Every erection drug that got pulled, ranked by how bad the idea was

What it was

Alprostadil, the same prostaglandin used in injections and in MUSE, formulated as a topical gel or cream with a chemical absorption enhancer to carry it through skin. MacroChem's version was Topiglan; NexMed, later Apricus, built Vitaros.

Why it was sold

The pitch was obvious and honest: alprostadil works, needles are the reason men quit it, so put it in a cream. The market for a needle-free alprostadil is every man who was ever offered penile injections and said no.

Why it was pulled

Topiglan reached Phase III around 2000, hit potency and consistency problems, and quietly disappeared after MacroChem was acquired. Vitaros was rejected by the FDA in 2008 over a carcinogenicity signal from its absorption enhancer in a mouse study, was approved in Europe in 2013, then received a second FDA complete response letter in February 2018 citing safety and manufacturing deficiencies. It is still sold in the UK and parts of Europe. It never reached the United States.

What we learned

A good idea can lose on the excipient. The enhancer that made the cream work was the thing the regulator could not clear, and nobody lied about anything. This is the bottom of the list because it is barely a bad idea at all.

What it was

A dopamine agonist dissolved under the tongue, marketed by Abbott as Uprima and by Takeda as Ixense. A central lever on arousal rather than peripheral hydraulics. We covered the pharmacology and its compounded revival in the apomorphine troches piece.

Why it was sold

It was the first serious oral competitor to sildenafil, it worked through a different mechanism, and in more than 5,000 trial participants the 3 mg dose produced erections firm enough for intercourse in 49.4% of attempts against a 24.3% baseline. That is a real effect, honestly measured.

Why it was pulled

Fainting. Public Citizen's June 2000 letter to the FDA counted roughly one man in thirty with syncope or hypotension at the 4 mg dose, including one who lost consciousness while driving. An FDA advisory committee had voted 9 to 3 that the benefit outweighed the risk; TAP withdrew the US application anyway. Europe approved it in May 2001, and the marketing authorisation was allowed to expire in May 2006, in the EMA's words for commercial reasons. Modest efficacy plus nausea is not a business against Viagra.

What we learned

Uprima did everything right and still lost, which is the point. The trials were real, the numbers were published, the side effect was disclosed, and the market delivered the verdict. Read the apomorphine troches piece for what happened when the same molecule came back without the trials.

What it was

Nastech Pharmaceutical's intranasal apomorphine spray, developed in the early 2000s for erectile dysfunction and female sexual dysfunction, meant to deliver the drug faster and with less nausea than the sublingual tablet.

Why it was sold

Uprima had proved the mechanism and demonstrated the problem. A spray that hit faster and avoided the fainting would have owned the niche. Pharmacia licensed it in 2002, then handed it back in 2003 to satisfy antitrust concerns from the Pfizer merger. A company selling Viagra could not also own Viagra's rival.

Why it was pulled

It was never pulled because it never launched. Nastech's 2004 Phase II maximum-tolerated-dose study reported no fainting across roughly 700 doses and nausea under 2% at the lower doses, then the program went to the FDA for guidance and simply faded from the company's filings. No Phase III, no approval, no product.

What we learned

A better delivery route does not fix a modest drug. The nose solved apomorphine's tolerability problem and left its efficacy problem exactly where it was, and nobody was going to fund a Phase III against a pill that already worked better.

What it was

A smooth-muscle relaxant, originally an opium-poppy alkaloid, injected directly into the corpus cavernosum. Ronald Virag reported it in 1982, and for the rest of that decade it was the intracavernosal drug, often mixed with phentolamine. Papaverine is still one of the three ingredients in compounded trimix.

Why it was sold

Because it worked, and nothing else did. Before 1982 the options were implants or nothing. A drug that produced a reliable erection on demand in men with vascular disease was a genuine revolution, and every injection program since descends from it.

Why it was pulled

Nobody banned it; alprostadil replaced it. The harm was documented in the follow-up. A 1990 Cleveland Clinic series of 100 men on papaverine with or without phentolamine found a fibrotic complication rate of 31% at twelve months, correlated with the number of injections. Priapism after a diagnostic papaverine dose ran 2.7% in a 672-man series and 5% in a 495-man series. When intracavernosal alprostadil arrived, a 1996 review put its priapism and fibrosis rates at 4% and 8%, and the field moved.

What we learned

First-generation drugs pay the tuition. Papaverine's fibrosis and priapism numbers are why modern injection programs monitor, why alprostadil became the base, and why the four-hour rule is printed on every handout. The idea was excellent. The molecule was wrong.

What it was

Phentolamine, an alpha-blocker approved decades earlier for blood-pressure crises in pheochromocytoma, reformulated by Zonagen as a fast-dissolving oral tablet for mild-to-moderate erectile dysfunction, with Schering-Plough as the worldwide marketing partner from 1997.

Why it was sold

Phentolamine already worked as an injectable ingredient, it was an old molecule with a known safety file, and an oral version could reach market fast. Schering-Plough launched it in Latin America while the FDA was still reviewing the US application.

Why it was pulled

In August 1999 the FDA put Zonagen's phentolamine trials on clinical hold after a two-year rat study showed male rats on long-term daily doses developing abnormal proliferation of brown fat tissue. Zonagen's shares fell 32.5% in a day. The hold was lifted in 2000, the FDA asked for new studies, and the product never got a US approval. Its efficacy in the published trials was, in the review literature's own word, modest.

