Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2012 Publisher: Novartis Pharmaceuticals UK Limited Frimley Business Park Frimley Camberley Surrey GU16 7SR
Prevention of chronic cumulative cardiotoxicity caused by doxorubicin or epirubicin use in advanced and/or metastatic adult breast cancer patients who have received a prior cumulative dose of 300 mg/m² of doxorubicin or a prior cumulative dose of 540 mg/m² of epirubicin when further anthracycline treatment is required.
CARDIOXANE is administered by a short intravenous infusion (15 minutes), approximately 30 minutes prior to anthracycline administration at a dose equal to 10 times the doxorubicin-equivalent dose and 10 times the epirubicin-equivalent dose.
Thus it is recommended that CARDIOXANE is given at a dose of 500 mg/m2 when the commonly used dosage schedule for doxorubicin of 50 mg/m2 is employed or 600 mg/m2 when the commonly used dosage schedule for epirubicin of 60 mg/m2 is employed.
CARDIOXANE is contraindicated in children and adolescents up to 18 years of age (see section 4.3).
In patients with moderate to severe renal dysfunction (creatinine clearance <40ml/min) the dexrazoxane dose should be reduced by 50%.
The dosage ratio should be kept, i.e., if the anthracycline dose is reduced the dexrazoxane dose should be reduced accordingly.
Intravenous use.
For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
The signs and symptoms of overdose are likely to consist of leucopenia, thrombocytopenia, nausea, vomiting, diarrhoea, skin reactions and alopecia. There is no specific antidote and symptomatic treatment should be provided.
Management should include prophylaxis and treatment of infections, fluid regulation, and maintenance of nutrition.
Before opening: 3 years.
After reconstitution and dilution: Chemical and physical in-use stability of reconstituted and subsequently diluted CARDIOXANE is 4 hours at 25°C.
From a microbiological point of view, reconstituted and subsequently diluted CARDIOXANE should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user, and should not be longer than 4 hours at 2°C to 8°C (in the refrigerator) with protection from light.
Before opening: Do not store above 25°C. In order to protect from light store in the original package.
Prescribers should refer to national or recognised guidelines on handling cytotoxic agents when using CARDIOXANE. Reconstitution should only be carried out by trained staff in a cytotoxic designated area. The preparation should not be handled by pregnant staff.
Use of gloves and other protective clothing to prevent skin contact is recommended. Skin reactions have been reported following contact with CARDIOXANE. If CARDIOXANE powder or solution contacts the skin or mucosal surfaces, the affected area should immediately be rinsed thoroughly with water.
For reconstitution the contents of each vial should be dissolved in 25 ml Water for Injections. The vial contents will dissolve within a few minutes with gentle shaking. The resultant solution has a pH of approximately 1.6. This solution should be further diluted before administration to the patient.
To avoid the risk of thrombophlebitis at the injection site, CARDIOXANE should be diluted prior to infusion with one of the solutions mentioned in the table below. Preferably solutions with a higher pH should be used. The final volume is proportional to the number of vials of CARDIOXANE used and the amount of infusion fluid for dilution, which can be between 25 ml and 100 ml per vial.
The table below summarises the final volume and the approximate pH of reconstituted and diluted product for one vial and four vials of CARDIOXANE. The minimum and maximum volumes of infusion fluids to be used per vial are shown below.
| Infusion fluid used for dilution | Volume of fluid used to dilute 1 vial of reconstituted CARDIOXANE | Final volume from 1 vial | Final volume from 4 vials | pH (approximate) |
| Ringer Lactate | 25 ml | 50 ml | 200 ml | 2.2 |
| 100 ml | 125 ml | 500 ml | 3.3 | |
| 0.16M Sodium Lactate* | 25 ml | 50 ml | 200 ml | 2.9 |
| 100 ml | 125 ml | 500 ml | 4.2 |
* Sodium Lactate 11.2% should be diluted by a factor of 6 to reach a concentration of 0.16M
The use of larger dilution volumes (with a maximum of 100 ml of additional infusion fluid per 25 ml reconstituted CARDIOXANE) is usually recommended to increase the pH of the solution. Smaller dilution volumes (with a minimum of 25 ml of additional infusion fluid per 25 ml reconstituted CARDIOXANE) can be used if needed, based on the haemodynamic status of the patient.
CARDIOXANE is for single use only. Reconstituted and subsequently diluted product should be used immediately or within 4 hours if stored between 2°C and 8°C.
Parenteral drug products should be inspected visually for particulate matter whenever the solution and container permit. CARDIOXANE is normally a colourless to yellow solution immediately on reconstitution, but some variability in colour may be observed over time, which does not indicate loss of activity if the product has been stored as recommended. It is however recommended to dispose of the product if the colour immediately on reconstitution is not colourless to yellow.
Any unused solution should be discarded in accordance with local requirements. Adequate care and precaution should be taken in the disposal of items used to reconstitute and dilute CARDIOXANE.
Vials (Type I brown glass), containing 500 mg of powder, closed with a chlorobutyl rubber stopper and an aluminium cap with pre-cut strip. The product is further enclosed in an outer carton. It is supplied in packs of 1 and 4 vials. Not all pack sizes may be marketed.
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