History of ED Drugs: Sildenafil, Vardenafil, Tadalafil, Avanafil


Erectile dysfunction is a condition that has been spoiling men’s lives since the olden days. The perceptions about this health disorder and treatment options have kept changing over time. And ED wasn’t always acceptable – in France, for example, a man who had erectile dysfunction was considered a criminal in the 16th and 17th centuries. The judges would inspect the accused in a court and impotence was a legal reason for divorce.

The Early Treatment Methods

In the 19th century, extract from sheep testes was used as an injectable medicine in men suffering from impotence. This was a source of testosterone, and the practice continued until the 20th century when testosterone was purified.

In the 1920s, Dr. John Brinkley used goat gland implants to treat erectile dysfunction. He also recommended mercurochrome injections, but his medical license was revoked by the medical board of Kansas State forcing him to open a clinic across the border in Mexico and continue his experiments there.

In the 1960s, a vacuum pump was invented by Geddings Osborn. The device which works by creating a vacuum and sucking blood into the erectile tissue is actually still being used by many. Inflatable penile implants, in their turn, became available in the 1970s and were quite popular for several decades among those who didn’t mind surgical interventions into their nether regions.

Before the era of prescription meds for ED, men also used herbs and nutritional adjustments in attempts to treat impotence – most of the time with little to no success, unfortunately.

The Era of ED Medication

The hope to discover erectile dysfunction meds was reignited when Gilles Brindley, a physiologist, demonstrated that papaverine could induce an erection. Brindley’s studies laid the basis for using vasodilators in treating erectile dysfunction. One of the more popular drugs of that period was alprostadil, which was injected into the penis to boost erection. Another example was phentolamine (an alpha blocker), which was also used as an impotence medication (although off-label).

The Breakthrough

The era of PDE-5 inhibitors started with the discovery of entirely new ED medications that worked quickly, safely and, most importantly, didn’t require surgery or use of other invasive techniques.

Sildenafil (Viagra)

The story of sildenafil began when a group of scientists at Pfizer’s facility in Sandwich, UK got down to work on a new drug for angina and hypertension. During the clinical trials, a keen nurse noticed something bizarre − the male subjects in the study were lying on their tummies. Intrigued, the nurse tried to find a reason for this. She discovered that the men were having erections and lying on their bellies in attempt to conceal the embarrassing side effects of the medication. The drug was originally meant to dilate blood vessels in the heart was also dilating blood vessels in the penis! The manufacturers, therefore, decided to market the drug as treatment for erectile dysfunction. It was patented in 1996 and got approval by the FDA in 1998, becoming the first oral impotence medication in the United States.

The success of Viagra on the market was remarkable as evidenced by the thousands of prescriptions dispensed just a week after the drug was launched. Viagra was also featured in a number of TV shows such as ‘The Man, The Myth, The Viagra’ in 1999. The little blue pills courted controversy in several instances including its reported use by the CIA to lure allies to help them fight the Taliban insurgency.

The annual sales of Viagra started to decline with the entry of Cialis and Levitra on the market as well as the appearance of counterfeits. By 2007, the total share of Viagra on the market had dropped by almost half. In 2012, Viagra reclaimed its glory, and Pfizer recorded over $2 billion in revenue from selling the blue pills. However, the figures have been dwindling since then with the company reaching only $1.2 billion in revenue from Viagra sales in 2017.

Viagra was only available in land-based pharmacies until 2007 when Boots Pharmacy in the UK tried Internet sales, offering the drug for online purchase after consultation with a specialist. In 2013, Pfizer set up its own site for selling Viagra online. In 2017, a version of Viagra called Viagra Connect became available over the counter in the UK market. Viagra Connect is manufactured by Pfizer, and you don’t need a prescription to purchase it.

In 2013, Viagra’s patent expired in Europe and many other regions leading to the influx of generics on the market. In late 2017, generic sildenafil versions such as Teva sildenafil became available in the US.

Sildenafil was also approved in 2005 to treat pulmonary arterial hypertension under the brand name Revatio.

Vardenafil (Levitra)

Vardenafil, another PDE-5 inhibitor was discovered by Bayer Pharmaceuticals. In 2001, it was shown that the compound is effective against all forms of erectile dysfunction regardless of the cause or severity.

In 2001, Bayer and GlaxoSmithKline agreed to co-promote vardenafil and market it in various parts of the world. In August 2003, the FDA approved vardenafil hydrochloride sold under the brand name Levitra as a medication for erectile dysfunction in men. This became the second oral ED medication in the US market after Viagra.

Tadalafil (Cialis)

Cialis was discovered after Glaxo Wellcome and ICOS had partnered to develop new drugs. Studies on tadalafil were not initially intended to make the drug an impotence drug, but this use of the new medication was primarily influenced by the outcomes of clinical trials on sildenafil. The agreement between Glaxo and ICOS lapsed, and Eli Lilly partnered with ICOS to market tadalafil in 1998.

In November 2003, tadalafil was approved as a drug for erectile dysfunction in men under the brand name Cialis. The drug has a long half-life, and it can remain active for up to 36 hours. This attribute gave Cialis the edge over Levitra and Viagra, boosting its global sales significantly. Later in 2007, Eli Lilly bought ICOS and claimed full rights on Cialis.

In 2011, the FDA approved Cialis for the treatment of benign prostate hyperplasia which is a condition that typically affects aging men, and it is characterized by an enlarging prostate.

Avanafil (Stendra)

Avanafil is another PDE-5 inhibitor manufactured by Vivus Inc. The drug is marketed under the brand name Stendra. It got FDA approval in 2012, after which Vivus partnered with Menarini in 2013 to commercialize avanafil in several countries in Europe and Oceania.

The chapter on the development of ED meds seems to be a long way from closure because new drugs are still being developed. Udenafil, another PDE-5 inhibitor is on course, as well as Vitaros, which is an alprostadil cream.

North America holds the largest percentage of consumers of ED meds followed by Europe and Asia. Since the discovery of PDE-5 inhibitors, there has been a decline in the stigma that was initially associated with erectile dysfunction. Many people have come out to seek treatment. In 2016, for example, more than 2 million prescriptions of sildenafil were dispensed compared to half the number in 2006. The prices of the brand-name pills are very high and unaffordable for many people, but with most of the patents expiring, the influx of generics will no doubt cause a drop in market prices of ED meds. More is still to come in the story of ED medication and who knows, maybe a drug that is superior to PDE-5 inhibitors is in the pipeline.