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As any sports fan knows, thanks to the incessant drumbeat of game-time Viagra and Cialis commercials, mixing erectile dysfunction drugs with nitrates for chest pain can cause an unsafe drop in blood pressure. Most medical guidelines strongly warn men not to take both types of medications.

Researchers in Denmark and the U.S., however, have recently found that a substantial number of men are nevertheless obtaining overlapping prescriptions for both classes of drugs. But evidence suggests that they don’t appear to suffer negative health outcomes, such as heart attacks, as a result.

“We were a little surprised that we didn’t find an increased risk,” said Dr. Anders Holt, a researcher at Copenhagen University Hospital Herlev-Gentofte. He is the lead author of a study published Monday in the Annals of Internal Medicine that identified a steep escalation in the co-prescribing of erectile dysfunction drugs and nitrates among Danish men. The researchers reported no conflicting ties to the pharmaceutical industry.

So how are men managing to navigate taking the drugs safely?

While the new study couldn’t tease out how men timed taking each medication, Holt speculated that one possible explanation for the lack of apparent health consequences is that people with coronary artery disease typically take longer-acting nitrate medications in the morning and tend to take erectile dysfunction drugs in the evenings. The span of time might be sufficient to prevent harmful drug interactions.

But medical groups such as the American Heart Association advise men to avoid taking nitrates within at least 24 hours of shorter-acting erectile dysfunction drugs, including Viagra (sildenafil) and Levitra (vardenafil), and within at least 48 hours of a longer-acting drug, such as Cialis (tadalafil).

In 2019, more than 4 million men and women in the U.S. received prescriptions for the top three nitrates — nitroglycerine, nitrofurantoin and isosorbide — according to the drug statistics website ClinCalc.com’s list of the top 300 medications. About 1.4 million men were prescribed Viagra and Cialis.

A 2008 study estimated that 3 percent of men in the U.S. experience severe erectile dysfunction, 6 percent experience moderate dysfunction and 26 percent experience mild dysfunction. And a 2020 paper estimated that 2.4 million men ages 40 and older have physician-diagnosed chest pain. 

Both erectile dysfunction medications and nitrates cause blood vessels to dilate, which can dramatically escalate if the drugs are taken close together, potentially causing a sharp drop in blood pressure. That raises the risk of major cardiovascular health events, such as heart attacks or strokes.

Experts also strongly advise against consuming amyl nitrate, known as “poppers” and used as a recreational drug, with erectile dysfunction medications.

Spacing out doses of erectile dysfunction and nitrate medications “will decrease the chances that there will be a drug interaction,” said Dr. Robert A. Kloner, a professor of medicine at the University of Southern California, who led some of the key studies that established the American Heart Association’s safety protocol. (Kloner is a paid consultant for Sanofi, which has an agreement with Eli Lilly to sell Cialis in several countries if it were to become an over-the-counter medication.)

In the new Danish study, Holt and his colleagues analyzed medical records from nearly 250,000 Danish men ages 30 to 85 with ischemic heart disease. About 42,000 of them had stretches during which they received ongoing nitrates prescriptions. 

From 2000 to 2018, the researchers found, the rate at which men received erectile dysfunction drug prescriptions increased tenfold among the entire group while soaring twentyfold among those on nitrates. By the last five years of the study period, 9 percent of those in the latter group filled at least one prescription for a drug such as Viagra within three years of having started nitrates.

The authors looked at health outcomes during periods when the men received prescriptions for both drug types and compared them to outcomes during stretches when they received just one such medication. The data suggested that receiving concurrent prescriptions for the two drug classes wasn’t associated with any increase in heart health problems, such as cardiac arrest, heart attack or stroke.

Kloner, who wasn’t involved with the research, said the findings suggest “that health care providers are likely becoming more comfortable co-prescribing these two classes of drugs despite the guidelines and are at least educating their patients about not taking them right at same time.”

The study is limited by the fact that the study authors couldn’t know for sure when men were actually taking each of the medications. But when they adjusted their analysis to focus on periods from one to four weeks after the men received new erectile dysfunction drug prescriptions, the findings held.

The authors suggest that it’s also possible that some men may, indeed, experience drops in blood pressure from taking both drugs but that that doesn’t lead to health problems substantial enough for them to visit an emergency room. The researchers had access only to hospital data, not to medical records from general practitioners.

The study also couldn’t account for drugs men obtained on the black market — a common practice among those seeking medications like Viagra. 

A U.S. study from the drugmaker Sanofi, published in The Journal of Sexual Medicine in August, reached similar findings. The pharma researchers analyzed electronic medical records covering 2012 to 2016 from more than 168,000 U.S. men who had at least one erectile dysfunction drug prescription. Out of 480,000 men who had one or more nitrate prescriptions, 3,167 received medications from both drug classes during overlapping periods — without any apparent increased risk of cardiovascular health problems.

The study also had access to health care providers’ appointment notes. Those records indicated that in perhaps half of the co-prescription cases, the physicians did caution their patients about the dangers of taking the medications together or instructed them about mitigating the risk of drug interactions.

Holt stressed that men’s sexual health and well-being are as important as the rest of their physical health.

“You can definitely possess both drugs,” Holt advised men who are candidates for both nitrates and erectile dysfunction medications. “But certainly don’t take them at the same time. We don’t have evidence that that’s safe.”

Raymond Rosen, an adjunct full professor of psychiatry and behavioral services at the University of California, San Francisco School of Medicine, said, “Erectile dysfunction drugs like Viagra have been a boon to many men and their partners who suffer from this common but potentially disruptive male disorder.”

“New evidence,” said Rosen, who wasn’t involved in either of the recent studies, “has challenged this long-held belief” that men can’t take both nitrates and erectile dysfunction drugs. 

Still, he said, “men should always consult with their physician or health provider before making changes in either of these medications.”

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