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| {{DrugProjectFormSinglePage
| | #REDIRECT [[Radium-223 chloride]] |
| |authorTag={{AP}}
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| |genericName=Radium chloride (Ra-223)
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| |indicationType=treatment
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| |indication=patients with castration-resistant [[prostate cancer]], symptomatic [[bone metastases]] and no known visceral metastatic disease
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| |adverseReactions=[[nausea]], [[diarrhea]], [[vomiting]], and [[peripheral edema]]
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| |blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b>
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| |blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
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| |offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Radium chloride in adult patients.
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| |offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Radium chloride in adult patients.
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| |offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Radium chloride in pediatric patients.
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| |offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Radium chloride in pediatric patients.
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| |contraindications=*Xofigo is contraindicated in pregnancy.
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| *Xofigo can cause fetal harm when administered to a pregnant woman based on its mechanism of action.
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| *Xofigo is not indicated for use in women.
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| *Xofigo is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus
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| |warnings=====Bone Marrow Suppression====
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| *In the randomized trial, 2% of patients on the Xofigo arm experienced [[bone marrow failure]] or ongoing [[pancytopenia]] compared to no patients treated with [[placebo]]. There were two deaths due to [[bone marrow failure]] and for 7 of 13 patients treated with Xofigo, bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced [[bone marrow failure]], 54% required blood transfusions. Four percent (4%) of patients on the Xofigo arm and 2% on the placebo arm permanently discontinued therapy due to [[bone marrow suppression]].
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| *In the randomized trial, deaths related to vascular hemorrhage in association with [[myelosuppression]] were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with [[placebo]]. The incidence of infection-related deaths (2%), serious infections (10%), and [[febrile neutropenia]] (<1%) were similar for patients treated with Xofigo and [[placebo]]. [[Myelosuppression]]; notably [[thrombocytopenia]], [[neutropenia]], [[pancytopenia]], and [[leukopenia]]; has been reported in patients treated with Xofigo. In the randomized trial, [[complete blood counts]] (CBCs) were obtained every 4 weeks prior to each dose and the nadir CBCs and times of recovery were not well characterized. In a separate single-dose phase 1 study of Xofigo, [[neutrophil]] and [[platelet]] count nadirs occurred 2 to 3 weeks after Xofigo administration at doses that were up to 1 to 5 times the recommended dose, and most patients recovered approximately 6 to 8 weeks after administration.
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| *Hematologic evaluation of patients must be performed at baseline and prior to every dose of Xofigo. Before the first administration of Xofigo, the [[absolute neutrophil count]] ([[ANC]]) should be ≥ 1.5 x 109/L, the [[platelet]] count ≥ 100 x 109/L and [[hemoglobin]] ≥ 10 g/dL. Before subsequent administrations of Xofigo, the [[ANC]] should be ≥ 1 x 109/L and the [[platelet]] count ≥ 50 x 109/L. If there is no recovery to these values within 6 to 8 weeks after the last administration of Xofigo, despite receiving supportive care, further treatment with Xofigo should be discontinued. Patients with evidence of compromised [[bone marrow]] reserve should be monitored closely and provided with supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for [[bone marrow failure]].
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| *The safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use with chemotherapy is not recommended due to the potential for additive [[myelosuppression]]. If chemotherapy, other systemic radioisotopes or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued.
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| |clinicalTrials=<i>Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.</i>
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| *In the randomized clinical trial in patients with metastatic castration-resistant [[prostate cancer]] with [[bone metastases]], 600 patients received intravenous injections of 50 kBq/kg (1.35 microcurie/kg) of Xofigo and best standard of care and 301 patients received placebo and best standard of care once every 4 weeks for up to 6 injections. Prior to randomization, 58% and 57% of patients had received [[docetaxel]] in the Xofigo and placebo arms, respectively. The median duration of treatment was 20 weeks (6 cycles) for Xofigo and 18 weeks (5 cycles) for [[placebo]].
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| *The most common adverse reactions (≥ 10%) in patients receiving Xofigo were [[nausea]], [[diarrhea]], [[vomiting]], and [[peripheral edema]] (Table 3). Grade 3 and 4 adverse events were reported among 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in Xofigo-treated patients (≥ 10%) were [[anemia]], [[lymphocytopenia]], [[leukopenia]], [[thrombocytopenia]], and [[neutropenia]].
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| *Treatment discontinuations due to adverse events occurred in 17% of patients who received Xofigo and 21% of patients who received placebo. The most common hematologic laboratory abnormalities leading to discontinuation for Xofigo were [[anemia]] (2%) and [[thrombocytopenia]] (2%).
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| Table 3 shows adverse reactions occurring in ≥ 2% of patients and for which the incidence for Xofigo exceeds the incidence for placebo.
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| [[file:Radium AR1.png|none|400px]]
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| ====Laboratory Abnormalities====
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| Table 4 shows hematologic laboratory abnormalities occurring in > 10% of patients and for which the incidence for Xofigo exceeds the incidence for placebo.
