In Section 4.4 Special Warnings and Precautions for Use
An additional warning has been added advising that Abraxane should not be substituted for or with other paclitaxel formulations.
In Section 4.5 Interactions with other medicinal products and other forms of interaction
The examples of drugs known to inhibit either CYP2C8 or CYP3A4 have been expanded to include ketoconazole and other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, and nelfinavir)
In Section 4.8 Undesirable effects Table 1 has been updated to include the following effects:
bone marrow supression (very common)
severe hypersensitivity (rare)
keratitis (uncommon)
arrhythmia, supraventricular tachycardia (common)
bradycardia, cardiac arrest (rare)
pulmonary emboli, pulmonary thromboembolism (uncommon)
nail pigmentation, nail changes (common)
radiation pneumonitis (rare)
Additionally, hyperbilirubinaemia has been removed from the hepatobiliary disorders SOC and appears as increased bilirubin in the Investigations SOC
In Section 5.2 Pharmacokinetic properties the following information has been added:
In a repeat dose study with 12 patients receiving Abraxane administered intravenously at the approved dose, intrapatient variability in systemic paclitaxel exposure (AUCinf) was 19% (range = 3.21%-27.70%). There was no evidence for accumulation of paclitaxel with multiple treatment courses.
The protein binding of paclitaxel following Abraxane was evaluated by ultrafiltration. The fraction of free paclitaxel was significantly higher with Abraxane (6.2%) than with solvent-based paclitaxel (2.3%). This resulted in significantly higher exposure to unbound paclitaxel with Abraxane compared with solvent-based paclitaxel, even though the total exposure is comparable. This is possibly due to paclitaxel not being trapped in Cremophor EL micelles as with solvent-based paclitaxel.
In Section 6.3 Shelf life
The shelf-life of the unopened vials has been increased from 2 to 3 years.
For the storage of the reconstituted solution in the vial, where health care practitioners were advised to store the vials in the original carton in order to protect the product from light, a clarifying statement has been added: "Alternative light-protection may be used in the clean room."
In Section 6.4 Special precautions for storage
For the unopened vials the following text has been added:
"This medicinal product does not require any special temperature storage conditions"
In Section 7 Marketing Authorisation Holder the address has been updated
