Pharmacovigilance in action: Utilizing VigiBase data to improve clozapine safety

Abstract

Why was the review done? Marketers develop a package insert after a medical drug is licensed for use in each country. The package insert describes the known benefits and risks of the drug at the time it was licensed. After licensing, post-marketing studies are continued to look for possible undetected adverse drug reactions; this process is called pharmacovigilance. These pharmacovigilance studies should be done by the drug agencies in all countries. These national agencies send their reports to the international pharmacovigilance database, VigiBase. VigiBase is managed by the World Health Organization and is located in Uppsala, Sweden. Clozapine is a second-generation antipsychotic medication that was licensed in 1989 in the United States for treatment-resistant schizophrenia and then approved by other countries. In 1989 there was major concern about clozapine causing agranulocytosis (loss of white blood cells), so a hematological monitoring system was required in the United States. Later, myocarditis was associated with clozapine in pharmacovigilance studies. What did the authors do? They systematically reviewed VigiBase studies on clozapine adverse drug reactions and identified 18 studies that described clozapine adverse drug reactions in detail. What do these results mean? These VigiBase studies indicate that the respiratory aspiration – aspiration pneumonia – pneumonia spectrum, along with other infections, are significant causes of fatal outcomes in clozapine-treated patients, but this is not mentioned in any clozapine package insert. On the positive side, VigiBase data confirms other literature that clozapine may have specific anti- suicidal effects not present in other antipsychotics.