EMA đánh giá lại tỉ lệ lợi ích/nguy cơ của tất cả các thuốc có chứa hoạt chất trimetazidine

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Vastarel MR (Trimetazidine) được đăng ký tại Việt nam từ năm 2003 với chỉ định điều trị dự phòng các cơn đau thắt ngực.

Vastarel MR (Trimetazidine) được đăng ký tại Việt nam từ năm 2003 với chỉ định điều trị dự phòng các cơn đau thắt ngực.

Sau một vài ca hiếm hoi báo cáo về tính hiệu quả và tác dụng phụ liên quan đến việc sử dụng một số trimetazidine, theo quy trình Cảnh giác Dược thường quy, Cơ quan quản lý Dược phẩm Pháp AFSSAPS đề nghị Cơ quan quản lý Dược phẩm Châu Âu (EMA) đánh giá lại tỉ lệ lợi ích/nguy cơ của tất cả các thuốc có chứa hoạt chất trimetazidine.

Ngày 13 tháng 3 năm 2012, EMA đã tổ chức đánh giá lại một cách toàn diện hiệu quả Vastarel MR. Và EMA đã khẳng định rõ lợi ích của Vastarel MR trên hiệu quả chống đau thắt ngực là hoàn toàn vượt trội so với nguy cơ. Quyết định này đưa ra dựa trên hơn 300 nghiên cứu đăng tải trên các tạp chí y khoa uy tín trên thế giới chứng minh hiệu quả chống đau thắt ngực mạnh mẽ của Vastarel MR.

Ngày 22 tháng 6 vừa qua, Cơ quan quản lý Dược phẩm Châu Âu (EMA) đã công bố thông cáo báo chí, chính thức xác nhận quyết định trên và khuyến cáo sử dụng Vastarel MR cho tất cả bệnh nhân đau thắt ngực ổn định

Sau đây là những kết luận chính của EMA:

  • EMA khuyến cáo sử dụng Vastarel MR trong điều trị cho bệnh nhân đau thắt ngực ổn định
  • Đối với các chỉ định khác (ù tai, chóng mặt hoặc rối loạn thị giác), lợi ích của trimetazidine chưa được chứng minh đầy đủ
  • Bác sĩ nên tiếp tục kê toa sản phẩm như một phối hợp để điều trị triệu chứng cho những BN đau thắt ngực ổn định chưa được kiểm soát tốt hoặc không dung nạp với điều trị đầu tay.
  • Không kê toa sản phẩm cho bệnh nhân bị bệnh Parkinson, những bệnh nhân bị hội chứng Parkinson với triệu chứng run và hội chứng bàn chân không yên hoặc có liên quan đến các rối loạn vận động khác, cũng như bệnh nhân bị suy thận nặng

Vastarel MR đang được Bộ Y tế Việt Nam cho phép lưu hành, giới thiệu và nhập khẩu bình thường. Hiệu quả vượt trội và độ an toàn cao đã được chứng minh của Vastarel MR giúp thuốc được tiếp tục kê toa cho tất cả bệnh nhân đau thắt ngực mà không nên có bất kỳ sự gián đoạn nào.

Nhân đây, xin được nhấn mạnh, đến thời điểm hiện nay, Vastarel MR là trimetazidine duy nhất được Cơ quan quản lý Dược phẩm Châu Âu (EMA) đánh giá và xác nhận hiệu quả vượt trội của thuốc so với nguy cơ. Do đó, kê toa Vastarel MR cho bệnh nhân đau thắt ngực là đảm bảo cho bệnh nhân nhận được hiệu quả điều trị cao nhất với độ dung nạp tối ưu.

2507201201

 

21 June 2012

EMA/412151/2012

EMEA/H/A-31/1305

 

Questions and answers on the review of medicines containing trimetazidine (20 mg tablets, 35 mg modified release tablet and 20 mg/ml oral solution)

Outcome of a procedure under Article 31 of Directive 2001/83/EC as amended

 

 

On 21 June 2012,the European Medicines Agency completed a review of thesafetyand effectiveness oftrimetazidine followingconcerns over its effectiveness and reports of movementdisorders such as parkinsoniansymptoms with these medicines. The Agency’sCommittee forMedicinal Products for Human Use (CHMP) concluded that the benefits continue to outweigh the risksin patients with angina pectoris but that treatment should be restricted to add-on to existing treatments in patients who are not adequatelycontrolled by or who are intolerant to other medicines for angina pectoris.For the symptomatic treatmentof tinnitus, vertigo and visualfield disturbances, theCHMP concluded that the benefits no longer outweigh the risks and that theseuses shouldno longer be authorised. In addition, the Committee recommended new contraindications and warnings to reduce and manage the possible risk of movement disorders, associated with the use of this medicine.

