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| The United Kingdom: Cyproterone acetate: new advice to minimise risk of meningioma (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that risk of meningioma with cyproterone acetate increases with increasing cumulative dose.
Cyproterone acetate is a synthetic progestogen with anti-androgenic activity. High-dose products containing 50–100 milligram (mg) are used in the treatment of prostate cancer (Cyprostat) and hypersexuality disorders (Androcur). Low-dose products containing 2mg cyproterone acetate in combination with 35 microgram (µg) ethinylestradiol (Dianette and Co-cyprindiol) are approved for use in the treatment of acne and hirsutism. There is also evidence for off-label use of high-dose cyproterone as hormone therapy in gender reassignment and in female patients for conditions related to androgen sensitivity such as acne, hirsutism, and baldness.
The association of high dose (50mg per day) cyproterone acetate with meningioma was first described in 2008 and a warning on the possible risk of meningioma together with a contraindication in patients with meningioma or a history of meningioma was added to the product information for high dose cyproterone products.
A recent French epidemiological cohort study in women demonstrated that the relationship between cyproterone and meningioma is dose-dependent, and the risk increases with increasing cumulative dose. In the study, patients with a cumulative exposure to cyproterone of between 36g and 60g had an estimated 11-times-higher risk of meningioma than patients with cumulative exposures lower than 3g. A 36g cumulative exposure equates to a daily dose of 100mg cyproterone for 1 year.
A European review of the new study data concluded that treatment with cyproterone 50mg or 100mg should be restricted to situations in which alternative treatments or interventions are unavailable or considered inappropriate, for all indications except prostate carcinoma. The lowest possible effective dose should be used for all patients. If a patient taking cyproterone at any dose for any indication develops a meningioma, treatment should be stopped immediately and permanently discontinued. Overall, the risk of meningioma is still considered to be rare (between 1 in 1,000 patients and 1 in 10,000 people, depending on the dose and duration of treatment). The risk increases with increasing cumulative doses. Low-dose cyproterone (2mg) in combination with ethinylestradiol (Dianette, Co-cyprindiol), indicated for the treatment in women of acne and/or hirsutism has not been shown to be associated with an increased risk of meningioma. However, as an increased risk is still plausible, low-dose combination products are now contraindicated in patients with meningioma or a history of meningioma. A warning regarding the risk of meningioma has also been added to the product information for low-dose cyproterone products.
Up to 12 May 2020, there have been 10 Yellow Card reports in the UK describing meningioma, which were suspected to be associated with high-dose cyproterone used in male hypersexuality (4), gender reassignment (4), and female hirsutism (2). The mean age of these cases was 62.1 years, and all had taken cyproterone for a prolonged time (14–36 years where information was provided). There were no reports of meningioma with low-dose cyproterone acetate in combination with ethinylestradiol.
Meningiomas are the most common intracranial tumours, with an annual incidence of 6 cases per 100,000 in the general population. They arise from the meningeal coverings of the brain and spinal cord and can be single or multiple. Sex hormones are likely to have a role in the development of meningiomas as approximately 70% express progestogen receptors and 30% express estrogen receptors. Meningiomas are usually benign, but as they are space occupying lesions, they can put pressure on neurological structures. This can cause a variety of symptoms including changes in vision, hearing loss or ringing in the ears (tinnitus), loss of smell, headaches that worsen with time, memory loss, seizures, or weakness in extremities. Clinicians should be vigilant for these symptoms and signs in patients taking cyproterone, but should also be aware that meningiomas can be asymptomatic.
Healthcare professionals are advised:
- A review has confirmed a cumulative dose-dependent association between cyproterone acetate and the known increased risk of meningioma; the risk is thought to be rare overall, but is highest for doses of 25mg per day and above.
- Do not use cyproterone for any indication in patients with a meningioma or a history of a meningioma.
- Be vigilant for symptoms and signs of meningioma in patients taking cyproterone; stop treatment permanently if a meningioma is diagnosed in a patient taking cyproterone.
- Only use cyproterone for control of libido in severe hypersexuality or paraphilias (sexual deviation) in adult men when other interventions are considered inappropriate.
- Advice on use of cyproterone in the management of patients with prostate cancer remains unchanged.
- For low-dose cyproterone (2mg) in combination with ethinylestradiol, a risk of meningioma has not been demonstrated but since the risk with higher-dose products appears to be cumulative, use is now contraindicated in patients with previous or current meningioma.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/cyproterone-acetate-new-advice-to-minimise-risk-of-meningioma
In Hong Kong, there are 9 registered pharmaceutical products containing cyproterone acetate: 3 products contain 50mg of cyproterone acetate; 6 products contain 2mg of cyproterone acetate in combination with ethinyloestradiol. All products are prescription-only medicines. So far, the Department of Health (DH) has not received any case of adverse drug reaction related to cyproterone acetate.
Related news was previously issued by the European Medicines Agency, and was posted on the Drug Office website on 15 Feb 2020 and 28 Mar 2020. Letters to inform local healthcare professionals were issued by the DH on 17 Feb 2020. As previously reported, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Tuesday, Jun 30, 2020
Issued at HKT 16:00
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