracyclines is a life-threatening CHF, which 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 application of the drug, the restoration of the blood picture is observed during the third week.

Dose-dependent reversible leukopenia and neutropenia are a manifestation of toxicity, which limits the dose of the drug. Clinical manifestations of severe myelosuppression may include chills, infections, sepsis / septicemia, septic shock, hemorrhages, tissue hypoxia or death.

From the digestive system: nausea, vomiting, anorexia, dehydration, mucositis, stomatitis, abdominal pain, heartburn, erosion / ulcers, diarrhea, colitis (including neutropenic enterocolitis with perforation), increased activity of "liver" enzymes and increased serum bilirubin concentration. Mukositis (mainly stomatitis, less often esophagitis) usually develops quite early after the initiation of therapy and, in case of severe damage, in a few days can progress to ulceration of the mucous membrane.In most patients, these symptoms disappear after three weeks of therapy.

Rare complications from the gastrointestinal tract (perforation, bleeding) have been rare in patients with acute leukemia or other ailments that may lead to gastrointestinal complications, as well as in patients taking drugs that may also lead to the development of complications in the gastrointestinal system.

From the urinary system: staining the urine in red for 1-2 days after taking the drug.

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.

Other: increased body temperature, hyperuricemia due to rapid lysis of tumor cells ("tumor lysis" syndrome), secondary leukemia (acute myeloid leukemia or myelodysplastic syndrome) with or without preleukemic phase with a latent period of 1 to 3 years. Most often, secondary leukemia is observed when anthracyclines are used in combination with anti-tumor agents that break DNA structure,when patients in advance received serious cytotoxic therapy or after increasing the dose of anthracyclines.

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. Medical observation is necessary for possible development of gastrointestinal bleeding and severe damage to the gastrointestinal mucosa.

Interaction:

Combined chemotherapy with Zavedos and other drugs of similar effect can lead to an additive toxic effect, especially with regard to the hematopoiesis / bone marrow and gastrointestinal system.

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

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

Changing the function of the liver or kidney as a result of concomitant therapy can disrupt the metabolism of idarubicin, as well as its pharmacokinetics, therapeutic efficacy and / or increase its toxicity.

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

Special instructions:

Zavedos® should only be used under the supervision of a physician with experience in performing cytotoxic chemotherapy.

Before the start of treatment with Zavedos, patients should completely stop the signs of acute toxicity (such as stomatitis, neutropenia, thrombocytopenia and generalized infections) that developed as a result of previous therapy with cytotoxic drugs.

Idarubicin is a strong suppressor of the bone marrow. Severe myelosuppression should be expected in all patients taking idarubicin in therapeutic doses. Before and during each cycle of therapy, a blood test should be performed with a count of the leukocyte count.

To reduce the risk of severe toxic cardiac damage, it is recommended to monitor it regularly before and during therapy with Zavedos®function (using the same evaluation methodology throughout the follow-up period), including evaluation 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 Zavedos® 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 areas, previous therapy with other anthracyclines or anthracenedions, simultaneous use of other drugs that suppress the contractile ability of the heart or cardiotoxic drugs (for example, trastuzumab). Anthracyclines, including idarubicin, should not be given in combination with other cardiotoxic drugs until careful monitoring of the patient's cardiac activity is established.Patients receiving anthracyclines after discontinuation treatment other cardiotoxic drugs (especially those with a long half-life, such as trastuzumab), are also susceptible to greater cardiotoxic effects of these drugs. The half-life of trastuzumab is approximately 28 to 38 days, the drug can be in the bloodstream up to 27 weeks. Therefore, physicians should avoid the use of anthracycline therapy for at least 27 weeks after cessation of treatment with trastuzumab (as possible). If anthracyclines are prescribed before the end of this period, careful monitoring of the patient's cardiac function is recommended. Zavedos® cardiotoxicity due to the use of the drug can 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 anthracendones is additive.

Limit cumulative doses for oral administration of Zavedos® have not yet been established.Available data on the oral administration of Zavedos ® in a total cumulative dose of up to 400 mg / m²suggest a low probability of cardiotoxicity.

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

Before prescribing Zavedos® to patients with GI disease with increased risk of bleeding and / or perforation, the physician should estimate the ratio of the perceived benefit from the use of the drug and the risk of complications.

Patients taking Zavedos ® should be closely monitored, as there may be gastrointestinal bleeding and severe mucosal damage.

In connection with the possible development of hyperuricemia, patients during therapy are recommended to determine the level of uric acid, the content of potassium, calcium, phosphate and creatinine in serum blood. Hydration, alkalinization of urine and prevention with allopurinol allow to minimize the risk of complications associated with the syndrome of "tumor lysis".Men and women receiving Zavedos® should use reliable contraceptive methods.

The introduction of live or weakened vaccines in patients with depressed immunity receiving chemotherapy, including idarubicin, can lead to the development of serious and sometimes fatal infections. Vaccination with live vaccines should be avoided in patients receiving idarubicin. You can inject killed or weakened vaccines, but the effect of vaccination can be reduced. When working with Zavedos, 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; In case of contact with eyes, remove eyelids and rinse eyes (eyes) with plenty of water for at least 15 minutes.

Effect on the ability to drive transp. cf. and fur:The effect of Zavedos® on the ability to drive a car and other complex mechanisms has not been systematically evaluated.

Form release / dosage:Capsules of 5 mg, 10 mg and 25 mg.

Packaging:1 capsule in a vial of dark glass (III type), sealed with an aluminum screw cap with protection from opening by children and control of the first opening with a polyethylene liner and polyethylene cover cover. 1 bottle with instructions for use in a cardboard box.

Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N011970 / 01

Date of registration:07.06.2010 / 29.08.2014

Expiration Date:Unlimited

Manufacturer: & nbsp

NERPHARMA, Srl. Italy

Representation: & nbspPfizer LtdPfizer LtdUSA

Information update date: & nbsp10.10.2017

Illustrated instructions

Instructions

Zavedos® (Zavedos®)