radium Ra 223 dichloride
SOLUTION FOR INJECTION
Activimeter Dial Setting
Procedure for Xofigo®
Indication
Xofigo is indicated for the treatment of adults with castration-resistant prostate
cancer, symptomatic bone metastases and no known visceral metastases.
Radium Ra 223 dichloride (Ra-223) is primarily an alpha emitter; however, beta particles and photons (gamma
and x-rays) are also emitted during decay. The gamma radiation associated with the decay of Ra-223 and its
daughters allows for the radioactivity measurement of Xofigo with standard instruments.
The methodology used for measurement of Xofigo dosages to patients as given in this procedure may be used
as a standard operating procedure (SOP) for determining the appropriate dial setting for use with Ra-223. An
example form is provided with this procedure for recordkeeping.
Procedure for Ra-223 activimeter Dial Setting:
Step
1
A reference standard containing a secondary NIST
traceable amount of Ra-223 dichloride solution
will be provided in a vial to the facility from your
country distributor. The reference standard will
include paperwork containing the source activity
and a decay correction factor table.
Step
2
Conduct standard quality control and background
correction of the activimeter according to the
manufacturer’s instructions and facility SOPs.
Step
3
Using the paperwork that accompanies the
Ra-223 reference standard, enter the following
into the form provided:
•Activity at reference date (to 1 decimal place)
•Reference date and time
•Date and time of calibration for this activimeter
Step
4
Using the decay correction factor table included
with the Ra-223 reference standard, determine
the decay correction factor based on the number
of days between the reference date and date/time
that this dial setting is being established, and
record it on the form.
Step
5
Calculate the decay-corrected activity by
multiplying the reference activity by the decay
factor, and record on the form.
Step
7
Record the ID number of the Ra-223 reference
standard.
Step
8
Place the Ra-223 reference standard in the
activimeter, making sure the sample is centered in
the measuring chamber. Adjust the activimeter’s
dial setting according to the instrument’s
operating manual, until the activimeter reading
matches the calculated decay-corrected activity
of the reference sample, as determined in Step
5, and record this activity and dial setting on
the form. Once the dial setting is determined, it
should be used for all subsequent radioactivity
measurements of Ra-223.
Step
9
A total of 3 measurements of the Ra-223
reference standard utilizing the activimeter dial
setting for Ra-223 should be performed. Record
the results on the form. Make sure to allow
the activimeter time to return to background
level between the measurements. All repeat
measurements should be essentially the same as
determined in Step 8, but must each be within
±5% of the decay-corrected reference standard
activity; if not, repeat the measurement.
Step
10
Record the facility name, name of individual
performing calibration, e-mail address, signature,
and date completed.
Note: The licensee will not need to perform any geometrical testing.1
Step
6
Record the manufacturer, model, and serial
number of the activimeter on the form.
1. Bergeron D, Zimmerman B, Cessna J. Development of secondary standards
for 223Ra. Appl Radiat Isot. 2010;68:1367-1370.
Activimeter requirements may vary by
Agreement State regulation.
