“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Saturday, July 26, 2025

Co-dydramol


Co-dydramol is a combination analgesic medication used for the relief of moderate pain that is not adequately controlled by paracetamol alone. It combines two active ingredients: dihydrocodeine, a semi-synthetic opioid analgesic, and paracetamol (acetaminophen), a non-opioid analgesic and antipyretic. The combination provides synergistic pain relief through complementary mechanisms of action and is commonly prescribed in the UK and other Commonwealth countries, though it is less available in the United States.

This combination offers an opioid-sparing approach, allowing effective pain relief with relatively lower doses of dihydrocodeine than would be required in monotherapy. However, the potential for opioid dependence, paracetamol overdose, and central nervous system (CNS) depression requires careful prescribing and monitoring.

1. Drug Classification

  • Therapeutic class: Analgesic combination

  • Pharmacological class: Opioid (dihydrocodeine) + non-opioid analgesic (paracetamol)

  • ATC Code: N02BE71

  • Legal status:

    • UK: Prescription-only medicine (POM)

    • US: Not commonly available; dihydrocodeine is a Schedule II/III controlled substance

    • Controlled Drug Status: Dihydrocodeine is a Schedule II opioid, but in combination products like Co-dydramol it is subject to Schedule V or non-controlled status, depending on local regulations

2. Composition and Formulations

Co-dydramol is available in oral tablet form and comes in multiple strengths, typically varying in the dihydrocodeine content while the paracetamol content remains constant at 500 mg per tablet.

Common UK Formulations

Product NameParacetamol (mg)Dihydrocodeine (mg)
Co-dydramol 10/50050010
Co-dydramol 20/50050020
Co-dydramol 30/50050030


Brand names include Remedeine, Paramol, and Tylex DHC.

  • Paramol (7.46/500 mg) is available OTC in the UK, but only in limited pack sizes.

3. Mechanism of Action

A. Paracetamol (Acetaminophen)

  • Inhibits central cyclooxygenase (COX) enzymes, especially COX-2

  • Increases the pain threshold and has antipyretic activity

  • Weak or no anti-inflammatory effects

B. Dihydrocodeine

  • Semi-synthetic opioid agonist, structurally related to codeine

  • Binds to μ-opioid receptors in the central nervous system

  • Inhibits ascending pain pathways, altering perception and emotional response to pain

  • Has mild antitussive properties

The combined action results in enhanced analgesia via different pharmacologic targets, which is helpful in moderate pain states.

4. Therapeutic Indications

  • Moderate acute pain unrelieved by paracetamol, ibuprofen, or aspirin alone

  • Postoperative pain

  • Dental pain

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

  • Headache and migraine (only short-term use; not preferred)

  • Menstrual pain

  • Injury-related pain

5. Dosage and Administration

A. Adults and Adolescents (>12 years)

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

  • Maximum daily dose:

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

    • Dihydrocodeine: Varies depending on strength (maximum 120–180 mg/day commonly recommended)

B. Children

  • Not recommended <12 years (opioid component contraindicated due to risk of respiratory depression)

C. Elderly

  • Use with caution; consider lower initial doses due to increased sensitivity

6. Pharmacokinetics

A. Paracetamol

  • Absorption: Rapid, peak plasma in 30–60 minutes

  • Metabolism: Liver via glucuronidation and sulfation

  • Excretion: Renal

  • Half-life: 2–3 hours

B. Dihydrocodeine

  • Absorption: Rapid oral absorption

  • Bioavailability: ~20% due to first-pass metabolism

  • Metabolism: Liver (CYP2D6) to active metabolite dihydromorphine

  • Half-life: ~4 hours

  • Excretion: Renal (as metabolites)

7. Contraindications

  • Hypersensitivity to paracetamol, dihydrocodeine, or excipients

  • Acute respiratory depression

  • Chronic obstructive pulmonary disease (COPD)

