Can you take cyclobenzaprine with hydrocodone? What are the risks?

October 12, 2025 •

3 min read

Combining CNS depressants like cyclobenzaprine and hydrocodone is highly clinically significant and should be avoided due to the risk of serious side effects, including profound sedation, respiratory distress, coma, and even death. Both drugs act on the central nervous system, and their combined effect can be dangerously amplified.

Quick Summary

Combining cyclobenzaprine and hydrocodone is dangerous due to heightened central nervous system depression. This leads to increased sedation, impaired coordination, and a severe risk of respiratory depression and overdose. Use this combination only under strict medical guidance, if at all.

Key Points

High-Risk Combination: Combining cyclobenzaprine and hydrocodone is considered highly dangerous and should generally be avoided due to the risk of severe complications.
Central Nervous System (CNS) Depression: Both drugs are CNS depressants, and their combined effect can cause profoundly increased sedation, slowed breathing, coma, and even death.
Respiratory Depression: The most serious risk is respiratory depression, where breathing slows to a dangerous level, which can be fatal if not treated immediately.
Serotonin Syndrome: The combination also increases the risk of serotonin syndrome, a potentially life-threatening condition caused by an excess of serotonin in the brain.
Enhanced Side Effects: The interaction potentiates other side effects, including extreme drowsiness, dizziness, impaired judgment, and severe constipation.
Strict Medical Supervision: If co-administration is unavoidable, it must be under strict medical supervision with dosage limitations and close monitoring. Alternatives are preferred.
Avoid Alcohol: Combining this medication mix with alcohol further increases the risk of serious CNS depression and should be avoided.

Understanding the Dangers of Combining CNS Depressants

Hydrocodone is a powerful opioid pain reliever, while cyclobenzaprine is a muscle relaxant. Both medications function as central nervous system (CNS) depressants, meaning they slow down brain activity. While effective for their intended purposes, their combined use poses significant risks that healthcare professionals generally advise against. The danger lies in the synergistic effect of taking two CNS depressants together, which can amplify their side effects far beyond what would be experienced with a single medication.

The Gravest Risk: Respiratory Depression

Respiratory depression is the most critical and life-threatening risk associated with combining cyclobenzaprine and hydrocodone. Both drugs independently slow down the body's respiratory drive, and when taken together, this effect is dangerously potentiated. In severe cases, this can lead to breathing becoming slow, shallow, or stopping altogether, resulting in brain damage, coma, and death. The risk is highest for individuals with pre-existing respiratory conditions, the elderly, or those taking higher doses.

Profound Sedation and Impairment

Beyond the risk to breathing, the combination can cause extreme drowsiness and sedation. Patients may experience dizziness, difficulty concentrating, impaired coordination, and slowed reaction times. These effects can lead to accidents and injuries, especially when operating machinery or driving. Impairment of judgment and motor skills can significantly disrupt daily life and pose a serious threat to safety.

The Threat of Serotonin Syndrome

Another significant risk is serotonin syndrome, a potentially life-threatening condition caused by excessive levels of the neurotransmitter serotonin in the brain. Cyclobenzaprine is structurally similar to tricyclic antidepressants, and some opioids like hydrocodone also have serotonergic properties. Combining them can increase the risk of this syndrome, leading to a range of symptoms from mild to severe, including:

Rapid heartbeat
High blood pressure
Excessive sweating
Agitation or confusion
Hallucinations
Nausea and vomiting
Tremors or muscle rigidity

Other Amplified Side Effects

In addition to the major risks, combining these drugs can exacerbate other common side effects. Both medications have anticholinergic properties, which can lead to increased constipation, blurred vision, and dry mouth. The combination can also contribute to hypotension, or low blood pressure, causing lightheadedness and fainting.

