August 29, 2016
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### Xofigo

"A Louisiana-based biopharmaceutical company is betting that its experimental immunotherapeutic vaccine can keep previously untreated prostate cancer in check.

The company, OncBioMune Pharnaceuticals, Inc, in Baton Rouge, is planning t"...

## Xofigo

Indications
Dosage
How Supplied

### INDICATIONS

Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

#### Recommended Dosage

The dose regimen of Xofigo is 55 kBq (1.49 microcurie) per kg body weight, given at 4 week intervals for 6 injections. Safety and efficacy beyond 6 injections with Xofigo have not been studied.

The volume to be administered to a given patient should be calculated using the:

• Patient's body weight (kg)
• Dosage level 55 kBq/kg body weight or 1.49 microcurie/kg body weight
• Radioactivity concentration of the product (1,100 kBq/mL; 30 microcurie/mL) at the reference date
• Decay correction factor to correct for physical decay of radium-223.

The total volume to be administered to a patient is calculated as follows:

 Volume to be administered (mL) = Body weight in kg × 55 kBq/kg body weight Decay factor × 1,100 kBq/mL

or

The total volume to be administered to a patient is calculated as follows:

 Volume to be administered (mL) = Body weight in kg ×1.49 microcurie/kg body weight Decay factor ×30 microcurie/mL

Table 1: Decay Correction Factor Table

 Days from Reference Date Decay Factor Days from Reference Date Decay Factor -14 2.296 0 0.982 -13 2.161 1 0.925 -12 2.034 2 0.870 -11 1.914 3 0.819 -10 1.802 4 0.771 -9 1.696 5 0.725 -8 1.596 6 0.683 -7 1.502 7 0.643 -6 1.414 8 0.605 -5 1.330 9 0.569 -4 1.252 10 0.536 -3 1.178 11 0.504 -2 1.109 12 0.475 -1 1.044 13 0.447 14 0.420 The Decay Correction Factor Table is corrected to 12 noon Central Standard Time (CST). To determine the decay correction factor, count the number of days before or after the reference date. The Decay Correction Factor Table includes a correction to account for the 7 hour time difference between 12 noon Central European Time (CET) at the site of manufacture and 12 noon US CST, which is 7 hours earlier than CET.

Immediately before and after administration, the net patient dose of administered Xofigo should be determined by measurement in an appropriate radioisotope dose calibrator that has been calibrated with a National Institute of Standards and Technology (NIST) traceable radium-223 standard (available upon request from Bayer) and corrected for decay using the date and time of calibration. The dose calibrator must be calibrated with nationally recognized standards, carried out at the time of commissioning, after any maintenance procedure that could affect the dosimetry and at intervals not to exceed one year.

Administer Xofigo by slow intravenous injection over 1 minute.

Flush the intravenous access line or cannula with isotonic saline before and after injection of Xofigo.

#### Instructions For Use/Handling

##### General Warning

Xofigo (an alpha particle-emitting pharmaceutical) should be received, used and administered only by authorized persons in designated clinical settings. The receipt, storage, use, transfer and disposal Xofigo are subject to the regulations and/or appropriate licenses of the competent official organization.

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

The administration of Xofigo is associated with potential risks to other persons (e.g., medical staff, caregivers and patient's household members) from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations.

For Drug Handling

Follow the normal working procedures for the handling of radiopharmaceuticals and use universal precautions for handling and administration such as gloves and barrier gowns when handling blood and bodily fluids to avoid contamination. In case of contact with skin or eyes, the affected area should be flushed immediately with water. In the event of spillage of Xofigo, the local radiation safety officer should be contacted immediately to initiate the necessary measur ements and requir ed procedur es to decontaminate the area. A complexing agent such as 0.01 M ethylene-diaminetetraacetic acid (EDTA) solution is recommended to remove contamination.

For Patient Care

Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. When handling bodily fluids, simply wearing gloves and hand washing will protect caregivers. Clothing soiled with Xofigo or patient fecal matter or urine should be washed promptly and separately from other clothing.

