Paracetamol as a toxic substance for children: aspects of legislation in selected countries

Abstract

Paracetamol is used widely in pediatrics because it has a high drug safety when used in therapeutic dosages. In case of overdose the majority of paracetamol is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is responsible for the severe toxic effects. The covalent connection between NAPQI and hepatic proteins leads to hepatocellular damage and possibly to severe liver failure. The antidote for paracetamol is N-acetylcysteine (NAC). It is a precursor of glutathione and aids to fill glutathione stores. The Rumack-Matthew nomogram should be used to decide on antidote treatment. Pediatric drug metabolism differs from adult metabolism. Children have a larger liver size compared to their body weight than adults, resulting in a higher metabolism rate. Young children seem to be less sensitive to acute intoxication than adults. One hypothesis to explain the lower rate refers to the larger liver size. The acute toxic dosage for children is more than 200 mg/kg body weight. There seems to be a global increase in accidental pediatric paracetamol overdose. Governmental websites of various European Union (EU) countries were searched for legal information on paracetamol availability in pharmacies and non-pharmacy stores. Various EU countries permit prescription-free sales of paracetamol in pharmacies and non-pharmacy stores. In Sweden paracetamol 500 mg may be sold in both pharmacies and non-pharmacies in a maximum pack size of 20 units. In the United Kingdom (UK) paracetamol 500 mg is listed in the general sales list with a maximum pack size of 30 effervescent tablets or 16 tablets. In Ireland paracetamol 500 mg may be sold in a maximum pack size of 12 units in a non-pharmacy. In the Netherlands paracetamol 500 mg is legal to be sold in a maximum pack size of 50 units in a drug store and with a maximum of 20 units in any other non-pharmacy. Several countries in the European Union are permitted to offer paracetamol prescription-free in pharmacies and non-pharmacy stores without legal guidance on the storage position within the store. Further research is needed to investigate whether paracetamol is located directly accessible to young children within the stores in EU countries which permit prescription-free sales of paracetamol.

Activity of the liver mitochondrial aspartate aminotransferase and malate dehydrogenase in rats with toxic hepatitis under conditions of alimentary protein deficiency

“…Such a case might be a problem in developing countries, where low dietary protein associated with high levels of pollutants and xenobiotics in the environment as well as administration of untested or old generation drugs in the medicine is a common issue. For example, acetaminophen (known also as paracetamol), one of the most widely used analgesics in the therapeutic practice in developing countries, possesses a high risk to cause liver injury [8]. However, the effects of acetaminophen administration associated with low protein intake on metabolic processes liver cells remains unknown.…”

La fiebre en el niño: una mirada reflexiva a las prácticas de cuidado

“…En este sentido, hay estudios que sostienen que la percepción de seguridad que sienten los padres sobre este medicamento puede contribuir al uso de una dosis inadecuada (52, 53) y a la falta de reconocimiento de los niños con mayor riesgo de presentar intoxicación, lo cual puede retrasar el diagnóstico y el tratamiento adecuados (54)(55)(56).…”

Preparation and in vitro evaluation of hydrophobic‐modified montmorillonite stabilized pickering emulsion for overdose acetaminophen removal

“…Clinically, when acetaminophen is administered beyond a therapeutic dose, the blood concentration reaches 150–200 mg/L within 0.5–4 h, resulting in acute liver failure . In such cases, many clinical manifestations will appear, such as appetite loss, nausea, and vomiting, and even mental symptoms along with hepatic encephalopathy and mental disorder, because of acetaminophen hepatotoxicity .…”