Codeine+Paracetamol

ATC code

N02AA59

Therapeutic class

Opioid combination analgesic · Non-opioid analgesic + weak opioid

Forms

oral tablet, effervescent tablet

Brand names

Co-codamol (GB) · Tylenol with Codeine (#3, #4) (US) · Dafalgan Codéine (FR) · Codoliprane (FR) · Algidol (ES) · Dolocatil Codeína (ES)

Overall confidence

medium

Regulatory sources consulted

WHO Analgesic Ladder
Flockhart Table
Clinical Pharmacology Knowledge Base
General Pharmacovigilance Principles

Approved indications

Treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (used alone).

Contraindications

Absolute

Hypersensitivity to codeine, paracetamol, or other opioids.
Severe hepatocellular insufficiency.
Acute or severe respiratory depression, severe obstructive pulmonary disease.
Known CYP2D6 ultra-rapid metabolizers.
Children under 12 years of age.
Breastfeeding.

Clinical warnings

Boxed warning · Hepatotoxicity: Contains paracetamol. The risk of severe liver damage is higher with doses exceeding 4 grams/day, use with other paracetamol-containing products, or alcohol consumption. — Clinical Practice
Boxed warning · Addiction, Abuse, and Misuse: Risk of opioid use disorder, overdose, and death. Assess each patient's risk prior to prescribing. — Clinical Practice
Major warning · Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor for this, especially during initiation or following a dose increase. — Clinical Practice

Drug interactions

HighBenzodiazepinesN05BA
Mechanism: Additive depressant effect on the central nervous system (CNS), increasing the risk of profound sedation, respiratory depression, coma, and death.
Recommendation: Avoid concomitant use. If necessary, limit dosages and durations of both drugs and monitor closely for sedation and respiratory depression.
FDA Drug Safety Communication
ModerateCYP2D6 Inhibitors (e.g., Fluoxetine, Paroxetine, Bupropion)N06A
Mechanism: Inhibition of CYP2D6, blocking the conversion of codeine (prodrug) to morphine (active metabolite), which can result in a lack of analgesic efficacy.
Recommendation: Avoid the combination or monitor for lack of analgesic efficacy. Consider an alternative analgesic not dependent on CYP2D6 metabolism.
Flockhart Table

Adverse events

Common (≥1%)

nausea · vomiting · constipation · somnolence · dizziness

Rare but serious

severe hepatotoxicity · liver failure · severe respiratory depression · anaphylaxis · paralytic ileus · Stevens-Johnson syndrome

Pregnancy and lactation

Pregnancy: Use only if benefit outweighs risk. Prolonged use in the third trimester can cause neonatal withdrawal syndrome. Lactation: Contraindicated. Codeine passes into breast milk and can cause serious toxicity in the infant, especially if the mother is a CYP2D6 ultra-rapid metabolizer.