Can doxazosin be taken safely for an extended period of time?

From the Guidelines

Doxazosin can be taken safely for an extended period of time, as evidenced by studies showing its long-term efficacy and safety in managing lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH) 1. When considering long-term use, it's essential to weigh the benefits against potential risks and monitor patients regularly. The study published in The Journal of Urology 1 demonstrated that men treated with a combination of doxazosin and finasteride for up to 5.5 years experienced a mild increase in post-void residual (PVR) volume and a mild decrease in bladder contractility index, with no instances of urinary retention. Key points to consider when prescribing doxazosin for extended periods include:

• Obtaining a PVR measurement before treatment and monitoring it at follow-up appointments 1
• Starting with alpha-blockers alone and adding anticholinergics in selected cases, as combination therapy may increase the risk of drug-related adverse events 1
• Regularly assessing blood pressure, symptoms, and potential side effects during extended treatment
• Being aware of common side effects, such as dizziness, fatigue, headache, or nasal congestion, which may diminish over time as the body adjusts to the medication.

From the FDA Drug Label

2.1 Dosing Information Following the initial dose and with each dose increase of doxazosin tablets, monitor blood pressure for at least 6 hours following administration. If doxazosin tablets administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

13. 1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis and Mutagenesis: Chronic dietary administration (up to 24 months) of doxazosin mesylate at maximally tolerated doses of 40 mg/kg/day in rats and 120 mg/kg/day in mice revealed no evidence of carcinogenic potential
14. 2 Animal Toxicology and Pharmacology An increased incidence of myocardial necrosis or fibrosis was observed in long-term (6 to 12 months) studies in rats and mice (exposure 8 times human AUC exposure in rats and somewhat equivalent to human C max exposure in mice).

Long-term safety of doxazosin has been evaluated in animal studies, which showed no evidence of carcinogenic potential 2 and 3. However, an increased incidence of myocardial necrosis or fibrosis was observed in long-term studies in rats and mice.

• The clinical significance of these findings is unclear.
• No conclusion can be drawn regarding the long-term safety of doxazosin in humans based on the available data.
• Caution should be exercised when prescribing doxazosin for extended periods.

From the Research

Safety of Long-Term Doxazosin Use

• Doxazosin has been shown to be safe for long-term use in treating benign prostatic hyperplasia (BPH) and hypertension 4, 5, 6, 7.
• A study published in 1997 found that doxazosin was well tolerated with almost 90% of adverse experiences considered mild or moderate in severity, and the most common adverse events were dizziness, headache, and fatigue in normotensive and hypertensive patients 4.
• Another study published in 1996 noted that doxazosin improves urinary flow rates and symptoms in patients with BPH, and its effects have been demonstrated in controlled clinical studies, both within weeks and long-term 5.
• A 2004 study found that doxazosin mesylate is an alpha1-adrenoceptor antagonist that is beneficial in BPH, and its main side effects are those commonly associated with lowering blood pressure, although it lowers blood pressure to a lesser extent in normotensives than hypertensives 8.
• The Hypertension and BPH Intervention Trial (HABIT) published in 1999 found that doxazosin is an effective antihypertensive agent when used in combination with agents from other antihypertensive classes in patients with poorly controlled hypertension and BPH, and is also successful as monotherapy for controlling both BPH and hypertension in patients with mild to moderate hypertension 7.

Efficacy of Doxazosin for BPH and Hypertension

• Doxazosin has been shown to be effective in treating BPH, with significant increases in maximum and average urinary flow rates, and improvements in total, obstructive, and irritative BPH symptoms 4, 5, 6, 7.
• The drug has also been found to be effective in treating hypertension, with sustained blood pressure decreases in hypertensive patients, and is well tolerated in normotensive patients with few withdrawals from the study due to decreased blood pressure or hypotension 4, 7.
• Doxazosin has been used successfully in combination with other antihypertensive agents, including beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors, in patients with hypertension that is uncontrolled with monotherapy 6, 7.