Doxazosin

General information

The α ₁ -adrenoceptor antagonist doxazosin has similar adverse effects to those of prazosin. In a review of its clinical pharmacology and therapeutic uses, reports of tolerability included an update from previously unpublished pooled data on file [ ]. In 339 patients treated with doxazosin for hypertension compared with 336 treated with placebo, adverse effects were essentially the same as those reported in 665 patients being treated for benign prostatic hyperplasia compared with 300 treated with placebo. Dizziness (19% versus 9% and 16% versus 9%) and fatigue (12% versus 6% and 8% versus 2%) were reported significantly more often than with placebo (figures for patients with hypertension and benign prostate hyperplasia respectively, versus placebo). However, in hypertensive patients somnolence was reported more often than with placebo (5% versus 1%). In patients with benign prostatic hyperplasia the following adverse effects were reported significantly more often than with placebo: hypotension (17% versus 0%), edema (2.7% versus 0.7%), and dyspnea (2.6% versus 0.3%).

The use of doxazosin as add-on therapy in patients with primary hypertension not adequately controlled with other antihypertensive drugs and co-existent impaired glucose metabolism has been investigated in an open study [ ]. Doxazosin was given for 16 weeks in addition to other therapy and led to mean reductions of blood pressure of 15/8 mmHg as well as associated favorable effects on glucose and lipid parameters. Adverse drug reactions were uncommon (2.3% of total of 264 trial entrants) and consisted of a small number of cases of edema, dizziness, headache, and weakness only.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) [ ] was a multicenter comparison of drugs from each of three classes of antihypertensive agents (amlodipine, lisinopril, and doxazosin) with chlortalidone as an active control, in 24 335 adults with hypertension and at least one other coronary heart disease risk factor. In an interim analysis (median follow-up 3.3 years) there was no significant difference in the rates of fatal coronary heart disease or non-fatal myocardial infarction, or in total mortality between doxazosin and chlortalidone, but doxazosin was associated with higher rates of stroke (RR = 1.19; CI = 1.01, 1.40) and combined cardiovascular disease (RR = 1.24; CI = 1.17, 1.33). Considered separately, the risk of congestive heart failure was doubled (RR = 2.04; CI = 1.79, 2.32). Mean systolic blood pressure with doxazosin was about 2–3 mmHg higher than with chlortalidone and mean diastolic pressure was similar in the two groups. The authors concluded that the difference in blood pressure control did not account for the differences in cardiovascular end-points.

Doxazosin, and perhaps the whole class of α-blockers, should no longer be considered as first-line antihypertensive therapy. Doxazosin can still be used for symptom relief in patients with nocturia secondary to prostatic hyperplasia, although it should probably be avoided in patients with manifest or latent congestive heart failure [ ]. This issue has been intensely debated [ ].

Phenoxybenzamine and doxazosin have been compared in 35 patients with pheochromocytoma [ ]. Hemodynamic, pharmacological, and biochemical indicators of α- and β-adrenoceptor blockade were measured before, during, and after anesthesia and surgery in eight patients pretreated with phenoxybenzamine and in 27 patients pretreated with doxazosin. Doxazosin (2–16 mg/day) was as effective as phenoxybenzamine in controlling arterial blood pressure and heart rate before and during surgery and it caused fewer adverse effects.

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