There are many medications that are contraindicated with the use of PDE5 inhibitors. Sildenafil and tadalafil are the most commonly prescribed treatments for ED and they generally should not be combined. One drug that has been studied in combination with PDE5 inhibitors is apomorphine. On its own, apomorphine has been shown to be more effective than a placebo at treating erectile dysfunction. For some men, a treatment with just sildenafil or tadalafil does not produce the desired effects. A combination treatment can be made by a compounding pharmacy that includes both apomorphine and tadalafil, for example, that may provide some benefit for these patients.
What is Apomorphine?
Despite the name, apomorphine is not actually a form of morphine or an opiate. The name provides a kind of marketing dilemma but not an actual dilemma for patients. There is no addictive potential and no recreational use of the drug besides its ability to improve sexual activity. It does not bind to opioid receptors. Apomorphine is a non-selective dopamine agonist that works differently than PDE5 inhibitors by working on the central nervous system instead of the vascular system of the penis.
An analog of apomorphine is found naturally occurring in the blue lotus and it is possible ancient Egyptians were aware of its ability to promote erections. It was first synthesized in 1845 and used in farm animals, then the late 1800s it was used to treat alcoholism by reducing alcoholic cravings and symptoms of alcohol abuse (like “the shakes”). Apomorphine is now FDA approved (as Apokyn) to treat loss of body movement control in patients with Parkinson’s disease. This is in the form of an injection however not a troche. Oral dosages of apomorphine have a low bioavailability as there is significant first-pass metabolism.
Generally doses of 2mg or 3mg apomorphine are well tolerated, although higher doses may produce more adverse effects. The 4mg dose provides similar effects to the 3mg dose – and the 3mg dose produces less side effects. Clinical trials have shown that apomorphine is more effective than placebo in treating erectile dysfunction, except in patients who have had radical prostatectomy. Generally the effects of apomorphine are relatively fast – with erections occurring around 18-19 minutes for 2/3 men after taking a sublingual dosage form. Nausea is the most common side effect although with regular usage this side effect tends to dissipate.
PDE5 Inhibitors vs. Apomorphine
Apomorphine works directly in the brain – stimulating nerves that trigger the relaxation of smooth muscle in the corpus cavernosum. PDE5 inhibitors block PDE5, which is an enzyme found in the walls of blood vessels, which causes blood vessels to relax. This effectively increases blood flow to the penis to improve erections. There are additional pharmacokinetic differences between the PDE5 inhibitors – tadalafil, sildenafil, and vardenafil. Combining PDE5 inhibitors or PDE5 inhibitors with nitrates is almost always contraindicated. However apomorphine works in a different way than these medications and allows them to be used together without the significant increase in adverse effects.
Compounded ED Combination
National Pharmacy compounds a combination troche for buccal administration that includes apomorphine and tadalafil. This combination of erectile dysfunction drugs can only be made by a compounding pharmacy.
Articles
Apomorphine for the Treatment of Erectile Dysfunction: Systematic Review and Meta-Analysis – Archives of Sexual Behavior
The evaluation of apomorphine for the treatment of erectile dysfunction – Expert Opinion on Drug Metabolism and Toxicology