Epicin 10

Product Description

Description

Epirubicin hydrochloride is an anthracycline cytotoxic agent, intended for intravenous administration. The pH of the solution has been adjusted to 3.0 with hydrochloric acid, NF. Epirubicin hydrochloride is the 4-epimer of doxorubicin and is a semi-synthetic derivative of daunorubicin.

Composition

Each vial contains Epirubicin Hydrochloride BP 10 mg/5 ml & 50 mg/25 ml solution for injection.

Mechanism of action

Epirubicin is an anthracycline cytotoxic agent. Epirubicin forms a complex with DNA by intercalation of its planar rings between nucleotide base pairs, with consequent inhibition of nucleic acid (DNA and RNA) and protein synthesis.

Such intercalation triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Epirubicin also inhibits DNA helicase activity, preventing the enzymatic separation of double-stranded DNA and interfering with replication and transcription. Epirubicin is also involved in oxidation/reduction reactions by generating cytotoxic free radicals..

Pharmacokinetics

Bioavailability                NA

Protein binding            77%

Metabolism   Hepatic glucuronidation and oxidation

Excretion        Biliary and renal

Indications

Epirubicin Hydrochloride is used in the treatment of a wide range of neoplastic conditions, including breast, ovarian, gastric, lung and colorectal carcinomas, malignant lymphomas, leukaemias and multiple myeloma. Intravesical administration of epirubicin hydrochloride has been found to be beneficial in the treatment of superficial bladder cancer, carcinoma-in-situ and in the prophylaxis of recurrences after transurethral resection.

Dosage and administration

Conventional doses:

When Epirubicin hydrochloride is used as a single agent, the recommended dosage in adults is 60-90 mg/m2 body area; the drug should be injected IV over 3-5 minutes and, depending on the patients’ haematomedullary status, the dose should be repeated at 21 day intervals.

High doses:

Epirubicin hydrochloride as a single agent for the treatment of lung cancer at high doses should be administered according to the following regimens:

Lung cancer

Small cell lung cancer (previously untreated): 120 mg/m2 day 1, every 3 weeks.

Non-small cell lung cancer (squamous, large cell and adenocarcinoma previously untreated):

135 mg/m2 day 1 or 45 mg/m2 days 1, 2, 3, every 3 weeks. For high dose treatment, epirubicin may be given as an intravenous bolus over 3-5 minutes or as an infusion of up to 30 minutes duration.

Breast cancer

In the adjuvant treatment of early breast cancer patients with positive lymph nodes, intravenous doses of epirubicin ranging from 100 mg/m2 (as a single dose on day 1) to 120 mg/m2 (in two divided doses on days 1 and 8) every 3-4 weeks, in combination with intravenous cyclophosphamide and 5-fluorouracil and oral tamoxifen, are recommended.

The drug should be given as an I.V. bolus over 3-5 minutes or as an infusion up to 30 minutes. Lower doses (60-75 mg/ m2 for conventional treatment and 105-120 mg/ m2 for high dose schedules) are recommended for patients whose bone marrow function has already been impaired by previous chemotherapy or radiotherapy, by age, or neoplastic bone-marrow infiltration. The total dose per cycle may be divided over 2-3 successive days.

Possible side effects

In early breast cancer, acute adverse events occurring in ≥10% of patients are leukopenia, neutropenia, anemia, thrombocytopenia, amenhorrhea, lethargy, nausea/vomiting, mucositis, diarrhea, infection, conjunctivitis/keratitis, alopecia, local toxicity and rash/itch.

Contraindications

Patients should not be treated with Epirubicin Hydrochloride Injection if they have any of the following conditions: baseline neutrophil count < 1500 cells/mm3; severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias, previous treatment with anthracyclines up to the maximum cumulative dose, hypersensitivity to epirubicin, other anthracyclines or anthracenediones or severe hepatic dysfunction.

Drug interactions

Drug interactions with epirubicin have been observed with cimetidine, dexverapamil, dexrazoxane, docetaxel, interferon alfa-2b, paclitaxel and quinine. Epirubicin used in combination with other cytotoxic agents may result in additive myelotoxicity.

Special precautions

Epirubicin should be used with caution in elderly, toxic effects are more marked because the clearance is reduced. In hepatic disease, dose reduction according to degree of hepatic failure is advised to avoid serious toxicity. It should be administered only under the supervision of a physician experienced in the use of the chemotherapy. The FDA currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Epirubicin may cause increase in skin sensitivity towards sunlight. Do not have any vaccinations during its use. Cautions should be taken in allergic patients.

How to use

Epirubicin Hydrochloride 2 mg/ml Injection may be further diluted, under aseptic conditions, in Glucose 5% or Sodium Chloride 0.9% and administered as an intravenous infusion.

Stability

solutions are stable for 24 hours when stored at 2 to 8°C (36 to 46°F).

Storage

Store refrigerated between 2°C and 8°C (36°F and 46°F). Do not freeze. Protect from light.

Presentations

Epicin® 10 mg Inj.: Each box contains one vial of Epirubicin Hydrochloride BP 10 mg Inj.