What we learned

An old drug is not a free pass. The same oral phentolamine had been marketed in the US from 1952 to 1984 for other indications with a history of hypotension and severe diarrhea, and the long-term animal toxicology had simply never been done for daily use in healthy men. Vasomax was sold across two borders before that question was answered, which is why it sits above the honest failures.

What it was

An alpha-2 antagonist from the bark of the West African yohimbe tree, used for erectile dysfunction since the 1800s and sold in the US for decades as a prescription tablet under names like Yocon, without ever holding an FDA approval for that use.

Why it was sold

It predates the rules. Yohimbine was on the market before anyone required proof, and once sildenafil arrived in 1998 nobody was going to fund the trials for an unpatentable century-old alkaloid. Alvaro Morales's 2000 review put it plainly: meta-analyses of the few small trials favour it over placebo, and properly designed human studies have never been done.

Why it was pulled

In two directions. In 1989 the FDA's over-the-counter aphrodisiac rule listed yohimbine and yohimbine hydrochloride by name among ingredients that cannot be generally recognized as safe and effective, and made non-compliant OTC products subject to regulatory action after January 1990. The prescription tablets lingered as unapproved drugs. Yohimbe bark then re-entered through the supplement door, where NIH's complementary-medicine center notes a 2015 analysis found most products do not state their yohimbine content, the amounts vary widely, and the compound is linked to arrhythmia, blood-pressure problems, heart attacks, and seizures.

What we learned

No trial means no dose, no interaction data, and no way to know what is in the bottle. Yohimbine may even work a little; we will probably never find out, and it has been sold to men on that uncertainty for a hundred years. That is a bad idea that got grandfathered in.

What it was

An herbal capsule marketed by Biotab Nutraceuticals with a celebrity spokesman and a promise, repeated in every ad, that it would make a man larger.

Why it was sold

Because the claim is unfalsifiable at the point of sale and the category was unregulated. As a dietary supplement it needed no trial, and the enlargement promise reaches a customer who is embarrassed to ask anyone whether it is true.

Why it was pulled

Twice by the same prosecutor. In 2006 the Orange County District Attorney obtained a $300,000 settlement against Biotab's principals over the enlargement claims, with an injunction against repeating them. In July 2011 the same office obtained $1.75 million, at the time the largest settlement in the county's history for violating a prior injunction, for continuing to make the claim without substantiation, charging customers for unordered product, failing to process refunds, and selling lots that exceeded California's lead limit without a Proposition 65 warning.

What we learned

There is no oral pill that increases penile size, and there has never been one. A product that says otherwise is telling you what it thinks of you. The lead was a bonus. Our enhancement piece covers what the evidence actually supports.

What it was

Berkeley Premium Nutraceuticals' "once-daily tablet for natural male enhancement," sold nationally from 2001 with the grinning Smilin' Bob television character, fabricated customer-satisfaction surveys reporting 96% approval, and physicians credited with the formula who did not exist.

Why it was sold

The same customer as ExtenZe, reached at far greater scale, with a business model built on a free trial that silently enrolled buyers in recurring credit-card charges. The product barely mattered. The billing did.

Why it was pulled

By a federal jury. In February 2008 founder Steven Warshak was convicted on 93 counts including conspiracy, mail fraud, bank fraud, and money laundering; the indictment described roughly $100 million taken from consumers and banks through the auto-ship scheme and deliberate double-charging to manipulate refund statistics. He was sentenced to 25 years, later reduced to 10, and the Department of Justice eventually returned about $24 million in forfeited funds to more than 138,000 victims.

What we learned

When the ad has a fake doctor, the science was never the product. Enzyte is the template for every subscription supplement funnel that followed it, and the reason we read the cancellation terms before we read the ingredient list.

What it was

Hundreds of products, mostly capsules sold at convenience stores, gas stations, and online marketplaces under names like Gold Rhino 25000, Black Rhino, Rhino 7, and countless others, labelled as herbal and found on FDA laboratory analysis to contain undeclared sildenafil, tadalafil, or chemical analogs of them such as sulfoaildenafil and dimethylsildenafil.

Why it was sold

Because the drug works and the label lies. A capsule with real PDE5 inhibitor in it produces a real effect, which generates real word of mouth for a product that never has to disclose what it contains, pass a manufacturing inspection, or warn anyone about nitrates.

Why it was pulled

Continuously, and never entirely. The FDA's public list of tainted sexual-enhancement and energy products runs to more than four hundred notifications since 2012, and the agency states the list covers only a small fraction of what is on the market. In November 2018 it issued a blanket warning against Rhino-branded products after identifying more than 25 variants with hidden drugs since 2007, citing reports of chest pain, severe headaches, and prolonged erections that ended in surgery and hospitalisation for dangerous blood-pressure drops.

What we learned

This is the worst idea on the list because it combines every failure above it: no trial, real pharmacological harm, and a label that is a lie by design. The analogs are the tell. Sulfoaildenafil exists for one reason, to be a sildenafil that a basic sildenafil test does not catch. The men hurt by these products were not reckless; most did not know they were taking a drug at all.