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| [[file:Radium AR2.png|none|400px]]
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| *As an adverse reaction, grade 3-4 [[thrombocytopenia]] was reported in 6% of patients on Xofigo and in 2% of patients on placebo. Among patients who received Xofigo, the laboratory abnormality grade 3-4 [[thrombocytopenia]] occurred in 1% of [[docetaxel]] naïve patients and in 4% of patients who had received prior [[docetaxel]]. Grade 3-4 [[neutropenia]] occurred in 1% of [[docetaxel]] naïve patients and in 3% of patients who have received prior [[docetaxel]].
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| ====Fluid Status====
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| *Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as [[diarrhea]], [[nausea]], and [[vomiting]] which may result in [[dehydration]]. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or [[hypovolemia]].
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| ====Injection Site Reactions====
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| *[[Erythema]], [[pain]], and [[edema]] at the injection site were reported in 1% of patients on Xofigo.
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| ====Secondary Malignant Neoplasms====
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| *Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including [[osteosarcomas]], in rats following administration of radium-223 dichloride, Xofigo may increase the risk of [[osteosarcoma]] or other secondary malignant neoplasms.
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| *However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs. 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow up for patients on the trial.
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| ====Subsequent Treatment with Cytotoxic Chemotherapy====
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| *In the randomized clinical trial, 16% patients in the Xofigo group and 18% patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy.
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| |alcohol=Alcohol-Radium chloride interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
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| }}
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| {{Chembox new
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| | Name = Radium chloride
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| | Section1 = {{Chembox Identifiers
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| | CASNo = 10025-66-8
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| }}
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| | Section2 = {{Chembox Properties
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| | Formula = RaCl<sub>2</sub>
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| | MolarMass = 296.94 g/mol
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| | MeltingPt = }}
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| }}
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| '''Radium chloride''', RaCl<sub>2</sub>, was the first [[radium]] [[Chemical compound|compound]] to be prepared in a pure state and was the basis of [[Marie Curie]]'s original separation of radium from [[barium]].<ref>[[Marie Curie|Curie, M.]]; [[Andre Debierne|Debierne, A.]] (1910). ''C. R. Hebd. Acad. Sci. Paris'' '''151''':523–25.</ref> The first preparation of radium metal was by the [[electrolysis]] of a solution of radium chloride using a mercury cathode.
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| ==Preparation==
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| Radium chloride crystallises from solution as the di[[hydrate]]. It may be dehydrated by heating to 100 °C in air for one hour followed by 5½ hours at 520 °C under [[argon]].<ref>Weigel, F.; Trinkl, A. (1968). ''Radiochim. Acta'' '''9''':36–41.</ref> If the presence of other anions is suspected, the dehydration may be effectuated by fusion under [[hydrogen chloride]].<ref>Hönigschmid, O.; Sachtleben, R. (1934). ''Z. Anorg. Allg. Chem.'' '''221''':65–82.</ref>
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| ==Properties==
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| Radium chloride is a white solid with a blue-green [[luminescence]], especially when heated. It is less soluble in water than other [[alkaline earth metal]] chlorides, a fact which is used in the first stages of the separation of radium from [[barium]] by [[fractional crystallization]]. It is only sparingly soluble in [[Azeotrope|azeotropic]] [[hydrochloric acid]] and virtually insoluble in concentrated hydrochloric acid.<ref>Erbacher, O. (1930). ''[[Ber. Dtsch. Chem. Ges.]]'' '''63''':141–56.</ref>
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| Gaseous radium chloride exists as RaCl<sub>2</sub> molecules, as with other alkaline earth metal [[halide]]s. The gas shows strong absorptions in the visible spectrum at 676.3 [[nanometre|nm]] and 649.8 nm (red): the [[Bond dissociation energy|dissociation energy]] of the radium–chlorine bond is estimated as 2.9 [[electronvolt|eV]],<ref>Lagerqvist, A. (1953). ''Arkiv Fisik'' '''6''':141–42.</ref> and its [[Bond length|length]] as 292 [[picometre|pm]].<ref>Karapet'yants, M. Kh.; Ch'ing, Ling-T'ing (1960). ''Zh. Strukt. Khim.'' '''1''':277–85; ''J. Struct. Chem. (USSR)'' '''1''':255–63.</ref>
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| ==Uses==
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| Radium chloride is still used for the initial stages of the separation of radium from barium during the extraction of radium from [[pitchblende]]. The large quantities of material involved ([[tonne]]s of ore for [[milligram]]s of radium) favour this less costly (but less efficient) method over those based on [[radium bromide]] or [[radium chromate]] (used for the later stages of the separation).
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| ==Sources==
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| *''Gmelins Handbuch der anorganischen Chemie (8. Aufl.)'', Berlin:Verlag Chemie, 1928, pp. 60–61.
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| *''Gmelin Handbuch der anorganischen Chemie (8. Aufl. 2. Erg.-Bd.)'', Berlin:Springer, 1977, pp. 362–64.
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| ==References==
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| {{reflist|2}}
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| [[Category:Radium compounds]]
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| [[Category:Chlorides]]
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| [[Category:Metal halides]]
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