Nimesulide is an active ingredient which possesses two contrasting characteristics, on the one hand is an excellent anti-inflammatory drug capable of inhibiting in a more selective way the enzyme protein methabolism COX-2 causing less side effects at the gastric level, on the other hand is a drug that can cause serious side effects at the liver, primarily of idiosyncratic type, violent and specific reactions to a substance, usually harmless. The toxic effects in liver are due to the fact that after the metabolization of the drug, the concentration of the drug increases in the hepatobiliary compartment with the formation of reactive metabolites of oxygen that covalently modify proteins causing oxidative stress and mitochondrial damage in hepatocytes and an increased liver transaminases. At the base of these changes there may also be alterations of cytochrome P450, responsible for metabolizing the drug. These side effects have led to the development of fulminant hepatitis and death of some genetically predisposed patients. For this reason, some countries, including Finland and Ireland, revoked the sell authorization of medicines containing nimesulide, with drawing from the market. In the other countries and in Italy have been made some restrictions in the therapeutic indications of the product, marked for adults only and for a maximum of therapy of 200 mg a day for no more of 15 days, exclusively for the treatment of acute pain and sold only under written medical prescription. These restrictions are studied to avoid prolonged use of the drug and to determine a safe dosage so as to minimize the risk of developing severe hepatotoxic reactions.
La nimesulide è un principio attivo che possiede due caratteristiche contrapposte, da un lato è un ottimo farmaco antinfiammatorio in grado di inibire in maniera più selettiva il protide enzimatico COX-2 causando minor effetti collaterali a livello gastrico, dall’altro è un farmaco in grado di causare gravi effetti collaterali a livello epatico, principalmente di tipo idiosincratico, ossia violente e particolari reazioni ad una sostanza, generalmente innocua. Gli effetti tossici epatici sono dovuti al fatto che dopo la metabolizzazione del farmaco aumenta la concentrazione dello stesso nel comparto epatobiliare con la formazione di metaboliti reattivi dell’ossigeno che in modo covalente modificano le proteine causando stress ossidativo e danno mitocondriale negli epatociti e aumento delle transaminasi epatiche. Alla base di questi cambiamenti possono esserci anche alterazioni a carico degli enzimi del citocromo P450 responsabile della metabolizzazione del farmaco. Questi effetti collaterali hanno portato allo sviluppo di epatiti fulminanti e al decesso di alcuni pazienti predisposti geneticamente. Per tal motivo alcuni stati, tra cui la Finlandia e l’Irlanda, revocarono l’autorizzazione all’immissione in commercio dei farmaci contenenti il principio attivo, ritirandolo dal mercato. Negli altri stati e in Italia vennero effettuate delle restrizioni nelle indicazioni terapeutiche del prodotto indicandolo per i soli adulti e per un massimo di terapia di 200mg al giorno per 15 giorni, esclusivamente per il trattamento del dolore acuto e vendibile solo dietro prescrizione medica redatta correttamente. Queste restrizioni sono state studiate per evitare l’uso prolungato del farmaco e per stabilire un dosaggio sicuro in modo da ridurre al minimo il rischio di sviluppare reazioni epatotossiche gravi.
La Nimesulide: benefici e rischi
CASTOLDI, ALICE LUDOVICA
2014/2015
Abstract
Nimesulide is an active ingredient which possesses two contrasting characteristics, on the one hand is an excellent anti-inflammatory drug capable of inhibiting in a more selective way the enzyme protein methabolism COX-2 causing less side effects at the gastric level, on the other hand is a drug that can cause serious side effects at the liver, primarily of idiosyncratic type, violent and specific reactions to a substance, usually harmless. The toxic effects in liver are due to the fact that after the metabolization of the drug, the concentration of the drug increases in the hepatobiliary compartment with the formation of reactive metabolites of oxygen that covalently modify proteins causing oxidative stress and mitochondrial damage in hepatocytes and an increased liver transaminases. At the base of these changes there may also be alterations of cytochrome P450, responsible for metabolizing the drug. These side effects have led to the development of fulminant hepatitis and death of some genetically predisposed patients. For this reason, some countries, including Finland and Ireland, revoked the sell authorization of medicines containing nimesulide, with drawing from the market. In the other countries and in Italy have been made some restrictions in the therapeutic indications of the product, marked for adults only and for a maximum of therapy of 200 mg a day for no more of 15 days, exclusively for the treatment of acute pain and sold only under written medical prescription. These restrictions are studied to avoid prolonged use of the drug and to determine a safe dosage so as to minimize the risk of developing severe hepatotoxic reactions.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/17999