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Doxazosin Mesylate

Pronunciation

Pronunciation: dox-AZ-oh-sin MES-i-late
Class: Alpha-1 adrenergic blocker

Trade Names

Cardura
- Tablets 1 mg
- Tablets 2 mg
- Tablets 4 mg
- Tablets 8 mg

Cardura XL
- Tablets, extended-release 4 mg
- Tablets, extended-release 8 mg

Apo-Doxazosin (Canada)
Cardura-1 (Canada)
Cardura-2 (Canada)
Cardura-4 (Canada)
Gen-Doxazosin (Canada)

Pharmacology

Selectively blocks postsynaptic alpha-1 adrenergic receptors, resulting in dilation of arterioles and veins.

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Pharmacokinetics

Absorption

Extended-release (ER) tablets

Relative bioavailability of 4 and 8 mg dose is 54% and 59%, respectively, compared with immediate-release (IR) product. C max for 4 and 8 mg dose is 10.1 and 25.8 ng/mL, respectively. T max for 4 and 8 mg dose is 8 and 9 h, respectively. Food increases C max and AUC approximately 32% and 18%, respectively.

IR tablets

T max is 2 to 3 h. Bioavailability is approximately 65%. Enterohepatic recycling. Food decreases C max 18% and AUC 12%.

Distribution

Approximately 98% bound to plasma proteins (IR and ER).

Metabolism

Liver

First-pass metabolism; extensively metabolized by O-demethylation or hydroxylation to several active metabolites.

Elimination

The t ½ is approximately 22 h.

Feces

63% of dose; 4.8% as unchanged drug.

Urine

9% of dose; trace amount as unchanged drug.

Elimination is biphasic.

ER

Apparent elimination t ½ is 15 to 19 h.

Special Populations

Hepatic Function Impairment

40% increase in exposure.

Indications and Usage

Treatment of benign prostatic hyperplasia (BPH); treatment of hypertension, alone or in combination with other agents (IR only).

Contraindications

Hypersensitivity to doxazosin, prazosin, or terazosin.

Dosage and Administration

BPH
Adults

PO

ER

4 mg once daily with breakfast. Dose may be increased to 8 mg after 3 to 4 wk (max, 8 mg once daily). If treatment is stopped for several days, restart therapy at 4 mg once daily.

IR Initial dose

1 mg/day.

Maintenance

Increase to 2 mg, and thereafter to 4 and 8 mg every day, which is the max dose for BPH. Recommended titration interval is 1 to 2 wk.

Hypertension
Adults

PO

Initial dose

1 mg every day.

Maintenance

Based on standing BP response, may increase to 2 mg and thereafter to 4, 8, and 16 mg.

General Advice

  • Patients should swallow ER tablets whole and not chew, divide, cut, or crush them.
  • Administer ER tablets with breakfast.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Cimetidine

10% increase in mean AUC of doxazosin.

Tadalafil, vardenafil

BP-lowering effect of doxazosin may be increased. Alpha-1 adrenergic blockers (including doxazosin) are contraindicated in patients receiving tadalafil or vardenafil.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension, palpitation, postural hypotension (2%); arrhythmia (1%); palpitations, peripheral ischemia, syncope, tachycardia (less than 1%); bradycardia, cerebral vascular accidents, MI (postmarketing).

CNS

Dizziness (19%); headache (16%); fatigue/malaise (12%); asthenia (7%); somnolence (5%); vertigo (4%); nervousness (2%); anxiety, ataxia, depression, hypertonia, insomnia, kinetic disorder, paresthesia (1%); agitation, anorexia, hypesthesia (postmarketing).

Dermatologic

Increased sweating, pruritus, rash (1%); alopecia, urticaria (postmarketing).

EENT

Rhinitis (3%); abnormal vision (2%); conjunctivitis/eye pain, epistaxis, tinnitus (1%); blurred vision, floppy iris syndrome (postmarketing).

GI

Nausea (3%); abdominal pain, diarrhea, dry mouth, dyspepsia (2%); constipation, flatulence (1%); GI irritation and bleeding, vomiting (postmarketing).

Genitourinary

Polyuria, sexual dysfunction (2%); impotence, urinary incontinence, UTI (1%); gynecomastia, hematuria, micturition disorder, micturition frequency, nocturia, priapism (postmarketing).

Hematologic-Lymphatic

Leukopenia, purpura, thrombocytopenia (postmarketing).

Hepatic

Abnormal LFTs, cholestatic hepatitis, hepatitis, jaundice (postmarketing).

Metabolic-Nutritional

Edema (4%).

Musculoskeletal

Back pain (3%); arthralgia/arthritis, muscle cramps, muscle weakness, myalgia (1%).

Respiratory

Respiratory tract infection (5%); dyspnea (3%); respiratory disorder (1%); aggravated bronchospasm (postmarketing).

Miscellaneous

Chest pain, pain (2%); face edema, flushing, influenza-like symptoms (1%); allergic reaction, hot flashes (postmarketing).

Precautions

Monitor

Monitor BP and pulse. Assess changes in urinary symptoms, such as dribbling, frequency, hesitancy, nocturia, volume, weak stream.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Use of ER tablets in severe hepatic function impairment is not recommended.

Cataract surgery

Intraoperative floppy iris syndrome has occurred during cataract surgery in patients on or previously treated with alpha-1 blockers.

“First-dose” effect

Marked hypotension (especially orthostatic) and syncope may occur 2 to 6 h after the first few doses, after reintroduction with rapid increase in dosing, or after addition of another antihypertensive.

GI disorders

Administer ER product with caution in patients with preexisting severe GI narrowing. Obstructive symptoms have occurred in patients with known strictures in association with ingestion of nondeformable ER formulations.

Leukopenia/Neutropenia

Mean WBC and neutrophil counts decreased 2.4% and 1%, respectively. No patients became symptomatic as a result of the low WBC or neutrophil count.

Lipids

Slight decrease in total serum cholesterol and LDL may occur as well as increase in HDL.

Priapism

Occurs rarely; may lead to permanent impotence if not promptly treated.

Prostate cancer

Rule out before starting therapy.

Overdosage

Symptoms

Hypotension.

Patient Information

  • Advise patient to take prescribed dose every day, morning or evening, without regard to meals but to take with food if stomach upset occurs.
  • Advise patient that medication will be started at a low dose and then gradually increased as tolerated until max benefit is obtained.
  • Inform patient to swallow the ER formulation whole and not to chew, divide, cut, or crush tablets.
  • Instruct patient to take the ER formulation with breakfast.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Inform hypertensive patient that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Instruct hypertensive patient to continue taking other BP medications as prescribed by health care provider.
  • Emphasize to hypertensive patient importance of the following modalities on BP: weight control, regular exercise, smoking cessation, and moderate intake of alcohol and salt.
  • Instruct hypertensive patient in BP and pulse measurement skills.
  • Advise hypertensive patient to monitor and record BP and pulse at home and to inform health care provider if abnormal measurements are noted. Also advise patient to take record of BP and pulse to each follow-up visit.
  • Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
  • Caution patient that drug may cause dizziness or fainting and to avoid driving or performing hazardous tasks for 24 h after the first dose, after a dosage increase, and after interruptions of therapy when treatment is resumed.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patient with BPH to contact health care provider if urinary symptoms do not improve or if they worsen while taking this medication.
  • Instruct patient to report the following symptoms to health care provider: dizziness, fainting, prolonged or painful erection, other adverse reactions.

Copyright © 2009 Wolters Kluwer Health.

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