When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
Change to section 4.4 - Special warnings and precautions for use
Change to wording regarding traceability
Change to section 4.6 - Pregnancy and lactation
Change to heading to include ‘Fertility’
Change to section 6.6 - Special precautions for disposal and other handling
Change to heading to “Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product”
Change to section 8 - MA number
Addition of zeros
Change to section 9 - Date of renewal of authorisation
Date of first authorisation included and date of renewal stated as ‘last renewal’.
Change to section 10 - Date of revision of the text
Changed to September 2011
Change to section 5.1 - Pharmacodynamic properties
A systematic review has also been performed involving more than 9000 cancer patients participating in 57 clinical trials. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.08 in favour of controls (95% CI: 0.99, 1.18; 42 trials and 8167 patients). An increased relative risk of thromboembolic events (RR 1.67, 95% CI: 1.35, 2.06, 35 trials and 6769 patients) was observed in patients treated with recombinant human erythropoietin. There is an increased risk for thromboembolic events in patients with cancer treated with recombinant human erythropoietin and a negative overall impact on survival cannot be excluded. The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with chemotherapy to achieve haemoglobin concentrations less than 13 g/dl, is unclear because few patients with these characteristics were included in the data reviewed. A patient-level data analysis has also been performed on more than 13,900 cancer patients (chemo-, radio-, chemoradio-, or no therapy) participating in 53 controlled clinical trials involving several epoetins. Meta-analysis of overall survival data produced a hazard ratio point estimate of 1.06 in favour of controls (95% CI: 1.00, 1.12; 53 trials and 13,933 patients) and for the cancer patients receiving chemotherapy, the overall survival hazard ratio was 1.04 (95% CI: 0.97, 1.11; 38 trials and 10,441 patients). Meta-analyses also indicate consistently a significantly increased relative risk of thromboembolic events in cancer patients receiving recombinant human erythropoietin (see Section 4.4).
26th May 2010
Change section 4.4 - Amend Section 4.4 to update the existing Pure Red Cell Aplasia (PRCA) related warnings and to advise physicians of the observed risks associated with the unapproved use of erythropoiesis stimulating agents (ESAs) to treat anaemia related to ribavirin/interferon therapy for chronic hepatitis C.
Change section 10 – Changed to 30th March 2010
4.4
Special Warnings and Precautions for Use
· Hyperkalaemia. Revisions to the existing text. · Porphyria. Addition of a warning regarding the possibility of an exacerbation of porphyria during treatment in patients with chronic renal failure.
· Porphyria. Addition of a warning regarding the possibility of an exacerbation of porphyria during treatment in patients with chronic renal failure.
4.6
Pregnancy and Lactation
· Addition of advise that, as erythropoetin is present in human milk, EPREX® should be used in caution with nursing women.
10.
DATE OF REVISION OF THE TEXT
Updated to: 3rd June 2009
Change to section 7 updated to Holmers Farm Way
Change to section 10 updated to 14th October 2008
4.2
Posology and method of administration
Change of sub heading from Adult cancer patients with symptomatic anaemia receiving chemotherapy to Treatment of patients with chemotherapy induced anaemia.
Update to section regarding haemoglobin concentration - aim for between 10 and 12g/dl. Eprex should be administered in order to increase haemoglobin to not greater than 12g/dl. Plus additional text on the administration of Eprex and monitoring of the patient.
Patients should be monitored closely to ensure that the lowest approved dose of erythropoiesis-stimulating agent (ESA) is used to provide adequate control of the symptoms of anaemia.
Addition of - In all patients, haemoglobin levels should be closely monitored due to a potential increased risk of thromboembolic events and fatal outcomes when patients are treated at haemoglobin levels above the target for the indication of use.
Paragraph added on clinical studies and additional information on tumour progression.
Addition of - This medicinal product contains less than 1 mmol sodium (23 mg) per dose i.e. essentially “sodium free”.
Addition of - In order to improve the traceability of the ESA all measures necessary and possible to ensure it should be taken (e.g. exact information on the product used should be documented in an appropriate way). Furthermore, patients should only be switched from one ESA to another under appropriate supervision.
4.8
Undesirable effects
Reclassified according to the MedDRA system organ classes.
5.1
Pharmacodynamic properties
Addition of information on studies regarding survival and tumour progression.
6.4
Special precautions for storage
Addition of - For the purpose of ambulatory use, the patient may remove EPREX from the refrigerator and store it not above 25°C for one single period of up to 3 days.
6.5
Nature and contents of container
Addition of information regarding needle safety device.
6.6
Instructions for use, handling and disposal
Addition of - Before use, leave the EPREX syringe to stand until it reaches room temperature. This usually takes between 15 and 30 minutes.
Addition of - The product is for single use only. Only take one dose of EPREX from each syringe removing unwanted solution before injection. Refer to section 3. How to use EPREX (instructions on how to inject EPREX) of the package leaflet.
Deletion of - if you know or suspect that the product has been left at room temperature for more than 60 minutes before injection
Changed to July 2008
Improved Electronic Presentation
Change from Epoetinum alfa to Epoetin alfa throughout SmPC