Pharmacovigilance is the science of detecting, assessing, and preventing adverse effects from medicines. It is important for patient safety and treatment outcomes, especially for new drugs and drug combinations where safety is not fully known. Nepal employs core pharmacovigilance activities for drugs used to treat drug-resistant tuberculosis, including monitoring all patients on these regimens for serious and other significant adverse events. Effective pharmacovigilance requires global cooperation to understand rare or long-term safety issues that may not be detected in individual clinical trials or treatment programs.

1. PHARMACOVIGILANCE
(Narrative of workshop attended in KTM on August 22 and 23, organized by WHO & NTP)
By
Dr. Pawan KB Agrawal,
MBBS, MDGP (IOM, Maharajgunj)
Consultant, General Practice & Emergency.
5th September 2018.

3. AE Vs ADR
• Adverse event
• Any negative or harmful health experience that takes place during the
treatment, which may or may not be associated with medicine.
• Adverse drug reactions
• A harmful effect suspected to be caused by a medicine when used at normal
therapeutic doses.

4. Effect of Adverse Drug Reactions
• Additional morbidity
• Treatment interruption
• Treatment failure
• Reduced quality of life
• Death
• Hospitalisation rate: 6.5-8.8%
• Economic impact: cost 4th following cardiovascular disease, cancer and
diabetes in US.

5. • Most AE s are predictable from pharmacology or know interactions
• Most are preventable

6. Pharmacovigilance
• The science and activities relating to detection, assessment,
understanding and prevention of adverse effects or any other
possible drug related problem.
The importance of pharmacovigilance, WHO, 2002.

7. Signal
• WHO defines signal as a reported information on a possible
relationship between an adverse event and a drug, the relationship
being unknown or incompletely documented previously.
• Can be a new information about an adverse effect or
• Additional information about already known AE
• Population at risk
• Dose range
• Drug drug interaction

8. Why??
• To prevent and manage adverse drug reactions for patient safety
• To improve health related quality of life and treatment outcomes.
• To disseminate and cooperate in local, national and global platforms
for public health and safety.

10. Pharmacovigilance in DR TB
• New TB drugs are used only in limited number of selected groups.
(Phase IIb trials)
• Insufficient data to capture rare events.
• Limited experience in programmatic use.
• Safety is not clear in specific groups like: elderly ; children; pregnancy
and lactation & PLHIV.
• Off label use (beyond indication) of some repurposed medicines like
linezolid and clofazimine

11. Pharmacovigilance in DR TB
• Combination of new and old TB drugs may result in risk of
unrecognized drug-drug medicines.

14. Pharmacovigilance in DR TB
• Risk for public confidence if signals are not detected in timely fashion.
• Drug safety has not been a standard monitoring requirement for TB
program.

15. Moving forward
• The feasibility of effective and fully oral treatment regimen for DR TB

16. Types
• Spontaneous reporting (passive or voluntary)
• Depends upon motivation, usually low in number and often incomplete.
• Cohort event monitoring

17. Active Drug Safety Monitoring and Management
• Active and systematic clinical and laboratory assessment of patients
on treatment with new TB drugs, novel MDR TB regimens and XDR TB
regimens to detect manage and report suspected or confirmed drug
toxicities.
• 3 categories

18. • Core: SAEs
• Intermediate: SAEs + AEs of special interest
• Advanced: SAE + AEs of special interest + AEs of clinical significance

19. Serious adverse events
• AEs leading to
• Death
• Lifethreatening
• Hospitalization
• Birth defect or congenital anomaly

20. AEs of special interest
• AEs documented during clinical trials

21. AEs of clinical significance
• Other AEs that meet any of the following criteria:
• Serious
• Special interest
• Lead to change in dose or treatment including discontinuation

24. Components of ADR reporting

26. Dechallenge Vs Rechallenge
• Dechallenge: withdrawal of medicine from a patient following an
adverse event.
• Positive and negative
• Rechallenge: Reintroduction of medicines under the previous
conditions, following withdrawal and recovery from an adverse event.
• Positive and negative

27. Causality assessment
• Essential components:
• Time to onset
• Response to dechallenge
• Response to rechallenge
• Feasible alternative explanations
• Six categories
• Certain, probable, possible, unlikely, unclassified and unassessable

28. Causality assessment
• Essential components:
• Time to onset
• Response to dechallenge
• Response to rechallenge
• Feasible alternative explanations
• Six categories
• Certain, probable, possible, unlikely, unclassified and unassessable

29. Causality assessment

30. Causality assessment
• Essential components:
• Time to onset
• Response to dechallenge
• Response to rechallenge
• Feasible alternative explanations
• Six categories
• Certain, probable, possible, unlikely, unclassified and unassessable

31. Regulatory actions
• Update product information
• Safety communication
• Further monitoring
• Restrictions on indication
• Reclassification
• Withdrawal from market

32. Nepal and Pharmacovigilance
• Nepal employs core package of aDSM.
• 21 DR TB centers
• Eligibility criteria: all patients receiving DR TB regimen

36. Keys
• All medicines have potential to cause harm.
• Pharmacovigilance is the science and activities relating to detection,
assessment, understanding and prevention of adverse effects or any
other possible drug related problem.
• Pharmacovigilance requires global cooperation.
• The recommendation for use of novel treatment options comes with
a condition to undertake appropriate drug safety and monitoring.
• Nepal has employed core package of aDSM for DR TB drugs.