radium-223 dichloride

Action and Spectrum

Mechanism of action 

It (also known as Xofigo) is a radiopharmaceutical used to treat bone metastases in patients with prostate cancer. The mechanism of action of radium-223 dichloride is that it emits alpha particles, which are highly ionizing and can damage or kill cancer cells. The alpha particles have a concise range, typically less than 50 microns, so they only affect the cells near the radium-223 atoms. This reduces the risk of damage to healthy cells and surrounding tissue 

Spectrum 

The spectrum of activity of radium-223 dichloride is limited to bone metastases, as the alpha particles do not have enough energy to travel through soft tissue 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Anemia 

Leukopenia 

Nausea 

Vomiting peripheral edema 

All toxicity grades 

Lymphocytopenia 

Diarrhea 

Neutropenia 

1-10% 

Renal failure and impairment 

Pancytopenia 

All toxicity grades 

Dehydration 

Erythema, pain, and edema at the injection site

Black Box Warning

Contraindication / Caution

Contraindications 

It is a radiopharmaceutical that is not indicated for use in women and is contraindicated in women who are or may become pregnant because it can cause foetal harm. The alpha particles emitted by radium-223 can damage or kill cells, which can harm a developing foetus. Women who are pregnant or planning to become pregnant should not be treated with radium-223 dichloride. If a patient becomes pregnant during treatment with radium-223 dichloride, the treatment should be stopped immediately  

Caution 

• The safety and efficacy of concomitant chemotherapy have not been established for radium-223 dichloride, so outside of a clinical trial, concomitant use with chemotherapy is not recommended due to the potential for additive myelosuppression. 
• It is not recommended in combination with abiraterone acetate plus prednisone/prednisolone outside clinical trials; increased fractures and mortality have been reported. 
• It is also important to note that radiation can potentially affect spermatogenesis, so sexually active men should be advised to use condoms. Their female partners of reproductive potential should use a highly effective contraceptive method during and for six months after completing treatment. 

Pregnancy / Lactation

Pregnancy consideration: It is contraindicated in women who are or may become pregnant because it can cause foetal harm 

Lactation: Safety and efficacy not established 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

An alpha particle-emitting radiopharmaceutical is a medical imaging agent containing the radioactive element radium. It targets bone metastases and areas of increased bone turnover caused by cancer. The radium in the radiopharmaceutical mimics calcium and binds to the bone mineral hydroxyapatite, causing double-strand DNA breaks in the cancer cells at the site of the metastases, ultimately leading to their death 

Pharmacodynamics 

When administered, the radium-223 in the drug binds to bone mineral hydroxyapatite, which is present in areas of increased bone turnover, such as bone metastases. The alpha particles emitted by radium-223 cause double-strand DNA breaks in the cancer cells, leading to their death. Additionally, radium-223 dichloride also has an anti-angiogenic effect, which leads to the inhibition of new blood vessel formation and contributes to cell death 

Pharmacokinetics 

Absorption 

The absorption of Radium Ra 223 dichloride (Xofigo) is linear 

Distribution 

The drug is rapidly cleared from the blood and distributed primarily into bone or excreted into the intestine 

Metabolism 

It is an isotope that decays and is not metabolized 

Elimination/excretion 

The elimination of the drug is primarily through faecal excretion, with about 63% of the dose excreted from the body within 7 days after injection, after correcting for decay. At 48 hours after injection, the cumulative faecal excretion was 13% (range 0 -34%), and the cumulative urine excretion was 2% (range 1 -5%). 

Adminstartion

Administration 

Intravenous administration 

Before administering the drug, it is important to inspect it visually for particulate matter and discoloration to ensure it is safe for use. 

The drug is supplied as a ready-to-use IV solution and should not be diluted or mixed with other solutions. It should be administered via slow IV injection over 1 minute. 

After the injection, it is essential to flush the IV line or cannula with 0.9% NaCl before and after injection to ensure that all the drug is delivered and to prevent contamination. 

Storage 

It (Xofigo) should be stored at room temperature, below 40°C (104°F). It should be stored in its original container or an equivalent radiation shielding container to protect it from light and moisture and to ensure safe handling. 

It is important to note that the drug is radioactive and should be stored in a designated area accessible only to authorized personnel. Any spills or leaks should be handled immediately according to proper procedures and guidelines. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: radium-223 dichloride 

Pronounced: [ RAY-dee-um-Ra-223 dye-KLOR-ide ] 

Why do we use radium-223 dichloride? 

It is a radiopharmaceutical used to treat prostate cancer that has spread to the bones (bone metastases) and cannot be treated with surgery.