Codeine is an opioid medication used for pain and cough, but it carries a significant risk of severe drug interactions. Combining codeine with certain substances can result in life-threatening complications, including profound sedation, respiratory depression, coma, and death. It is crucial to inform your healthcare provider about all medications, supplements, and other substances you are taking.
Major Contraindications and Interactions
Central Nervous System (CNS) Depressants
Combining codeine with other CNS depressants is highly dangerous as both substances slow brain activity and bodily functions, leading to an amplified effect. The FDA has issued warnings about combining opioids with other CNS depressants due to the high overdose risk. Avoid:
- Alcohol: Increases risk of extreme sedation, respiratory depression, and overdose.
- Benzodiazepines: Medications for anxiety and sleep, such as alprazolam, diazepam, and lorazepam, can cause profound sedation, slowed breathing, coma, and death.
- Other Opioids: Increases risk of respiratory depression and overdose.
- Antihistamines: Some allergy and cold medications can cause significant drowsiness.
- Muscle Relaxants: Can cause additive CNS depressant effects.
Monoamine Oxidase Inhibitors (MAOIs)
MAOIs are antidepressants that should never be combined with codeine due to the risk of hypertensive crisis or serotonin syndrome.
- Hypertensive Crisis: A sudden, dangerous spike in blood pressure.
- Serotonin Syndrome: A potentially fatal reaction with symptoms like confusion, agitation, sweating, muscle spasms, and rapid heartbeat.
Wait at least 14 days after stopping an MAOI before taking codeine. Examples of MAOIs include phenelzine and tranylcypromine, as well as linezolid and methylene blue.
Serotonergic Drugs
Other medications that affect serotonin levels can also cause serotonin syndrome when mixed with opioids. These include:
- Antidepressants: SSRIs, SNRIs, and TCAs.
- Migraine Medications: Triptans.
- Other Drugs: Certain anti-nausea medications and herbal supplements.
Medications Affecting Codeine's Metabolism (CYP450 Enzymes)
Codeine is metabolized by liver enzymes, particularly CYP2D6. Some drugs can inhibit these enzymes, reducing the conversion of codeine to active morphine, while others can speed up metabolism. Both can be dangerous.
- CYP2D6 Inhibitors: Reduce codeine's pain relief. Examples include certain SSRIs (fluoxetine, paroxetine) and some antifungals (ketoconazole).
- CYP3A4 Inhibitors/Inducers: Can alter codeine levels. Inhibitors include certain macrolide antibiotics (clarithromycin), while inducers include rifampin and some seizure medications.
Comparison Table: High-Risk Codeine Interactions
| Drug Class | Example Drugs | Interaction Type | Potential Risk |
|---|---|---|---|
| CNS Depressants | Alcohol, Alprazolam (Xanax), Diazepam (Valium) | Additive CNS Depression | Profound sedation, respiratory depression, coma, death |
| Monoamine Oxidase Inhibitors (MAOIs) | Phenelzine (Nardil), Linezolid | Serotonin Syndrome, Hypertensive Crisis | High blood pressure, confusion, fever, seizure, fatality |
| Serotonergic Drugs | SSRIs (Fluoxetine), Triptans | Serotonin Syndrome | Mental status changes, muscle spasms, sweating, tremor |
| CYP2D6 Inhibitors | Fluoxetine, Paroxetine | Inhibited Metabolism | Reduced analgesic effect of codeine |
| Anticholinergics | Atropine, Oxybutynin | Anticholinergic Overload | Increased constipation, blurred vision, risk of paralytic ileus |
Other Significant Interactions
Anticholinergic Drugs
Combining codeine with anticholinergic medications can increase side effects, primarily by slowing gastrointestinal motility. This can lead to severe constipation or, rarely, paralytic ileus. Examples include medications for bladder problems (oxybutynin) and stomach cramps (dicyclomine).
Herbal Supplements
Certain herbal supplements can interact dangerously with codeine.
- St. John's Wort: Can affect how the body processes medications, including opioids.
- Tryptophan: Can increase the risk of serotonin syndrome.
Conclusion
Codeine has numerous potentially life-threatening interactions. The most critical risk involves combining it with other CNS depressants, which can lead to fatal respiratory depression. Serotonin syndrome or hypertensive crisis is a serious risk when codeine is combined with MAOIs and other serotonergic drugs. Other medications can also alter codeine's metabolism, affecting its effectiveness and side effects. Always consult your doctor or pharmacist about all medications, including prescriptions, over-the-counter drugs, and supplements, to ensure safety. For more information on opioid safety, refer to resources from reputable organizations like the National Institute on Drug Abuse (NIDA).
Keypoints
- Avoid CNS Depressants: Never mix codeine with alcohol, benzodiazepines (e.g., Xanax, Valium), or other opioids due to the high risk of fatal respiratory depression.
- MAOI Warning: Do not take codeine with Monoamine Oxidase Inhibitors (MAOIs) or within 14 days of stopping them, as this can trigger a hypertensive crisis or serotonin syndrome.
- Serotonin Syndrome Risk: Be cautious when taking codeine with other serotonergic drugs, including some antidepressants and migraine medications, to avoid a dangerous buildup of serotonin.
- Metabolism Alterations: Certain medications, such as some antibiotics and antifungals, can interfere with the liver enzymes that process codeine, altering its effectiveness and side effects.
- Talk to Your Doctor: Always inform your doctor or pharmacist about all medications, supplements, and herbal products you are taking to prevent harmful drug interactions with codeine.