Comparison: Cyclobenzaprine vs. Hydrocodone vs. Combination


Aspect	Cyclobenzaprine (Flexeril) Alone	Hydrocodone Alone	Cyclobenzaprine + Hydrocodone Combination
Drug Class	Muscle Relaxant	Opioid Pain Reliever	CNS Depressants
Primary Function	Reduces muscle spasms	Relieves moderate to severe pain	Enhanced sedation and pain relief (extremely risky)
Central Nervous System (CNS) Effects	Causes drowsiness, dizziness, fatigue	Causes drowsiness, dizziness, and sedation	Profound sedation, respiratory depression, coma, and death
Serotonin Syndrome Risk	Present, especially with other serotonergic agents	Present, as some opioids can increase serotonin	Significantly increased
Anticholinergic Effects	Dry mouth, constipation, blurred vision	Constipation, dry mouth	Potentiated, leading to severe constipation
Driving/Operating Machinery	Not recommended due to drowsiness	Not recommended due to sedation	Extremely dangerous; should be avoided entirely
Addiction Potential	Low potential	High potential for dependency and addiction	High potential due to hydrocodone

Expert Medical Guidance is Crucial

Given these risks, most doctors will avoid prescribing cyclobenzaprine and hydrocodone together. If a doctor deems it absolutely necessary, they will use the lowest possible dose for the shortest duration and require close patient monitoring for signs of CNS depression. Alternatives may be explored to manage pain and muscle spasms without the need for a high-risk combination. These alternatives might include over-the-counter anti-inflammatory drugs like ibuprofen, physical therapy, or other muscle relaxants with a different side-effect profile.

Signs of Danger and When to Seek Help

If you are taking these or other CNS depressants and experience any of the following symptoms, seek immediate emergency medical attention:

Signs of respiratory depression: Slow, shallow, or labored breathing.
Signs of severe CNS depression: Extreme drowsiness, confusion, inability to stay awake, or loss of consciousness.
Signs of serotonin syndrome: Agitation, hallucinations, rapid heartbeat, or high blood pressure.

Conclusion: Prioritize Safety and Medical Consultation

The combination of cyclobenzaprine and hydrocodone is a high-risk scenario that can lead to severe and potentially fatal outcomes, primarily due to heightened central nervous system depression. While medication interactions can be complex, the principle is clear: never mix powerful CNS depressants without explicit, careful, and controlled medical supervision. Always be transparent with your healthcare provider about all medications, supplements, and other substances you are taking to ensure your safety. Open communication with your doctor is the most effective way to manage your health and avoid dangerous drug interactions.

For more information on drug interactions and safe prescribing practices, see the National Institute on Drug Abuse website.

Frequently Asked Questions

If you accidentally combine these medications, monitor yourself or the person closely for symptoms of CNS depression, such as extreme drowsiness, confusion, slowed or shallow breathing, or loss of consciousness. Seek emergency medical attention immediately if any severe symptoms occur.

Beyond severe risks, the combination commonly causes heightened drowsiness, dizziness, confusion, difficulty concentrating, impaired coordination, and dry mouth. Severe constipation is also a frequent side effect due to the anticholinergic properties of both drugs.

No. The combination of these two CNS depressants causes significant impairment of judgment, reaction time, and motor skills. It is extremely dangerous to drive or operate hazardous machinery while under their influence.

Your doctor may recommend safer alternatives, such as non-opioid pain relievers like ibuprofen or naproxen for inflammation. Physical therapy, rest, and heat or cold therapy are also effective non-pharmacological treatments. There are other muscle relaxants that may have fewer or different interactions, which your doctor can evaluate.

This depends on the half-life of both drugs and your doctor's specific advice. Always consult your healthcare provider, as they can provide the safest and most personalized guidance based on your overall health and medication regimen. It is not recommended to self-manage the timing of these powerful medications.

Yes, the major drug interaction risk of CNS depression applies to all formulations of hydrocodone. This includes extended-release versions (like Hysingla ER) and combination products (like Norco, which contains hydrocodone and acetaminophen).

You should tell your doctor and pharmacist about all medications, supplements, vitamins, and over-the-counter products you are taking. This includes herbal supplements like St. John's Wort and anything that can cause drowsiness. This information is vital for preventing dangerous drug interactions.