What precautions should be taken when combining sildenafil (phosphodiesterase type 5 inhibitor) with creatine (cr) monohydrate?

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Last updated: June 22, 2025View editorial policy

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From the Guidelines

When combining sildenafil with creatine monohydrate, it is crucial to exercise caution due to potential interactions that may affect blood pressure regulation and kidney function. The primary concern is that sildenafil, a phosphodiesterase type 5 inhibitor, can cause significant vasodilation, which may be compounded by creatine monohydrate's potential to cause water retention, thereby affecting blood pressure and increasing cardiovascular strain 1. To mitigate these risks, several precautions should be taken:

  • Consult with a healthcare provider before using these substances together, especially for individuals with pre-existing cardiovascular conditions, hypertension, or kidney disease.
  • Maintain adequate hydration, aiming for at least 2-3 liters of water daily, to reduce kidney stress associated with creatine use.
  • Initiate treatment with lower doses of both substances to assess tolerance, typically starting with 25mg of sildenafil and 3-5g of creatine daily.
  • Monitor for enhanced side effects, including headaches, flushing, dizziness, and gastrointestinal discomfort, which can be exacerbated by the combination of these substances. It is also important to note that nitrates should not be administered to patients who have recently received a phosphodiesterase inhibitor like sildenafil, especially within 24 hours, due to the risk of severe hypotension 1. Given the potential for adverse interactions, a cautious approach is warranted when combining sildenafil with creatine monohydrate, prioritizing careful monitoring and dose adjustment under healthcare supervision to minimize risks to morbidity, mortality, and quality of life.

From the Research

Precautions with Creatine Monohydrate and Sildenafil

  • There is limited research directly addressing the combination of sildenafil and creatine monohydrate.
  • Sildenafil is a phosphodiesterase type 5 inhibitor used to treat erectile dysfunction, and its use has been associated with transient reductions in blood pressure and negligible effects on heart rate 2, 3.
  • Creatine monohydrate is a dietary supplement that increases muscle performance in short-duration, high-intensity resistance exercises, with few adverse effects reported, the most common being transient water retention 4.
  • When considering the use of sildenafil with other substances, it is crucial to note that the concomitant use of sildenafil and organic nitrates is contraindicated due to the risk of potentiated decreases in blood pressure 2, 3, 5.
  • However, the combination of sildenafil with antihypertensive agents may lead to additive but not potentiating blood pressure decreases, and is generally considered safe and effective for treating erectile dysfunction in patients with hypertension 5.
  • Given the lack of direct evidence on the interaction between creatine monohydrate and sildenafil, it is essential to monitor for any potential adverse effects, such as changes in blood pressure or kidney function, when using these substances together 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Creatine supplementation.

Current sports medicine reports, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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