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Saturday, July 26, 2025

Co-codamol for adults


Co-codamol is a combination analgesic that contains two active ingredients:

  • Paracetamol (also known as acetaminophen) — a non-opioid analgesic and antipyretic

  • Codeine phosphate — a weak opioid analgesic

It is used in adults and adolescents aged 12 years and older for the relief of moderate to severe pain when paracetamol or ibuprofen alone is insufficient. Co-codamol is widely used, but it carries significant precautions, particularly due to the opioid (codeine) component, which can lead to dependency, respiratory depression, and constipation if misused or overused.

Available Strengths and Formulations

Co-codamol is available in multiple fixed-dose combinations, usually defined by the amount of codeine phosphate per tablet, with the paracetamol dose standardized at 500 mg:

  • 8/500 mg: 8 mg codeine + 500 mg paracetamol — over-the-counter (OTC) in some countries (UK)

  • 15/500 mg: 15 mg codeine + 500 mg paracetamol — prescription-only

  • 30/500 mg: 30 mg codeine + 500 mg paracetamol — prescription-only

  • Effervescent tablets, capsules, oral solutions, and soluble forms may also be available depending on country

Note: Strengths >12.8 mg codeine/tablet are not available without prescription in most regulatory jurisdictions.

Mechanism of Action

Co-codamol exerts its analgesic effect through two synergistic mechanisms:

Paracetamol:

  • Acts centrally by inhibiting prostaglandin synthesis in the hypothalamus

  • Provides analgesia and antipyresis but no anti-inflammatory effect

Codeine:

  • A prodrug that is metabolized in the liver (via CYP2D6) to morphine, its active metabolite

  • Binds to mu-opioid receptors in the CNS to modulate pain perception

  • Has mild antitussive and sedative properties as well

Therapeutic Indications

Co-codamol is indicated for the short-term treatment of moderate to severe pain that is not controlled by non-opioid analgesics alone, including:

  • Postoperative pain

  • Musculoskeletal pain (e.g., back pain, osteoarthritis)

  • Headache and migraine (second-line)

  • Dental pain

  • Dysmenorrhea

  • Traumatic injuries (e.g., sprains, strains)

  • Neuropathic pain (adjunctive use)

Dosage and Administration

Adults and Adolescents (≥12 years and ≥40 kg):

  • 1 to 2 tablets every 4 to 6 hours as needed

  • Maximum dose:

    • Paracetamol: 4,000 mg/day (4 grams) (i.e., max 8 tablets of 500 mg)

    • Codeine: 240 mg/day

Example Max Tablet Count per Day:

  • 8/500 mg: Max 8 tablets/day (4,000 mg paracetamol + 64 mg codeine)

  • 15/500 mg: Max 8 tablets/day (4,000 mg paracetamol + 120 mg codeine)

  • 30/500 mg: Max 8 tablets/day (4,000 mg paracetamol + 240 mg codeine)

Important Notes:

  • Do not exceed 4 g/day of paracetamol due to risk of hepatotoxicity

  • Do not use for more than 3 consecutive days without reassessment due to risk of codeine dependence

  • Take with or after food to minimize gastric irritation

Contraindications

  • Children under 12 years of age

  • Post-operative pain management in children under 18 after tonsillectomy or adenoidectomy

  • Known hypersensitivity to codeine, paracetamol, or any excipients

  • Severe respiratory depression

  • Acute asthma attack

  • Known CYP2D6 ultra-rapid metabolizers

  • Paralytic ileus

  • Liver failure or active liver disease

Precautions

  • Use caution in patients with:

    • Hepatic impairment (especially alcoholics or patients with hepatitis)

    • Renal impairment

    • Asthma or respiratory disease

    • Prostatic hypertrophy

    • Hypotension

    • Hypothyroidism

    • Adrenal insufficiency (Addison’s disease)

    • History of drug abuse or opioid dependence

  • Monitor for:

    • Signs of overdose

    • Constipation or ileus

    • Drowsiness or confusion

    • Respiratory depression

  • Tolerance and dependence may develop with prolonged use

Side Effects

Common

  • Constipation

  • Nausea

  • Vomiting

  • Drowsiness

  • Dizziness

  • Dry mouth

  • Headache

  • Itching or rash (hypersensitivity)

Less Common

  • Urinary retention

  • Euphoria or dysphoria

  • Mood changes

  • Respiratory depression (especially in overdose)

  • Sedation

  • Liver enzyme elevations

Rare

  • Hepatic failure (due to paracetamol overdose)

  • Anaphylaxis

  • Severe skin reactions (e.g., Stevens-Johnson Syndrome)

Drug Interactions

Increased Risk of CNS Depression with:

  • Alcohol

  • Benzodiazepines (e.g., diazepam)

  • Antipsychotics

  • Antihistamines (sedating H1 blockers)

  • Tricyclic antidepressants

  • Muscle relaxants

  • Gabapentinoids (pregabalin, gabapentin)

Pharmacokinetic Interactions:

  • Enzyme inducers (e.g., rifampin, phenytoin, carbamazepine) reduce efficacy

  • Enzyme inhibitors (e.g., fluoxetine, paroxetine, quinidine) increase codeine toxicity

  • CYP2D6 inhibitors may block conversion of codeine to morphine, reducing analgesia

Paracetamol-specific:

  • Avoid co-administration with other paracetamol-containing drugs to prevent overdose

  • Caution with warfarin (risk of INR elevation with chronic use)

Use in Special Populations

Pregnancy

  • Not recommended during the third trimester due to risk of neonatal respiratory depression and withdrawal

  • Short-term use in early pregnancy may be considered under medical supervision

Lactation

  • Contraindicated: Codeine is secreted in breast milk; risk of morphine toxicity in infants (especially from ultra-rapid metabolizer mothers)

Elderly

  • Increased sensitivity to opioids

  • Greater risk of sedation, falls, constipation, and delirium

Codeine Metabolism Warning

Codeine is a prodrug activated via CYP2D6 to morphine:

  • Ultra-rapid metabolizers → dangerously high morphine levels → respiratory depression or death

  • Poor metabolizers → inadequate pain relief

Genetic testing is not routinely done before prescribing, but caution is advised in all patients.

Overdose Risk

Paracetamol toxicity:

  • Early signs may be absent

  • After 24–48 hours: Liver enzyme elevation, hepatic necrosis

  • Potentially fatal liver failure

  • Treated with N-acetylcysteine (NAC) antidote

Codeine overdose:

  • Respiratory depression

  • Pinpoint pupils

  • Coma

  • Treat with naloxone (opioid antagonist)

Patient Counseling Points

  • Take exactly as prescribed; do not exceed maximum daily dose

  • Do not combine with other paracetamol-containing products

  • Avoid alcohol

  • May cause drowsiness; do not drive or operate machinery

  • Watch for signs of liver toxicity: nausea, yellowing of skin/eyes, dark urine

  • Use for short-term pain relief only (maximum 3 days without reassessment)

  • Do not stop suddenly if taken long-term — taper under supervision

  • Seek help if constipation, confusion, or difficulty breathing develops

Regulatory and Prescribing Information

  • OTC availability (UK): Only 8/500 mg formulation in small packs

  • Prescription-only in most countries for higher strengths

  • Included in BNF, FDA, MHRA, and EMA formularies with usage restrictions

  • Part of opioid regulation programs due to risk of misuse and addiction




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