Does Alfuzosin (generic name) exacerbate Impaired renal function?

From the Guidelines

Alfuzosin does not exacerbate impaired renal function, and its use is considered safe in patients with varying degrees of kidney function, including those with mild to moderate kidney impairment, without requiring dose adjustments. This medication is an alpha-blocker primarily used to treat benign prostatic hyperplasia (BPH) by relaxing muscles in the prostate and bladder neck, which improves urinary flow. According to the American Urological Association (AUA) guideline on management of BPH 1, alfuzosin is one of the appropriate treatment options for patients with lower urinary tract symptoms (LUTS) secondary to BPH. The guideline notes that alpha-blocker therapy, including alfuzosin, is based on the hypothesis that clinical BPH is partly caused by alpha1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction.

Some key points to consider when using alfuzosin in patients with impaired renal function include:

• Alfuzosin is primarily metabolized by the liver rather than excreted by the kidneys, which explains why it has minimal impact on kidney function 1.
• For patients with severe kidney impairment (creatinine clearance below 30 mL/min), caution is advised, but the medication is not contraindicated.
• By improving urinary flow in men with BPH, alfuzosin may indirectly benefit kidney health by reducing urinary retention and the risk of urinary tract infections or kidney damage from back pressure.
• As with any medication, patients should report any unusual symptoms to their healthcare provider, but kidney deterioration is not a known or common side effect of alfuzosin therapy.

It is essential to note that the AUA guideline 1 emphasizes the importance of considering the individual patient's overall health status, including concomitant hypertension, when selecting an alpha-blocker for the treatment of LUTS secondary to BPH. However, in terms of renal function, alfuzosin is not known to exacerbate impaired renal function, and its use can be considered safe in patients with varying degrees of kidney function.

From the FDA Drug Label

The Pharmacokinetic profiles of UROXATRAL 10 mg tablets in subjects with normal renal function (CLCR>80 mL/min), mild impairment (CLCR 60 to 80 mL/min), moderate impairment (CLCR 30 to 59 mL/min), and severe impairment (CLCR less than 30 mL/min) were compared. Relative to subjects with normal renal function, the mean Cmax and AUC values were increased by approximately 50% in patients with mild, moderate, or severe renal impairment [see Warnings and Precautions (5.2) and Use in Specific Populations (8. 6)].

Alfuzosin and Renal Impairment: The FDA drug label indicates that alfuzosin is not directly contraindicated in patients with renal impairment. However, the pharmacokinetic profiles show that the mean Cmax and AUC values were increased by approximately 50% in patients with mild, moderate, or severe renal impairment.

• This suggests that alfuzosin may accumulate to higher levels in patients with impaired renal function, which could potentially increase the risk of adverse effects.
• However, the label does not explicitly state that alfuzosin exacerbates impaired renal function.
• Therefore, caution should be exercised when administering alfuzosin to patients with renal impairment, and patients should be monitored for potential adverse effects 2.

From the Research

Alfuzosin and Impaired Renal Function

• The effect of renal impairment on the safety and pharmacokinetics of alfuzosin was evaluated in a study published in the Journal of Clinical Pharmacology 3.
• The study found that mean Cmax values increased by a factor of 1.20,1.52, and 1.20 in subjects with mild, moderate, or severe renal impairment, respectively, compared with controls.
• Values for AUC(0-infinity) were 1.46,1.47, and 1.44, respectively, indicating that alfuzosin could be safely administered to patients with impaired renal function, and dosage adjustment does not seem necessary 3.
• Another study published in the Journal of Human Hypertension found that the pharmacokinetics of doxazosin, a similar medication, are similar in patients with normal and impaired renal function, and that doxazosin can be used effectively in both at similar doses 4.
• However, it is noted that renal blood flow is well preserved during long-term treatment with doxazosin, but effects on glomerular filtration rates are less consistent and small reductions may occur 4.
• A review of the therapeutic use of alfuzosin in the management of benign prostatic hyperplasia found that alfuzosin is well tolerated and effective in controlling symptoms associated with BPH, with no dosage titration required 5.
• The use of antihypertensive agents, including alfuzosin, in patients with renal insufficiency necessitates careful consideration of dosages, titration, and monitoring, as renal function must be estimated to appropriately make dosage adjustments 6.
• A study published in Clinical Interventions in Aging found that alfuzosin 10 mg once daily is a well-tolerated and effective treatment option for aging men with LUTS/BPH, with minimal vasodilatory and sexual function side effects, even in those with comorbidities 7.