**10. Strategies to diminish adverse drugs reactions**

The main strategies for reducing adverse drug reactions are: drug interaction calculators, renal insufficiency calculators, prescribing programs and collaboration between pharmacists, pharmacologists and clinical physicians.

The world Health Organization defines pharmacovigilance as the science and activities related to the detection, assessment, understanding, and prevention of adverse affects or any other possible drug-related problem. The field has grown significantly in recent years as postapproval safety studies for new medication become increasingly required, encompassing retrospective analysis of heath-care claims databases, meta-analysis, patients registries, and prospective case-control studies.

Recognition, reporting and careful characterization of these troubling, often unexpected ADRs are vital to future prevention of these event because detection of patterns and common features of ADRs can enhance our understanding of new mechanism and risk factors. The expansion of electronic database capabilities in hospital and primare-care setting offers the promise of better safety-based detection and monitoring systems that can detect ADRs earlier and prevent ADRs in the future. Hospital informatics systems linking to electronic medical records and including patient genotype with medication ordering and dispensing will reduce medication errors and inappropriate prescribing while improving

Adverse Reactions and Gastrointestinal Tract 521

1. Temporal relationship of start of drug to ALT>2x ULN Score Initial treatment 5–90 days; subsequent treatment course: 1–15 days 2 Initial treatment <5 or >90 days; subsequent treatment course: >15 days 1 From cessation of drug: <15 days, or <15 days after subsequent treatment 1 Otherwise 0

Decreases >50% within 8 days 3 Decreases >50% within 30 days 2 No information or decrease >50% after >30 days, or inconclusive 0 Decrease <50% after 30 days or recurrent increase -2

No alcohol use 0 Alcohol use 1 Age <55 years 0 Age >55 years 1

No concomitant drug administered 0 Concomitant drug with suggestive or compatible time of onset -1 Concomitant known hepatotoxin with suggestive or compatible time of onset -2 Concomitant drug with positive rechallenge or validated diagnostic test -3

All primary and secondary causes reasonably ruled out: 2 All 6 primary causes ruled out 1 4 or 5 primary causes ruled out 0 < 4 primary causes ruled out (max. negative score for items 4 and 5: –4) -2 Nondrug cause highly probable -3

Package insert or labelling mention 2 Published case reports but not in label 1 Reaction unknown 0

Positive (ALT doubles with drug in question alone) 3 Compatible (ALT doubles with same drugs as given before initial reaction) +1 1

reaction occurred) -2 Not done, or indeterminate result 0

Reprinted from Toxicologic Pathology, 33, Lee, W.M. & Senior, J.R., Recognizing drug-induced liver injury: current problems, possible solutions, pp.155-64, copyright © 2005 by the Society of Toxicologic

5. Nondrug causes: Six are primary: recent hepatitis A, B, or C, biliary obstruction, acute

Secondary group: Underlying other disease; possible CMV, EBV or HSV infection

alcoholic hepatitis (AST > 2x ALT), recent hypotension

6. Previous information on hepatotoxicity of the drug in question

Negative (Increase in ALT but <2x ULN, same conditions as when

Score Interpretation: Highly probable >8; Probable 6–8;

Pathology. Reprinted by Permission of SAGE Publications.

Table 1. RUCAM Hepatocellular Injury Scale

Total (range of algebraic sum: –8 to +14)

Possible 3–5; Unlikely 1–2; Excluded <0

2. After drug cessation- difference between peak ALT and upper limits normal

**13. Appendix 2**  Subject Information

3. Risk factors

4. Concomitant drug

7. Rechallenge

detection of ADRs. Also, the review of prescription by pharmacists can achieve a diminution in the appearance of adverse drug reactions.

It´s also important to recognize people specially susceptible to ADRs: elderly, women, polipharmacy, renal insufficiency and presence of drug-drug interactions. In this special population we have to be careful with prescription of new drugs and its dosing.