 

Whatistrimetazidine?

 

Trimetazidineis amedicine used to prevent anginaattacks,which are suddenpains to thechest, jaw and back brought on by physicaleffort,due to reduced blood flowto theheart.Angina is commonly associated with a narrowing of the blood vessels that supply the heart,called the coronaryarteries.

 

Trimetazidineis a ‘metabolic agent’,amedicine which has an effecton metabolism (the process by which substances are broken down inthe body).It is believed to protect against myocardial ischaemia (reduced blood supply to the heart muscle) by increasing the rate at which glucose is broken down.

 

Trimetazidineis also used to treat the symptoms ofvertigo (a spinning sensation) and tinnitus (ringing sensation in the ears),and to treat reduced vision and visualfielddisturbances(unclear or disturbed vision) due to problems affecting the blood vessels.

 

Medicines containing trimetazidine have been available since the1970s and are currentlymarketed in Bulgaria,Cyprus, Czech Republic, Denmark, Estonia, France,Germany,Greece,Hungary, Ireland, Italy, Latvia,Lithuania,Luxembourg,Malta, Poland,Portugal, Romania, Slovakia, Sloveniaand Spain.

They are marketedunder the invented name Vastareland other trade names.

 

Whywastrimetazidinereviewed?

 

In April2011,the French medicines regulatory agency concluded that,basedon a reviewof the evidence in France,the risks of medicines containingtrimetazidine were greater than the benefits for allthe authorised indications.A mainconcern was that the effectiveness of trimetazidine had not been convincinglydemonstrated in any ofthe authorised indications, since the studies supporting the authorised uses had severalmethodological weaknessesand onlyshowed a smallbenefit.

 

In addition, there were concerns regarding the safety of trimetazidine-containing medicines following reports of Parkinson syndrome (a group of symptomsthat include shaking, slow movementand muscle stiffness) and other motor disorders such as tremor(shaking), muscle rigidity and walking disorders, and restless legs syndrome (a disorder where the patient has uncontrollable urges to move the limbs

to stop uncomfortable, painfulor odd sensations in the body, usually at night). These symptoms were seen insome patients withno previous history of Parkinson syndrome,and in manycases their symptomsresolved whenthey stopped taking trimetazidine.

 

Despite strengthening the warningsin the prescribing information of these medicines,the French agency remained concerned that the benefitsfor trimetazidine did not outweigh its risks. Consequently,on 22 April2011 it asked the CHMP to issue an opinion on thebenefit-risk balance of trimetzidine-containing medicines,andon whether the marketing authorisation for these medicines should be maintained, varied, suspended or withdrawn across the EU.

 

WhichdatahastheCHMPreviewed?

 

The CHMP looked at datafromclinical studies, the published literature,spontaneous reports of side effectsand data submitted by the companies that marketmedicines containing trimetazidine.

 

WhataretheconclusionsoftheCHMP?

 

Regarding the use of trimetazidinein angina pectoris,the Committee noted that the studies carried out to show its effects had some limitations and were often of shortduration. Although the studies did not show that the benefits outweighed the risksfor trimetazidine when used alone as first-line treatment, the studies supported theuse oftrimetazidine as add-on to existing treatments inpatients who are not adequatelycontrolled by or intolerantto other medicines for angina pectoris.To address the lack of long-termdata on trimetazidine,a study investigating the long-termeffects of trimetazidine willbe carried out.

 

Regarding the use oftrimetazidinein tinnitus, vertigo and visualfield disturbances, the studies had poor methodology and didnot demonstratea clinical benefit of trimetazidine when comparedwith placebo (a dummy treatment)or alternative medicines. In addition the CHMP noted thattrimetazidine is often used to treat these conditionsin older patients for longer and at higher doses than recommended, increasingthe risk of side effects such as falls which undermines the use of trimetazidine for these conditions.

 

An analysis ofrelevant safetydata showed that movementdisorders, including Parkinsonism, cannot be excludedwith trimetazidine,although these arenot commonand are reversible after discontinuing trimetazidine.The CHMP thereforerecommended that a warningshould be included in theproduct informationontrimetazidine-induced parkinsonism, its diagnosisand management.It also recommended contraindicating trimetazidine in patients withParkinsondisease or parkinsonian symptoms and in patientswith severely reduced kidney function.


Based on theevaluation ofthe currently available data and the scientific discussion within the Committee,the CHMP concluded thatthe benefits of trimetazidine continue to outweighitsrisks when used as addon treatmentin patients with angina pectoris,but that changes should be made to the product information to ensure the safeuse of these medicines. For use intinnitus,vertigoand visual field disturbances,the benefits nolonger outweigh the risks and the CHMP recommended that these uses should no longer be authorised.Written communication willbe distributed to doctors at national leveltoinformthem of the changestothe approveduses of trimetazidine.

