Can You Take Viagra and Cialis Together?
Can You Take Viagra and Cialis Together?
A Comprehensive Clinical Guide to PDE5 Inhibitor Combination Therapy
Medically reviewed by Courtney LaSumner Bass, NP | Last Updated: December 2024
KEY TAKEAWAYS
Combining full doses of Viagra (sildenafil) and Cialis (tadalafil) without medical supervision can cause dangerous blood pressure drops
Under clinician supervision, low-dose combination therapy may benefit men with severe or treatment-resistant erectile dysfunction
Research shows combination therapy improved erectile function in men with severe ED who didn't respond to single medications alone
Always consult a qualified healthcare provider before combining ED medications—never self-experiment with multiple PDE5 inhibitors
If you've tried Viagra (sildenafil) or Cialis (tadalafil) for erectile dysfunction and wondered whether combining them might deliver better results, you're not alone. Many men—particularly those with severe or treatment-resistant ED—ask whether using both medications together could enhance their effectiveness.
The short answer: it's complicated. While combining full doses of these medications on your own is potentially dangerous and strongly discouraged, emerging clinical evidence suggests that carefully managed, low-dose combination therapy under medical supervision may offer benefits for specific patient populations. This comprehensive guide examines the science, safety considerations, and clinical protocols surrounding PDE5 inhibitor combination therapy.
Understanding How PDE5 Inhibitors Work
Before discussing combination therapy, it's essential to understand the mechanism of action that makes both Viagra and Cialis effective. Both medications belong to a class called phosphodiesterase type 5 (PDE5) inhibitors, and they share the same fundamental mechanism of action—with some important pharmacokinetic differences.
The Erection Physiology
When sexual arousal occurs, the nervous system releases nitric oxide in the penile erectile tissue. This triggers a cascade that produces cyclic guanosine monophosphate (cGMP), which causes the smooth muscles in penile blood vessels to relax, allowing increased blood flow and creating an erection.
The enzyme PDE5 naturally breaks down cGMP, which is why erections don't last indefinitely. PDE5 inhibitors work by blocking this enzyme, allowing cGMP to accumulate longer and maintain the erection. Importantly, these medications do not cause erections on their own—sexual stimulation is still required to initiate the process.
Sildenafil vs. Tadalafil: Key Pharmacological Differences
While both medications inhibit PDE5, they have distinct pharmacological profiles:
Sildenafil (Viagra): Onset of action typically 30-60 minutes; duration of effect approximately 4-6 hours; may be affected by high-fat meals; primarily metabolized by CYP3A4 (79%) and CYP2C9 (20%).
Tadalafil (Cialis): Onset of action 30 minutes to 2 hours; remarkably long duration of up to 36 hours (earning it the nickname "weekend pill"); not significantly affected by food; metabolized almost exclusively by CYP3A4.
These differences in pharmacokinetics are clinically significant. A 2017 systematic review and meta-analysis published in International Urology and Nephrology found that while both medications demonstrate comparable efficacy and safety profiles, patients and their partners showed a statistically significant preference for tadalafil (OR 8.04, 95% CI 4.99-12.96), primarily due to its longer duration of action and freedom from meal timing concerns.
The Risks of Unsupervised Combination Therapy
Self-medicating with multiple PDE5 inhibitors simultaneously carries significant cardiovascular risks that must be clearly understood.
Hypotension and Cardiovascular Risks
Both sildenafil and tadalafil cause vasodilation—relaxation of blood vessel walls throughout the body. When used individually at recommended doses, this typically results in modest blood pressure reductions of 5-10 mmHg systolic. However, combining two PDE5 inhibitors creates an additive vasodilatory effect that can lead to:
Severe symptomatic hypotension (dangerously low blood pressure)
Orthostatic hypotension causing dizziness, lightheadedness, or fainting
Syncope (loss of consciousness)
In severe cases, cardiovascular events including heart attack or stroke
A 2011 study published in Circulation examined PDE5 inhibitor drug interactions and found that when combined with other vasodilating agents (including nitrates and alpha-blockers), PDE5 inhibitors can cause "pronounced systemic vasodilation and severe hypotension." The authors noted that many patients with ED share risk factors with coronary artery disease patients, making careful medication management essential.
Contraindications and Dangerous Drug Interactions
Beyond the risks of combining PDE5 inhibitors, these medications have absolute contraindications that apply regardless of how they're used:
Nitrates (nitroglycerin, isosorbide mononitrate/dinitrate): Potentially fatal hypotension. Must wait 24-48 hours after last PDE5 inhibitor dose before administering nitrates.
Riociguat (guanylate cyclase stimulator): Contraindicated due to additive hypotensive effects.
Alpha-blockers: Significant hypotension risk; requires stable alpha-blocker therapy and lowest PDE5 inhibitor dose if combination necessary.
CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, erythromycin): Increase PDE5 inhibitor plasma concentrations, potentially amplifying side effects.
