1. Pharmacovigilance workshop
Clinical Review of ADR
Pharmacovigilance workshop

2. Primohead and colleagues
18825 patient admissions analysed
1225 admissions with an ADR, (6.5%)
80% admission as inpatient
median bed stay was eight days.
Most were preventable
4% of the hospital bed capacity.
The overall fatality was 0.15% (28)
BMJ VOLUME JULY 2004

3. Types of ADRs A= augmented B= Bizarre C= Continuous D= Delayed
E= End of use withdrawal

4. Clinical review Assessing the clinical details
Determining the duration to onset of each event
Noting data on de-challenge and re-challenge (if any)
Assessing severity and seriousness;
Checking the outcome of each event;
Drug interaction
Relationship assessment

5. Assessing the clinical details
Detailed history
For example, sometimes a “stomach upset” is reported, but this description is too vague.
Is it dyspepsia, nausea, vomiting, diarrhea

6. Determining the duration and onset of each event:
When did the event occur?
What is the relation of the event to taking the drug?

8. Data on de-challenge/re- challange
Stopping the medicine
Partial or complete
Results could be positive or negative
Re-challenge
Has to be under close supervision
Negative/Positive

9. Seriousness of the reaction
Not serious
Hospitalisation
Permanent disability
Life threatening
Congenital anomalies
Death

10. Severity
Mild
Moderate
Severe

11. Recovering with sequelae
Outcomes
ADR
Recovered
Recovering
Recovering with sequelae
Died
Un-known

12. Drug interaction

13. Relationship of ADR to drug
Start of drug
Onset of ADR
Challenge
De-challenge
Days/hours

14. Skin Cutaneous drug reactions 10-20%.
Idiosyncratic... Due to an immune response.
Can occur from 1-14 after starting therapy
Ranges from mild urticaria to potentially life threatening e.g. TEN and SJS

15. Co-Trimoxazole Molibiliform eruptions Steven Johnson Syndrome
Histologic examination reveals a lymphocytic interface dermatitis with vacuolar changes at the dermal-epidermal junction and papillary dermal edema and eosinophils. Dyskeratotic cells may be found along the dermal-epidermal junction (Crowson and Magro, 1999).

16. Mucosal involvement with Steven Johnson syndrome
Ocular Involvement

17. Identifying the drug as causative
Other causes for the eruption...
Relationship between drug use and onset of the rash.
Improvement when drug is stopped.
Reactivation upon re-challenge of the drug
Known cutaneous reaction with drug
SJS implicated with many drugs mainly sulphonamides but can occur with any antibiotic

18. Drug induced liver disorders
Up to one-half of the cases of acute liver failure
Common cause of drug withdrawal
Idiosyncratic or Predictable
Acute or chronic
E.g. Isoniazid, rifampicin, pyrazinamide

19. Clinical Presentation

20. Symptoms Asymptomatic Symptomatic:
malaise, low-grade fever, anorexia, nausea, vomiting, right upper quadrant pain, jaundice, acholic stools, or dark urine. Patients with cholestasis can report pruritus.

21. Risk factors for Drug induced liver disorders

22. Key elements Drug exposure preceded the onset of liver injury
Underlying liver disease is excluded
Stopping the drug leads to improvement in the liver injury
Re-challenge = severe recurrence

24. Others associated with Anti TB drugs
Other gastrointestinal
Retinitis
Neuropathies
Renal
Drowsiness…………………