Pharmacovigilance in Action: Utilizing VigiBase Data to Improve Clozapine Safety
Notice bibliographique
Résumé
Purpose: Clozapine is an antipsychotic which was approved in 1989 for treatment-resistant schizophrenia in the United States (US). There were few randomized trials before its approval and potentially lethal clozapine adverse drug reactions (ADRs), such as agranulocytosis and myocarditis were identified by pharmacovigilance. VigiBase, the WHO global database, is a cornerstone of international pharmacovigilance efforts for ADR identification during post-marketing surveillance. This systematic review of the literature explores additional contributions to the knowledge of clozapine ADRs from recent VigiBase studies. Methods: Using the terms ”clozapine AND VigiBase” we conducted an article search in PubMed on September 5, 2024. Of the 29 articles, 11 were excluded and 18 described in the Results section. Results: All clozapine ADRs were described in two VigiBase studies. One on pregnancy indicated no increased risk with clozapine compared with other antipsychotics; the other reported 191,557 clozapine ADRs, including 22,956 fatal outcomes through January 15, 2023, and paid attention to the reporting style of the top 4 reporting countries (the US, the United Kingdom, Canada and Australia). Infections were described in three VigiBase studies where clozapine treatment was associated with infections, respiratory aspiration, and pneumonia. Rapid titration can lead to localized clozapine-induced inflammations including myocarditis, pericarditis or pancreatitis, or generalized inflammations such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Clozapine-induced inflammation was described in four VigiBase studies, two focused on all ages (myocarditis and DRESS) and two on youth (myocarditis and another on pericarditis and pancreatitis). Other specific ADRs were described in nine VigiBase studies (hematological malignancies, rhabdomyolysis, sialorrhea, seizures, diabetes mellitus, drug-induced parkinsonism, withdrawal symptoms, and suicidal behaviors). Conclusion: The spectrum of respiratory aspiration – aspiration pneumonia – pneumonia and other infections are significant causes of fatal outcomes in clozapine-treated patients. Clozapine had anti-suicidal effects versus other antipsychotics across all VigiBase labels of suicidal behavior. Plain Language Summary: 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. Keywords: clozapine/adverse effects, clozapine/therapeutic use, clozapine/toxicity, drug labeling, product surveillance, postmarketing, schizophrenia
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,058 | 0,188 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,008 |
| Bibliométrie | 0,014 | 0,012 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,005 | 0,005 |
| Science ouverte | 0,002 | 0,003 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».