What are the side effects of Doxazosin (alpha-1 adrenergic blocker)?

Doxazosin Side Effects

Doxazosin causes orthostatic hypotension and dizziness as its most common side effects, with significant concerns for increased heart failure risk and weight gain, making it unsuitable as a first-line antihypertensive agent. 1

Cardiovascular Side Effects

Orthostatic Hypotension and Syncope

• Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours of administration, though symptomatic episodes can occur later than a few hours after dosing 2
• Syncope risk exists, particularly after the initial dose or after dosage increases 2
• Orthostatic hypotension occurs frequently enough that alpha-1 blockers like doxazosin are specifically noted as being "associated with orthostatic hypotension, especially in older adults" 1
• Concomitant use with PDE-5 inhibitors results in additive blood pressure lowering and symptomatic hypotension 2

Heart Failure Risk

• In the ALLHAT trial, doxazosin was associated with a significantly increased risk for congestive heart failure compared with chlorthalidone, with a doubling of heart failure risk 1
• This finding led to doxazosin being discontinued as a first-line agent in that major trial 1
• Alpha-adrenergic blockers such as doxazosin should be avoided in patients with heart failure and might be used only if other drugs are inadequate to achieve blood pressure control at maximum tolerated doses 1

Weight Gain and Fluid Retention

• Doxazosin was associated with significant weight gain, likely secondary to extracellular fluid volume expansion 1
• Edema occurs in 2.7% of BPH patients (vs 0.7% placebo) and appears to be dose-related 2
• Asthenia associated with alpha-blockers as a class might contribute to weight gain by altering energy balance 1

Neurological Side Effects

Common Central Nervous System Effects

• Dizziness is the most frequent side effect, occurring in 15.6% of BPH patients (vs 9.0% placebo) and 19% of hypertensive patients (vs 9% placebo) 2
• Somnolence occurs in 3.0% of BPH patients (vs 1.0% placebo) and 5% of hypertensive patients (vs 1% placebo) 2
• Headache is commonly reported across clinical trials 2, 3
• Fatigue/malaise affects 8.0% of BPH patients (vs 1.7% placebo) and 12% of hypertensive patients (vs 6% placebo) 2

Additional Neurological Effects

• Hypoesthesia has been reported in post-marketing surveillance 2
• Vertigo is noted as a plausible adverse reaction in both BPH and hypertensive populations 2

Respiratory Side Effects

• Dyspnea occurs in 2.6% of BPH patients (vs 0.3% placebo) 2
• Rhinitis affects 3% of hypertensive patients (vs 1% placebo) 2
• Epistaxis has been reported as plausibly related to doxazosin use 2
• Bronchospasm aggravation has been identified in post-marketing experience 2

Ophthalmologic Side Effects

Intraoperative Floppy Iris Syndrome (IFIS)

• IFIS has been observed during cataract surgery in patients on or previously treated with alpha-1 blockers 2
• This syndrome is characterized by: a flaccid iris that billows with intraoperative irrigation, progressive intraoperative miosis despite preoperative dilation, and potential iris prolapse toward phacoemulsification incisions 2
• There is no apparent benefit to stopping alpha-1 blocker therapy prior to cataract surgery, but surgeons should be prepared for surgical modifications 2

Genitourinary Side Effects

• Polyuria occurs in 2% of hypertensive patients (vs 0% placebo) 2
• Hematuria, micturition disorder, micturition frequency, and nocturia have been reported in post-marketing surveillance 2
• Priapism (painful penile erection sustained for hours) has been associated with alpha-1 antagonists including doxazosin and can lead to permanent impotence if not promptly treated 2
• Gynecomastia has been reported in post-marketing experience 2

Hematologic Side Effects

Leukopenia and Neutropenia

• Decreases in mean white blood cell (WBC) and mean neutrophil counts were observed in controlled clinical trials 2
• In cases with follow-up, WBC and neutrophil counts returned to normal after discontinuation 2
• No patients became symptomatic from low WBC or neutrophil counts 2
• Thrombocytopenia has been reported in post-marketing surveillance 2

Gastrointestinal Side Effects

• Dry mouth occurs in 1.4% of BPH patients (vs 0.3% placebo) 2
• Nausea is frequently reported 4
• Vomiting has been identified in post-marketing experience 2

Hepatobiliary Side Effects

• Cholestasis and cholestatic hepatitis have been reported in post-marketing surveillance 2

Dermatologic and Musculoskeletal Side Effects

• Urticaria has been reported in post-marketing experience 2
• Hot flushes are plausibly related to doxazosin use 2
• Muscle cramps and muscle weakness have been identified in post-marketing surveillance 2

Cardiac Side Effects Beyond Hypotension

• Palpitations are plausibly related to doxazosin in BPH patients 2
• Bradycardia has been reported in post-marketing experience 2
• Hypotension (distinct from orthostatic) occurs in 1.7% of BPH patients (vs 0% placebo) 2

Immunologic Side Effects

• Allergic reactions have been reported in post-marketing surveillance 2

Clinical Context and Severity

Most adverse experiences (almost 90%) are considered mild or moderate in severity 5. The side effect profile, particularly the cardiovascular risks, has resulted in guideline recommendations that alpha-1 blockers should not be used as first-line antihypertensive agents 1. They may be considered as second-line agents specifically in patients with concomitant benign prostatic hyperplasia 1.