Paracetamol

ATC code

N02BE01

Therapeutic class

Analgesic and antipyretic · Anilide

Forms

oral tablet, oral solution, effervescent tablet, suppository, solution for infusion

Brand names

Doliprane (FR) · Tylenol (US) · Panadol (GB) · Antidol (ES) · Efferalgan (FR)

Overall confidence

high

Regulatory sources consulted

AEMPS CIMA: https://cima.aemps.es/cima/dochtml/ft/83208/FT_83208.html
ANSM BDPM: https://base-donnees-publique.medicaments.gouv.fr/affichageDoc.php?specid=69995434&typedoc=R
PubMed PMID:37436926 ↗
PubMed PMID:34681816 ↗
PubMed PMID:34556849 ↗
PubMed PMID:34642179 ↗
PubMed PMID:36414224 ↗
Clinical Pharmacology knowledge
AEMPS CIMA · nº registro 83208 ↗
ANSM BDPM · CIS 69995434 ↗

Approved indications

Symptomatic treatment of mild to moderate pain and febrile states.
Pain associated with knee and hip osteoarthritis (efficacy questioned in recent studies).

Contraindications

Absolute

Hypersensitivity to paracetamol or to any of the excipients.
Severe hepatocellular insufficiency.

Clinical warnings

Major warning · Risk of severe hepatotoxicity in case of overdose. Liver damage can be fatal. Do not exceed the maximum daily dose and avoid using multiple products containing acetaminophen. — AEMPS CIMA
Serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported. — AEMPS CIMA
Caution in patients with renal impairment, chronic alcoholism, chronic malnutrition, or dehydration. — AEMPS CIMA

Drug interactions

LowWarfarin and other coumarin anticoagulantsB01AA03
Mechanism: Chronic use of high doses of paracetamol (>2 g/day) may enhance the anticoagulant effect, possibly by inhibiting the synthesis of vitamin K-dependent clotting factors.
Recommendation: Monitor INR regularly in patients on anticoagulants, especially when starting, stopping, or changing the dose of chronic paracetamol therapy.
AEMPS CIMA
HighFlucloxacillinJ01CF05
Mechanism: Concomitant use has been associated with high anion gap metabolic acidosis (pyroglutamic acidosis), particularly in patients with risk factors such as sepsis, malnutrition, or renal impairment.
Recommendation: Use with caution. Monitor the patient for signs of metabolic acidosis. Consider alternatives if the risk is high.
ANSM BDPM
ModerateEnzyme inducers (e.g., Carbamazepine, Phenytoin, Rifampicin, St. John's Wort)N03AF01
Mechanism: They increase paracetamol metabolism through minor oxidative pathways (CYP2E1, CYP3A4), leading to increased production of the hepatotoxic metabolite NAPQI. This increases the risk of liver damage, even at therapeutic doses.
Recommendation: Avoid concomitant use if possible. If necessary, limit the dose and duration of paracetamol treatment and monitor liver function.
Clinical Pharmacology knowledge

Adverse events

Common (≥1%)

general malaise · hypersensitivity reactions · hypotension (IV route) · increased transaminases

Rare but serious

hepatotoxicity (from overdose) · thrombocytopenia · agranulocytosis · toxic epidermal necrolysis · Stevens-Johnson syndrome

Pregnancy and lactation

FDA category: Consult HCP

Although traditionally considered safe, recent epidemiological and experimental studies suggest a possible association between prenatal exposure to paracetamol and an increased risk of neurodevelopmental (ADHD, ASD) and urogenital disorders in the fetus. It is recommended to use only if medically indicated, at the lowest effective dose for the shortest possible time, after consulting a healthcare professional.

Recent literature (PubMed)

Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease.
Chidiac AS, et al. · Expert Opin Drug Metab Toxicol · 2023 · Relevance 5/5
Revisión exhaustiva sobre la sobredosis de paracetamol, su mecanismo de hepatotoxicidad y el tratamiento con acetilcisteína. Estima que el paracetamol está implicado en el 56% de los casos de insuficiencia hepática aguda grave. Aboga por cambios legislativos para reducir el riesgo de sobredosis, especialmente con formulaciones de liberación modificada.
Paracetamol use during pregnancy - a call for precautionary action.
Bauer AZ, et al. · Nat Rev Endocrinol · 2021 · Relevance 5/5
Declaración de consenso de 91 científicos y clínicos que, basándose en la creciente evidencia epidemiológica y experimental, piden precaución en el uso de paracetamol durante el embarazo. La exposición prenatal podría alterar el desarrollo fetal, aumentando los riesgos de trastornos neuroconductuales, reproductivos y urogenitales. Recomiendan usarlo solo si está médicamente indicado, a la dosis más baja y por el menor tiempo posible.
Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis.
da Costa BR, et al. · BMJ · 2021 · Relevance 4/5
Metaanálisis en red de 192 ensayos (102,829 participantes) que evalúa analgésicos para la artrosis. Concluye que el paracetamol tiene una baja probabilidad de alcanzar una reducción del dolor mínimamente relevante desde el punto de vista clínico, siendo significativamente menos eficaz que la mayoría de los AINEs orales y tópicos.
Paracetamol (Acetaminophen) and the Developing Brain.
Bührer C, et al. · Int J Mol Sci · 2021 · Relevance 4/5
Revisión sobre las crecientes preocupaciones de que el uso de paracetamol en el embarazo pueda causar TDAH y TEA en la descendencia. Los estudios epidemiológicos sugieren un aumento del riesgo relativo del 25% con una relación dosis-efecto. Se discuten los posibles mecanismos moleculares, incluyendo el estrés oxidativo en el cerebro fetal.
Pharmaceutical treatment of osteoarthritis.
Richard MJ, et al. · Osteoarthritis Cartilage · 2023 · Relevance 4/5
Revisión narrativa sobre el tratamiento farmacológico de la artrosis. Señala que medicamentos antes considerados convencionales, como el paracetamol, son cada vez menos aceptados debido a las preocupaciones sobre su eficacia y seguridad, y que las guías de práctica clínica están cambiando sus recomendaciones.