Sildenafil and Flexeril (Cyclobenzaprine) Interaction
There is no clinically significant drug-drug interaction between sildenafil and cyclobenzaprine (Flexeril), and these medications can be used together safely in most patients. Cyclobenzaprine is not listed among the documented interacting drugs with sildenafil in major cardiovascular and pharmacology guidelines.
Mechanism Analysis
Sildenafil is primarily metabolized through the CYP3A4 and CYP2C9 pathways 1. The clinically significant interactions occur with:
- CYP3A4 inhibitors (ketoconazole, erythromycin, ritonavir, clarithromycin) which increase sildenafil levels 1
- CYP3A4 inducers (rifampin, phenytoin) which decrease sildenafil levels 1
- Organic nitrates - absolutely contraindicated due to potentially fatal hypotension 1, 2
Cyclobenzaprine does not significantly inhibit or induce these metabolic pathways and is not mentioned in comprehensive drug interaction tables for sildenafil 1.
Blood Pressure Considerations
The primary safety concern with sildenafil involves its vasodilatory effects, not interactions with muscle relaxants. Sildenafil causes modest blood pressure reductions (typically 8/7 mmHg systolic/diastolic) that are generally well-tolerated 2.
Key blood pressure interactions include:
- Nitrates: Contraindicated - causes synergistic, potentially fatal hypotension 3, 2, 4
- Alpha-blockers: Requires caution - may cause symptomatic orthostatic hypotension 2, 4
- Calcium channel blockers (amlodipine): Additive but not synergistic blood pressure reduction of 8/7 mmHg 3, 2
- Other antihypertensives (beta-blockers, ACE inhibitors, diuretics): Small additive decreases without significant adverse events 5, 2
Cyclobenzaprine does not have significant vasodilatory properties and would not be expected to potentiate sildenafil's blood pressure effects.
Documented Sildenafil Interactions Requiring Attention
The interactions that actually matter clinically are:
Absolute Contraindications
- Any form of organic nitrates (nitroglycerin, isosorbide) - wait 24 hours after sildenafil before nitrate use 2, 4
Dose Adjustment Required
- Strong CYP3A4 inhibitors: Ritonavir, saquinavir, ketoconazole, erythromycin require starting sildenafil at 25mg 6, 1
- HMG-CoA reductase inhibitors (statins): Sildenafil may increase simvastatin/atorvastatin levels through competition for CYP3A4 metabolism, increasing rhabdomyolysis risk 1
Use With Caution
- Alpha-blockers: Initiate sildenafil at lowest dose (25mg) in patients stable on alpha-blocker therapy 2, 4
- Bosentan: Decreases sildenafil levels by 50% while increasing bosentan levels by 50% 1
Clinical Bottom Line
Cyclobenzaprine and sildenafil can be prescribed together without dose adjustment or special monitoring beyond standard precautions for each medication individually. The absence of cyclobenzaprine from comprehensive interaction tables in European Heart Journal 1, American Heart Association 1, and European Respiratory Journal 1 guidelines confirms no clinically meaningful interaction exists.
Focus your attention instead on screening for the truly dangerous interactions: nitrate use (absolute contraindication), alpha-blocker use (requires caution), and strong CYP3A4 inhibitors (requires dose reduction) 1, 2.