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This Month's Question:

To optimize treatment for erectile dysfunction (ED), clinicians must weigh several patient-specific factors when deciding which phosphodiesterase type 5 (PDE5) inhibitor to recommend. One such factor is planned versus unplanned intimacy. What information should primary care clinicians (PCCs) communicate to their patients regarding this concept, and how does this apply to the PDE5 inhibitors?

Response by Ridwan Shabsigh, MD, Posted 07/26/06:

PDE5 inhibitors are the first-line pharmacotherapy for ED because they have been shown to be safe, effective, and well tolerated in diverse populations of men and to have markedly improved ED treatment.¹ When determining a treatment strategy for ED, PCCs should include a patient’s lifestyle choices, personal and partner preferences, and psychosocial factors in the decision-making process.^2-4 A couple’s moments of intimacy can be either planned or unplanned, determined by their preferences and life circumstances. A man seeking treatment for ED must be made aware by the PCC of the pharmacologic characteristics of each therapy to be able to select the one that best fits the couple’s intimacy routine and allows them the full benefit of the medication.

The 3 PDE5 inhibitors have different durations of activity and half-lives. The duration of activity and terminal half-life of sildenafil are up to 4 hours.⁵ For vardenafil, the duration of activity is not reported in the package insert; however, the terminal half-life is reported as 4 to 5 hours.⁶ Tadalafil’s terminal half-life is about 17.5 hours, and the duration of activity is up to 36 hours.⁷ A study by Hedelin and Ströberg found that younger men preferred tadalafil and its longer window of opportunity, whereas older men chose the shorter-acting agents.¹ A longer effectiveness period allows for flexibility for couples more likely to have unplanned intimacy, whereas the shorter duration of action may be desired by couples engaging in planned intimacy who know they will require the treatment for a specific period.

For patients treated with tadalafil, the reduced need to schedule intercourse confers freedom from associating sexual activity with taking medication, perhaps removing psychological and behavioral barriers connected with an on-demand regimen and allowing a more desirable and familiar sexual behavior pattern to develop.^8,9 With the pressure of acting within a specific timeframe removed, anxiety is reduced for the patient and his partner, allowing them to focus on other aspects of a satisfying physical relationship besides actual intercourse: affection, intimacy, foreplay, and friendship.¹⁰

On the other hand, agents with shorter durations of action offer alternative benefits. A man who is not concerned about the timing of sexual activity or a couple with a defined sexual script may prefer a shorter duration therapy.¹⁰ Also, men being treated for other chronic conditions may be concerned, as may be their partners, about having a drug active in their system for longer than necessary.¹⁰ However, it is important to mention that no side effects or interactions have been reported that are specifically related to the long duration of action of tadalafil.^10,11 All PDE5 inhibitors are contraindicated with nitrates. If chest pain occurs after sexual activity with PDE5 inhibitors, nitrates can be given 24 hours after sildenafil or vardenafil and 48 hours after tadalafil.¹¹

Several effective medications are available for the management of ED. To optimize treatment outcomes and recommend a PDE5 inhibitor that suits a patient’s lifestyle, the PCC must consider several factors, not the least of which is the planned or unplanned nature of the timing of sexual activity by the patient and his partner.

References

1. Hedelin H, Ströberg P. Treatment for erectile dysfunction based on patient-reported outcomes: to every man the PDE5 inhibitor that he finds superior. Drugs. 2005;65:2245-2251.

2. Dunn ME. Restoration of couple’s intimacy and relationship vital to reestablishing erectile function. J Am Osteopath Assoc. 2004;104(suppl 4)S6-S10.

3. Kuritzky L. Primary care issues in the management of erectile dysfunction. In: Seftel AD, Padma-Nathan H, McMahon CG, Giuliano F, Althof SE, eds. Male and Female Sexual Dysfunction. NewYork, NY: Elsevier; 2004:229-234.

4. Lue TF, Giuliano F, Montorsi F, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med. 2004;1:6-23.
   
   
5. Viagra^® (sildenafil) prescribing information. Pfizer Inc: New York, NY; 2005.

6. Levitra^® (vardenafil) prescribing information. Bayer Pharmaceuticals Corp: West Haven, Conn; 2005.

7. Cialis^® (tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, Ind and Bothell, Wash; 2005.

8. Moncada I, Damber JE, Mirone V, et al. Sexual intercourse attempt patterns with two dosing regimens of tadalafil in men with erectile dysfunction: results from the SURE study in 14 European countries. J Sex Med. 2005;2:668-674.

9. Hatzichristou D, Vardi Y, Papp G, Pushkar D, Basson BR, Kopernicky V. Effect of tadalafil on sexual timing behavior patterns in men with erectile dysfunction: integrated analysis of randomized, placebo controlled trials. J Urol. 2005;174:1356-1359.

10. Dunn ME, Althof SE, Perelman MA. Phosphodiesterase type 5 inhibitors’ extended duration of response as a variable in the treatment of erectile dysfunction [review]. Int J Impot Res. In press.

11. Kostis JB, Jackson G, Rosen R, et al. Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). Am J Cardiol. 2005;96:313-321.