XOFIGO Solution for injection Ref.[9648] Active ingredients: Radium-223 dichloride

Xofigo should be administered only by persons authorised to handle radiopharmaceuticals in designated clinical settings (see section 6.6) and after evaluation of the patient by a qualified physician.

Posology

The dose regimen of Xofigo is an activity of 55 kBq per kg body weight, given at 4 week intervals for 6 injections.

Safety and efficacy beyond 6 injections with Xofigo have not been studied.

For details on the calculation of the volume to be administered see section 12.

Special populations

Elderly

No overall differences in safety or efficacy were observed between elderly (aged ≥65 years) and younger patients (aged <65 years) in the phase III study.

No dose adjustment is considered necessary in elderly patients.

Hepatic impairment Safety and efficacy of Xofigo have not been studied in patients with hepatic impairment.

Since radium-223 is neither metabolised by the liver nor eliminated via the bile, hepatic impairment is not expected to affect the pharmacokinetics of radium-223 dichloride.

No dose adjustment is considered necessary in patients with hepatic impairment.

Renal impairment

In the phase III clinical study, no relevant differences in safety or efficacy were observed between patients with mild renal impairment (creatinine clearance [CLCR]: 50 to 80 mL/min) and normal renal function. Limited data are available for patients with moderate (CLCR: 30 to 50 mL/min) renal impairment. No data are available for patients with severe (CLCR <30 mL/min) renal impairment or end-stage renal disease. However, since excretion in urine is minimal and the major route of elimination is via the faeces, renal impairment is not expected to affect the pharmacokinetics of radium-223 dichloride.

No dose adjustment is considered necessary in patients with renal impairment.

Paediatric population

There is no relevant use of Xofigo in the paediatric population in the indication of prostate cancer.

Method of administration

Xofigo is for intravenous use. It must be administered by slow injection (generally up to 1 minute).

The intravenous access line or cannula must be flushed with isotonic sodium chloride 9 mg/mL (0.9%) solution for injection before and after injection of Xofigo.

For additional instructions on the use of the medicinal product, see sections 6.6 and 12.

There have been no reports of inadvertent overdosing of Xofigo during clinical studies.

There is no specific antidote. In the event of an inadvertent overdose, general supportive measures, including monitoring for potential haematological and gastrointestinal toxicity should be undertaken.

Single Xofigo doses containing an activity of up to 276 kBq per kg body weight were evaluated in a phase I clinical trial and no dose-limiting toxicities were observed.

Shelf life: 28 days.

This medicinal product does not require any special temperature storage conditions. Storage of Xofigo should be in accordance with national regulation on radioactive materials.

Colourless Type I glass vial closed with a grey bromobutyl rubber stopper either with or without foil-clad made of Ethylene tetrafluoroethylene (ETFE), both capped with aluminium seal, containing 6 mL of solution for injection.

The vial is stored in a lead pot.

General warnings

Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of the competent official organisation.

Xofigo should be handled in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Radiation protection

The gamma radiation associated with the decay of radium-223 and its daughters allows for the radioactivity measurement of Xofigo and the detection of contaminations with standard instruments.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, faeces, vomiting etc. Radiation protection precautions in accordance with national regulations must therefore be taken. Care should be used when handling materials, such as bed linen, that come into contact with such body fluids. Although radium-223 is predominantly an alpha emitter, gamma and beta radiation is associated with the decay of radium-223 and its radioactive daughter isotopes. The external radiation exposure associated with handling of patient doses is considerably lower in comparison to other radiopharmaceuticals for therapeutic purposes as the administered radioactivity will usually be below 8 MBq. However, in keeping with the ALARA (“As Low As Reasonably Achievable”) principle, for minimisation of radiation exposure, it is recommended to minimise the time spent in radiation areas, to maximise the distance to radiation sources, and to use adequate shielding.

Any unused product or waste materials should be disposed of in accordance with local regulations. Any materials used in connection with the preparation or administration of Xofigo are to be treated as radioactive waste.