Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Xatral SR (Sanofi-Aventis)
10 mg prolonged-release tablets
Approved indication: benign prostatic hyperplasia
Australian Medicines Handbook section 13.2.1

Alpha1 adrenergic blocking drugs such as prazosin can be used in the treatment of benign prostatic hyperplasia. They work by relaxing the smooth muscle of the bladder and prostate. Prescribers can now consider using alfuzosin as an alternative to prazosin, tamsulosin and terazosin in patients who have symptoms of benign prostatic hyperplasia.

Early studies used 2.5 mg and 5 mg tablets, but the manufacturer is now marketing a 10 mg prolonged-release formulation. The tablet is taken daily after a meal as bioavailability is reduced if it is taken on an empty stomach. The half-life is about nine hours and only slightly increases with age. Most of a dose is metabolised, then excreted in the faeces. As this metabolism involves cytochrome P450 3A4, alfuzosin may interact with inhibitors of this enzyme such as the imidazole antifungals. Hepatic insufficiency is a contraindication.

In the early 1990s, 5 mg sustained-release tablets were studied for three months in 390 men with symptomatic benign prostatic hyperplasia. A twice-daily dose significantly reduced symptom scores and the urine flow rate improved significantly more with alfuzosin than with placebo. The amount of residual urine was also significantly reduced.1

A pooled analysis of three subsequent studies of a 10 mg sustained-release formulation reported results after 12 weeks of treatment. Compared with 482 men given placebo, the 473 who were randomised to receive alfuzosin had a significant improvement in lower urinary tract symptoms. The absolute decrease in the 35-point international prostate symptom score (IPSS) was 4.2 points with placebo and 6 points with alfuzosin. There was also a significant improvement in the urinary peak flow rate.2

In an open-label extension of one of these studies, 310 men took alfuzosin 10 mg for nine months. The improvements in the IPSS and urine flow were maintained.3

Another one of the trials included 158 patients taking 0.4 mg tamsulosin, which is also an alpha1 adrenergic blocker. After 12 weeks their IPSS had reduced by 6.5 points which was identical to the reduction seen in the 154 patients who were randomised to take alfuzosin 10 mg. These changes were significantly greater than the 4.6 point reduction seen in the 153 patients who took placebo.4

When alfuzosin was compared with doxazosin in 210 men, both drugs significantly improved urinary flow rates over 14 weeks. The reduction in the IPSS was significantly greater with doxazosin (9.2 points) than with alfuzosin (7.5 points). The residual volume of urine was also significantly less with doxazosin. However, this trial used the 2.5 mg and 5 mg formulations of alfuzosin and the mean dose was less than 10 mg, which is now the recommended dose.5

Alfuzosin has also been studied as an adjunctive treatment in the management of acute urinary retention. Following catheterisation, 238 men were given daily alfuzosin and 122 were given a placebo. The catheters were removed after two doses and treatment continued for the day after removal. A return to satisfactory micturition was achieved by 61.9% of the alfuzosin group and 47.9% of the placebo group. A group of 165 responders was then randomised to take alfuzosin or a placebo for six months. During this period surgery for prostatic hyperplasia was needed by 17.1% of the alfuzosin group and 24.1% of the placebo group. Approximately 14 men would need to be treated for six months for one to avoid surgery.6

As alpha1 adrenergic blocking drugs cause vasodilation, adverse effects such as postural hypotension may be expected. Patients may complain of dizziness or faintness. Particular caution is required if alfuzosin is prescribed for patients who are taking antihypertensive drugs.

In the pooled analysis 9.5% of patients taking alfuzosin stopped treatment compared with 8.7% of the placebo group. Symptoms associated with vasodilation occurred in 6.6% of elderly patients and 8.3% of those with hypertension.2In a meta-analysis alfuzosin caused significantly more dizziness, hypotension or syncope than placebo.7

Alfuzosin has been available overseas for many years. No specific safety problems have emerged, but there could be a risk of the 'floppy iris syndrome', a complication in cataract surgery, which has been reported with similar drugs such as tamsulosin.

Although alfuzosin has some statistically significant effects, their clinical relevance is less clear. As the IPSS has to change by at least three points to be noticed, the benefit of alfuzosin over placebo is modest. In the pooled analysis, placebo increased the maximum urinary flow by 12.5%, while alfuzosin increased it by 26.1%. However, the absolute increases were 1.1 mL/second and 2.3 mL/second. The difference, of 1.2 mL/second, may not be clinically important.2

A meta-analysis has evaluated the efficacy of all the alpha1 adrenergic blocking drugs used to treat the symptoms of benign prostatic hyperplasia. It found no difference between the drugs. They all improve symptom scores and peak urinary flow.7

Read about The Transparency Score manufacturer provided additional useful information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Note on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).

References

  1. Buzelin JM, Roth S, Geffriaud-Ricouard C, Delauche-Cavallier MC; ALGEBI Study Group. Efficacy and safety of sustained-release alfuzosin 5 mg in patients with benign prostatic hyperplasia. Eur Urol 1997;31:190-8.
  2. Roehrborn CG, van Kerrebroeck P, Nordling J. Safety and efficacy of alfuzosin 10 mg once-daily in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a pooled analysis of three double-blind, placebo-controlled studies. BJU Int 2003;92:257-61.
  3. van Kerrebroeck P, Jardin A, van Cangh P, Laval KU; ALFORTI Study Group. Long-term safety and efficacy of a once-daily formulation of alfuzosin 10 mg in patients with symptomatic benign prostatic hyperplasia: open-label extension study. Eur Urol 2002;41:54-61.
  4. Nordling J. Efficacy and safety of two doses (10 and 15 mg) of alfuzosin or tamsulosin (0.4 mg) once daily for treating symptomatic benign prostatic hyperplasia. BJU Int 2005;95:1006-12.
  5. De Reijke TM, Klarskov P. Comparative efficacy of two α1-adrenoreceptor antagonists, doxazosin and alfuzosin, in patients with lower urinary tract symptoms from benign prostatic enlargement. BJU Int 2004;93:757-62.
  6. McNeill SA, Hargreave TB, Roehrborn CG; ALFAUR Study Group. Alfuzosin 10 mg once daily in the management of acute urinary retention: results of a double-blind placebo-controlled study. Urology 2005;65:83-90.
  7. Nickel JC, Sander S, Moon TD. A meta-analysis of the vascular-related safety profile and efficacy of α-adrenergic blockers for symptoms related to benign prostatic hyperplasia. Int J Clin Pract 2008;62:1547-59.