Pharmacovigilance in Ukraine: focus on ARV

treatment

Olena MatvieievaState Expert CenterMinistry of Health of Ukraine,Kiev, 2010

Population: 46,3 m

Territory: 603,700 km2

Regions: 25 +2 (Kiev and Sevastopol)

Hospitals: 2,801

Universities: 19

Physicians: 224,925

Pharmacists: 38,000

Ukraine

In order to ensure the adoption of appropriateregulatory decisions concerning the medicinalproducts authorized within the Community, havingregard to information obtained about adversereactions to medicinal products under normalconditions of use, the Member States shall establisha pharmacovigilance system.

Directive 2001/83/ЕС of the European Parliament and the Council of the European Union of 6.11.2001

Law “On Medicines” (1996)

Order of Ministry of Health of Ukraine (N898, 2006)

Based on ICH Guidelines (THE RULES GOVERNING MEDICINAL PRODUCTS IN THE EUROPEAN UNION, VOLUME 9 – Pharmacovigilavce Medicinal Products for Human and Veterinary use EC), EC Directives 2001/83, 75/319, 85/870, 93/39

Order of Ministry of Health of Ukraine (N531, 2009)

Pharmacovigilance Legislation System

Ministry of Health

State Expert CenterPharmacovigilance

Department

Regional centers (n=27)

Regulatory Authorities

Full member of the WHO Program for International Drug Monitoring since 2002

Membership in WHO Program for International Drug Monitoring (since June 2002)

• Personnel (n=15)

• Regional centers (n=27); Personnel (n=76)

• ADR Database received from physicians of Ukraine 1996-01.11.2010 (n=42,160)

• CIOMS Database received from Marketing Authorization Holder (MAH) 2009-01.11.2010 (n=3,404)

Ukrainian Pharmacovigilance Department

Collecting, analyzing ADRs reports

Regulatory issues/decisions

Alerting healthcare professionals, MAHs and public in case of risk

Safety monitoring in regions

Educational and training courses

Exchange of safety data

Expert evaluation of renewal files

Main Responsibilities

ADR Monitoring in Ukraine

State Expert Center MoH of Ukraine

Health State Administration

Post-registration Surveillance Board/ Pharmacovigilance

department

Regional Centers Leading general practitioners

Marketing Authorization Holders (MAHs)

Physicians

Ministry of Health of Ukraine

ADR Spontaneous Reporting in Ukraine

(1996-01.11.2010)

7242

5514

6849

41474102

52814190

283 298 257

3246

670200

1200

2200

3200

4200

5200

6200

7200

1996

-199

9

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

01.01

-01.1

1.201

0

Drugs Classes Associated with ADR(according to ATC)

30,1

17,3

12,910,410,2

6,94,5

2,41,3 1,1 0,90,8 0,7 0,5

0

5

10

15

20

25

30

35

%

Antimicrobial

Cardiovascular

Neurological

Blood formation agents

Digestive, hepatic

Musculosceletal

Respiratory

Antineoplastic

Dermatologicals

Various

Genito-urinary system

Sensory organs

Systemic hormonal preparations

Antiparasitic products

Non-Serious/Serious ADRs (2007-2009)

18,6 23,0 20,3

81,4 77,0 79,7

0

20

40

60

80

100

2007 2008 2009

%

non-serious ADR

serious ADR

PV in HIV Care

101 181 officially registered PLWH (330 000 estimated)

Prevalence of HIV in age group of 15 years and older is 0.82%

2008 – 18 963 - 2009 – 19 840

19 370 people are on ARV treatment as of July 1, 2010

260 treatment sites: 60 prescribe ARVs, 200 – distribute

93% of all patients are on first line and 7% on second line regimen;

ADRs vs. On ARV Treatment

1299 3056 47777657

10629

15871

25010

412

140

149

301

02000400060008000

1000012000140001600018000

2003 2004 2005 2006 2007 2008 2009

On ART ADRs in HIV

% of reported ADRs in HIV care

0.25

1.90

0.00 0.08 0.13

1.40

1.83

0.00

0.50

1.00

1.50

2.00

2003 2004 2005 2006 2007 2008 2009

%

ARVs Associated with ADR (n=950)