radium Ra 223 dichloride
SOLUTION FOR INJECTION
Form for Establishing an Ra-223 activimeter Dial Setting
Section 1: Decay correction of Ra-223 sample and activimeter dial setting
Activity at
reference date
[kBq]
Reference date/time;
mm/dd/yy; hh:mm
Date/time of
dial setting
determination
of activimeter
mm/dd/yy; hh:mm
(Step 3)
(Step 3)
(Step 3)
Activimeter: manufacturer, model, serial number
(Step 6)
(Step 6)
(Step 6)
Decay factor
(from decay
correction
table)
Decay-corrected
activity of Ra-223
reference sample
[kBq]
(Step 4)
(Step 5)
Reference
sample ID
number
Dial setting
(calibration number)
for Ra-223
(Step 7)
(Step 8)
Section 2: Measurements (Note: first and second repeat measurements should be essentially the same
[ie, within 5% of the decay-corrected reference standard activity as obtained in Step 8])
Activity measurement
at calibrated dial setting
[kBq]
Activity measurement at
calibrated dial setting
[kBq]
Second repeat activity
measurement [kBq]
(Step 8)
(Step 9)
(Step 9)
Facility name
(Step 10)
Performed by (print name)
E-mail address
(Step 10)
(Step 10)
Signature and date
(Step 10)
(Step 10)
radium Ra 223 dichloride
SOLUTION FOR INJECTION
For further information, please visit www.xofigo.com
© 2013 Bayer Pharma AG. November 2013
G.SM.ON.10.2013.0838
Essential Information
Xofigo 1000 kBq/mL solution for injection (Refer to full Summary of Product Characteristics before prescribing). • Composition1: Active ingredient: radium Ra 223 dichloride (radium-223 dichloride, 1000 kBq/mL, corresponding
to 0.53 ng radium-223 at the reference date). Each vial contains 6 mL of solution (6.0 MBq radium-223 dichloride
at the reference date). Excipients1: Water for injections, sodium citrate, sodium chloride, hydrochloric acid,
dilute.
• I ndication: Treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases
and no known visceral metastases. Xofigo should be administered only by persons authorised to handle
radiopharmaceuticals in designated clinical settings.
• Contraindications:
There are no known contraindications.
• Warnings and Precautions: Bone marrow suppression, notably thrombocytopenia, neutropenia, leukopenia and
pancytopenia, has been reported. Haematological evaluation of patients must be performed at baseline and
prior to every dose. In case there is no recovery in values for absolute neutrophil count (ANC) and haemoglobin
within 6 weeks after the last administration of Xofigo despite receiving standard of care, further treatment with
Xofigo should only be continued after careful benefit/risk evaluation. Patients with evidence of compromised
bone marrow reserve e.g. following prior cytotoxic chemotherapy and/or radiation treatment (EBRT) or patients
with advanced diffuse infiltration of the bone (EOD4; “superscan”), should be treated with caution as an
increased incidence of haematological adverse reactions such as neutropenia and thrombocytopenia has
been observed. Limited available data indicate that patients receiving chemotherapy after Xofigo had a similar
haematological profile compared to patients receiving chemotherapy after placebo. Crohn’s disease and
ulcerative colitis: due to the faecal excretion of Xofigo, radiation may lead to aggravation of acute inflammatory
bowel disease, therefore Xofigo should only be administered to these patients after a careful benefit-risk
assessment. In patients with untreated imminent or established spinal cord compression, treatment with
standard of care, as clinically indicated, should be completed before starting or resuming treatment with Xofigo.
In patients with bone fractures, orthopaedic stabilisation of fractures should be performed before starting
or resuming treatment with Xofigo. In patients treated with bisphosphonates and Xofigo, an increased risk of
development of osteonecrosis of the jaw (ONJ) cannot be excluded. In the phase III study, cases of ONJ have
been reported in 0.67% patients (4/600) in the Xofigo arm compared to 0.33% patients (1/301) in the placebo
arm. However, all patients with ONJ were also exposed to prior or concomitant bisphosphonates and prior
chemotherapy. Xofigo contributes to a patient’s overall long-term cumulative radiation exposure and therefore
may be associated with an increased risk of cancer and hereditary defects. No cases of Xofigo-induced cancer
have been reported in clinical trials in follow-up of up to three years. Depending on the volume administered,
this medicinal product can contain up to 2.35 mmol (54 mg) sodium per dose.
• Undesirable effects: Very common: thrombocytopenia, diarrhoea, vomiting, nausea; Common: neutropenia,
pancytopenia, leukopenia, injection site reactions; Uncommon: lymphopenia.
• Classification for supply: Medicinal product subject to restricted medical prescription.
• Marketing Authorisation Holder: Bayer Pharma AG. 13342 Berlin. Germany.
• Date of revision of the underlying Prescribing Information: November 2013.
1
List of excipients should only be included when required according to national legislation.