Contents

Epirubicin HCl

Indication

Epirubicin Hydrochloride is used, alone or with other antineoplastics, in acute leukaemias, lymphomas, multiple myeloma, and in solid tumours including Wilms’ tumour, cancer of the bladder, breast and stomach.

Dosage / Direction For Use

It is given as a single agent in usual doses of 60 to 90 mg/m2 as a single dose every 3 weeks; this dose may be divided over 2 to 3 days if desired. A regimen of 12.5 to 25 mg/m2 once a week has also been tried in palliative care. High-dose regimens of 120 mg/m2 or more every 3 weeks, or 45 mg/m2 for 3 consecutive days every 3 weeks have been used.Doses may need to be reduced if Epirubicin is given with other antineoplastics. Doses should also be reduced in patients with liver impairment and in those whose bone-marrow function is impaired by age or previous chemotherapy or radiotherapy.A total cumulative dose of 0.9 to 1 g/m2 should not generally be exceeded, because of the risk of cardiotoxicity.Epirubicin has also been given by intravesical instillation in the local treatment of bladder cancer. Instillation of 50 mg weekly as a 0.1% solution (in sodium chloride 0.9% or sterile water) for 8 weeks has been suggested, reduced to 30 mg in 50 mL weekly if chemical cystitis develops; for carcinoma in-situ, the dose may be increased, if tolerated, to 80 mg in 50 mL weekly. For the prophylaxis of recurrence in patients who have undergone transurethral resection, 50 mg weekly for 4 weeks, followed by 50 mg instilled once a month for 11 months is the suggested regimen. The solution should be retained in the bladder for 1 hour. Blood counts be made routinely during treatment with Epirubicin and cardiac function should be carefully monitored. Liver function should be assessed before if possible during therapy. Or as prescribed by the physician.

Overdosage

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Administration

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Contraindication

Epirubicin are generally contraindicated in patients with heart disease.

Special Precaution

Sections of the package insert to incorporate information related to cardiotoxicity relative to dosing with other cardiotoxic drugs and risk of infection following vaccination.Injection-Related Reactions: Epirubicin injection is administered by intravenous infusion. Venous sclerosis may result from an injection into a small vessel or from repeated injections into the same vein.Extravasation of Epirubicin during the infusion may cause local pain, severe tissue lesion (vesication, severe cellulitis), and necrosis.Hematologic: Epirubicin can suppress bone marrow function as manifested by leukopenia, thrombocytopenia and anemia.Cardiac: Do not administer Epirubicin in combination with other cardiotoxic agents unless the patient’s cardiac function is closely monitored. Patients receiving Epirubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity.Secondary Leukemia: The occurrence of secondary acute myelogenous leukemia, with or without a preleukemic phase, has been reported in patients treated with anthracyclines. Secondary leukemia is more common when such drugs are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of the anthracyclines have been escalated. These leukemia can have a short 1-3 year latency period.Coadministration with Cimetidine: Cimetidine increased the AUC of epirubicin by 50%. Stop Cimetidine treatment during treatment with Epirubicin.Male Fertility and Reproductive Outcomes: Males with female sexual partners of childbearing potential should use contraception during and after cessation of fludarabine phosphate therapy. Fludarabine phosphate may damage testicular tissue and spermatozoa. Possible sperm DNA damage raises concerns about loss of fertility and generic abnormalities in fetuses. The duration of this effect is uncertain.Laboratory Testing: Assess blood counts, including absolute neutrophil counts, and liver function before and during each cycle of therapy with Epirubicin. Perform repeated evaluations of LVEF during therapy.Inflammation following irradiation: As with other anthracyclines, administration of Epirubicin after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.

Adverse Reactions

Epirubicin cause pronounced bone-marrow depression, which may be dose-limiting. White cell count reaches the lowest-point of 10 to 15 days after a dose and usually recovers by about 21 days.The anthracyclines may produce cardiac toxicity, both as an acute, usually transient disturbance of cardiac function marked by ECG abnormalities and, sometime arrhythmias; and as a delayed, sometimes fatal, irreversible congestive heart failure, which may occur suddenly. Severe cardiotoxicity is more likely in adults receiving total cumulative doses of doxorubicin greater than 450 to 550 mg/m2, and may occur months or even years after use.Gastrointestinal disturbances include moderate or sometimes severe nausea and vomiting; stomatitis and oesophagitis may progress to ulceration. More rarely, facial flushing, conjunctivitis, and lacrymation may occur. Alopecia occurs in the majority of patients. The urine may be coloured red. Occasional hypersensitivity reactions may occur. Hyperuricaemia may occur due to tumour lysis syndrome. Doxorubicin and other anthracyclines are very irritant and thrombophlebitis and streaking of the skin over the vein used for injection has been reported; extravasation is serious and may produce extensive local necrosis and ulceration. Intravesical instillation can cause bladder and urethral irritation, haematuria, and haemorrhagic cystitis.

Drug Interaction

Cardioactlve Compounds: Do not administer Epirubicin in combination with other cardiotoxic agents unless the patient’s cardiac function is closely monitored. Patients receiving Epirubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as trastuzumab, may also be at an increased risk of developing cardiotoxicity.Cimetidine: Cimetidine increases the exposure to Epirubicin. Stop Cimetidine during treatment with Epirubicin.Other Cytotoxic Drugs: Epirubicin used in combination with other cytotoxic drugs may show on-treatment additive toxicity, especially hematologic and gastrointestinal effects.Paclitaxel: The administration of Epirubicin immediately prior to or after paclitaxel increased the systemic exposure of Epirubicin and 7-deoxydoxorubicin aglycone.Docetaxel: The administration of epirubicin immediately prior to or after docetaxel did not have an effect on the systemic exposure of epirubicin, but increase the systemic exposure of epirubicinol and 7-deoxydoxorubicin aglycone.Radiation Therapy: There are few data regarding the coadministration of radiation therapy and Epirubicin. In adjuvant trials of Epirubicin-containing CEF-120 or FEC-100 chemotherapies, breast irradiation was delayed until after chemotherapy was completed. This practice resulted in no apparent increase in local breast cancer recurrence relative to published accounts in the literature. A small number of patients received Epirubicin-based chemotherapy concomitantly with radiation therapy but had chemotherapy interrupted in order to avoid potential overlapping toxicities. It is likely that use of Epirubicin with radiotherapy may sensitize tissues to the cytotoxic action of irradiation. Administration of Epirubicin after previous radiation therapy may induce an inflammatory recall reaction at the site of the irradiation.Concomitant Therapies-Hepatic Function: Epirubicin is extensively metabolized by the liver.

Storage

Store at temperatures not exceeding 25°C.

Description

Each vial contains: Epirubicin Hydrochloride 50 mg.

Action

Pharmacology: Pharmacokinetics: After intravenous doses Epirubicin is rapidly and extensively distributed into body tissues, and undergoes metabolism in the liver, with the formation of Epirubicinol (13-hydroxyepirubicin) and appreciable amounts of glucoronide derivatives. Epirubicin is eliminated mainly in bile, with a terminal plasma elimination half-life of about 30 to 40 hours. About 10% of a dose is recovered in urine within 48 hours. Epirubicin does not cross the blood-brain barrier