ADRIAMYCIN SOLUTION FOR INJECTION 2 MG/ML [SIN10566P]

Product Info

ADRIAMYCIN SOLUTION FOR INJECTION 2 MG/ML

[SIN10566P]

4.1 Therapeutic indications

ADRIAMYCIN 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, ovarian carcinoma, etc. The main antitumour activities are listed in Table 1. ADRIAMYCIN 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

Dosage

Care in the administration of ADRIAMYCIN 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 60–75 mg/m² 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, or prior therapy, or neoplastic marrow infiltration.

An alternative dose schedule is 30 mg/m² on each of three successive days repeated every 4 weeks. The adult dosage regimens may be suitable for paediatric cases.

The recommended lifetime cumulative dose limit is 550 mg doxorubicin/m² body surface area. ADRIAMYCIN has been administered as an intra-arterial infusion for 1–3 days at doses of 45–100 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

ADRIAMYCIN must be handled with care. If contact with the skin occurs, wash thoroughly with soap and water.

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 ADRIAMYCIN be slowly administered into the tubing of a freely running intravenous infusion of sodium chloride solution for injection or 5% glucose solution for 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 3–5 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. Dilute ADRIAMYCIN 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 be 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 requested not to urinate for 1 hour, after which the bladder should be emptied of solution.

5. The procedure should be repeated at monthly intervals.

Until specific compatibility data are available, it is not recommended that ADRIAMYCIN be mixed with other drugs. Contact with alkaline solutions should be avoided since this can lead to hydrolysis of doxorubicin. ADRIAMYCIN should not be mixed with heparin due to chemical incompatibility that may lead to precipitation.

Doxorubicin should not be mixed with fluorouracil (e.g., in the same IV infusion bag or at the Y-site of an IV infusion line) since it has been reported that these drugs are incompatible to the extent that a precipitate might form. If concomitant therapy with doxorubicin and fluorouracil is required, it is recommended that the IV line be flushed between the administration of these drugs. Also see Section 6.2 Incompatibilities – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

ADRIAMYCIN 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 Contraindications).

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 Special warnings and precautions for use – 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 Sections 4.4 Special warnings and precautions for use and 4.6 Fertility, pregnancy and lactation – 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 other anthracyclines and anthracenediones (see Section 4.4 Special warnings and precautions for use – 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.