The Evidence for Supervised Low-Dose Combination Therapy
Despite the risks of unsupervised combination use, clinical research has explored whether carefully managed, low-dose combination therapy might benefit specific patient populations—particularly men with severe or treatment-resistant ED.
The Cui et al. Study (2015)
A landmark study published in Andrologia by Cui and colleagues evaluated 180 men with ED randomized 1:1 to receive either tadalafil 5mg once daily alone, or tadalafil 5mg once daily combined with sildenafil 50mg as needed before sexual activity.
Key Findings:
Patients with severe ED in the combination group showed significantly higher total IIEF-5 (International Index of Erectile Function) scores compared to tadalafil alone
Men with moderate and severe ED demonstrated superior improvement in erectile rigidity (IIEF-5 Question 2 scores)
Sexual encounter success rates (SEP4, SEP5) and partner satisfaction improved significantly in the combination group
Critically, there was no significant difference in adverse event incidence between the two groups
The authors concluded: "Combined medication can better improve erectile function, especially for patients with severe ED."
2024 Systematic Review on Combination Therapy
A comprehensive review published in UroPrecision in March 2024 examined the available evidence on PDE5 inhibitor combination therapies. The review confirmed that while combination therapy showed benefits specifically for patients with severe ED, "no benefit or minimal difference was observed in patients with mild and mild-to-moderate ED."
This finding has important clinical implications: combination therapy is not appropriate for all ED patients, but rather represents a potential option for those with more severe dysfunction who haven't achieved adequate response to monotherapy.
JAMA Network Meta-Analysis (2021)
A systematic review and meta-analysis published in JAMA Network Open analyzed 44 studies including 3,853 men to evaluate combination therapies for ED. The analysis found that:
Combination therapy compared to monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24)
Addition of daily tadalafil showed a weighted mean difference of 1.70 points in IIEF scores (95% CI, 0.79-2.61)
Patients with monotherapy-resistant ED showed significant improvement with combination approaches (WMD, 4.38; 95% CI, 2.37-6.40)
The research concluded that "combination therapy should be the initial preference in patients with hypogonadism or prostatectomy-induced ED"
Cardiovascular Benefits of PDE5 Inhibitor Therapy
Beyond treating erectile dysfunction, PDE5 inhibitors have demonstrated significant cardiovascular benefits that may be relevant to treatment decisions.
A major 2024 study published in The American Journal of Medicine analyzed data from over 509,000 men with ED from the TriNetX database. The research found that PDE5 inhibitor use was associated with:
34% reduction in all-cause mortality with tadalafil (RR 0.66) and 24% reduction with sildenafil (RR 0.76)
27% reduction in myocardial infarction risk with tadalafil and 17% reduction with sildenafil
34% reduction in stroke risk with tadalafil and 22% reduction with sildenafil
Significant reductions in venous thromboembolism and dementia risk
Notably, tadalafil showed more pronounced cardiovascular benefits compared to sildenafil, potentially due to its longer duration of action providing more sustained vascular effects.
Who Might Benefit from Combination Therapy?
Based on the available evidence, supervised low-dose combination therapy may be considered for:
Men with severe ED who have not achieved satisfactory response to maximum doses of a single PDE5 inhibitor
Patients with treatment-resistant ED due to underlying vascular, neurogenic, or post-surgical causes
Men with prostatectomy-induced ED
Patients with hypogonadism (when combined with testosterone replacement therapy)
Combination therapy is NOT appropriate for:
Men with mild or mild-to-moderate ED (no benefit demonstrated)
Patients who haven't tried single-agent therapy at adequate doses
Anyone with contraindications to PDE5 inhibitors (nitrate use, certain cardiac conditions, hypotension)
Men who have not been evaluated and supervised by a qualified healthcare provider
What to Expect from Individual Medications
For most men, a single PDE5 inhibitor—properly dosed and used according to medical guidance—provides effective treatment for erectile dysfunction. Understanding what each medication offers can help inform discussions with your healthcare provider.
Sildenafil (Viagra)
Typical dosing: 25mg, 50mg, or 100mg taken 30-60 minutes before sexual activity
Duration: Approximately 4-6 hours of effect
Food considerations: High-fat meals may delay onset of action
Common side effects: Headache, flushing, nasal congestion, dyspepsia, visual changes (blue tint)
Best for: Men who prefer on-demand medication and don't need prolonged duration
Tadalafil (Cialis)
As-needed dosing: 10mg or 20mg taken 30 minutes to 2 hours before sexual activity
Daily dosing: 2.5mg or 5mg taken once daily for consistent effect
Duration: Up to 36 hours of effect ("weekend pill")
Food considerations: Not significantly affected by food intake
Common side effects: Headache, dyspepsia, back pain, muscle aches, nasal congestion
Best for: Men who prefer spontaneity, daily low-dose therapy, or need treatment for concurrent BPH symptoms
The Importance of Medical Supervision
If you're considering whether combination therapy might be appropriate for your situation, working with a qualified healthcare provider is essential—not optional. Here's why medical supervision matters:
Comprehensive evaluation: ED often indicates underlying cardiovascular disease. A thorough evaluation can identify risk factors that affect medication safety and may reveal health issues requiring attention.
