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Saturday, July 26, 2025

Co-codaprin


Co-codaprin (aspirin and codeine)


Co-codaprin is a fixed-dose combination analgesic containing aspirin, a non-steroidal anti-inflammatory drug (NSAID), and codeine phosphate, a mild opioid. It is used for the relief of mild to moderate pain, particularly when single-agent therapy (such as paracetamol or aspirin alone) is ineffective. By combining two analgesics with distinct mechanisms—aspirin for anti-inflammatory and analgesic action and codeine for central pain modulation—co-codaprin offers synergistic pain control.

This medication is used primarily in the UK and Commonwealth countries, and it is available in both prescription and over-the-counter forms, depending on the strength and national regulations.

1. Drug Classification

  • Therapeutic Class: Analgesic combination

  • Pharmacologic Classes:

    • Aspirin: NSAID (salicylate group)

    • Codeine: Opioid analgesic

  • ATC Code: N02BA51

  • Controlled Drug Status:

    • UK: Pharmacy (P) medicine for low-dose products (e.g., ≤8 mg codeine), prescription-only (POM) for higher strengths

    • US: Not commonly available in this combination

    • EU/MENA: Regulated; mostly prescription-only

2. Components and Available Formulations

A. Active Ingredients

ComponentDose per Tablet (Typical OTC Formulation)
Aspirin400 mg to 500 mg
Codeine phosphate8 mg, 15 mg, or 30 mg


B. Common Brands

  • Co-codaprin (generic)

  • Codis (UK): 500 mg aspirin + 8 mg codeine

  • Askit Powders (historical; discontinued due to safety concerns)

  • Other compounded or pharmacy-supplied versions

3. Mechanism of Action

A. Aspirin (Acetylsalicylic Acid)

  • Irreversibly inhibits cyclooxygenase (COX-1 and COX-2)

  • Reduces prostaglandin synthesis, resulting in:

    • Anti-inflammatory effect

    • Analgesic effect

    • Antipyretic effect

    • Antiplatelet effect (at lower doses)

B. Codeine Phosphate

  • A prodrug that undergoes hepatic conversion via CYP2D6 to morphine

  • Acts centrally by agonizing μ-opioid receptors

  • Inhibits ascending pain pathways and alters pain perception and response

Together, they provide multi-modal pain relief, targeting both peripheral and central pain mechanisms.

4. Indications

  • Mild to moderate acute pain not relieved by aspirin or paracetamol alone

  • Dental pain

  • Muscle and joint pain

  • Postoperative pain

  • Headaches and migraines (non-recurrent use only)

  • Menstrual pain

  • Toothache

  • Occasionally used for fever or flu-related pain, though not first-line

5. Dosing and Administration

A. Adults and Adolescents (12 years and older)

  • Dose: 1–2 tablets every 4–6 hours as needed

  • Maximum daily dose:

    • Aspirin: 4,000 mg/day

    • Codeine phosphate: 120 mg/day (limit due to addiction risk)

    • Total tablets: No more than 8 per 24 hours

B. Children (<12 years)

  • Contraindicated due to risk of respiratory depression and Reye’s syndrome (aspirin-related)

C. Administration Notes

  • Take after food to reduce gastric irritation

  • Swallow whole with water

  • Do not exceed recommended dose due to risk of hepatotoxicity and respiratory depression

6. Pharmacokinetics

A. Aspirin

  • Absorption: Rapid in stomach and small intestine

  • Onset: 15–30 minutes

  • Half-life:

    • Aspirin: 15–20 minutes

    • Salicylic acid (metabolite): 2–3 hours

  • Metabolism: Hepatic

  • Excretion: Renal

B. Codeine

  • Absorption: Well absorbed orally

  • Onset: 30–60 minutes

  • Half-life: ~3 hours

  • Metabolism: Liver (CYP2D6 to morphine)

