Radium-223 Dichloride - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

What Is Radium-233 Dichloride?

As more people learned about advanced prostate cancer that has spread to the bones, doctors started working on new targeted ways to treat it. Radium-223 is a radioactive drug that was created to help treat bone tumors in men with prostate cancer that don't respond to other treatments. It works by sending alpha particles straight to bone cancer areas. This helps kill cancer cells while causing minimal damage to healthy tissue around them. Radium-223 treatments can help people live longer and feel less pain in their bones, but they don't cure the cancer.

Medication by itself is not enough to properly control the disease. Managing pain, hormonal therapies, regular monitoring, and emotional support are all important parts of comprehensive care for people with advanced prostate cancer who want to improve their general quality of life.

FDA-Approval Date

Radium 223 was granted approval by the FDA (Food and Drug Administration) on May 15, 2013, for the treatment of men with metastatic castrate-resistant prostate cancer after a phase III randomized trial that showed increased overall survival rates.

Drug Group:

Radium-233 dichloride belongs to the group of inorganic compounds called alkaline earth metal chlorides. The presence of chlorine characterizes these compounds as the largest halogen atom and lanthanide as the heaviest metal atom.

Uses of Radium-223 Dichloride:

Radium-223 dichloride treatment is an advanced cancer treatment used for patients with castration-resistant prostate cancer, a type of prostate cancer that continues to grow even after hormone-lowering therapy. It is usually given to patients whose cancer has progressed despite previous treatments or when other treatment options are no longer suitable.

This medicine is used when the cancer has spread to the bones and is causing symptoms, but it Hhas not spread to other major organs such as the liver or lungs.

Dosage and Administration:

• Recommended Dose: Radium-233 dichloride is administered at 50 kBq (kilo becquerel) per kg body weight at four weekly intervals for six injections.

• Dosage Forms and Strengths: Radium-223 dichloride injection is provided in single-use vials. Each contains a 6 mL solution with a total radioactivity of 6,000 kBq/vial (162 microcurie/vial) at the reference date.

• Dosage Calculations: The dose of radium-223 dichloride is calculated based on the patient’s body weight.

  • The recommended dose is 50 kBq per kg of body weight (or 1.35 microcurie per kg).

  • The injection has a radioactivity concentration of 1,000 kBq/mL (27 microcurie/mL) on the reference date.

  • Because radium-223 naturally decays over time, a decay factor is used to correct the dose before administration.

Administration:

An intravenous injection of Radium-233 dichloride can be administered gradually over a minute.

Contraindications:

Since Radium-233 dichloride may have negative effects on the fetus, it should not be given during pregnancy.

Warnings and Precautions:

• Bone Marrow Depression: Blood counts should be checked at the start of treatment and before each dose of radium-223 dichloride to detect possible bone marrow suppression. If blood counts do not improve within 6 to 8 weeks, the treatment should be discontinued. Patients with already low bone marrow reserves require close monitoring, and therapy should be stopped if they develop severe or life-threatening complications that cannot be managed with supportive care.

For Patients:

Things to Know Before Injecting Radium -233 Dichloride

• Radium-233 dichloride should not be combined with Abiraterone and Prednisolone, as it may increase the risk of bone fractures and death rates.

• If the patient is to be administered Radium-233 dichloride after treatment with Abiraterone and Prednisolone, the patient must wait 5 days before commencing treatment.

• If the patient has to undergo other chemotherapy after Radium-233 dichloride, then the patient has to wait for at least 30 days before starting the therapy. If the patient is taking calcium, phosphate, or vitamin D supplements, the doctor will stop these medications for a period before the commencement of treatment.

Side Effects of Radium-223

Like many medicines used in cancer treatment, radium-223 dichloride can cause some side effects. These effects vary from person to person, and not everyone will experience them.

• Common Blood-Related - The drug can lower platelet levels (thrombocytopenia) and certain white blood cells, which may increase the risk of bleeding and infections. Patients should contact a doctor if they notice unusual bruising, excessive bleeding, fever, or frequent infections.

• Common Side Effects - Some commonly reported effects include nausea, vomiting, diarrhea, and bone fractures.

• Dehydration Risk - Some patients may develop dehydration. Warning signs include decreased urination, dry skin, dizziness, and intense thirst. Drinking enough fluids is important, and any symptoms of dehydration should be reported to a healthcare provider promptly.

• Changes in the Blood Cell Count - In some cases, all three major types of blood cells, red blood cells, white blood cells, and platelets, may decrease together, a condition known as pancytopenia.

• Less Common Side Effects - These include a decrease in lymphocytes (a type of white blood cell) known as lymphopenia, and weakening of bones due to osteoporosis.

