Last reviewed 2026-04-22 · How we verify

Codeine paracetamol

Codeine acts as a weak opioid agonist while paracetamol inhibits prostaglandin synthesis, together providing analgesic and antipyretic effects.

Codeine acts as a weak opioid agonist while paracetamol inhibits prostaglandin synthesis, together providing analgesic and antipyretic effects. Used for Moderate acute pain, Mild to moderate chronic pain.

At a glance

Mechanism of action

Codeine binds to opioid receptors in the central nervous system to reduce pain perception, while paracetamol (acetaminophen) inhibits cyclooxygenase enzymes to decrease prostaglandin production, lowering pain and fever. The combination provides synergistic analgesia for moderate pain relief with lower opioid doses than codeine alone.

Approved indications

• Moderate acute pain
• Mild to moderate chronic pain

Common side effects

• Constipation
• Nausea
• Dizziness
• Drowsiness
• Vomiting
• Headache
• Hepatotoxicity (paracetamol overdose)

Key clinical trials

• Examining Analgesic Synergy and Efficacy in Trauma Care (PHASE4)
• Paracetamol With or Without Ketoprofen in the Management of Pain for Patients Receiving Brachytherapy (KETOCOL-1304) (PHASE2)
• E7 TCR T Cells for Human Papillomavirus-Associated Cancers (PHASE1, PHASE2)
• Opioid-Free Pain Control Regimen Following Robotic Radical Prostatectomy (PHASE2, PHASE3)
• Comparing Analgesic Regimen Effectiveness and Safety for Surgery for Kids Trial (PHASE4)
• Opioid-Free Pain Protocol After Shoulder Arthroplasty (PHASE4)
• Opioid-Sparing Joint Replacement (PHASE3)
• Reduced Opioid Prescription After Laparoscopic Hysterectomy (NA)

Primary sources

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