 

The fullchanges made tothe information to doctors and patients are detailedhere.

 

Whataretherecommendationsforpatients

There is no need for an urgent changein treatment, but doctorswillreview their patients’ treatmentattheir next routine appointment.

 

Patients currentlyreceiving trimetazidine for tinnitus, vertigo and disturbances invision should consult theirdoctor so they can switchto an appropriate alternative treatment.

 

  Patients currentlyreceiving trimetazidine for angina pectoris should consulttheir doctor to ensure that itis themost appropriate treatmentfor their condition ortoarrangealternative treatment if necessary.

 

  Patients whohaveany questions should speak to their doctor or pharmacist.

 

Whataretherecommendationsforprescribers?

 

There is no need for an urgent change in treatment, but doctors should review their patients’ treatment at their next routine appointment.

Prescribers should no longer prescribe trimetazidine for treating tinnitus, vertigo and disturbances in vision and switch patients to appropriate alternative treatment.

Trimetazidine should only be used in the symptomatic treatment of angina pectoris, and only as add-on to existing treatments in patients who are not adequately controlled by or who are intolerant to other medicines for angina pectoris.

Prescribers must not prescribe trimetazidine in patients with Parkinson disease or parkinsonian symptoms and in patients with severely reduced kidney function. For patients with moderately reduced kidney failure and elderly patients, the dose should be reduced.

Trimetazidine should be discontinued permanently in patients who develop movement disorders such as parkinsonian symptoms. If parkinsonian symptoms persist for more than four months after discontinuation, a neurologist’s opinion should be sought.

 

A EuropeanCommissiondecision on this opinion willbe issued in due course.

 

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22 June 2012

EMA/CHMP/417861/2012

 

Press Office

 

European Medicines Agency recommends restricting use of trimetazidine-containing medicines

Restricted indication for patients with stable angina pectoris and deletion of existing indications for treatment of vertigo, tinnitus and vision disturbance

 

The European Medicines Agency has recommended restricting the use of trimetazidinecontaining medicines in the treatment of patients with angina pectoris to secondline, addon therapy. For all

other indications the Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that

the benefits of these medicines were not sufficiently demonstrated and did not outweigh the risks. The

CHMP therefore recommended their deletion from the marketing authorisation.

 

There is no need for an urgent change in treatment, but doctors should review their patients’

treatment at their next routine appointment.

 

Doctors should no longer prescribe trimetazidine for the treatment of patients with tinnitus, vertigo or disturbances in vision. Patients who are taking trimetazidine in these indications should discuss alternatives with their doctor.

 

Doctors can continue to prescribe trimetazidine for the treatment of angina pectoris, but only as an addon therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line anti-anginal therapies.

 

The review was initiated by France, mainly because of concerns that the efficacy of trimetazidine was not sufficiently demonstrated. It also looked at reports regarding the occurrence of movement disorders such as Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Although patients usually recovered fully within four months after treatment with trimetazidine was discontinued, the Committee recommended new contraindications and warnings to reduce and manage the possible risk of movement disorders associated with the use of this medicine.

Doctors are advised not to prescribe the medicine to patients with Parkinson disease, parkinsonian symptoms, tremors, restless leg syndrome orother related movement disorders, nor to patients with severe renal impairment.

 


Doctors should exercise caution when prescribing trimetazidine to patients with moderate renal impairment and to elderly patients, and consider dose reduction in these patients.

 

Trimetazidine should be discontinued permanently in patients who develop movement disorders such as Parkinsonian symptoms. If Parkinsonian symptoms persist for more than four months after discontinuation, a neurologist’s opinion should be sought.

 

The CHMP’s opinion will be sent to the European Commission for the adoption of a binding decision throughout the European Union.

 

 

Notes

1. This press release, together with all related documents, is available on the Agency‘s website.

 

2. Medicines containing trimetazidine have been available since the 1970s and are currently marketed in Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Poland, Portugal, Romania, Slovakia, Slovenia and Spain. They are marketed under the invented name Vastarel and other trade names.

 

3. The review of trimetazidine-containing medicines was conducted in the context of a formal review under Article 31 of Directive 2001/83/EC, initiated at the request of France.

 

4. More information on the work of the European Medicines Agency can be found on its website:

www.ema.europa.eu

 

 

 

Contact our press officers

Monika Benstetter or Martin Harvey Allchurch

 

Tel. +44 (0)20 7418 8427

 

E-mail: press@ema.europa.eu