Drug interaction assessment: Your provider can review all medications, supplements, and health conditions to identify potential dangerous interactions.
Appropriate dosing: If combination therapy is considered, careful dose selection and titration significantly reduces risk.
Monitoring: Ongoing assessment ensures treatment safety and allows adjustment based on response and side effects.
Alternative options: Your provider can discuss other evidence-based approaches that might be more appropriate for your situation.
"Treatment decisions for erectile dysfunction should be individualized based on patient characteristics, comorbidities, and treatment goals. Self-experimentation with combination therapy is never recommended." — Arsenal Men's Health Clinical Team
The Bottom Line
Can you take Viagra and Cialis together? The evidence suggests that under careful medical supervision, low-dose combination therapy may benefit a specific subset of patients—those with severe or treatment-resistant erectile dysfunction who haven't achieved satisfactory results with single-agent therapy.
However, this is not a DIY approach. Combining full doses of PDE5 inhibitors without proper medical evaluation and supervision poses real cardiovascular risks. The safety profile seen in clinical studies specifically involved low doses administered under controlled conditions with appropriate patient selection.
For most men with ED, a single properly-dosed PDE5 inhibitor provides effective treatment. If you're not achieving satisfactory results, the solution is not to start combining medications on your own—it's to work with a healthcare provider who can:
Optimize your current medication dosing
Address underlying causes of ED that may be limiting response
Consider alternative or adjunctive treatments (testosterone, shockwave therapy, vacuum devices)
Determine if supervised combination therapy might be appropriate for your specific situation
Take the Next Step with Arsenal Men's Health
At Arsenal Men's Health, we specialize in comprehensive, clinician-led treatment for erectile dysfunction and other men's health concerns. Our board-certified providers understand that effective ED treatment requires more than a prescription—it requires a partnership focused on your individual needs, goals, and safety.
Whether you're new to ED treatment or haven't achieved satisfactory results with current therapy, we're here to help you explore all evidence-based options—including determining whether advanced approaches might be appropriate for your situation.
Ready to optimize your sexual health?
Book Your Free Consultation Today
(385) 666-6292 | arsenalmenshealth.com
References
Cui H, Liu B, Song Z, et al. Efficacy and safety of long-term tadalafil 5 mg once daily combined with sildenafil 50 mg as needed at the early stage of treatment for patients with erectile dysfunction. Andrologia. 2015;47(1):20-24. doi:10.1111/and.12216
Mykoniatis I, Kalyvianakis D, Kapoteli P, et al. Assessment of Combination Therapies vs Monotherapy for Erectile Dysfunction: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(2):e2036337. doi:10.1001/jamanetworkopen.2020.36337
Gong B, Ma M, Xie W, et al. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis. Int Urol Nephrol. 2017;49(10):1731-1740. doi:10.1007/s11255-017-1644-5
Kloner RA, Hutter AM, Emmick JT, et al. Drug Interactions With Phosphodiesterase-5 Inhibitors Used for the Treatment of Erectile Dysfunction or Pulmonary Hypertension. Circulation. 2011;123:1062-1069. doi:10.1161/CIRCULATIONAHA.110.944603
Dhaliwal A, Gupta M. PDE5 Inhibitors. [Updated 2023 Apr 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
Owen J, et al. Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction: A literature review. UroPrecision. 2024;2(1):e38. doi:10.1002/uro2.38
Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. J Urol. 2018;200(3):633-641. doi:10.1016/j.juro.2018.05.004
Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int. 1999;84(1):50-56. doi:10.1046/j.1464-410x.1999.00142.x
Giuliano F, Hatzichristou D, et al. Benefits of Tadalafil and Sildenafil on Mortality, Cardiovascular Disease, and Dementia. Am J Med. 2024. doi:10.1016/j.amjmed.2024.10.022
Hatzichristou D, d'Anzeo G, Porst H, et al. Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6-month observational study (EDATE). BMC Urol. 2015;15:111. doi:10.1186/s12894-015-0107-5
U.S. Food and Drug Administration. VIAGRA (sildenafil citrate) tablets, for oral use. Prescribing Information. 2017.
U.S. Food and Drug Administration. CIALIS (tadalafil) tablets, for oral use. Prescribing Information. 2011.
MEDICAL DISCLAIMER
This article is for educational purposes only and does not constitute medical advice. Treatment decisions should be made in consultation with a qualified healthcare provider who can evaluate your individual health status, medical history, and specific needs. Never start, stop, or change any medication without professional medical guidance. Erectile dysfunction can be a sign of underlying health conditions that require evaluation.
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