DOXAZOSIN MESYLATE
Clinical safety rating
safeAnimal studies have demonstrated safety
Selective antagonist of alpha-1 adrenergic receptors on vascular smooth muscle, causing vasodilation and reduced peripheral vascular resistance, leading to decreased blood pressure. Also relaxes smooth muscle in the prostate and bladder neck, improving urinary flow.
| Metabolism | Extensively metabolized in the liver via O-demethylation and hydroxylation, primarily by CYP3A4. |
| Excretion | Approximately 63% of the dose is excreted in feces via biliary elimination, and about 9% is excreted unchanged in urine. The remainder is metabolized, with metabolites excreted in urine and feces. |
| Half-life | Terminal elimination half-life is approximately 22 hours. This long half-life supports once-daily dosing for hypertension and benign prostatic hyperplasia. |
| Protein binding | Approximately 98-99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.5-1.5 L/kg, indicating extensive distribution into tissues and extravascular spaces. |
| Bioavailability | Oral bioavailability is approximately 65% due to first-pass metabolism. Food does not significantly affect absorption. |
| Onset of Action | Oral: Antihypertensive effect begins within 1-2 hours, with peak effect at 2-6 hours. For benign prostatic hyperplasia, symptomatic improvement may be noted within 1-2 weeks. |
| Duration of Action | Antihypertensive effect persists for 24 hours with once-daily dosing. The duration for benign prostatic hyperplasia is sustained with continued administration. |
| Molecular Weight | 451.5 |
Hypertension: Initial 1 mg PO once daily (morning or bedtime); may increase to 2 mg, 4 mg, 8 mg, or 16 mg once daily as needed. BPH: Initial 1 mg PO once daily, titrate to 2 mg, 4 mg, or 8 mg once daily. Maximum 8 mg/day for BPH, 16 mg/day for hypertension.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment needed for renal impairment. Doxazosin is minimally renally excreted. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh C). In mild-moderate impairment (Child-Pugh A or B), use with caution; consider starting at 1 mg once daily and titrate slowly. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. Not recommended for use in children. |
| Geriatric use | Use cautiously due to increased risk of orthostatic hypotension, dizziness, and falls. Start at 1 mg once daily, titrate slowly. Monitor blood pressure carefully. |
| 1st trimester | Limited human data; animal studies show no teratogenic effects at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | May cause hypotension in pregnant women; monitor blood pressure. Avoid use during labor as it can cause hypotension and potential uteroplacental insufficiency. |
| 3rd trimester | Same as t2. Avoid use near term due to risk of neonatal hypotension and hypoxia. |
Clinical note
Other antihypertensive drugs can have additive effects Can cause marked first-dose hypotension and syncope.
| Placental transfer | Doxazosin crosses the placenta; animal studies indicate transfer, human data limited. |
| Breastfeeding | Doxazosin is excreted into breast milk in low amounts. No adverse effects have been reported in breastfed infants. Use with caution in nursing mothers, especially with preterm infants or those with renal impairment. |
| Lactation Rating | L2 (Limited data, probably compatible) |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, doxazosin showed no teratogenic effects in rats and rabbits at doses up to 20 and 8 mg/kg/day, respectively. There are no adequate and well-controlled studies in pregnant women. Potential fetal risks include possible hypotension and reduced placental perfusion, especially in the second and third trimesters. Use only if potential benefit justifies risk. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate. Assess for signs of hypotension, dizziness, and syncope. Fetal monitoring includes ultrasound for growth and amniotic fluid assessment if used for hypertensive disorders. |
| Fertility Effects | In animal studies, doxazosin did not impair fertility in rats. In humans, no specific studies on fertility. A theoretical risk of decreased libido and erectile dysfunction in males; no direct effect on female fertility known. |
■ FDA Black Box Warning
None
| Common Effects | BPH |
| Serious Effects |
Hypersensitivity to doxazosin or any component of the formulationConcomitant use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension
| Precautions | Orthostatic hypotension and syncope, especially with first dose ('first-dose effect'), Risk of intraoperative floppy iris syndrome (IFIS) during cataract surgery, Hepatic impairment may decrease metabolism, Priapism (rare), Drowsiness/somnolence, caution with operating machinery |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels. No other significant food interactions. |
| Clinical Pearls | First-dose syncope can occur; start with 1 mg at bedtime. Titrate slowly based on standing blood pressure. Monitor for orthostatic hypotension, especially in elderly. May cause intraoperative floppy iris syndrome (IFIS) during cataract surgery. Also used for benign prostatic hyperplasia (BPH) and hypertension. |
| Patient Advice | Take the first dose at bedtime to minimize dizziness. · Avoid sudden standing; rise slowly from sitting or lying positions. · May cause drowsiness; do not drive until you know how the medication affects you. · Avoid alcohol, as it can increase dizziness and drowsiness. · Inform your surgeon if you are taking this drug before cataract surgery. · Do not skip doses or discontinue abruptly; consult your doctor. |
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