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Codeine is an opioid analgesic with uses similar to those of morphine, but is much less potent as an analgesic and has only mild sedative effects. Its primary site of action is at the mu opioid receptors distributed throughout the central nervous system.

Codeine reduces intestinal motility through both a local and possibly central mechanism of action. Codeine also suppresses the cough reflex by a direct central action, probably in the medulla or pons.

The abuse potential of codeine is lower than other opiates.


  • Codeine provides relief from mild to moderate pain
  • Antitussive in the control of non-productive cough.

[edit] DOSAGE



  • 15 mg – 60 mg up to 6 times a day for the relief of pain. If these doses fail to relieve pain, larger doses rarely succeed and may give rise to restlessness and excitement. The maximum recommended daily dose is 300 mg.
  • For non-productive cough the usual dose is 10 mg – 20 mg every 4-6 hours to a maximum total of 120 mg in 24 hours.


  • Known hypersensitivity to codeine
  • Pre-existing respiratory depression
  • Obstructive airways disease
  • Asthma
  • Acute alcoholism
  • Head injuries or conditions in which intracranial pressure is raised
  • Patients at risk of paralytic ileus


  • Death Related to Ultra-Rapid Metabolism of Codeine to Morphine:
    Ultra-Rapid metabolizers due to the CYP2D6 gene duplication may experience exaggerated and even potentially dangerous opioidergic effects; respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine. Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine.
    The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing)
  • Head Injuries: In the presence of head injury or other intracranial lesions, the respiratory-depressant effects of codeine may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Codeine also produce other CNS-depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries.
  • Abuse Potential: Codeine is potentially abusable. Consequently, its extended use is not recommended
  • Codeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Avoid such tasks while taking it.


  • Alcohol and other CNS depressants may produce an additive CNS depression. Avoid drinking alcohol or taking other CNS depressants.


Codeine is well absorbed after oral administration. It is metabolised in the liver, mainly to the glucuronide conjugates, morphine (about 10%) and norcodeine (about 10%), which, with codeine, are excreted in the urine. Most of the excretion products appear in the urine within 6 hours and excretion of up to 86% of the dose is almost complete in 24 hours. The volume of distribution of codeine is 3.5 L/kg and at therapeutic blood levels, about 30% is protein bound.


  • Pregnancy Category C (US). Risk-benefit must be considered because opioid analgesics cross the placenta. Regular use during pregnancy may cause physical dependence in the fetus, leading to withdrawal symptoms (convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, and diarrhea, sneezing and yawning) in the neonate.
  • Nursing mothers: Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare.
    However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine’s active metabolite, morphine, leading to higher-thanexpected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants. If a codeine-containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby.


The commonest side effects for codeine are nausea, vomiting, constipation, drowsiness, and confusion.

Tolerance usually develops with long-term use.

Dependence may occur.

Larger doses produce respiratory depression and hypotension with circulatory failure and deepening coma.

Convulsions may occur especially in infants and children.



The first toxic symptoms are nausea, vomiting, and evidence of circulatory and respiratory depression.


Immediate treatment should consist of gastric lavage, artificial respiration and eventual treatment with naloxone HCl 400 mcg I.V., I.M. or S.C., to be repeated as needed every 2-3 minutes.





Antitussives / Cough
Cough suppressants Benzonatate   Butamirate   Codeine   Dextromethorphan   Dihydrocodeine   Dropropizine   Levocloperastine   Levodropropizine   Nepinalone   Oxolamine
Mucolytics Acetylcysteine   Ambroxol (Oral)   Bromhexine   Carbocisteine   Erdosteine   Guaifenesin   Neltenexine