• Jaw-Related Complications -

  • Patients should seek medical attention if they develop symptoms such as jaw pain, swelling, numbness, a feeling of heaviness in the jaw, or loose teeth.

  • In rare cases, a condition called osteonecrosis of the jaw, where bone tissue in the jaw begins to die, has been reported.

  • This has mostly been seen in patients who were also taking medications called bisphosphonates before or during treatment.

• Injection-Site Reactions - After the injection, some people may experience mild reactions where the drug was given, such as pain, swelling, or redness of the skin.

For Doctors:

Clinical Pharmacology:

• Mechanism of Action: Radium-223 dichloride works by behaving like calcium in the body. It attaches to areas in the bones where cancer has spread and where bone activity is high. The drug releases alpha radiation, which damages the DNA of nearby cancer cells and helps destroy them. The radiation travels only a very short distance, so damage to surrounding healthy tissues is limited.

• Pharmacodynamics: Studies have shown that radium-223 treatment can improve several blood markers of bone activity. These markers indicate changes in bone formation and bone breakdown, suggesting that the drug helps control disease activity in bones affected by cancer.

• Pharmacokinetics: After being injected into a vein, radium-223 quickly leaves the bloodstream and mainly moves to the bones. A small amount remains in the blood for a short time. Within minutes, the drug can also be found in the bone and the digestive system. Very little is taken up by other organs such as the heart, liver, kidneys, bladder, or spleen.

• Metabolism: Radium-223 is not processed by the body like normal medicines. Instead, it naturally breaks down over time because it is a radioactive substance.

• Elimination: Most of the drug leaves the body through the stool. Only a small amount is excreted in the urine. Differences in how quickly food moves through the intestines can affect how fast the drug leaves the body. People with slower intestinal transit may be exposed to slightly more radiation in the gut, though it is unclear whether this increases digestive side effects.

What Does Radium-223 Dichloride Contain?

It is supplied as a clear, colorless, sterile solution for intravenous injection, with a pH of 6-8. In the body, radium exists as a free divalent ion in the solution.

Radium-223 dichloride is supplied as a clear, colorless, sterile solution for intravenous injection, with a pH of 6-8. In the body, radium exists as a free divalent ion in the solution. Each milliliter of the solution contains 1,000 kBq of radium-223 dichloride (about 27 microcuries), which is equivalent to 0.53 nanograms of radium-223. A single vial contains 6 mL of solution, providing 6,000 kBq (162 microcuries) of radium-223 dichloride. The solution also contains sodium chloride to maintain

Half-Life of Radium-223

The half-life of radium-223 is about 11.4 days. During radioactive decay, radium-223 passes through several stages before becoming stable lead-207. Most of the released energy is in the form of alpha particles (about 95%), which are responsible for the main therapeutic effect. Smaller amounts are released as beta particles (about 3.6%) and gamma radiation (about 1.1%).

Nonclinical Toxicology:

• Carcinogenicity: There are no animal studies specifically designed to assess whether radium-223 dichloride causes cancer. However, in repeated-dose studies in rats, bone tumors (osteosarcomas) were observed 7 to 12 months after treatment at doses similar to those used in humans. Other tumors, such as lymphoma and mammary gland cancer, were also reported in long-term studies.

• Genotoxicity: No specific genetic toxicity studies have been carried out with radium-223 dichloride. However, the drug works by inducing double-strand breaks in DNA, a known effect of radiation.

• Effects on Fertility: Radium-223 dichloride may affect fertility and reproductive function due to its radiation effects. However, there are currently no animal studies evaluating its impact on male or female fertility.

Use in Specific Population:

• Pediatric Use: The safety and effectiveness of radium-223 dichloride in children have not been fully studied, so its use in pediatric patients has not been clearly established.

• Elderly Use: No dose adjustment is required for older adults.

• Patients with Liver Impairment: Dose modification is generally not needed in patients with liver problems. Radium-223 dichloride is not metabolized in the liver and is not excreted through bile, so liver impairment is unlikely to affect how the drug works in the body.

• Patients with Renal Impairment: Patients with kidney impairment usually do not need dose adjustments. Most of the drug is eliminated through feces rather than the kidneys, so kidney function has minimal effect on its clearance.

• Male Patients with Reproductive Potential:

  • Contraception: Radiation from this treatment may affect sperm production. Sexually active men should use effective contraception, such as barrier methods, during treatment and for at least six months afterward to prevent pregnancy in their partners.

  • Fertility: The radiation may affect future fertility. Men who plan to have children later should discuss this risk with their doctor and may consider sperm banking before starting treatment.