  • Severe hepatic or renal impairment

  • Head injury or raised intracranial pressure

  • Paralytic ileus

  • Children <12 years, especially post-tonsillectomy/adenoidectomy

  • Breastfeeding

8. Warnings and Precautions

  • Hepatotoxicity: due to paracetamol overdose or in chronic alcohol users

  • Respiratory depression: opioid-related risk, especially in elderly

  • Sedation: additive with alcohol, benzodiazepines, antihistamines

  • CYP2D6 polymorphism: ultrarapid metabolizers may have exaggerated opioid effects

  • Tolerance, dependence, and abuse potential

  • Constipation: common side effect; consider prophylactic laxative

  • Driving or operating machinery: warn about sedation and cognitive impairment

9. Adverse Effects

A. Paracetamol-related

  • Hepatotoxicity (especially in overdose)

  • Hypersensitivity reactions (rare)

  • Thrombocytopenia, leukopenia (rare hematological effects)

B. Dihydrocodeine-related

  • Drowsiness

  • Nausea, vomiting

  • Constipation

  • Dizziness or vertigo

  • Respiratory depression (dose-dependent)

  • Euphoria/dysphoria

  • Dependence and withdrawal with prolonged use

C. Serious (Rare)

  • Anaphylaxis

  • Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN)

  • Hypotension

  • Seizures (with overdose)

10. Drug Interactions

A. CNS Depressants (additive effects)

  • Alcohol

  • Benzodiazepines

  • Sedative antihistamines

  • Antipsychotics

  • General anesthetics

B. Liver Enzyme Modifiers

  • Enzyme inducers (e.g., rifampin, phenytoin, carbamazepine) → reduce efficacy or increase hepatotoxicity of paracetamol

  • Enzyme inhibitors (e.g., fluoxetine, quinidine) → ↑ dihydrocodeine levels

C. Other Interactions

  • MAO inhibitors: risk of serotonin syndrome

  • Warfarin: high doses of paracetamol may potentiate anticoagulant effect

  • CYP2D6 inhibitors: reduce opioid analgesia

11. Overdose and Toxicity

A. Paracetamol Overdose

  • Hepatic necrosis is primary concern

  • Early signs: nausea, vomiting, diaphoresis

  • Treatment: activated charcoal (if <1 hr), N-acetylcysteine (NAC) to prevent liver damage

B. Dihydrocodeine Overdose

  • Respiratory depression, pinpoint pupils, coma

  • Treatment: naloxone (opioid antagonist), supportive care

12. Pregnancy and Lactation

  • Pregnancy:

    • Paracetamol is generally safe (Category B)

    • Dihydrocodeine: use only if necessary; prolonged use may cause neonatal withdrawal

  • Lactation:

    • Not recommended; dihydrocodeine is excreted in breast milk and may cause CNS depression in infants

13. Monitoring Parameters

  • Pain control effectiveness

  • Signs of sedation or respiratory depression

  • Bowel function

  • Liver function tests (in chronic or high-dose use)

  • Signs of misuse, abuse, or dependence

14. Abuse and Dependence Potential

  • Dihydrocodeine is an opioid and can lead to physical dependence and tolerance

  • Co-dydramol abuse has been reported in patients with chronic pain

  • Paracetamol-containing products have risk of unintentional overdose

  • Regulatory efforts include:

    • Limiting tablet quantity per prescription

    • Patient education

    • Use of prescription monitoring programs

15. Alternatives

A. Non-opioid options

  • Paracetamol alone

  • NSAIDs (e.g., ibuprofen, naproxen)

  • Topical analgesics (e.g., diclofenac gel)

B. Opioid alternatives

  • Co-codamol (codeine + paracetamol)

  • Tramadol (mild to moderate opioid)

  • Morphine (for severe pain; requires careful titration)

C. Adjuvant analgesics

  • Amitriptyline or gabapentin for neuropathic pain

  • Muscle relaxants for musculoskeletal pain




on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)