Usage
Doxazosin is prescribed for:
- Hypertension: To lower blood pressure and reduce the risk of cardiovascular events like strokes and heart attacks.
- Benign Prostatic Hyperplasia (BPH): To relieve symptoms like difficulty urinating, frequent urination, and urgency by relaxing the muscles in the bladder and prostate.
Pharmacological Classification: Doxazosin is an alpha-1 adrenergic receptor blocker (alpha-blocker).
Mechanism of Action: Doxazosin works by blocking alpha-1 adrenergic receptors, which leads to relaxation of smooth muscle in blood vessels and the prostate. This relaxation lowers peripheral vascular resistance, reducing blood pressure, and eases urinary flow in BPH.
Alternate Names
Doxazosin is also known by the international nonproprietary name (INN) doxazosin.
Brand Names: Cardura, Cardura XL, Doxadura.
How It Works
Pharmacodynamics: Doxazosin selectively blocks postsynaptic alpha-1 adrenergic receptors, causing vasodilation and a decrease in peripheral vascular resistance. In BPH, it relaxes smooth muscle in the prostate and bladder neck, improving urine flow.
Pharmacokinetics:
- Absorption: Doxazosin is well-absorbed after oral administration, reaching peak plasma concentrations in 2-3 hours for immediate-release and 8-9 hours for extended-release formulations.
- Metabolism: It is extensively metabolized in the liver, primarily via O-demethylation and hydroxylation.
- Elimination: Doxazosin is eliminated primarily in the feces, with a small portion excreted in urine. The elimination half-life is around 22 hours for immediate-release and 30 hours for the extended-release.
Mode of Action: Doxazosin competitively binds to postsynaptic alpha-1 adrenergic receptors in vascular smooth muscle and the prostate. This inhibits the binding of norepinephrine, preventing vasoconstriction and smooth muscle contraction.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Doxazosin specifically antagonizes alpha-1 adrenergic receptors.
Elimination Pathways: Primarily hepatic metabolism followed by fecal excretion; minor renal excretion.
Dosage
Standard Dosage
Adults:
- Hypertension (Immediate-release): Initial dose: 1 mg once daily. May be titrated up to 16 mg once daily as needed, usually at intervals of 1-2 weeks. Usual maintenance dose is 2-4 mg daily.
- BPH (Immediate-release): Initial dose: 1 mg once daily. May be titrated up to 8 mg once daily, usually at intervals of 1-2 weeks. Usual maintenance dose is 2-4 mg daily.
- BPH (Extended-release): Initial dose: 4 mg once daily with breakfast. May be increased to 8 mg once daily if needed based on response and tolerability. The maximum recommended dose is 8 mg daily.
Children: Doxazosin is not recommended for use in children as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 0.5-1 mg daily for immediate release) and titrate cautiously due to increased risk of orthostatic hypotension. Extended-release formulation is generally preferred in the elderly.
- Patients with Renal Impairment: No dose adjustment is typically required.
- Patients with Hepatic Dysfunction: Use with caution in mild-to-moderate hepatic impairment; avoid use in severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with coronary artery disease. Monitor patients with diabetes for changes in blood glucose.
Clinical Use Cases
Doxazosin is not typically used in acute clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is primarily for chronic conditions like hypertension and BPH.
Dosage Adjustments
Adjust dosage based on individual patient response and tolerability, paying close attention to blood pressure and postural symptoms.
Side Effects
Common Side Effects:
Dizziness, lightheadedness, headache, fatigue, orthostatic hypotension, edema, rhinitis, dyspnea, nausea, asthenia.
Rare but Serious Side Effects:
Syncope, palpitations, priapism, myocardial infarction, stroke, intraoperative floppy iris syndrome (IFIS).
Long-Term Effects:
Chronic complications are uncommon, but may include orthostatic hypotension.
Adverse Drug Reactions (ADR):
IFIS during cataract surgery, first-dose syncope, priapism, allergic reactions.
Contraindications
Hypersensitivity to doxazosin or other quinazolines, history of orthostatic hypotension, concomitant use of potent CYP3A4 inhibitors (e.g., boceprevir). In BPH, contraindications include bladder outlet obstruction, anuria, or concomitant severe renal insufficiency.
Drug Interactions
- CYP450 Interactions: Doxazosin is metabolized by CYP3A4. Inhibitors of CYP3A4 may increase doxazosin levels.
- Other Interactions: Other antihypertensive medications (additive hypotensive effects), PDE5 inhibitors (e.g., sildenafil, vardenafil, tadalafil - increased risk of hypotension), alpha-blockers (additive effects).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not assigned. Doxazosin should be used during pregnancy only if the potential benefit outweighs the potential risk.
- Breastfeeding: Doxazosin is present in human milk. The effects on nursing infants are unknown.
Drug Profile Summary
- Mechanism of Action: Alpha-1 adrenergic receptor blocker.
- Side Effects: Dizziness, headache, fatigue, orthostatic hypotension.
- Contraindications: Hypersensitivity, orthostatic hypotension.
- Drug Interactions: Antihypertensives, PDE5 inhibitors, CYP3A4 inhibitors.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: 1-16mg daily for hypertension (immediate-release), 1-8 mg daily for BPH (immediate-release), 4-8 mg daily for BPH (extended release).
- Monitoring Parameters: Blood pressure (especially postural), symptoms of BPH, signs of adverse events.
Popular Combinations
Doxazosin may be used in combination with thiazide diuretics, beta-blockers, calcium channel blockers, or ACE inhibitors for hypertension.
Precautions
Monitor blood pressure closely, especially when initiating therapy or adjusting dosage. Caution patients about potential for postural hypotension. Rule out prostate cancer before starting treatment for BPH. Inform patients undergoing cataract surgery of the risk of IFIS.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxazosin?
A: See section on Dosage above.
Q2: What are the common side effects of Doxazosin?
A: Common side effects include dizziness, lightheadedness, headache, fatigue, and orthostatic hypotension.
Q3: What are the contraindications for using Doxazosin?
A: Contraindications include hypersensitivity to doxazosin or other quinazolines and a history of orthostatic hypotension.
Q4: How does Doxazosin interact with other medications?
A: Doxazosin can interact with other antihypertensive medications, PDE5 inhibitors, and CYP3A4 inhibitors.
Q5: Can Doxazosin be used during pregnancy or breastfeeding?
A: Use with caution. Consult with a specialist to assess potential risks and benefits.
Q6: What is the mechanism of action of Doxazosin?
A: Doxazosin is an alpha-1 adrenergic receptor blocker.
Q7: How should Doxazosin be administered?
A: Orally, once daily, with or without food (immediate-release); with breakfast (extended-release).
Q8: What should I monitor in a patient taking Doxazosin?
A: Monitor blood pressure, especially orthostatic measurements, as well as BPH symptoms and any potential adverse reactions.
Q9: What are some important precautions to consider when prescribing Doxazosin?
A: Start with a low dose and titrate slowly to minimize the risk of first-dose syncope. Monitor patients for postural hypotension and inform them about the potential for dizziness. Advise patients undergoing cataract surgery of the risk of IFIS.
A: Immediate-release Doxazosin is taken once daily and has a shorter duration of action. Extended-release Doxazosin is taken once daily with breakfast and provides more consistent blood levels throughout the day. The extended-release formulation is not indicated for the treatment of hypertension.
