Posology : מינונים

4.2 Posology and method of administration                                treatment with myelosuppressive agents. Their bone marrow               Cardiotoxicity is a risk of anthracycline treatment that may be to normal values in most cases by day 21. Thrombocytopenia               Intravesical administration Doxorubicin is frequently used in combination chemotherapy               reserve may be insufficient.                                            manifested by early (i.e. acute) or late (i.e. delayed) events.
and anaemia may also occur. Clinical consequences of severe
Early (i.e. acute) events: Early cardiotoxicity of doxorubicin                                                                                    Intravesical administration of doxorubicin may cause symptoms regimens with other cytotoxic drugs.                                     Elderly                                                                                                                                          myelosuppression include fever, infections, sepsis/septicaemia, consists mainly of sinus tachycardia and/or ECG abnormalities            septic shock, haemorrhage, tissue hypoxia or death.
of chemical cystitis (i.e., dysuria, frequent urinary, nocturia,
Doxorubicin hydrochloride should be administered only under              The dosages may be reduced in elderly patients.                         such as non-specific ST-T wave changes. Tachyarrhythmias,                                                                                         stranguria, haematuria, necrosis of the bladder wall).
the supervision of a qualified physician experienced in cytotoxic        Paediatric population                                                   including premature ventricular contractions and ventricular             Secondary leukaemia                                                      Special attention is needed in case of catheter therapy. Also, patients must be carefully and frequently monitored       In view of the substantial risk of doxorubicin-induced cardiotoxicity   tachycardia, bradycardia, as well as atrioventricular and bundle-        Secondary leukaemia with or without a preleukaemic phase,                problems (i.e., urethral obstruction caused by invasion of during the treatment.                                                    during childhood certain maximum cumulative dosages that                branch block have also been reported. These effects do not               has been reported in patients treated with anthracyclines.               intravesical tumour). Intravesical administration is contraindicated Due to the risk of an often lethal cardiomyopathy, the risks and         depend on the youth of patients should be applied. In children          usually predict subsequent development of delayed cardiotoxicity         Secondary leukaemia is more common when such drugs are                   for tumours that have penetrated the bladder (beyond T1).
benefits to the individual patient should be assessed before             (under 12 years of age) the maximal cumulative dose is usually          and are generally not a consideration for discontinuation of             given in combination with DNA-damaging antineoplastic agents,            Excipients each application.                                                        considered 300 mg/m2, whereas in adolescents (over 12 years             doxorubicin treatment. However, a reduction in the amplitude             when patients have been heavily pretreated with cytotoxic drugs or when doses of the anthracyclines have been escalated. These           Sodium Prior to start of the treatment it is recommended to measure             of age) the maximal cumulative dose is set to 450 mg/m2. For            of the QRS-wave and a prolongation of the systolic time interval the liver function by using conventional tests such as AST,              infants the maximal cumulative dosages are still indecisive, but        are considered more indicative of anthracycline-induced cardiac          leukaemias can have a 1 to 3 year latency period.                        1 vial of 5 ml of Doxorubicin Teva contains 18 mg sodium, ALT, ALP and bilirubin, as well as measuring renal function              even lower tolerability is assumed.                                     toxicity. As a rule, an absolute decrease with ≥10% or a decrease                                                                                 equivalent to 0.9% of the WHO recommended maximum daily Gastrointestinal disorders                                               intake of 2 g sodium for an adult.
(see section 4.4).                                                       Dosage for children should be reduced, since they have an               below 50%, in patients with normal initial LVEF-values, is a sign        Doxorubicin induces nausea and vomiting. Mucositis/stomatitis Analysis of left ventricular ejection fraction (LVEF) using ultrasound   increased risk for cardiac toxicity, especially late. Myelotoxicity     of an impairment of the heart function. Continued treatment                                                                                       1 vial of 10 ml of Doxorubicin Teva contains 35 mg sodium, or heart scintigraphy should be performed in order to assess             should be anticipated, with nadirs at 10 to 14 days after start         with doxorubicin must in these cases be carefully evaluated.
usually appears early after initiation of treatment, which, if severe,   equivalent to 1.8% of the WHO recommended maximum daily may progress within a few days to mucosal ulcerations. Most              intake of 2 g sodium for an adult.
the heart condition of the patient. This control should be made          of treatment. Please refer to current treatment protocols and           Late (i.e. delayed) events: Delayed cardiotoxicity usually develops      patients recover from this in the third week of therapy.
prior to the start of the treatment and after each accumulated           the specialist literature.                                              late in the course of therapy with doxorubicin or within 2 to 3 months                                                                            1 vial of 25 ml of Doxorubicin Teva contains 89 mg sodium, dose of approximately 100 mg/m2 (see section 4.4).                                                                                               after treatment termination, but later events, several months to An antiemetic prophylaxis is recommended.                                equivalent to 4.4% of the WHO recommended maximum daily Intravesical administration                                             years after completion of treatment, have also been reported.            Note: Doxorubicin should not be used in the presence of                  intake of 2 g sodium for an adult.
