EBEDOXO 2MG/ML INJECTION [SIN13676P]

Product Info

EBEDOXO 2MG/ML INJECTION

[SIN13676P]

4.1 Therapeutic indications
Doxorubicin has been used successfully to produce regression in neoplastic conditions such as acute leukaemia, Wilms' tumour, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, lymphomas of both Hodgkin's and non-Hodgkin's type, bronchogenic (lung) carcinoma, thyroid carcinoma, hepatomas and ovarian carcinoma etc. The main antitumour activities are listed in Table 1. Doxorubicin is also indicated by intravesical administration in the primary management of non-metastatic carcinoma of the bladder (Tis, T1, T2).

4.2 Dose and method of administration
General Directions
The product is for single use in one patient only.
Doxorubicin injection contains no antimicrobial agent.
Discard any residue.

The use of a Pharmacy Bulk Pack should be restricted to suitably qualified pharmacists operating in suitably equipped hospital pharmacies or compounding centres.

Do not administer doxorubicin by intramuscular or subcutaneous injection.

Dosage
Care in the administration of doxorubicin will reduce the chance of perivenous infiltration. It may also decrease the chance of local reactions such as urticaria and erythematous streaking.

The recommended dosage schedule is 60 to 75 mg/m² body surface area, as a single intravenous injection administered at 21-day intervals. The lower dose should be given to patients with inadequate marrow reserves due to old age, prior therapy, or neoplastic marrow infiltration. An alternative dose schedule is 30 mg/m² on each of three successive days, repeated every four weeks. The adult dosage regimens may be suitable for paediatric cases. The recommended lifetime cumulative dose limit is doxorubicin hydrochloride 550 mg/m² body surface area. Doxorubicin has been administered as an intra-arterial infusion for one to three days at doses of 45 to 100 mg/m². It is recommended that the total cumulative dose of doxorubicin for adults aged 70 or older be restricted to 450 mg/m² body surface area.

Method of Administration
Doxorubicin Injection must be handled with care. If contact with the skin occurs, wash thoroughly with soap and water. The product contains no antimicrobial preservative. The single dose vials should be used in one patient on one occasion only. Discard any residue. The solution is to be stored under refrigeration (2°C to 8°C) and should be protected from sunlight and retained in the carton until time of use.

Protective measures
The following protective recommendations are given due to the toxic nature of this substance:

• Personnel should be trained in good technique for reconstitution and handling.

• Pregnant staff should be excluded from working with this drug.

• Personnel handling doxorubicin should wear protective clothing: goggles, gowns and disposable gloves and masks.

• A designated area should be defined for reconstitution (preferably under a laminar flow system). The work surface should be protected by disposable, plastic-backed, absorbent paper.

• All items used for reconstitution, administration or cleaning, including gloves, should be placed in high-risk waste-disposal bags for high-temperature incineration.

• Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water.

• All cleaning materials should be disposed of as indicated previously.

• In case of skin contact thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush.

• In case of contact with the eye(s), hold back the eyelid(s) and flush the affected eye(s) with copious amounts of water for at least 15 minutes. Then seek medical evaluation by a physician.

• Always wash hands after removing gloves.

Intravenous infusion

It is recommended that doxorubicin be slowly administered into the tubing of a freely running intravenous infusion of sodium chloride 0.9% injection or glucose 5% injection. The tubing should be attached to a butterfly needle inserted preferably into a large vein. The rate of administration is dependent on the size of the vein and the dosage. However, the dose should be administered in not less than three to five minutes. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration.

Local erythematous streaking along the vein as well as facial flushing may be indicative of too rapid administration. A burning or stinging sensation may be indicative of perivenous infiltration and the infusion should be immediately terminated and restarted in another vein.

Intravesical administration

The following procedure is recommended.

1. The bladder should be catheterised and emptied.

2. Add doxorubicin to a final concentration of 80 mg in 100 mL of normal saline and instil via the catheter into the bladder.

3. The catheter should be removed and the patient instructed to lie on one side. At 15-minute intervals, the patient should alternate to the opposite side over a 1-hour period.

4. The patient should be instructed not to urinate for one hour, after which the bladder should be emptied of solution.

5. The procedure should be repeated at monthly intervals.

Doxorubicin should not be administered by intramuscular or subcutaneous injection as administration by these routes will result in severe tissue necrosis.

Doxorubicin has been used in combination with other approved chemotherapeutic agents.

Though evidence is available that at least in some types of neoplastic disease combination chemotherapy is superior to single agents, the benefits and risks of such therapy have not yet been fully elucidated.

Dosage adjustments

Use in hepatic impairment
Doxorubicin dosage must be reduced if hepatic function is impaired according to the following table:

Doxorubicin should not be administered to patients with severe hepatic impairment (see section 4.3)

Use in the Elderly
A lower dose may need to be considered in elderly patients with inadequate marrow reserves due to old age. It is recommended that the total cumulative dose of doxorubicin for adults aged 70 or older be restricted to 450 mg/m² body surface area.

Other Special Populations
A lower doses or longer intervals between cycles may need to be considered for pretreated patients, obese patients, or patients with neoplastic bone marrow infiltration (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

• Hypersensitivity to doxorubicin or any other component of the product, other anthracyclines or anthracenediones.

• Pregnancy and lactation (see section 4.4 and 4.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Contraindications for intravenous (IV) use:

• persistent myelosuppression or severe stomatitis induced by previous treatment with other antitumour agents or by radiotherapy;

• presence of generalised infection;

• severe arrhythmias;

• severe myocardial insufficiency;

• recent myocardial infarction;

• severe liver impairment;

• previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin and/or anthracyclines and anthracenediones (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Contraindications for intravesical use:

• invasive tumours that have penetrated the bladder wall;

• urinary infections;

• inflammation of the bladder;

• catheterisation of the bladder (e.g., due to massive intravesical tumours);

• haematuria.