0.10.10.21.33.9

3.94.7

5.68.8

16.7

17.2

32.5

2.12.8 Lamivudine/Zidovudine

Efavirenz

Stavudine

Nevirapine

Oseltamivir

Lopinavir/Ritonavir

Nelfinavir

Zidovudine

Abacavir

Didanosine

Lamivudine

Abacavir/Lamivudine/Zidovudine

Ritonavir

Tenofovir disoproxil

21.5 21.2

17.8

15.4

9.8

6.48.0

0

5

10

15

20

25

%

(n=950)

Red blood

CNS system

Gastro-intestinal system

Skin and appendages

Metabolic and nutritional

Liver and biliary system

Other

Type of ADR in HIV Care

Serious ADRs

18.8

5.54.3 4.1

2.41.4 1.3 1.2 0.5 0.4 0.3 0.1

0

5

10

15

20

(n=950)

%

Lamivudine/ZidovudineEfavirenzNevirapineStavudineZidovudineLopinavir/RitonavirAbacavirNelfinavirDidanosineOseltamivirLamivudineTenofovir disoproxil

Challenges

Underreporting, e.g.in 2009

the treatment of 40% of patients was changed because of serious ADRreceived only about 300 ADR reportssupposed to receive about 700 ADR reports

Assessing errors of lack of efficacy of ARV treatmentLack of compliance of physicians with legislation of MoH of Ukraine

Prime objectives

Organize and conduct training courses in pharmacovigilance for physicians in ARV centers in collaboration with WHOConduct training courses for physicians in ARV drugs efficacy in partnership with leading experts of MoH in ARV treatmentAdapt WHO recommendations and guidelines on ARV treatment to Ukrainian conditions

Key Achievements

Full membership of the WHO Program for International Drug Monitoring since 2002 763 ADR reports submitted to WHO database, signal formed and confirmed (Lyell's syndrome to midecamicine)Regulatory decisions were made for drugs, for example: polyvinylpyrrolidone, metamizole sodium, kava-kava products, rofecoxib, nitrofurans (per os use), theophylline (aminophylline), nimesulide, sibutramine, roziglitazone

Key Achievements

Spontaneous reporting was developed and implementedMethodical and organizational activity was arrangedFunctioning of regional centers was developedADR reports received from physicians were included into the state medical statistics (form N69)

Key Achievements

Drugs safety and efficacy monitoring was successfully completed in hospitals of Zhytomyr Region Volume 9A was translated and published in Ukraine in 2009Ukrainian Guidance on Pharmacovigilance was published in 2007Workshops and conferences on pharmacovigilance and safety of drugs are conducted for physicians and MAH on regular basisCurrent Ukrainian legislation on pharmacovigilance is in the process of harmonization with WHO, EC standards on pharmacovigilance

Pharmacovigilance and Formulary System

MoH of Ukraine

State Expert CenterPharmacovigilance 

Department

Regional Centers of Pharmacovigilance

Central Formulary Committee

Regional Formulary Committees

Leading Specialist of Therapy

Medicines safety and efficacy monitoring of 

hospitals Spontaneous ADRs

Clinical Pharmacist

Local Formulary Committees

New edition of Law of Ukraine “On Medicines” will include requirements for pharmacovigilance;

Trainings on PV in HIV and ADRs in ARV for HIV specialists

Spontaneous ADRs reporting system strengthening

Strengthening cooperation with HIV services

Legal basis for medical insurance

Implementation of National Formulary System

Inclusion of clinical pharmacists and clinical pharmacologists into the pharmacovigilance system

Information technology of pharmacovigilance should be improved.

Approaches for Improvement of Pharmacovigilance in HIV Care in

Ukraine

Thank you for your attention!