Intravenous (I.V.) administration of doxorubicin must be given
Doxorubicin hydrochloride can be given by intravesical instillation     Delayed cardiomyopathy is manifested by reduced LVEF and/or              inflammations, ulcerations or diarrhoea.                                 1 vial of 100 ml of Doxorubicin Teva contains 354 mg sodium, with great care and it is advisable to give the drug via the tubing of a freely running I.V. saline or 5% glucose within 3-5 minutes.        for treatment of superficial cancer of the bladder and to prevent       signs and symptoms of congestive heart failure (CHF), such as            Liver function                                                           equivalent to 17.7% of the WHO recommended maximum daily This method minimizes the risk of thrombosis development                 relapse after transurethral resection (T.U.R). The recommended          dyspnoea, pulmonary oedema, dependent oedema, cardiomegaly               The major route of elimination of doxorubicin is the hepatobiliary       intake of 2 g sodium for an adult.
and perivenous extravasation that result in severe cellulitis,           dose for intravesical treatment of superficial cancer of the bladder    and hepatomegaly, oliguria, ascites, pleural effusion and gallop         system. Serum total bilirubin should be evaluated before and is 30-50 mg in 25-50 ml of physiological saline per instillation.       rhythm. Subacute effects such as pericarditis/myocarditis have           during treatment with doxorubicin. Patients with elevated bilirubin 4.5 Interaction with other medicinal products and vesication and tissue necrosis. Doxorubicin can be administered intravenously as a bolus within minutes, as a short infusion for         The optimal concentration is about 1 mg/ml. The solution should         also been reported. Life-threatening CHF is the most severe              may experience slower clearance of the drug with an increase in              other forms of interaction up to an hour, or as a continuous infusion for up to 96 hours.           remain in the bladder for 1-2 hours. During this period the patient     form of anthracycline-induced cardiomyopathy and represents              overall toxicity. Lower doses are recommended in these patients          Doxorubicin is a major substrate of cytochrome P450 CYP3A4 A direct intravenous injection is not recommended due to the             should be turned 90° every 15 minutes. To avoid undesired dilution      the cumulative dose-limiting toxicity of the drug.                       (see section 4.2). Patients with severe hepatic impairment should        and CYP2D6, and P-glycoprotein (P-gp). Clinically significant risk of extravasation, which may occur even in the presence of           with urine the patient should be informed not to drink anything         Cardiac function should be assessed before patients undergo              not receive doxorubicin (see section 4.3).                               interactions have been reported with inhibitors of CYP3A4, adequate blood return upon needle aspiration.                            for a period of 12 hours before the instillation (this should reduce    treatment with doxorubicin and must be monitored throughout                                                                                       CYP2D6, and/or P-gp (e.g., verapamil), resulting in increased Tumour-lysis syndrome                                                    concentration and clinical effect of doxorubicin. Conversely, Doxorubicin should not be administered by the intramuscular,             the production of urine to about 50 ml/h). The instillation may be      therapy to minimize the risk of incurring severe cardiac impairment.
repeated with an interval of 1 week to 1 month, dependent on                                                                                     Doxorubicin may induce hyperuricaemia as a consequence of                inducers of CYP3A4 (e.g., rifampicin, phenobarbital, phenytoin, subcutaneous, oral or intrathecal route.                                                                                                         The risk may be decreased through regular monitoring of LVEF             the extensive purine catabolism that accompanies drug-induced whether the treatment is therapeutic or prophylactic.                   during the course of treatment with prompt discontinuation of                                                                                     St. John’s Wort) and of P-gp may decrease plasma levels of Intravenous administration                                               Note: Posology of S-liposomal doxorubicin and (conventional)            doxorubicin at the first sign of impaired function. The appropriate rapid lysis of neoplastic cells (tumour-lysis syndrome) in case          doxorubicin and may thus lead to a decrease in efficacy.
of high tumour burden. In these circumstances blood uric acid
The dose is usually calculated based on body surface area                doxorubicin are different. The two formulations cannot be used          quantitative method for repeated assessment of cardiac                   levels, potassium, calcium phosphate and creatinine should be Doxorubicin hydrochloride used in combination with cyclosporin
(mg/m2). The dosage schedule of doxorubicin administration may           interchangeably.                                                        function (evaluation of LVEF) includes multi-gated radionuclide                                                                                   might require dose-adjustment. At concomitant administration evaluated after initial treatment. Hydration, urine alkalinization, vary according to indication (solid tumours or acute leukaemia)