Introduction
Since the 1990s, when the first phosphodiesterase 5 inhibitor (PDE5 inhibitor) sildenafil (Viagra®) was introduced, these drugs have become the first-line treatment for men with erectile dysfunction (ED). Over time, PDE5 inhibitors have been shown to have even more benefits, from enhanced workouts to improved cognitive function, whether you have ED or not.
If you’ve been thinking of trying a PDE5 inhibitor, but can’t decide if you’re more of a sildenafil or tadalafil kind of guy, you may not have to choose. There are many benefits of combining PDE5 inhibitors, such as a faster onset of action and longer-lasting results, as long as you combine them safely.
Read on to find out the best PDE5 inhibitor combinations, how to combine them safely, and potential risks to consider.
Key takeaways:
- Combining certain PDE5 inhibitors may increase the efficacy of these drugs, especially for those who did not respond to monotherapy.
- When combining PDE5 inhibitors with different onsets to action and different half-lives, the benefits are experienced faster and for longer, making such combinations beneficial whether you have ED or not.
- Commercially available PDE5 inhibitors are typically formulated with high dosages of the active ingredient, making them unsafe to combine. Compounding low dosages under medical supervision is the only safe and recommended route to benefiting from the synergistic effect of combined PDE5 inhibitors.
What are PDE5 inhibitors?
PDE5 inhibitors like sildenafil, tadalafil, and vardenafil work as vasodilators. They improve blood flow by relaxing blood vessels in different parts of the body, including the penis, lungs, and brain. While they are considered a first-line treatment for ED, they are also prescribed for pulmonary hypertension and used off-label to increase lean muscle mass, enhance workout recovery, and improve cognitive function.
PDE5 inhibitors do not give spontaneous erections or increase your sexual desire. They simply help to improve your physical performance during sex, but you'll need to be sexually stimulated for them to work.
The science behind combining PDE5 inhibitors
Despite what you may think, combining PDE5 inhibitors will not give you an all-day erection, unless you develop the rare condition priapism, in which case you should contact your doctor immediately. When combined safely, some PDE5 inhibitors have a synergistic effect due to their different half-lives and how quickly they affect the user.
For instance, tadalafil has a longer half-life than other PDE5 inhibitors of around 17.5 hours, while vardenafil has a shorter half-life of 4-6 hours but a faster onset of action, working in as little as 15 minutes. This means that if you combine tadalafil with vardenafil in dosages approved by your doctor, you’ll experience the effects faster and for longer. If you’re using the medication for sexual enhancement, this translates to longer sessions and shorter down time between sessions. If you’re using the medication to improve your workouts, this means stronger pumps, more muscle production, and faster recovery. And if you’re using the medication for better cognitive function, you can take it before a demanding event for sharper mental performance that will last all day.
Evidence-based benefits of combining PDE5 inhibitors
While you should never take high doses of PDE5 inhibitors together, research has shown that combining the active ingredients at lower dosages may make the medications more effective, especially for those who did not respond as well to any one PDE5 inhibitor alone. This should only be done when prescribed by a medical provider.
In this 2015 study that combined tadalafil 5 mg daily with sildenafil 50 mg in the early treatment stages for erectile dysfunction, researchers found the combination resulted in “significant improvement” for those with severe symptoms. There was also no difference in adverse effects between those who took tadalafil alone or those who combined medications, proving the safety of combining low-dosage PDE5 inhibitors.
A more recent 2020 study found combining PDE5 inhibitors to be successful for patients who did not respond to tadalafil monotherapy for ED following a radical prostatectomy surgery. Combining daily tadalafil 5 mg with sildenafil 50 mg or udenafil 100 mg tablets on-demand helped 39.7%% of these patients achieve success. The researchers concluded that these findings can help prevent men from resorting to more invasive treatments for ED after surgery.
Potential risks and considerations when combining PDE5 inhibitors
You should never attempt combining PDE5 inhibitors without medical supervision. Combining these drugs at high doses increases the risks of side effects, which include:
- Extremely low blood pressure
- Dizziness
- Lightheadedness
- Fainting
- Nausea
- Increased risk of priapism
- Headache
- Back pain
- Vision changes
- Indigestion
PDE5 inhibitors may also not be safe for people taking nitrates, those with active coronary ischemia or congestive heart failure, people with low blood pressure, and those on antihypertensive therapy regimens. Always ask your doctor first to ensure this type of medication is safe for you.
Future outlook on PDE5 inhibitor combinations
Though more research is needed to understand the full benefits of combining PDE5 inhibitors, the future looks promising. Many of the health benefits of PDE5 inhibitors are already established and backed by studies that prove how versatile these medications already are.
Proven health benefits of PDE5 inhibitors so far include:
Potential health benefits still being investigated but showing promising results include using PDE5 inhibitors to increase fertility, prevent coronary events, improve cancer treatment, help manage diabetes, boost kidney function, and even treat depressive symptoms.
The bottom line: Combining PDE5 inhibitors may lead to improved health outcomes, but only under medical supervision.
Combining PDE5 inhibitors safely helps patients experience health benefits faster and for a longer period of time. This is especially true for those who did not respond to any one treatment alone. However, there are numerous health risks to consider, which is why combining PDE5 inhibitors should only be done under medical supervision.
Maximus offers three products combining the PDE5 inhibitors tadalafil and vardenafil for improved sexual function, enhanced workouts, and increased cognitive function. Learn more about: Blood Flow Protocol.
