The Dilemma of Diclofenac Injection for the Iranian

The Dilemma of Diclofenac Injection for the Iranian Health System Authors: Shalviri G, Cheraghali M, Gholami K, Kamali E, Daryabari N Institution: Ministry of Health and Medical Education Under-secretary for Food and Drug Research & Development Office Iranian Pharmacovigilance Center

Abstract • Problem Statement: A very high prescription rate of injectables is the most pronounced indication of irrational drug use in Iran. The Iranian Adverse Drug Reaction Monitoring Center received 6 reports of sciatic nerve damage following intramuscular injection of diclofenac sodium, in June 1998, and by the end of year the number of reports increased to more than 100. Since the reaction was a new and previously unknown ADR, the intervention of the Center was necessary to prevent further ADRs. • Objective: To assess the efficacy of different types of interventions to prevent further ADRs due to intramuscular injection of diclofenac sodium. • Design: Before/after study with no control group. • Setting and Population: All ADR reports received by the Iranian ADR Monitoring Center describing sciatic nerve damage induced by intramuscular injection of diclofenac sodium, from June 1998 to June 1999. • Intervention: Communicating with health professionals, implementing restrictions on local production and on availability. • Outcome Measures: Trend of injectable diclofenac usage and the ADRs. • Results: The total quantity of diclofenac sodium used has decreased from 85 million to 60 million ampoules. The number of ADR reports received shows an obvious reduction after intervention. • Conclusions: In order to reduce use of diclofenac injection, a multifactorial intervention was necessary to enforce rational drug use in the country.

Study Aims • To assess the efficacy of different types of interventions including: ü communicating with health professionals ü implementing restrictions on local production ü Implementing restrictions on availability on reduction of reported adverse drug reactions induced by intramuscular injection of diclofenac sodium.

Background & Setting • The high prescription rate of medicines is one of the most common reasons for irrational drug use, in which : misuse and overuse of injections seems to have an special importance because of high rate of adverse events

Methods • All ADR reports received by Iranian Pharmacovigilance Center describing walking difficulty following intramuscular injection of diclofenac sodium from 1996 to 2003 were assessed. • The number of ampoules used per year was determined based on the sale statistics. • The trend of yearly diclofenac usage and ADR reports were analyzed before and after different interventions.

Results • A total number of 161 ADRs describing walking difficulties following intramuscular injection of diclofenac sodium were reported to Iranian Pharmacovigilance Center from 1996 to 2003. • The sciatic nerve damage induced by intramuscular injection of diclofenac sodium was a new serious reaction not included in the labeling of the product.

The trend of reported ADRs Before & After First Intervention: Alerting Letters to Health Professionals Result: The total number of ADRs reduced from 63 in 1998 to 39 in 1999.

The trend of reported ADRs Before & After Second Intervention: Second intervention: Discontinuing local production and distributing Voltaren®. Result: There was no obvious reduction in the reported ADRs regarding the estimated rate for the reaction.

The trend of reported ADRs Before & After Third Intervention: Changing drug use protocol and restrictions to availability Result: Obvious Reduction in the number of reported ADRs from 30 in 2001 to 18 in 2002.

Diclofenac Sodium induced Nerve Damage and number of ampules used per year Vs interventions

Geographical distribution of ADR reports describing sciatic nerve damage induced by diclofenac sodium in Iran.

Discussion The Interventions of the Pharmacovigilance center was effective in preventing sciatic nerve damage induced by diclofenac sodium. Issuing Alerting letters to health professionals in combination with restriction of diclofenac usage to hospitals led to significant reduction in irrational prescribing of this product and finally overcome to this serious ADR.

Conclusion & Recommendations Different kinds of interventions including educational communication with health professionals and appropriate regulatory changes in drug availability, are necessary to promote rational drug use in the country which will result in reducing drug safety related morbidity and mortality.