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Codeine: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on April 6, 2022.

1. How it works

  • Codeine is an opioid analgesic (pain-reliever) that is related to morphine.
  • Codeine works by weakly binding to a specific opioid receptor, known as the mu-opioid receptor, but with much less affinity than morphine, which means its analgesic (pain-relieving effects) are much less.
  • Codeine belongs to the group of drugs known as opioids or opioid analgesics. Codeine may also be called a narcotic analgesic.

2. Upsides

  • May be used to treat mild-to-moderate pain that is unrelieved by nonopioid analgesics.
  • Generic codeine is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Drowsiness or dizziness which may impair reaction skills and affect a person's ability to drive or operate machinery. Avoid alcohol.
  • Codeine also slows down the motility of the gastrointestinal tract. This can lead to symptoms such as nausea, vomiting, constipation, and abdominal pain. Laxatives may be required.
  • Codeine may also affect blood pressure, manifesting as dizziness when standing; and stimulate histamine release, which may cause symptoms such as flushing, itchiness, sweating, or red eyes.
  • Codeine is addictive (habit-forming) and potentially abusable. Codeine should only be used short-term at the lowest effective dose and only when other nonopioid analgesics are not effective. Tolerance can also develop to codeine's analgesic effect (this means that the same dose does not provide as much pain relief as before). Legitimate supplies of products containing codeine may be sought out by drug seekers.
  • Abrupt discontinuation of codeine in a person who has become physically dependent on it may lead to a withdrawal syndrome and symptoms such as restlessness, pupil dilation, watery eyes and a runny nose, sweating, muscle aches, insomnia, irritability and gastrointestinal complaints. Babies born to mothers who are physically dependent on codeine will also be physically dependent.
  • Marked differences may exist in the analgesic effect provided by codeine due to genetic variations in the CYP 2D6 liver enzyme responsible for metabolizing codeine into morphine. Consider alternative analgesics if codeine is not having the desired pain-relieving effect.
  • Rarely, serious, life-threatening, breathing problems may occur attributable to the codeine component. The risk is greater with higher dosages of codeine, in people with pre-existing respiratory disease, in seniors or the frail, or in those taking other medications that cause respiratory depression (such as benzodiazepines). Not for use in children under the age of 18.
  • Codeine may interact with several drugs, including those that affect hepatic enzymes CYP 3A4 or CYP 2D6, and those that also cause respiratory depression (such as other opioids, benzodiazepines, and alcohol).
  • Interaction or overdosage may also cause serotonin syndrome. Symptoms include mental status changes such as agitation, hallucinations, coma, or delirium; a fast heart rate; dizziness; flushing; muscle tremor or rigidity; and stomach symptoms (including nausea, vomiting, and diarrhea).
  • Long-term use of codeine also affects the endocrine system, which may cause symptoms such as sexual dysfunction, an absence of periods, or infertility.
  • May not be suitable for some people including children of any age who have undergone a tonsillectomy or adenoidectomy, people with pre-existing respiratory depression or respiratory disease, with seizure disorders or a head injury, people with gastrointestinal obstruction, or recent use of monoamine oxidase inhibitors.
  • Should not be used during pregnancy or breastfeeding unless specifically recommended and monitored by a doctor. Can cause life-threatening withdrawal symptoms in a newborn.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Codeine is an effective pain-reliever; however, it is addictive, may cause constipation, and its pain-relieving effects vary markedly between individuals. Codeine should only be used for pain relief when other simpler analgesics, such as acetaminophen or ibuprofen, are not appropriate.

5. Tips

  • May be taken with or without food. Do not take more codeine than you have been prescribed. Codeine should be used short-term only. Long-term use may lead to addiction and dependence. Codeine may need to be discontinued slowly depending on the duration of use. Talk to your doctor about a tapering schedule. Never share your codeine with anyone. Do not keep your leftover medicine. Ask your pharmacy when the next take-back program is.
  • May cause sedation and affect your ability to drive or operate machinery. Do not drive or perform other hazardous tasks if codeine affects you in this way.
  • Use short-term (three days or less) only. Not recommended for long-term use.
  • Tell your doctor if you think you have become addicted to codeine or the usual dosage does not appear to be working.
  • Do not double up on other medications containing codeine (several cold and flu remedies also contain codeine).
  • Avoid alcohol while taking codeine. Alcohol can contribute to the sedative effects of codeine and also increase the risk of respiratory depression.
  • Codeine may make you feel dizzy when getting up from a lying down or sitting position to standing. Always get up slowly, but talk with your doctor if this dizziness results in a fall.
  • Codeine may cause constipation which can be relieved with laxatives. Drink 6 to 8 full glasses of water daily to prevent this effect. Talk to your doctor if you experience any troublesome side effects of before using a laxative..
  • Seek urgent medical advice if you experience any excessive sedation, breathing difficulties, wheezing, rash, itching, or facial swelling. Call emergency services if you suspect somebody has overdosed on codeine (pinpoint pupils may be indicative of overdosage).
  • Do not use during pregnancy or breastfeeding unless specifically recommended by your doctor.
  • Keep this medicine in a safe place and out of the reach of children and pets. Accidental ingestion can result in a fatal overdose of codeine, especially in children. Never give codeine to children under the age of 18.

6. Response and effectiveness

  • The analgesic effect of codeine reaches a peak in about two hours and the effects last for between four to six hours.
  • About 70-80% of a dose of codeine is metabolized by the liver into a number of metabolites, some active and some inactive. One of these active metabolites is morphine. About 5-10% of codeine is metabolized into morphine by the hepatic enzyme, CYP2D6. Experts believe some of the analgesic properties of codeine are due to it being converted into morphine. Note that up to 10% of Caucasians, 6% of Mexican-Americans, and 5% of African-Americans are poor metabolizers at CYP2D6 and are unlikely to metabolize codeine into morphine. 30% of Ethiopians, 20% of Saudis, 10% of Portuguese and Greeks, and 4% of North Americans are ultra-rapid metabolizers at CYP 2D6 and may experience excessive side effects, such as extreme sleepiness, confusion, and shallow breathing, even with normal dosages of codeine

7. Interactions

Medicines that interact with codeine may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with codeine. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with codeine include:

  • antibiotics, such as erythromycin
  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
  • antifungal agents, such as itraconazole and ketoconazole
  • anticonvulsants, such as carbamazepine, lamotrigine, phenytoin, phenobarbital, or primidone
  • antimigraine agents such as sumatriptan
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that may cause drowsiness, such as amphetamines, azelastine, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as hydrocodone, morphine)
  • buprenorphine
  • HIV medications such as darunavir or ritonavir
  • muscle relaxants, such as cyclobenzaprine
  • naltrexone
  • other medications that are CYP2D6 or CYP3A4 inhibitors or inducers
  • pentazocine
  • rifampin.

Avoid drinking alcohol or taking illegal or recreational drugs while taking codeine.

Note that this list is not all-inclusive and includes only common medications that may interact with codeine. You should refer to the prescribing information for codeine for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use codeine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2022 Revision date: April 6, 2022.