  • Excretion: Renal

7. Contraindications

  • Known hypersensitivity to aspirin, codeine, or other NSAIDs

  • Peptic ulcer disease or GI bleeding

  • Severe hepatic or renal impairment

  • Asthma or bronchospasm induced by NSAIDs

  • Children under 12 years

  • Post-tonsillectomy or adenoidectomy in <18 years

  • Pregnancy, especially third trimester (aspirin and opioids)

  • Breastfeeding (codeine excretion in milk)

  • Bleeding disorders (e.g., hemophilia)

8. Warnings and Precautions

  • Codeine metabolism varies; risk of toxicity in ultrarapid CYP2D6 metabolizers

  • Risk of dependency and tolerance with prolonged codeine use

  • Aspirin may cause:

    • GI ulceration

    • Bleeding

    • Renal impairment

  • Reye’s syndrome risk in children and teenagers with viral infections

  • May interact with anticoagulants (e.g., warfarin)

  • Avoid alcohol due to additive CNS and GI toxicity

9. Adverse Effects

A. Aspirin-Related

  • GI irritation: dyspepsia, gastritis, peptic ulcer

  • Bleeding: GI, epistaxis, bruising

  • Tinnitus (in overdose)

  • Hypersensitivity reactions: asthma, urticaria, anaphylaxis

B. Codeine-Related

  • Drowsiness and sedation

  • Constipation

  • Nausea, vomiting

  • Respiratory depression (dose-dependent)

  • Addiction, dependence

  • Dizziness or euphoria

C. Rare But Serious

  • GI hemorrhage or perforation

  • Renal papillary necrosis

  • Hepatic failure (with overdose)

  • Stevens–Johnson syndrome (very rare)

10. Drug Interactions

A. Aspirin Interactions

  • Warfarin and other anticoagulants: ↑ bleeding risk

  • SSRIs: additive GI bleeding risk

  • Methotrexate: toxicity risk due to decreased excretion

  • NSAIDs: additive GI and renal risk

  • ACE inhibitors/ARBs: reduced antihypertensive effect, renal toxicity

B. Codeine Interactions

  • CNS depressants: alcohol, benzodiazepines, sedating antihistamines

  • CYP2D6 inhibitors: fluoxetine, paroxetine → ↓ analgesic effect

  • MAO inhibitors: risk of serotonin syndrome

  • Naloxone: reverses opioid effects

11. Overdose and Toxicity

A. Aspirin Overdose

  • Metabolic acidosis

  • Tinnitus

  • Hyperventilation, respiratory alkalosis

  • Hypoglycemia

  • Coma in severe cases

B. Codeine Overdose

  • Respiratory depression

  • Pinpoint pupils

  • Bradycardia

  • Hypotension

  • Coma

Treatment:

  • Activated charcoal (early)

  • Naloxone for opioid reversal

  • IV fluids, bicarbonate for salicylate toxicity

  • Hemodialysis in severe salicylate poisoning

12. Pregnancy and Lactation

  • Pregnancy: Not recommended, especially in third trimester

    • Aspirin may prolong labor and increase bleeding

    • Codeine may cause neonatal withdrawal or respiratory depression

  • Breastfeeding: Avoid

    • Codeine is excreted in breast milk

    • Risk of CNS depression in infant, especially if mother is an ultrarapid CYP2D6 metabolizer

13. Monitoring Parameters

  • Pain control and symptom relief

  • Signs of GI toxicity (e.g., black stools, abdominal pain)

  • Signs of sedation or respiratory depression

  • Bowel function in patients using codeine regularly

  • Monitor for signs of dependency or misuse

14. Alternatives

A. Non-opioid Combinations

  • Paracetamol + ibuprofen (safer GI profile than aspirin)

  • Paracetamol alone for mild pain

  • NSAID monotherapy (e.g., naproxen, ibuprofen)

B. Other Opioid Combinations

  • Co-codamol (paracetamol + codeine)

  • Co-dydramol (paracetamol + dihydrocodeine)

  • Tramadol + paracetamol (prescription only)

C. Non-pharmacological alternatives

  • Physical therapy

  • Heat/cold packs

  • Cognitive behavioral therapy (CBT) for chronic pain




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