From the Guidelines
Codeine is associated with several side effects, including CNS depression, respiratory depression, and gastrointestinal issues.
Common Side Effects of Codeine
- CNS depressing effects, such as drowsiness and sedation
- Respiratory depression, which can be life-threatening in severe cases
- Gastrointestinal issues, such as nausea and constipation
Comparison with Other Analgesics
Codeine-acetaminophen combinations have been compared to non-specific NSAIDs (e.g., ibuprofen) and COX-2 specific NSAIDs (e.g., celecoxib) in terms of efficacy and side effects 1.
Key Findings
- Codeine-acetaminophen combinations have a higher risk of adverse effects, such as CNS depression and respiratory depression, compared to NSAIDs 1.
- The number needed to treat for codeine-acetaminophen was 6, indicating a lower efficacy compared to NSAIDs 1.
- Certain genotypes may not metabolize or may hyper-metabolize codeine into morphine, which can affect its efficacy and side effect profile 1.
Recommendations
Based on the available evidence, non-specific NSAIDs (e.g., ibuprofen) and COX-2 specific NSAIDs (e.g., celecoxib) are recommended over codeine-acetaminophen combinations for mild-moderate acute pain due to their safer side effect profile and higher efficacy 1.
From the FDA Drug Label
Warnings ... giving a higher dose than recommended by a doctor could result in serious side effects for your child. ... may cause or aggravate constipation Stop use and ask a doctor if symptoms do not improve within 7 days, tend to recur or are accompanied by fever and rash or persistent headache
The side effects of codeine include:
- Constipation
- Serious side effects can occur if a higher dose than recommended is given, especially in children The label also mentions that the following may be symptoms of a serious condition:
- Fever and rash
- Persistent headache 2
From the Research
Side Effects of Codeine
- The side effects of codeine include tolerance, dependence, and abuse liability 3
- Common side effects of acetaminophen/codeine combination are usually minor, such as nausea or vomiting, and central nervous system side effects like sedation or lightheadedness 4, 5
- The use of codeine can result in gastrointestinal side effects, but no significant differences in gastrointestinal side effects were reported in a study comparing hydrocodone/acetaminophen and codeine/acetaminophen 5
- Central nervous system side effects, such as sedation or lightheadedness, are more common with codeine than with hydrocodone 5
- The side effects of codeine are similar to those of morphine, and drugs for the side effects should be given to patients simultaneously when codeine is administered 6
- Low-dose codeine combinations are considered safe, with only mild to moderate side-effects observed 7