Radium-223 is primarily an alpha emitter, with a 95.3% fraction of energy emitted as alpha-particles. The fraction emitted as beta-particles is 3.6%, and the fraction emitted as gamma-radiation is 1.1%. The external radiation exposure associated with handling of patient doses is expected to be low, because the typical treatment activity will be below 8,000 kBq (216 microcurie). In keeping with the As Low As Reasonably Achievable (ALARA) principle for minimization of radiation exposure, it is recommended to minimize the time spent in radiation areas, to maximize the distance to radiation credits, and to use adequate shielding. Any unused product or materials used in connection with the preparation or administration are to be treated as radioactive waste and should be disposed of in accordance with local regulations.

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

##### Instructions For Preparation

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Xofigo is a ready-to-use solution and should not be diluted or mixed with any solutions. Each vial is for single use only.

##### Dosimetry

The absorbed radiation doses in major organs wer e calculated based on clinical biodistribution data in five patients with castration-resistant prostate cancer. Calculations of absorbed radiation doses were performed using OLINDA/EXM (Organ Level INternal Dose Assessment/EXponential Modeling), a software program based on the Medical Internal Radiation Dose (MIRD) algorithm, which is widely used for established beta and gamma emitting radionuclides. For radium-223, which is primarily an alpha particle-emitter, assumptions were made for intestine, red marrow and bone/osteogenic cells to provide the best possible absorbed radiation dose calculations for Xofigo, considering its observed biodistribution and specific characteristics.

The calculated absorbed radiation doses to differ ent organs are listed in Table 2. The organs with highest absorbed radiation doses were bone (osteogenic cells), red marrow, upper large intestine wall, and lower large intestine wall. The calculated absorbed doses to other organs are lower.

Table 2: Calculated Absorbed Radiation Doses to Organs

 Target Organ Mean (Gy/MBq) Mean (rad/mCi) Coefficient of Variation (%) Adrenals 0.00012 0.44 56 Brain 0.00010 0.37 80 Breasts 0.00005 0.18 120 Gallbladder wall 0.00023 0.85 14 LLI1 wall 0.04645 171.88 83 Small intestine wall 0.00726 26.87 45 Stomach wall 0.00014 0.51 22 ULI2 wall 0.03232 119.58 50 Heart wall 0.00173 6.40 42 Kidneys 0.00320 11.86 36 Liver 0.00298 11.01 36 Lungs 0.00007 0.27 90 Muscle 0.00012 0.44 41 Ovaries 0.00049 1.80 40 Pancreas 0.00011 0.41 43 Red marrow 0.13879 513.51 41 Osteogenic cells 1.15206 4262.60 41 Skin 0.00007 0.27 79 Spleen 0.00009 0.33 54 Testes 0.00008 0.31 59 Thymus 0.00006 0.21 109 Thyroid 0.00007 0.26 96 Urinary bladder wall 0.00403 14.90 63 Uterus 0.00026 0.94 28 Whole body 0.02311 85.50 16 1LLI: lower large intestine 2ULI: upper large intestine

### HOW SUPPLIED

#### Dosage Forms And Strengths

Xofigo (radium Ra 223 dichloride injection) is available in single-use vials containing 6 mL of solution at a concentration of 1,100 kBq/mL (30 microcurie/mL) at the reference date with a total radioactivity of 6,600 kBq/vial (178 microcurie/vial) at the reference date.

#### Storage And Handling

Xofigo (radium Ra 223 dichloride injection) is supplied in single-use vials containing 6 mL of solution at a concentration of 1,100 kBq/mL (30 microcurie/mL) with a total radioactivity of 6,600 kBq/vial (178 microcurie/vial) at the reference date (NDC 50419-208-01).

Store at room temperature, below 40° C (104° F). Store Xofigo in the original container or equivalent radiation shielding.

This preparation is approved for use by persons under license by the Nuclear Regulatory Commission or the relevant regulatory authority of an Agreement State.

Manufactured for: Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 07981. Manufactured in Norway. Revised: Mar 2016

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 4/4/2016

Indications
Dosage
How Supplied

### Xofigo FDA Prescribing Information

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## Xofigo

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