Pharmacology Update

Tadalafil Tablets for BPH (Cialis)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.

Tadalafil, Eli Lilly’s blockbuster drug for erectile dysfunction, has now been approved to treat signs and symptoms of benign prostatic hyperplasia. Tadalafil is the first drug of its class to be approved for this indication.

Indications

Tadalafil is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), erectile dysfunction (ED), as well as ED and the signs and symptoms of BPH.1

Dosage

The recommended dose for BPH is 5 mg taken at approximately the same time every day. Tadalafil for treatment of ED is dosed at 10 mg taken prior to anticipated sexual activity. The dose may be increased to 20 mg or decreased to 5 mg based on tolerability and effectiveness.1 Tadalafil may also be taken daily for ED at a starting dose of 2.5 mg once daily and increased to 5 mg daily based on efficacy and tolerability. For the combination of BPH and ED the recommended dose is 5 mg daily. The tablets may be taken without regard to meals.

Tadalafil is available as 2.5 mg, 5 mg, 10 mg, and 20 mg tablets.

Potential Advantages

Tadalafil provides a one-drug treatment for patients with BPH and unlike other medications for this indication (alpha blockers and 5-alpha reductase inhibitors), it is not associated with sexual dysfunction. The drug is effective for men with co-morbid ED and BPH. Intraoperative floppy iris syndrome has not been associated with tadalafil.

Potential Disadvantages

Tadalafil has minimal effect on improving maximum urinary flow.1-3 Tadalafil may enhance the effect of drugs with hypotensive effects (e.g., nitrates, antihypertensives, alcohol, alpha adrenergic blockers). Potent inhibitors and inducers of CYP3A4 can affect the levels of tadalafil.1

Comments

Phosphodiesterase-5 inhibitors have been used for ED for more than a decade. In recent years, there has been interest in evaluating the role of these agents in the management of lower urinary tract symptoms due to BPH. The exact mechanism of the effect is not clear but may be related to an increase in cGMP resulting in relaxation of smooth muscle.4 The efficacy and safety of tadalafil 5 mg once daily for the treatment of BPH was studied in three randomized, double-blind, placebo-controlled, 12-week studies.1 Two studies were in men with BPH and one in men with ED and BPH. The primary efficacy endpoint was change from baseline to week 12 of the International Prostate Symptom Score (IPSS). The IPSS is a 7-question, self-administered questionnaire assessing irritative and obstructive symptoms. Scores can range from 0 to 35. Maximum urinary flow rate was a secondary efficacy endpoint. In the first study (n = 410), tadalafil resulted in a decrease of 28% in IPSS score (baseline 17.3) compared to 13% (baseline 17.1; P < 0.001). In the second study (n = 324), reductions were 33% (baseline 17.1) and 22% (baseline 16.6), respectively (P = 0.004). There was no statistical difference in maximum urinary flow in either study. In patients with ED and BPH (n = 399), tadalafil showed a 33% reduction in IPSS (baseline 18.5) compared to 21% reduction (baseline 18.2) for placebo. Similar to the other studies, no significant difference in maximum urinary flow was observed. Tadalafil is well tolerated with only headache reported with a frequency greater than 5%.1 Treatment effect can be seen as early as 1 week and maintained after 1 year.5,6 The drug seems to work in BPH patients with or without ED.2 Compared to alpha adrenergic blockers, phosphodiesterase-5 inhibitors are generally less effective in terms of improvement of IPSS.7-9

Clinical Implications

BPH is a prevalent disease in middle-aged and older men. Current medical intervention recommended by the American Urological Association includes alpha adrenergic blockers, 5-alpha-reductase inhibitors (5-ARIs).7 Both alpha-blockers and 5-ARIs improve symptoms and maximum urinary flow. ED is also prevalent in this age group. Sexual dysfunction (ED, decreased libido, ejaculation disorders) has been reported with 5-ARs and to a lesser degree with alpha-blockers.7 Tadalafil relieves symptoms of BPH and improves ED, but has minimal or no effect on maximum urinary flow, and may be less effective in improving symptom scores.

References

1. Cialis Prescribing Information. Indianapolis, IN: Eli Lilly; October 2011.

2. Broderick GA, et al. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with or without erectile dysfunction. Urology 2010;75:1452-1458.

3. Laydner HK, et al. Phosphodiesterase 5 inhibitors for lower urinary tract symptoms secondary to benign prostatic hyperplasia. BJU Int 2010;107:1104-1109.

4. Rees RW, et al. Y-27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 2003;170:2517-2522.

5. Porst H, et al. Efficacy and safety of tadalafil once daily in the treatment of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Eur Urol 2011;60:1105-1113.

6. Donatucci CF, et al. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. BJU Int 2011;107:1110-1116.

7. Tuncel A, et al. Sildenafil citrate and tamsulosin combination is not superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. World J Urol 2010;28:17-22.

8. Kaplan SA, et al. Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. Eur Urol 2007; 51:1717-1723.

9. Liguori G, et al. Efficacy and safety of combined oral therapy with tadalafil and alfuzosin. J Sex Med 2009;6:544-552.

10. www.auanet.org/content/clinical-practice-guidelines/clinical-guidlines/cfm?sub+bph.