其 他 安 全 警 示
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| United Kingdom: Xofigo▼ (radium-223-dichloride): new restrictions on use due to increased risk of fracture and trend for increased mortality seen in clinical trial (English Only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that Xofigo▼ is now only authorised for use in patients with symptomatic bone metastases and no known visceral metastases who have had 2 previous systemic treatments for metastatic castration-resistant prostate cancer or who cannot receive other systemic treatments; and Xofigo▼ should not be used in combination with abiraterone acetate and prednisone/prednisolone.
Xofigo▼ was authorised in the European Union (EU) in 2013 for the treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastases.
In December 2017, following preliminary data from the ERA-223 study, it was advised that radium-223 dichloride should not be used in combination with abiraterone acetate and prednisone/prednisolone until a full review was completed of the study results and the benefit and risk of the medicine. In March 2018, this recommendation became a contraindication against the use of Xofigo with abiraterone acetate (Zytiga) and prednisone/prednisolone until the completion of the review.
The EU review has now concluded and new restrictions and recommendations have been added to the Summary of Product Characteristics and a letter sent to healthcare professionals.
The European review concluded that radium-223, either as monotherapy or in combination with an Luteinising Hormone Releasing Hormone (LHRH) analogue, increases the risk of fractures, especially in patients with a history of osteoporosis or in patients with fewer than 6 bone metastases.
Before, during, and after treatment, in all patients, carefully assess and monitor bone status (for example, by scintigraphy, bone mineral density) and risk of fractures (for example, presence of osteoporosis, less than 6 bone metastases, medication increasing fracture risk, low body-mass index). In men with a high baseline risk of fracture, carefully consider the benefit of treatment against the risks.
Fractures have occurred for up to 24 months after the first dose of radium-223, therefore closely monitor bone health for at least 24 months after discontinuation.
Use of bisphosphonates or denosumab has been shown to reduce the incidence of fractures in patients treated with radium-223. Therefore, consider use of these medicines before starting or resuming treatment with radium-223.
Further studies will be conducted to characterise the efficacy and safety of radium-223. The results of an observational study are expected in 2020 and those of a Phase 4 randomised double-blind study are due in 2024. Studies will look closely at the mechanisms responsible for the increased risk of fractures and possible increased mortality reported in the ERA-223 study.
The healthcare professionals are advised on the following :
- Radium-223 dichloride is not recommended in patients with a low level of osteoblastic bone metastases or in patients with asymptomatic bone metastases only.
- Carefully assess the benefits and risks of treatment before deciding whether to use radium-223 in patients with mildly symptomatic bone metastases.
- Do not use radium-223 in combination with, or within 5 days of discontinuation of, abiraterone acetate and prednisone/prednisolone
- The combination of radium-223 with other systemic cancer therapies other than LHRH analogues is not recommended; subsequent systemic cancer treatment should not be initiated for at least 30 days after the last administration of radium-223 dichloride
- Radium-223 dichloride can cause fractures — assess bone health status and risk of fractures before and during treatment and closely monitor bone health for at least 24 months after discontinuation; consider the use of bisphosphonates or denosumab to reduce fracture risk
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/xofigo-radium-223-dichloride-new-restrictions-on-use-due-to-increased-risk-of-fracture-and-trend-for-increased-mortality-seen-in-clinical-trial
In Hong Kong, Xofigo Solution for Injection 1100 KBQ/ml (HK-64332) is a pharmaceutical product containing radium-223 dichloride which is registered by Bayer Healthcare Ltd, and is a prescription-only medicine. So far, the Department of Health (DH) has received 11 cases of adverse drug reaction related to Xofigo, but none of them are related to death and fractures. Related news was previously issued by MHRA and other overseas drug regulatory authorities, and was posted on the Drug Office website since 2 Dec 2017, with the latest update posted on 30 Jul 2018. Letters to inform local healthcare professionals were issued by the DH on 16 Jul 2018. In light of the MHRA’s announcement and the reviews from other overseas authorities, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/ Wednesday, September 26, 2018
Issued at HKT 17:45
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