Neoquabin Special Precautions

Patients with hepatic dysfunction; Patients with renal dysfunction; Patients with myelosuppression; Patients with infectious complication; The elderly; Patients with chickenpox. (The fatal systemic disorder may occur.); Patients with experience the heart failure of the type described for other anthracyclines.
General: EPIRUBICIN Injection should be administered only under the supervision of qualified physicians experienced in the use of cytotoxic therapy. Before initial treatment with epirubicin, patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) of prior cytotoxic treatment. Also, initial treatment with EPIRUBICIN should be preceded by a careful baseline assessment of blood counts; serum levels of total bilirubin, AST, and creatinine; and cardiac function as measured by left ventricular ejection function (LVEF). Patients should be carefully monitored during treatment for possible clinical complications due to myelosuppression. Supportive care may be necessary for the treatment of severe neutropenia and severe infectious complications. Monitoring for potential cardiotoxicity is also important, especially with greater cumulative exposure to epirubicin.
Cardiotoxicity is a known risk of anthracycline treatment. Anthracycline-induced cardiac toxicity may be manifested by early (or acute) or late (delayed) events. Early cardiac toxicity of epirubicin consists mainly of sinus tachycardia and/or ECG abnormalities such as non-specific ST-T wave changes, but tachyarrhythmias, including premature ventricular contractions and ventricular tachycardia, bradycardia, as well as atrioventricular and bundle-branch block have also been reported. These effects do not usually predict subsequent development of delayed cardiotoxicity, are rarely of clinical importance, and are generally not considered an indication for the suspension of epirubicin treatment. Delayed cardiac toxicity results from a characteristic cardiomyopathy that is manifested by reduced LVEF and/or signs and symptoms of congestive heart failure (CHF) such as tachycardia, dyspnea, pulmonary edema, dependent edema, hepatomegaly, ascites, pleural effusion, gallop rhythm. Life-threatening CHF is the most severe form of anthracycline-induced cardiomyopathy. This toxicity appears to be dependent on the cumulative dose of EPIRUBICIN and represents the cumulative dose-limiting toxicity of the drug. If it occurs, delayed cardiotoxicity usually develops late in the course of therapy with EPIRUBICIN or within 2 to 3 months after completion of treatment, but later events (several months to years after treatment termination) have been reported.
In a retrospective survey, including 9144 patients, mostly with solid tumors in advanced stages, the probability of developing CHF increased with increasing cumulative doses of EPIRUBICIN. The estimated risk of epirubicin-treated patients developing clinically evident CHF was 0.9% at a cumulative dose of 550 mg/m², 1.6% at 700 mg/m², and 3.3% at 900 mg/m². The risk of developing CHF in the absence of other cardiac risk factors increased steeply after an epirubicin cumulative dose of 900 mg/m².
In another retrospective survey of 469 epirubicin-treated patients with metastatic or early breast cancer, the reported risk of CHF was comparable to that observed in the larger study of over 9000 patients.
Given the risk of cardiomyopathy, a cumulative dose of 900 mg/m² EPIRUBICIN should be exceeded only with extreme caution. Risk factors (active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, concomitant use of other drugs with the ability to suppress cardiac contractility) may increase the risk of cardiac toxicity. Although not formally tested, it is probable that the toxicity of epirubicin and other anthracyclines or anthracenediones is additive. Cardiac toxicity with EPIRUBICIN may occur at lower cumulative doses whether or not cardiac risk factors are present.
Although endomyocardial biopsy is recognized as the most sensitive diagnostic tool to detect anthracycline-induced cardiomyopathy, this invasive examination is not practically performed on a routine basis. Electrocardiogram (ECG) changes such as dysrhythmias, a reduction of the QRS voltage, or a prolongation beyond normal limits of the systolic time interval may be indicative of anthracycline-induced cardiomyopathy, but ECG is not a sensitive or specific method for following anthracycline-related cardiotoxicity. The risk of serious cardiac impairment may be decreased through regular monitoring of LVEF during the course of treatment with prompt discontinuation of EPIRUBICIN at the first sign of impaired function. The preferred method for repeated assessment of cardiac function is evaluation of LVEF measured by multi-gated radionuclide angiography (MUGA) or echocardiography (ECHO). A baseline cardiac evaluation with an ECG and a MUGA scan or an ECHO is recommended, especially in patients with risk factors for increased cardiac toxicity. Repeated MUGA or ECHO determinations of LVEF should be performed, particularly with higher, cumulative anthracycline doses. The technique used for assessment should be consistent through follow-up. In patients with risk factors, particularly prior anthracycline or anthracenedione use, the monitoring of cardiac function must be particularly strict and the risk-benefit of continuing treatment with EPIRUBICIN in patients with impaired cardiac function must be carefully evaluated. Special attention must be given to the infection and bleeding tendency exhibited by Epirubicin.
In case of prescription to a child and a patient with generative power, consider effect on sexual gland.
Cautions of Application: Epirubicin must not be given by the intramuscular or subcutaneous route.
Avoid intraperitoneal prescribing because of danger of intestinal obstruction.
Since intravenous administration may cause vascular pain, phlebitis, thrombus, site of injection and administration method should be cautioned, and administered as slow as possible.
Induration, necrobiosis may occur due to extravasation of the solution in intravenous injection.
Therefore, intravenous administration should be cautioned not to leak the solution.
Because stability may be reduced due to pH change in dissolving, avoid using together other medicine and dissolve in water for injection or a saline solution for injection.
Reconstituted solution should be used immediately.
Others: Epirubicin imparts a red coloration to the urine after administration and patients should be advised to expect this during active therapy. Tumors have been reported in the animal test with rat intravenously. Epirubicin is recognized as mutagenic for bacterium. Acute leukemia and preleukemia myelodysplastic syndrome (MSD) is reported to the patients with concomitant administration of Epirubicin and other antineoplastics.
Use in Pregnancy & Lactation: There is conclusive information as to whether Epirubicin may adversely affect human fertility or cause teratogenesis.
Experimental data, however, suggest that Epirubicin may harm the fetus and should, therefore, not be administered to pregnant women or to mothers who are breast feeding.
Use in Children: Use in children should be cautioned about manifestation of adverse effects.