Maybe Taking ED Drugs and Nitrates Is Possible
You've probably seen the Cialis commercials with handsome middle-aged men smiling and embracing their partner. At one point, the golden-voiced narrator says, "Do not take Cialis if you take nitrates for chest pain, as this may cause an unsafe drop in blood pressure."
"Do Not Mix With Nitrates," reads the warning on any bottle of Viagra.
For men taking erectile dysfunction (ED) medications known as phosphodiesterase type 5 (PDE5) inhibitors, the message is clear: ED drugs and nitrates don't mix.
However, a new study suggests there may be little or no risk in taking ED drugs and nitrates if done properly. Even then, the drugs are still contraindicated, so no one should take it upon themselves to start mixing them. Always speak to a cardiologist and/or a urologist first.
The authors of the study, which was published online in the Annals of Internal Medicine, analyzed medical records from almost 250,000 men in Denmark between the ages of 30 and 85 with ischemic heart disease (IHD), also known as coronary heart disease. About 42,000 of the men had periods during which they received ongoing prescriptions for nitrates. Nitrates (e.g., nitroglycerin, isosorbide mononitrate) work by easing chest pain (angina) and may prevent heart attacks by causing the blood vessels to relax and widen.
The study indicated that from 2000 to 2018, the use of PDE5 inhibitors increased 20-fold among patients with IHD who were taking nitrates. No statistically significant association between concomitant use of the two medications and cardiovascular adverse events could be identified. The researchers suggested co-prescription could be safe, because no increased risk of heart attack, stroke or cardiac arrest following prescription of both drugs was found.
What urologists think
Martin Kathrins, M.D., said he doubts the study's findings will change anyone's medical practice because they do not make clear what type of counseling the patients in the study were given.
"For all we know, the patient was counseled to actively not take a nitroglycerin sublingual tablet at around the time they're taking a PDE5 inhibitor," said Kathrins, an assistant professor of surgery at Harvard Medical School and a urologist at Brigham and Women's Hospital in Boston. "There's really no granular data on the timing of this, and the implication is fairly dangerous."
If a man has a cardiac event and he's on a nitrate, it's difficult to tease out the etiology, or cause, Kathrins said, adding there's still a strong possibility that dangerously low blood pressure is possible if nitrates and ED drugs are taken concurrently.
"This study, while it's definitely intriguing and it warrants further investigation, I don't think is quite enough ammunition to change clinical practice," he said.
One urologist declined to be interviewed about the study for this article, saying he would "rather not counter that absolute contraindication." A contraindication is a reason not to take a particular medical treatment due to the harm it may cause the patient. PDE5 inhibitors are contraindicated in patients taking nitrates.
On the other hand, urologist Jesse Mills, M.D., the director of the Men's Clinic at UCLA in Los Angeles and the author of the book "A Field Guide to Men's Health," said the study confirmed what he and some urologists have been doing "semi off-label" for as long as 15 years.
"As long as you have some separation between when you take your PDE5 inhibitor and if you need to take a nitrate, the risk is incredibly minimal," he said.
According to Mills, most cardiologists have been "pretty lax about this because it's such a small chance of causing that dangerous blood pressure and loss of cardiac perfusion."
"The only caveat to that is there are some people who have to be on long-acting nitrates like Isordil, where the guy takes it every day or twice a day," he added. "Then that's the only contraindication to being on the PDE5 inhibitors. That is a potential for a fatal heart event."
For men prescribed a nitrate who only take it occasionally when they're having chest pain, Mills said he's OK with prescribing them tadalafil (Cialis) or sildenafil (Viagra) "because the risk is so low and the frequency that they use their nitroglycerin is so low."
Getting a cardiologist involved
Kathrins said while he is "pretty stringent" when it comes to ED drugs and nitrates, sometimes he may have a conversation with the patient's cardiologist. The nitrates could be a legacy prescription that the man may not need. He may still have them, but he's already been revascularized, meaning he's had a procedure, such as a stent bypass, to open blocked arteries.
"Sometimes the cardiologist will say, 'Well, I didn't even know that he still had it. He can stop it.' The man can literally throw out the drug so it's not even around," Kathrins said. "There's always opportunities to discuss and clarify and reconcile his medications with what's listed in his history with what he's actually taking."
Mills pointed out that over the past two decades, revascularization procedures have improved to a point where if a man is on a nitrate, it's probably because he's already been revascularized.
"The nitrates are there just as an absolute emergency if he can't get to the hospital," Mills said. "It's a pretty thin Venn diagram of somebody who has not been revascularized and has a prescription for nitroglycerin. Those are probably the guys who are too sick, and they probably have no business taking Viagra in the first place."
Mills said if a man has such severe coronary disease that he still needs nitroglycerin, it's very likely his penile vascular disease is substantial enough that he probably would not even respond well to a PDE5 inhibitor.
If the patient has a need for nitroglycerin or is taking a nitrate-based antihypertensive, Kathrins would err away from prescribing him a PDE5 inhibitor. If controlling the underlying comorbidities doesn't work, Kathrins may explore other therapies for ED, such as a vacuum erection device, urethral suppository or penile injection therapy.
"Those would all be safe, actually, because there's no interaction with nitrate-based medications," he said.
Despite this study's findings, patients should always check with a cardiologist and a urologist to make sure everyone is on the same page before starting ED drugs in combination with nitrates.
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