Cruz Cesar, Araque Clara, Velasquez Ana L, Mendez Ricardo, Fischborn Hans. Pharmacovigilance Program. Farmalogica S.A. Bogota D.C., Colombia.

cesarcruzmd@gmail.com

Findings on self-report Adverse Drug Reactions related with the use of

systemic beta-lactams by a Pharmacovigilance Program

INTRODUCTION

Pharmacovigilance (PV) is a broad field in continuous developing that could be defined as the science and activities related to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem; starts since the prescription by the physician and is a continuous growing discipline that goes beyond from identifying and responding drug safety issues, its aim pursues the protection for patients from unnecessary harm by identifying previously unrecognized drug hazards, elucidating predisposing factors, refuting false safety signals and quantifying risk in relation to benefit. Despite several efforts, surveillance systems still report unexpected and serious adverse drug reactions (ADRs) repeatedly (1). This surveillance system in many countries depends on the self-report that lack basic information of critical aspects of quality and under report. The aim of this work has the intention to show a description of the reports generated by the PV programs within the hospitals about ADRs related to the use of systemic antibiotics in terms of quality of the information reported and the type of ADRs reported to the producer.

As a part of the National Program of PV leaded by the National Regulatory Agency Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA) the Hospitals, institutions that provide health services (IPS) and health care professionals are committed to report any case of ADRs or a suspected case to INVIMA and the pharmaceutical producer through a self-report format called FORAM or at INVIMA web-site, based on an observation of the case, collecting all the information related to the case from the medical records or

interviewing the patient after that proceed to analyze carefully each case by a PV committee that should take care about all the cases and based on the evidence and plausibility they postulate the relation between the event and the administration of the medicine (antibiotic in this case) they are free to choice any of the algorithms to try to give a quantification of each case. The National PV program receives these reports and analyzes each case and provides a conclusion based on the information for each case in order to give a feedback based on the conclusions and its validity to who reports and the pharmaceutical company which provides the drug related to the ADRs reported.

METHODS

The institutional PV program is permanent receiving reports related to the use of our products, because we are concern about the rational and appropriate use of antibiotics in order to prevent or decrease at least the overwhelming development of new and more complex mechanisms of resistance to antibiotics, bring to us the question about how properly the health care professionals identify and report the problems related with the use of antibiotics? To evaluate the quality of the report we follow the recommendations from the Good Pharmacovigilance Practices for the Americas by The Pan American Health Organization 2011 (GPP-PAHO) (2) this document is free available on line at www.paho.org and we evaluate the information required to do the analysis divided in four items: • First: information related to the patient that includes demographic information like age, sex, weight, height and a code to protect the privacy of identification. • Second: information about all drugs and herbal products used by the patient in the last 30 days, including over the counter products, the name of the generic and brand products, the way of administration, dates of beginning and the end of a given treatment, length of treatment, number of doses, name of the producer and number of lot. • Third: detail information about the ARDs, date of beginning of symptoms or clinical lab deviations; diagnosis of all diseases and relevant clinical records including allergies; length, course and the resolution of the clinical situation as well.• Fourth: information from who filled up the report including name, address, telephone, email.We found that none of the reports complete the full items description suggested by the GPP-PAHO. In the next table the description of adverse drug reactions (ADRs) reported are presented.

METHODS

22

Adverse drug reactions (ADRs)

Severe ADR

Non severe ADR

Failture of therapy (FT)

Unassessable/Unclassified

Antimicrobialmisuse

Anaphylactic reaction which requires ICU and ventilator support with non-fatal resolution in a patient with penicillin allergyv

Rash in patients who are receiving other antibiotics (vancomycin)

Thrombophlebitis in a patient who receives a NSAID (diclofenac) in the same I.V. line

Unexpected rash in patients with no previous history of allergy

Reports with significant lack of information that could not prove an FT (bacterial culture report, antibiogram, number of doses received and length of treatment)

MRSA bacteremia treated with meropenem

Viral pneumonia (H1N1) with piperacillin/tazobactam

S. maltophylia treated with meropenem

Meropenem resistant B. cepaciae treated with meropenem

A. baumanii carbapenemase producer treated with meropenem

1

1

3

15

8

2

1

1

1

2

2

7

Description of events related to adverse drug reactions (ADRs)

RESULTS

Between october 2011 - october 2013 twenty two reports from six cities were submitted and classified by type of ADRs 15 reports (68,2%) unexpected failure of therapy, 6 reports (27,3%) Non dose- related ARDs and 1 (4.5%) of these present a serious anaphylactic reaction which requires ICU admission and ventilator support with non-fatal resolution in a patient with history of penicillin allergy treated with cephazolin. The unexpected failure of therapy 15 reports lack crucial information for analysis (time of use, diagnosis, number of doses, other medicines used, reports of cultures and antibiograms); based on the information we conclude wrong use were detected in 7 reports (2 cases of MRSA bacteremia treated with meropenem, 1 case of H1N1 pneumonia treated with piperacillin tazobactam, 1 case of S. maltophylia and 1 case of B. cepaciae with decrease susceptibility treated meropenem and 2 cases treated with meropenem caused by carbapenemases strains producers.)

CONCLUSIONS

The self-report information is biased by under-report practice; here we show the wrong use of antibiotics is self-reported (31.8%) when the clinician suspect a failure instead that a wrong use of antibiotic. The rationale use of antimicrobials and effective surveillance programs should contribute to reduce the misuse of antimicrobials and should pursues stops the negative deep impact of antimicrobial resistance, as a standard goal of the national health system, that urges for improve equity in the quality of health services.

REFERENCES1. Pan American Network on Drug Regulatory Harmonization. Good Pharmacovigilance Practices for the Americas. 2011. Pan American Health Organization. www.paho.org 2. Antibiotic Allergy Gruchalla RS and Pirmohamed M. N Engl J Med 2006; 354:601-609 February 9, 2006 DOI: 10.1056/NEJMcp043986