Apomorphine for ED Results in Clinical Trials

Apomorphine for ED is a dopamine agonist that dissolves under the tongue and supports erections through the brain and spinal cord.^1,2 In nine placebo-controlled trials, it produced 6% to 27% more successful intercourse attempts than placebo.³ Head to head, sildenafil outperformed it on every measure.⁴ Sublingual apomorphine was approved for marketing in Europe,¹ while FDA-approved US apomorphine labels cover Parkinson's disease.⁵ If a PDE5 inhibitor does not suit you, your physician can weigh a compounded sublingual apomorphine as an option.

A Central Pathway to an Erection

Apomorphine activates dopamine D1 and D2 receptors.¹ Animal research supports a central site of action for its effect on erections, in the brain and also the spinal cord.² That made sublingual apomorphine (Uprima) the first ED drug acting on the central nervous system.²

Giuliano F et al. reported that apomorphine did not change sexual desire in clinical use, which they noted is a point to watch with any drug acting in the brain.² Apomorphine is aimed at the erection response. It is not a libido treatment, and low desire needs its own workup.

The Contrast With PDE5 Inhibitors

PDE5 inhibitors such as sildenafil and tadalafil act peripherally, outside the brain, which is the contrast Giuliano F et al. draw.² The PDE5 inhibitor page explains that mechanism, and sildenafil vs tadalafil compares the two most prescribed options. Your physician considers apomorphine mainly when that class does not fit you.^3,6 The sildenafil and tadalafil guides cover each tablet on its own.

Apomorphine for ED in Clinical Trials

The trial record gives you a real effect over placebo that is smaller than the effect of PDE5 inhibitors. It also shows weaker results in men with diabetes, after prostate surgery and with established vascular damage.

Results Against Placebo

Guillén V et al. pooled nine randomized controlled trials lasting 4 to 8 weeks.³ Every study found apomorphine better than placebo, with 6% to 27% more successful intercourse attempts. The one exception to statistical significance was a study of men who had undergone radical prostatectomy.³

A large single trial, by Dula E et al., randomized 569 men for 8 weeks.⁷ An erection firm enough for intercourse occurred in 48% to 53% of men on apomorphine, compared with 35% on placebo.⁷ That 35% placebo rate is worth keeping in mind when you read any ED drug's success figure.

Results Against Sildenafil

Eardley I et al. ran an open-label crossover trial in 139 men with ED who had never been treated.⁴ Each man used sildenafil for 8 weeks and apomorphine for 8 weeks. Successful intercourse rates were 75% on sildenafil and 35% on apomorphine.⁴ At the end, 96% of the men preferred sildenafil, and the authors found it superior on every measured endpoint.⁴

The open-label design is a limitation, because the men knew which drug they were taking. The gap was still large. Mohee A et al. reached the same conclusion: apomorphine is less effective than PDE5 inhibitors and is not a first-line option.⁶

Results in Diabetes and After Prostate Surgery

In trials limited to men with diabetes or men after radical prostatectomy, differences from placebo on erectile function scores were not clinically relevant.³ Briganti A et al. also reported a poor response in older men with several vascular risk factors and established vascular damage.¹ If your ED has a strong vascular or nerve component, your physician will likely look at other treatments first.

Regulatory Status in Europe and the US

Sublingual apomorphine was approved for marketing in Europe for ED.¹ By 2012, Mohee A et al. described it as no longer widely available in the Western world.⁶

In the US, FDA-approved apomorphine is labeled only for Parkinson's disease. APOKYN, for example, is an injection indicated for "off" episodes in advanced Parkinson's disease.⁵ No US apomorphine label lists ED, so a sublingual apomorphine prescribed for ED is a compounded, pharmacy-prepared form with no FDA-approved label of its own.¹¹ If your prescriber suggests it, you can ask what preparation it is, which pharmacy makes it and why it fits your case better than a labeled ED drug.

Side Effects and Drug Interactions

Across clinical studies of more than 5,000 patients, the most common side effects of sublingual apomorphine were nausea, headache and dizziness, each in under 7% of patients.⁸ In the Dula trial, nausea depended on dose and eased substantially in the second month.⁷ Stopping treatment because of side effects was more common on apomorphine than placebo, especially at higher doses.³

Fainting (syncope) was rare at the doses licensed in Europe, under 0.2%, and can occur at higher doses.⁸ The APOKYN label, written for injection in Parkinson's disease, lists syncope, low blood pressure, falling asleep during daily activities and QTc prolongation among its warnings.⁵ It also warns of priapism, and 3 of 361 APOKYN-treated men reported painful erections in its clinical studies.⁵

Nitrates and Blood Pressure Medicines

Guillén V et al. describe sublingual apomorphine as the only licensed oral ED drug not absolutely contraindicated with nitrates.³ That does not make the combination free of risk. In a trial of 162 men on blood pressure medicines or nitrates, using a higher-than-recommended apomorphine dose, apomorphine after long-acting nitrates lowered standing blood pressure. Men on alpha-blockers and calcium channel blockers had larger drops in standing systolic pressure, and two men in each nitrate group had symptomatic low blood pressure.⁹ If you take nitrates or blood pressure medicines, your physician needs that full list before any ED prescription.

Anti-Nausea Drugs in the 5HT3 Class

The APOKYN label, written for injection in Parkinson's disease, contraindicates APOKYN with 5HT3 antagonist anti-nausea drugs, such as ondansetron, granisetron, dolasetron and palonosetron, and with alosetron.⁵ It reports very low blood pressure and loss of consciousness when APOKYN was given with ondansetron.⁵ Sublingual apomorphine is the same molecule, so your physician applies that caution to any apomorphine prescription. Because nausea is apomorphine's most common side effect, tell your physician and pharmacist about any anti-nausea medicine before you take apomorphine.

Where Apomorphine Fits in an ED Plan

Apomorphine has a defined niche. Guillén V et al. describe it as an option for men who cannot take PDE5 inhibitors, such as men using nitrates.³ Mohee A et al. place it with men who did not respond to, or could not tolerate, other established ED drugs.⁶ Your physician may weigh these points with you:

• The cause of your ED. Vascular, hormonal, medication-related and psychological causes each point to different treatments. Erectile dysfunction causes and psychological ED cover the workup.
• Your PDE5 history. Whether you have tried a PDE5 inhibitor, and why it did not work, shapes the next step.
• Your medication list. Nitrates, blood pressure medicines and anti-nausea drugs change the safety picture.^5,9
• Your cardiovascular health. ED with vascular risk factors responded poorly to apomorphine in older men.¹
• Other options. PT-141 has its own evidence page if your physician raises it.

The dose and schedule are set by your prescriber. If apomorphine does not produce the agreed result, your plan changes.

The Opt Take on Apomorphine for ED

ED is a symptom with several possible causes, and the drug choice follows from which cause is yours. Blood vessels, hormones, medications, sleep and stress can all contribute. A failed PDE5 trial is one data point. Your labs, history and medication list together show the pattern behind it.

At Opt Health, you start with a panel of 55+ biomarkers and a 1:1 review with an Opt Health physician, who reviews your existing conditions and current medications. Your plan is built from those results and can include prescriptions shipped from our pharmacy to your home. Full labs and a physician consultation repeat every 3 to 4 months, so your plan is adjusted on what changed.

Get started: Begin with Opt Health, where a physician reads your labs, builds your plan, and adjusts it over the loop.

Frequently Asked Questions

This content is for informational purposes and does not replace evaluation, diagnosis, or treatment by a qualified medical professional.