Identification
- Summary
Radium Ra 223 dichloride is a radiopharmaceutical agent used to treat patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.
- Brand Names
- Xofigo
- Generic Name
- Radium Ra 223 dichloride
- DrugBank Accession Number
- DB08913
- Background
Radium Ra 223 Dichloride is a radiopharmaceutical containing the radioisotope radium-223 that emits short range but high linear energy alpha particles. As a cation, radium mimics calicum and binds to hydroxyapatite, which is a bone mineral found in areas of high bone turnover as seen in bone metastases. It was first approved by the FDA in May 2013 and is currently marketed under the brand name Xofigo, which was formerly called Alpharadin. Xofigo is indicated in patients who have metastatic bone cancer that is symptomatic with no visceral metastases and patients who have prostate cancer that is castration resistant. The FDA label includes a warning that Radium Ra 223 Dichloride should not be used in women who are pregnant or may become pregnant due to the high risk of fetal harm.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Radium Ra 223 dichloride (DB08913)
- Weight
- Average: 293.924
Monoisotopic: 292.956202554 - Chemical Formula
- Cl2Ra
- Synonyms
- Radium chloride Ra-223
- Radium Ra 223 dichloride
- Radium Ra-223 dichloride
- Radium-223 chloride
- Radium-223 dichloride
- External IDs
- BAY 88-8223
- BAY-88-8223
- BAY88-8223
Pharmacology
- Indication
Used in patients who have metastatic bone cancer that is symptomatic with no visceral metastases and patients who have prostate cancer that is castration resistant.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic castration-resistant prostate cancer •••••••••••• - Contraindications & Blackbox Warnings
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Physiologically, Radium Ra 223 Dichloride, prevents the spread of bone cancer by killing the associated bone cancer cells.
- Mechanism of action
Radium Ra 223 Dichloride is the radioisotope radium-223 that emits short range but high linear energy alpha particles. As a cation, radium mimics calicum and binds to hydroxyapatite, which is a bone mineral found in areas of high bone turnover as seen in bone metastases. The high energy damages bone cells by introducing double-stranded DNA breaks. This leads to cell death and prevention of the spread of the bone cancer cells. As well because of the alpha particle's short range of less than 10 cell diameters, its damaging effects would less likely affect the non-cancerous cells nearby.
- Absorption
Since Radium Ra 223 Dichloride is administered I.V., the bioavailability should be 100%.
- Volume of distribution
The volume of distribution was not quantified, but after 24 hours, there is only 1% radium-223 remaining in the blood. The rest of the radium-223 is distributed to bone (61% of the radioactive dose after 4 hours) and intestine (49% of the radioactive dose after 4 hours). No other organs were found to have significant uptake.
- Protein binding
There is negligible plasma protein binding.
- Metabolism
Radium-223 does not undergo metabolism because it is a radioisotope that decays.
- Route of elimination
Radium-223 is mainly eliminated through the feces (13%) and to a lesser extent in the urine (2%). It is also noted that the elimination rate of radium-223 from the intestines is variable due to the high variability of intestinal transit rates among patients. Therefore there could be more intestinal radiation exposure in patients with slower intestinal transit rates, but the significance of this in relation to toxicity is not known.
- Half-life
The half-life is relatively long at 11.4 days for radium-223.
- Clearance
The clearance rate of radium-223 was not quantified.
- Adverse Effects
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Because of its cytotoxic actions that have a high potential to cause fetal harm, Radium Ra 223 Dichloride is contraindicated in women who are pregnant or are of child bearing age. Other side effects include several hematological lab abnormalities, peripheral edema, nausea, vomiting, and diarrhea.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Radium Ra 223 dichloride is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Radium Ra 223 dichloride is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Radium Ra 223 dichloride is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Radium Ra 223 dichloride is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Radium Ra 223 dichloride is combined with Bupivacaine. - Food Interactions
- Drink plenty of fluids.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Radium Ra-223 cation ionic 9H414A99MD Not Available PZDJSXWIQXZUBJ-OIOBTWANSA-N - International/Other Brands
- Alpharadin
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Radium Ra 223 Dichloride Injection 90 uCi/1mL Intravenous Cardinal Health 414, Llc 2017-06-12 Not applicable US 
Xofigo Injection, solution 1100 kBq/mL Intravenous Bayer Ag 2016-09-08 Not applicable EU 
Xofigo Injection 30 uCi/1mL Intravenous Bayer HealthCare Pharmaceuticals Inc. 2013-05-20 Not applicable US
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of inorganic compounds known as alkaline earth metal chlorides. These are inorganic compounds in which the largest halogen atom is Chlorine, and the heaviest metal atom is a lanthanide.
