Is PDE5 Inhibitors (Sildenafil/Tadalafil) Safe with Citrulline?
Free · No account · based on published sources including NIH ODS, FDA drug labels, and peer-reviewed literature
Do NOT combine citrulline supplements with PDE5 inhibitors. This combination can cause dangerously low blood pressure and cardiovascular collapse. Seek immediate medical attention if experiencing dizziness, fainting, or chest pain.
Why this interaction occurs
Citrulline is converted to arginine in the kidneys, which is the direct substrate for nitric oxide synthase (NOS), dramatically increasing endogenous nitric oxide (NO) production. PDE5 inhibitors prevent the breakdown of cGMP, the second messenger of NO signaling, amplifying and prolonging vasodilation. The synergistic enhancement of the NO-cGMP pathway can produce profound, potentially life-threatening systemic hypotension, particularly during or after intense physical exercise when vasodilation is already maximal.
Evidence
Evidence level: strong.
Reported safety data
The FDA’s adverse event reporting system (FAERS) has received 639 reports mentioning Citrulline. This reflects reported cases involving the medication in general — not confirmed causation, and not specific to the Citrulline + supplement combination on this page.
FAERS reports are voluntary and cannot prove that a drug caused an event. Do not use report counts to assess the safety of this specific drug-supplement pair.
Frequently asked questions
Related interactions
All PDE5 Inhibitors (Sildenafil/Tadalafil) interactions → · All Citrulline interactions →
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Educational only — not medical advice.
Always confirm with your doctor or pharmacist.