Pharmacovigilance workshop Clinical Review of ADR Pharmacovigilance workshop

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 329 3 JULY 2004

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

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

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

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

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

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

Severity Mild Moderate Severe

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

Drug interaction

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

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

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).

Mucosal involvement with Steven Johnson syndrome Ocular Involvement

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

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

Clinical Presentation

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.

Risk factors for Drug induced liver disorders

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

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