Usage
Codeine is an opioid analgesic prescribed for the relief of mild to moderately severe pain. It also has antitussive properties and can be used to suppress coughs. It belongs to the pharmacological classifications of opioid analgesics and antitussives.
Codeine itself is a prodrug, meaning it’s metabolized by the body into its active form, morphine. Morphine binds to opioid receptors in the central nervous system, reducing the perception of pain and suppressing the cough reflex.
Alternate Names
Brand Names: Codeine is often found in combination medications with brand names varying depending on the formulation and country. Some examples include:
- Tylenol with Codeine
- Co-codamol
How It Works
Pharmacodynamics: Codeine primarily acts as a prodrug, converting to morphine in the liver via the CYP2D6 enzyme. Morphine binds to mu-opioid receptors in the brain, spinal cord, and other tissues, resulting in decreased pain perception and cough suppression. It also has some effect on kappa and delta opioid receptors. Codeine’s analgesic effect is considerably weaker than morphine’s.
Pharmacokinetics:
- Absorption: Codeine is readily absorbed orally.
- Metabolism: Primarily metabolized in the liver by CYP2D6 to morphine, norcodeine, and codeine-6-glucuronide. Genetic variations in CYP2D6 activity significantly influence codeine’s effectiveness and risk of adverse effects. Ultra-rapid metabolizers convert codeine to morphine very quickly, leading to higher morphine levels and increased risk of toxicity. Poor metabolizers may not experience adequate pain relief.
- Elimination: Metabolites are primarily excreted in the urine.
Mode of Action: Mu-opioid receptor binding inhibits neuronal activity by reducing neurotransmitter release and altering ion channel conductance. This leads to decreased pain signaling in the ascending pathways and suppression of the cough reflex in the medulla.
Elimination Pathways: Primarily renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Analgesia: 15-60 mg orally every 4-6 hours as needed, not to exceed 360mg/24h.
- Antitussive: 10-20 mg orally every 4-6 hours as needed, not to exceed 120 mg/24h.
Children:
Codeine is generally not recommended for children under 12 years old due to the risk of respiratory depression, especially in ultra-rapid metabolizers. If used in older children (12-18 years), the dose should be carefully determined by a physician based on weight and clinical condition, not to exceed 240mg/24h.
Special Cases:
- Elderly Patients: Lower initial dose and careful titration due to potential age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose reduction and careful monitoring are necessary due to decreased clearance. For creatinine clearance 10-50 mL/min, reduce dose by 25%.
- Patients with Hepatic Dysfunction: Codeine should be avoided or used with extreme caution and dose reduction due to altered metabolism and unpredictable effects.
- Patients with Comorbid Conditions: Careful evaluation is required, especially in patients with respiratory conditions, CNS depression, or a history of substance abuse.
Clinical Use Cases
Codeine is generally not recommended in the following settings due to the availability of safer and more effective alternatives:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Dose adjustments are required based on individual patient factors such as renal/hepatic function, age, and concomitant medications.
Side Effects
Common Side Effects:
- Drowsiness
- Constipation
- Nausea
- Vomiting
- Dizziness
- Lightheadedness
Rare but Serious Side Effects:
- Respiratory depression
- Seizures
- Allergic reactions (e.g., rash, itching, swelling)
- Hypotension
Long-Term Effects:
- Tolerance
- Physical dependence
- Adrenal insufficiency
Adverse Drug Reactions (ADR):
- Severe respiratory depression requiring intervention
- Anaphylaxis
Contraindications
- Respiratory depression
- Acute or severe asthma or hypercarbia
- Paralytic ileus
- Hypersensitivity to codeine
- Use in children <12 years old, or post tonsillectomy/adenoidectomy in children <18 years old
Drug Interactions
- Alcohol
- CNS depressants (e.g., benzodiazepines, antihistamines)
- MAOIs (Monoamine Oxidase Inhibitors)
- CYP2D6 inhibitors and inducers (e.g., some antidepressants, antifungals)
- Anticholinergic drugs (increased risk of urinary retention and constipation)
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Consult a medical professional for advice)
- Fetal risks include respiratory depression, neonatal abstinence syndrome, and birth defects.
- Codeine is excreted in breast milk and can cause serious side effects in nursing infants, especially in ultra-rapid metabolizers. Use alternative analgesics if possible.
Drug Profile Summary
- Mechanism of Action: Prodrug metabolized to morphine, which binds to mu-opioid receptors, reducing pain and suppressing cough.
- Side Effects: Drowsiness, constipation, nausea, vomiting, dizziness, respiratory depression (serious).
- Contraindications: Respiratory depression, acute asthma, paralytic ileus, hypersensitivity.
- Drug Interactions: Alcohol, CNS depressants, MAOIs, CYP2D6 inhibitors/inducers.
- Pregnancy & Breastfeeding: Caution advised, potential for fetal/neonatal harm.
- Dosage: Adults: 15-60 mg every 4-6 hours as needed. Children: Not recommended under 12 years.
- Monitoring Parameters: Respiratory rate, oxygen saturation, blood pressure, level of consciousness.
Popular Combinations
- Codeine + Acetaminophen (e.g., Tylenol with Codeine): Enhanced analgesia through different mechanisms.
- Codeine + Ibuprofen: Increased pain relief and reduced inflammation.
Precautions
- Assess respiratory function, especially in patients with underlying respiratory disease.
- Monitor for signs of CNS depression.
- Avoid alcohol and other CNS depressants.
- Caution in elderly patients and those with renal or hepatic impairment.
- Screen for CYP2D6 ultra-rapid metabolism, especially in children.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Codeine?
A: Adults: 15-60 mg orally every 4-6 hours as needed. Children: Not recommended for children under 12 years.
Q2: How does codeine work?
A: Codeine is metabolized to morphine, which binds to opioid receptors in the CNS, reducing pain perception.
Q3: What are the common side effects of codeine?
A: Common side effects include drowsiness, constipation, nausea, and vomiting.
Q4: Is codeine safe during pregnancy?
A: Codeine should be used with caution during pregnancy as it can cause respiratory depression and neonatal abstinence syndrome in the newborn. Consult a doctor before use.
Q5: Can codeine be used in children?
A: Codeine is generally not recommended for children under 12 years of age due to risk of respiratory problems. For older children, dosage should be carefully determined and monitored by a physician.
Q6: What are the signs of codeine overdose?
A: Signs of overdose include respiratory depression, pinpoint pupils, decreased level of consciousness, and bluish skin.
Q7: How should I adjust the codeine dose in patients with kidney problems?
A: Reduce the dose and increase the dosing interval in patients with renal impairment. Consult guidelines for specific recommendations.
Q8: Does codeine interact with other medications?
A: Yes, codeine can interact with alcohol, CNS depressants, MAOIs and other medications metabolized by CYP2D6.
Q9: What is the maximum daily dose of codeine?
A: The maximum daily dose for adults is generally 360 mg.
Q10: What should I do if a patient experiences respiratory depression while taking codeine?
A: Administer naloxone, an opioid antagonist, and provide respiratory support as needed.
