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Doxazosin: Experience-sharing interview with Professor Anthony Chi-Fai Ng

Professor Anthony Chi-Fai Ng
Professor, Department of Surgery, Director, S.H. Ho Urology Centre,
Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
8 months ago
1.    Where is doxazosin positioned in your treatment algorithm?

Doxazosin is a first-line treatment for men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), starting at 4 mg once daily in an gastrointestinal therapeutic system (GITS) formulation.1-3 If a response is not achieved, the dose can be uptitrated to 8 mg once daily.3

The stable haemodynamic effect of doxazosin GITS means it may also be considered for patients treated with multiple drug therapies, or who have hypertension or other conditions in which blood pressure is a concern.4

2.    In your clinical experience, how effective is doxazosin for your patients with BPH-LUTS, compared with other agents?

A recent meta-analysis found α-adrenoreceptor antagonists to be “highly effective” in patients with LUTS secondary to BPH, and doxazosin to be more effective than all other monotherapies,5 with a response being observed after one or two doses and a full therapeutic effect occurring within 1 to 2 weeks.1,6

Importantly, the broad-spectrum inhibition of doxazosin across α-1a, -1b and -1d adrenoreceptors may help improve BPH-LUTS by relieving both the voiding and irritative symptoms associated with BPH, including nocturia.1,7-9 Doxazosin also has a rapid onset of action with significant improvements in International Prostate Symptom Score (IPSS) occurring within 3 days versus placebo.10 Of particular note is that the obstructive (voiding)  and irritative (including nocturia) IPSS subscores improved after 3 and 7 days of doxazosin treatment, respectively, and the efficacy of doxazosin in reducing nocturia is maintained for at least 4 years.10,11 

When compared with tamsulosin, doxazosin GITS also further reduces patients’ IPSS, with significant improvements in IPSS obstructive subscores observed from Week 1 of treatment, and significantly better irritative subscores reported by Week 12 (Figure 1).12 However, improvements in irritative subscores with doxazosin versus tamsulosin have been reported as early as Week 4 in Chinese patients.13

HK-PFR-496a3i-HK-fig1

3.   What are the differences between the GITS formulation of doxazosin and the conventional formulation?

Both immediate-release (IR) and GITS doxazosin formulations have a half-life of 22 hours, but the IR formulation has a faster time to onset of action, with maximum serum concentrations being reached within 2 hours compared with 8–9 hours for the GITS formulation (Figure 2).3,14,15 

HK-PFR-496a3i-MY-fig2

The core of a doxazosin GITS tablet comprises a polymer surrounded by active drug. As fluid from the gastrointestinal tract diffuses into the tablet, the expanding polymer pushes against the drug layer, slowly releasing doxazosin through a small opening in the tablet membrane.3,9,15 Constant controlled release of the active drug minimizes the risk of fluctuations in serum drug concentrations and associated adverse effects, such as first-dose postural hypotension.4,9,16 This facilitates a higher starting dose of 4 mg doxazosin, and the reduced risk of hypotension allows dosing during the day instead of at night.3,4,9,16

4.   What is the safety profile of doxazosin in your patients?

Doxazosin GITS is well tolerated, with few side effects resulting in discontinuation; dizziness and postural hypotension appear to be less common than with the IR formulation.3,9,14,16

With regard to sexual function in patients with BPH, erectile dysfunction may be related to background medical conditions, such as metabolic syndrome, atherosclerosis or an enlarged prostate, which appear to be interlinked.17 However, doxazosin does not negatively affect sexual function in patients with BPH and erectile dysfunction.3,6,9,14,16

5.   Can doxazosin be combined with other medications commonly prescribed for patients with BPH?

Doxazosin can be co-administered with anticholinergic agents in patients with concomitant BPH and overactive bladder.1,2,3,14

A clinical study evaluating doxazosin GITS administered concomitantly with a phosphodiesterase-5 (PDE-5) inhibitor for patients with concomitant erectile dysfunction and BPH showed no cases of symptomatic hypotension or other clinically significant cardiovascular adverse events.18 Following the addition of a PDE-5 inhibitor to doxazosin GITS, the majority of new adverse events related to flushing and headaches that were mild and did not warrant further medical treatment.18 However, caution is advised when administering doxazosin with PDE-5 inhibitors (eg, sildenafil, tadalafil and vardenafil) as both drugs have vasodilating effects and may lead to symptomatic hypotension in some patients.3

6.   Do you have any advice or tips for urologists prescribing doxazosin?

Doxazosin GITS has a rapid onset of action, is effective in LUTS secondary to BPH and is well tolerated.5,9,16

It is important to remind patients that the doxazosin GITS tablet should be swallowed whole and, as the tablet’s outer coating is not absorbed, allay any patient concerns if they notice the tablet outer in their stool.3


References:

1. Gravas S, et al. Guidelines on the management of non-neurogenic male lower urinary tract symptoms (LUTS), including benign prostatic obstruction (BPO). Available at: https://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/. Accessed 29 June 2016. 
2. McVary K, et al. American Urological Association guideline: Management of benign prostatic hyperplasia (BPH). Available at: https://www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm. Accessed 29 June 2016. 
3. Cardura XL. Prescribing information. Available at http://www.mims.com/hongkong/drug/info/cardura%20xl/?type=full. Accessed 21 July 2016. 
4. Steers WD, Kirby RS. Prostate Cancer Prostatic Dis 2005;8:152–157. 
5. Yuan JQ, et al. Medicine 2015;94:e974. 
6. Oelke M, et al. Eur Urology 2013;64:118–140. 
7. Lepor H. Rev Urol 2007;9:181–190. 
8. Schwinn DA, Roehrborn CG. Int J Urol 2008;15:193–199. 
9. Fitzpatrick JM, Desgrandchamps F. BJU Int 2005;95:575–579. 
10. Roehrborn C, et al. Eur Urol 2005;48:445–452. 
11. Johnson T, et al. J Urol 2007;178:2045–2051. 
12. Chung MS, et al. Int J Clin Pract 2011;65:1193–1199. 
13. Zhang K, et al. Urology 2011;78:636–640. 
14. Cardura. Prescribing information. Available at http://www.mims.com/hongkong/drug/info/cardura/?type=brief. Accessed 21 July 2016.
15. Chung M, et al. Br J Clin Pharmacol 1999;48:678–687. 
16. Kirby RS, et al. BJU Int 2001;87:192–200. 
17. Selvin E, et al. Am J Med 2007;120:151–157. 
18. Ng CF, et al. J Urol 2008;180:1042–1068.

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