Co-codamol

Overview

Co-codamol combines two analgesics with complementary mechanisms: paracetamol (acetaminophen) provides central antipyretic and analgesic effects, while codeine is a weak opioid that is metabolised (via CYP2D6) to morphine to exert μ-opioid receptor analgesia. The combination targets pain through non-opioid and opioid pathways, offering better relief than either agent alone at the same doses. In many European countries, co-codamol is available in multiple strengths (for example, 8/500, 10/500, 15/500, 30/500 — codeine mg/paracetamol mg per tablet). Regulatory status varies by country: some low-dose products may be available from a pharmacist after clinical assessment, while higher-strength products are prescription-only. Local age restrictions, pack sizes, and supply controls aim to reduce misuse and accidental overdose.

Paracetamol has a favourable safety profile at recommended doses but carries a well-known risk of severe liver injury in overdose or with chronic supra-therapeutic use. Codeine adds opioid-class risks: sedation, constipation, nausea, dependence, and (at high exposure) respiratory depression. Because codeine is a prodrug, individuals who are ultra-rapid metabolisers of CYP2D6 can convert codeine to morphine more quickly and extensively, increasing toxicity risk; conversely, poor metabolisers may obtain little benefit. For safety, codeine-containing products are contraindicated in certain paediatric settings and in breastfeeding.

Co-codamol is intended for short-term relief of moderate pain when paracetamol or NSAIDs alone are ineffective or not tolerated (for example, dental pain, musculoskeletal injury, postoperative pain on discharge, tension-type headache refractory to simple analgesics, dysmenorrhoea). It is not a first-line option for chronic pain and should be used at the lowest effective dose for the shortest possible duration, with an explicit stop/review plan to minimise dependence and medication-overuse headache. Patients should be counselled carefully about total daily paracetamol limits (from all sources) and opioid side-effects, with particular attention to driving/operating machinery and avoiding alcohol or sedative co-medication.

Interactions

Important interactions include both pharmacodynamic (sedation/respiratory depression) and pharmacokinetic (CYP2D6 metabolism) considerations.

• Alcohol, benzodiazepines, sedating antihistamines, gabapentinoids, hypnotics, antipsychotics: Additive CNS/respiratory depression — avoid or use with close medical supervision.
• Other paracetamol-containing products: High risk of unintentional overdose; check labels carefully.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, bupropion, quinidine, terbinafine): Reduce conversion of codeine to morphine → reduced analgesia.
• CYP2D6 ultra-rapid metabolisers: Genetic trait (prevalence varies by ethnicity) may produce excessive morphine levels at standard doses → toxicity risk; avoid codeine in known ultra-rapid metabolisers.
• Enzyme inducers (e.g., rifampicin, carbamazepine, phenytoin, St John’s wort): Increase hepatotoxicity risk with paracetamol; specialist advice recommended.
• Warfarin: Regular paracetamol (≥2 g/day for several days) may raise INR in some patients — monitor more closely.
• Anticholinergics: May worsen opioid-induced constipation or urinary retention.

Keep an up-to-date list of medicines and supplements and show it at each medical/pharmacy visit.

Overdose / Missed Dose

Paracetamol toxicity is a medical emergency. Severe liver injury can occur even if you feel well initially. If you may have exceeded the maximum daily dose, or if you have taken a double dose close together by mistake, seek urgent medical advice immediately — treatment with N-acetylcysteine (NAC) is time-critical and most effective within 8–10 hours of overdose. Bring the medication packs and tell clinicians exactly what and when you took, including any cold/flu products.

Signs of opioid excess include marked drowsiness, pinpoint pupils, slow or shallow breathing, bluish lips, and inability to stay awake. Call emergency services at once. Bystanders should be prepared to perform basic life support while awaiting help.

Accidental double dose: If you take an extra dose within a short interval, do not take further tablets and contact a clinician/pharmacist for advice, especially if the total paracetamol in the last 24 hours may exceed 4 g, or if you feel unwell (nausea, abdominal pain, unusual sleepiness, slow breathing). Never “catch up” missed doses by doubling.

Missed dose: Take when remembered if not near the next dose. If it is almost time for the next dose, skip the missed tablet and resume your regular schedule. Maintain at least 4–6 hours between doses.

Harm-reduction advice: Avoid alcohol while taking co-codamol. Use a dosing diary or smartphone reminder to reduce timing errors. If pain persists beyond a few days, arrange clinical review rather than continuing unsupervised.

Storage

• Store below 25 °C in a dry place, protected from moisture and direct heat.
• Keep in the original blister/pack to retain batch and expiry details and to protect tablets from humidity.
• Keep out of sight and reach of children; consider a lockable medicine box where children live or visit.
• Do not keep leftover opioids “just in case.” Return unused tablets to a pharmacy take-back scheme; do not share with others.
• When travelling, carry in hand luggage with the dispensing label; follow local regulations for carrying opioid-containing medicines.

Always check the strength on the pack before dosing (e.g., 8/500 vs 30/500). If the tablet appearance changes after a brand switch, confirm the strength with your pharmacist to avoid dosing errors.