Doxazosin

Doxazosin is a long acting selective alpha 1 blocker used in hypertension and benign prostatic hyperplasia. Once daily dosing is possible because of its long half life. It is not a first line antihypertensive because of an excess of heart failure compared with a thiazide like diuretic in a large outcome study.

Classification. Selective post synaptic alpha 1 blocker; quinazoline.

Mechanism. Blocks alpha 1 receptors on vascular and prostatic smooth muscle, lowering peripheral resistance and bladder outlet tone. It also modestly lowers low density lipoprotein cholesterol.

Pharmacodynamics. Blood pressure falls gradually over 2 to 6 hours and lasts 24 hours. Orthostatic hypotension is most marked after the first dose and after dose increases.

Pharmacokinetics. Oral bioavailability about 65%; peak 2 to 6 hours; half life about 22 hours; extensive hepatic metabolism; mostly faecal excretion.

Hypertension, adult (add on).

• Start 1 mg once daily.

• Double the dose every 1 to 2 weeks as needed, to 2 mg, 4 mg, 8 mg.

• Usual maintenance 2 to 4 mg once daily; maximum 16 mg daily.

• Modified release preparation: 4 mg daily, increasing to 8 mg after 4 weeks.

Benign prostatic hyperplasia, adult.

• Start 1 mg once daily.

• Increase to 2 mg after 1 to 2 weeks, then 4 mg, then 8 mg if needed.

• Usual maintenance 2 to 4 mg; maximum 8 mg daily.

• Modified release: 4 mg daily, maximum 8 mg.

Resistant hypertension, adult. Add after a diuretic, a calcium channel blocker and a renin angiotensin agent when spironolactone is not tolerated; use the hypertension titration given here.

Children. Not established.

Restarting. If doxazosin is missed for several days, restart at 1 mg.

Contraindications. Hypersensitivity to quinazolines; history of orthostatic hypotension; micturition syncope; overflow bladder; anuria; symptomatic hypotension.

Warnings. First dose and dose increase orthostatic hypotension and syncope; give at bedtime. Intraoperative floppy iris syndrome. Priapism, rarely. May cause fluid retention; use with caution in heart failure. Caution in severe hepatic impairment.

Adverse effects. Dizziness, fatigue, headache, oedema, postural hypotension, rhinitis, somnolence, ejaculatory disorder, urinary incontinence.

Interactions. Phosphodiesterase 5 inhibitors: hypotension; with sildenafil, start at 25 mg or lower after a stable doxazosin dose. Strong CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin): raise doxazosin levels. Other antihypertensives add hypotension.

Special groups.

• Pregnancy: limited data; avoid unless essential.

• Breastfeeding: appears in milk; limited data; avoid.

• Older adults: start at 0.5 to 1 mg at bedtime; falls risk.

• Kidney impairment: no adjustment.

• Liver impairment: mild to moderate: use with caution; severe: not advised.

Formulations. Tablets 1 mg, 2 mg, 4 mg and 8 mg; modified release 4 mg and 8 mg.

Administration. Oral once daily at the same time, preferably at bedtime during titration. Do not crush modified release tablets.

Baseline. Sitting and standing blood pressure, prostate assessment, history of heart failure, eye history.

Monitoring. Blood pressure sitting and standing 2 to 6 hours after the first dose and after increases; weight and oedema for fluid retention; urinary symptoms.

Stopping. No taper is required.

Common prescribing errors. Starting above 1 mg; failing to tell the eye surgeon; using it as first line antihypertensive in a patient with heart failure risk.