Last reviewed 2026-04-22 · How we verify

Paracetamol + Codeine

Paracetamol reduces pain and fever by inhibiting prostaglandin synthesis in the central nervous system, while codeine is an opioid agonist that enhances analgesia through mu-receptor activation.

Paracetamol reduces pain and fever through inhibition of prostaglandin synthesis, while codeine is an opioid agonist that enhances analgesia through central nervous system depression. Used for Mild to moderate pain, Postoperative pain, Headache and migraine.

At a glance

Mechanism of action

Paracetamol (acetaminophen) works primarily through inhibition of cyclooxygenase enzymes in the brain and spinal cord, reducing prostaglandin production and thereby lowering pain perception and body temperature set point. Codeine is a weak opioid that binds to mu-opioid receptors and is partially metabolized to morphine, providing additional analgesic effects. The combination provides synergistic pain relief for moderate pain conditions.

Approved indications

• Moderate acute pain
• Mild to moderate chronic pain

Common side effects

• Constipation
• Nausea
• Dizziness
• Drowsiness
• Hepatotoxicity (paracetamol overdose)
• Respiratory depression

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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