Dear Healthcare Professional,

Sanofi, in agreement with the Pharmacological Committee of the State Center for Expertise and Standardization of Medicines, Medical Devices and Medical Equipment, informs you of the following important data regarding the use of Plaquenil (hydroxychloroquine):

Short information

• Hydroxychloroquine is not registered for use in the treatment of COVID-19 in any country in the world. Therefore, any use of hydroxychloroquine for COVID-19 is an off-label use.
• Healthcare professionals are advised not to use hydroxychloroquine off-label for the treatment of COVID-19 patients.
• It is known that the use of hydroxychloroquine can cause prolongation of the QT interval and lead to the development of cardiac arrhythmias, including pirouette-type arrhythmias in patients with risk factors. The severity of prolongation of the QT interval may also increase with an increase in the concentration of hydroxychloroquine. The risk of such a complication may be exacerbated by the simultaneous use of hydroxychloroquine with other drugs that prolong the QT interval, for example, azithromycin.
• Recently, there has been a significant increase in the number of cases of serious and life-threatening prolongation of the QT interval, arrhythmias of the "pirouette" type, syncope, sudden cardiac arrest, sudden cardiac death, which coincide with the simultaneous use of hydroxychloroquine with other drugs that prolong the QT interval. for example, azithromycin.
• Healthcare professionals who, despite our recommendations, have chosen to prescribe hydroxychloroquine off-label for the treatment of patients with COVID-19 should use caution, in particular in patients with risk factors (concomitant use of hydroxychloroquine with other drugs that prolong the QT interval, such as as some antimicrobial agents, including azithromycin), ECG monitoring in a hospital setting is recommended.

Prerequisites for this safety and efficacy recommendation

On June 17, WHO decided to suspend the SOLIDARITY clinical trial due to the lack of efficacy of HCQ in COVID-19. The RECOVERY study in the UK was previously discontinued for the same reasons. The FDA has also revoked the temporary approval for HCQ in the United States of America.

June 19, 2020 Novartis announced the premature termination of its clinical study using HCQ due to the difficulties in recruiting patients and, accordingly, the study was impracticable. On June 20, 2020, the NIH sponsored ORHID trial was prematurely stopped.

On June 22, 2020, Sanofi decided to discontinue two of its own HCQ studies, due to problems in recruiting new patients into the study, and in this regard, the inability to complete these studies in a timely manner. At the time of the premature termination of these 2 studies, no safety problems were identified with the use of the drug, but it is not possible to assess the effectiveness of the drug in COVID-19 based on the available data.

Hydroxychloroquine has a long half-life of 30 to 60 days.

It is known that hydroxychloroquine dose-dependently prolong the QT interval in some patients. This risk depends on many factors and is aggravated by the simultaneous use of hydroxychloroquine with other drugs that prolong the QT interval, in particular class IA and III antiarrhythmics, tricyclic antidepressants, antipsychotics, some antimicrobial agents (for example, azithromycin), as well as with some concomitant states:

• heart disease, heart failure, myocardial infarction;
• bradycardia with a heart rate of less than 50 beats per minute;
• ventricular rhythm disturbances;
• uncorrected hypocalcemia, hypokalemia and / or hypomagnesemia.

The drug should be used with caution in patients with liver or kidney disease, in whom a dose reduction of hydroxychloroquine may be required.

Over the past several months, in the midst of COVID-19 treatment, Sanofi's Global Pharmaceuticals Division has received a significant number of notifications of serious and life-threatening cases of prolonged QT interval, pirouette arrhythmias, syncope, sudden cardiac arrest and sudden cardiac death. In most cases, hydroxychloroquine was used concomitantly with other drugs that prolong the QT interval (for example, azithromycin). Most patients experienced a regression of symptoms after discontinuation of hydroxychloroquine.

Due to the seriousness of this situation, the decision to use hydroxychloroquine off-label should be carefully weighed, and its use in combination with other drugs

Atami, lengthening the QT interval, should be carried out under the supervision of a physician in a hospital setting, subject to the following conditions:

• using the lowest possible dose of hydroxychloroquine,
• cardiological monitoring at the beginning and during treatment,
• regular monitoring of serum potassium and magnesium levels,
• discontinuation of hydroxychloroquine with an increase in the QT interval by more than 60 msec, or with an absolute QTc value> 500 msec.

Reports of adverse events

Information on the use of the drug not according to a registered indication, adverse events, overdose and errors in taking the drug should be submitted to the Pharmacological Committee at the email address: farmkomitet@minzdrav.uz or to the address: 100002, Tashkent, st. Ozod, K. Umarov's passage, 16 or to the Sanofi company at the email address Uzbekistan.Pharmacovigilance@sanofi.com or by phone +998 90 977-14-30.

If you have any additional questions on the medical use of Plaquenil, you can contact Sanofi's medical information service at +998 90-990-87-48, or leave a message by filling out the feedback form on our website https://www.sanofi.uz/ru/contact.

You can familiarize yourself with the Instructions for the medical use of Plaquenil, which contains new information on drug interactions and precautions, on the Sanofi website https://www.sanofi.uz/ru/our-products.

Sincerely,

Sanofi-Aventis Group JSC, French Republic, in the Republic of Uzbekistan
Address: st. Oybeka, 24, office block 3D, 100015 Tashkent
Tel .: + 998 (78) 147.03.44 / 45 - Fax: + 998 (78) 147.03.47
www.sanofi.uz