What is the management for a Panadeine (paracetamol and codeine) overdose?

From the Guidelines

Management of a Panadeine overdose requires immediate medical attention focusing on both paracetamol and codeine toxicity, with administration of N-acetylcysteine (NAC) for paracetamol poisoning and naloxone for codeine toxicity, as well as supportive care to prevent morbidity, mortality, and improve quality of life. For paracetamol poisoning, NAC is the primary antidote, typically administered intravenously with a loading dose of 150 mg/kg over 60 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1. Treatment should begin within 8 hours of ingestion for maximum effectiveness, but can still be beneficial later. Activated charcoal (50g for adults) may be given if the patient presents within 1-2 hours of ingestion. For codeine toxicity, naloxone is administered at 0.4-2 mg IV, repeated every 2-3 minutes as needed to reverse respiratory depression, with the goal of improving ventilatory effort, not necessarily awakening the patient 1. Some key points to consider in the management of Panadeine overdose include:

• Naloxone administration should be based on clinical findings, not simply on presumed exposure to opioids or other substances 1
• The endpoint of naloxone administration is improved breathing, not awakening, and failure to recognize this may lead to the administration of multiple doses, increasing the risk of precipitated opioid withdrawal 1
• Supportive care, including airway management, oxygen supplementation, and IV fluids, is crucial in the management of Panadeine overdose
• Paracetamol levels should be measured at least 4 hours post-ingestion and plotted on a treatment nomogram to guide NAC therapy, and liver function tests and electrolytes should be monitored 1. NAC works by replenishing glutathione stores that detoxify paracetamol's toxic metabolite NAPQI, while naloxone competitively blocks opioid receptors to reverse codeine's effects. Early treatment is crucial as paracetamol can cause irreversible liver damage and codeine can cause fatal respiratory depression. The most recent and highest quality study, published in 2024, provides guidance on the management of patients exposed to xylazine-adulterated opioids, which may be relevant in some cases of Panadeine overdose 1.

From the Research

Management of Panadeine Overdose

The management of Panadeine (paracetamol and codeine) overdose involves several interventions to reduce absorption, prevent liver injury, and manage symptoms.

• Reducing Absorption: Activated charcoal, gastric lavage, and ipecacuanha can reduce the absorption of paracetamol, but the clinical benefit is unclear 2. Activated charcoal seems to have the best risk-benefit ratio.
• Antidotes: N-acetylcysteine (NAC) is the preferred antidote for paracetamol overdose, and it should be given to patients with overdose 2, 3, 4, 5. The optimal treatment schedule and timing to start treatment are crucial, with evidence suggesting that NAC administration within 8-24 hours from paracetamol overdose is efficacious in terms of mortality 5.
• Codeine Overdose: Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown 6. However, paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression.
• Liver Injury: Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres 4. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.
• Treatment Regimens: Different NAC regimens have been used, including intravenous (100-150 mg/kg) and oral (70-140 mg/kg), with varying lengths of treatment 3, 5. The most effective regimen is unclear, but NAC improves hepatotoxicity and reduces mortality 5.

Important Considerations

• Timing of Treatment: The timing of NAC treatment is critical, with evidence suggesting that initiation within 8-24 hours from paracetamol overdose is important to prevent or minimize liver damage 5.
• Respiratory Depression: While codeine can cause respiratory depression, paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression 6.
• Liver Transplantation: Liver transplantation has the potential to be life-saving in fulminant hepatic failure, but refinement of selection criteria for transplantation and long-term outcome reporting are required 2.