- Kingdom
- Inorganic compounds
- Super Class
- Mixed metal/non-metal compounds
- Class
- Alkaline earth metal salts
- Sub Class
- Alkaline earth metal chlorides
- Direct Parent
- Alkaline earth metal chlorides
- Alternative Parents
- Inorganic chloride salts
- Substituents
- Alkaline earth metal chloride / Inorganic chloride salt / Inorganic salt
- Molecular Framework
- Not Available
- External Descriptors
- inorganic chloride, radium molecular entity (CHEBI:74895)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- RJ00KV3VTG
- CAS number
- 444811-40-9
- InChI Key
- RWRDJVNMSZYMDV-SIUYXFDKSA-L
- InChI
- InChI=1S/2ClH.Ra/h2*1H;/q;;+2/p-2/i;;1-3
- IUPAC Name
- (223Ra)radium(2+) dichloride
- SMILES
- [Cl-].[Cl-].[223Ra++]
References
- General References
- Suominen MI, Rissanen JP, Kakonen R, Fagerlund KM, Alhoniemi E, Mumberg D, Ziegelbauer K, Halleen JM, Kakonen SM, Scholz A: Survival benefit with radium-223 dichloride in a mouse model of breast cancer bone metastasis. J Natl Cancer Inst. 2013 Jun 19;105(12):908-16. doi: 10.1093/jnci/djt116. Epub 2013 May 16. [Article]
- Nilsson S, Franzen L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernas B, Petersson U, Johannessen DC, Sokal M, Pigott K, Yachnin J, Garkavij M, Strang P, Harmenberg J, Bolstad B, Bruland OS: Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007 Jul;8(7):587-94. [Article]
- Bruland OS, Nilsson S, Fisher DR, Larsen RH: High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6250s-6257s. [Article]
- External Links
- KEGG Drug
- D10398
- PubChem Substance
- 175427151
- ChemSpider
- 28528370
- 1424174
- ChEBI
- 74895
- ChEMBL
- CHEMBL2107816
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Radium-223_chloride
- FDA label
- Download (552 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Metastatic Castration-Resistant Prostate Cancer (mCRPC) 1 3 Active Not Recruiting Treatment Prostate Cancer Metastatic to Bone 1 3 Completed Treatment Bone Metastases / Hormone-Refractory Prostate Cancer 1 3 Completed Treatment Neoplasms of the Prostate 3 3 Recruiting Treatment Metastatic Castration-Resistant Prostate Cancer (mCRPC) / Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 90 uCi/1mL Injection Intravenous 30 uCi/1mL Injection, solution Intravenous; Parenteral 1000 kBq/ml Injection, solution Intravenous 1100 kBq/ml Injection, solution Intravenous Solution Intravenous 6600 kBq Injection, solution 0.58 ng/ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6635234 No 2003-10-21 2020-01-03 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 74.7 mg/mL ALOGPS logP 0.37 ALOGPS logP 0 Chemaxon logS -0.6 ALOGPS pKa (Strongest Acidic) 3.09 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 0 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 0 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 0 m3·mol-1 Chemaxon Polarizability 1.78 Å3 Chemaxon Number of Rings 0 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9935 Blood Brain Barrier + 0.9786 Caco-2 permeable + 0.619 P-glycoprotein substrate Non-substrate 0.9022 P-glycoprotein inhibitor I Non-inhibitor 0.9785 P-glycoprotein inhibitor II Non-inhibitor 0.9947 Renal organic cation transporter Non-inhibitor 0.9221 CYP450 2C9 substrate Non-substrate 0.8005 CYP450 2D6 substrate Non-substrate 0.7503 CYP450 3A4 substrate Non-substrate 0.7412 CYP450 1A2 substrate Non-inhibitor 0.6359 CYP450 2C9 inhibitor Non-inhibitor 0.7872 CYP450 2D6 inhibitor Non-inhibitor 0.9067 CYP450 2C19 inhibitor Non-inhibitor 0.7673 CYP450 3A4 inhibitor Non-inhibitor 0.957 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9075 Ames test Non AMES toxic 0.7967 Carcinogenicity Carcinogens 0.7993 Biodegradation Not ready biodegradable 0.5273 Rat acute toxicity 2.4184 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9208 hERG inhibition (predictor II) Non-inhibitor 0.9622
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at June 27, 2013 03:05 / Updated at February 21, 2021 18:52