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Pronunciation
(doks AY zoe sin)
Generic Available (U.S.)
Yes: Excludes extended release tablet
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Immediate release formulation: Treatment of hypertension as monotherapy or in conjunction with diuretics, ACE inhibitors, beta-blockers, or calcium antagonists
Immediate release and extended release formulations: Treatment of urinary outflow obstruction and/or obstructive and irritative symptoms associated with benign prostatic hyperplasia (BPH)
Use: Unlabeled
Pediatric hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies. Delayed postnatal development was also noted. There are no adequate and well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
The extended release formulation is not indicated for use in women.
Contraindications
Hypersensitivity to quinazolines (prazosin, terazosin), doxazosin, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Angina: Discontinue if symptoms of angina occur or worsen.
• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery.
• Orthostatic hypotension/syncope: Can cause significant orthostatic hypotension and syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE-5 inhibitor is introduced. Patients should be cautioned about performing hazardous tasks when starting new therapy or adjusting dosage upward.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild-to-moderate hepatic impairment; not recommended in severe dysfunction.
• Prostate cancer: Rule out prostatic carcinoma before beginning therapy.
Special populations:
• Elderly: Avoid use as an antihypertensive due to high risk of orthostatic hypotension; alternative agents preferred due to a more favorable risk/benefit profile (Beers Criteria).
Dosage form specific issues:
• Extended release formulation: Consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction. Use caution in patients with increased GI retention (eg, chronic constipation) as doxazosin exposure may be increased. Not indicated for use in women or for the treatment of hypertension.
Adverse Reactions
Note: Type and frequency of adverse reactions reflect combined data from BPH and hypertension trials and immediate release and extended release products.
>10%: Central nervous system: Dizziness (5% to 19%), headache (5% to 14%)
1% to 10%:
Cardiovascular: Orthostatic hypotension (dose related; 0.3% up to 2%), edema (3% to 4%), hypotension (1% to 2%), palpitation (1% to 2%), chest pain (1% to 2%), arrhythmia (1%), syncope (2%), flushing (1%)
Central nervous system: Fatigue (8% to 12%), somnolence (1% to 5%), nervousness (2%), pain (2%), vertigo (2% to 4%), insomnia (1%), anxiety (1%), paresthesia (1%), movement disorder (1%), ataxia (1%), hypertonia (1%), depression (1%)
Dermatologic: Rash (1%), pruritus (1%)
Endocrine & metabolic: Sexual dysfunction (2%)
Gastrointestinal: Abdominal pain (2%), diarrhea (2%), dyspepsia (1% to 2%), nausea (1% to 3%), xerostomia (1% to 2%), constipation (1%), flatulence (1%)
Genitourinary: Urinary tract infection (1%), impotence (1%), polyuria (2%), incontinence (1%)
Neuromuscular & skeletal: Back pain (2% to 3%), weakness (1% to 7%), arthritis (1%), muscle weakness (1%), myalgia (≤1%), muscle cramps (1%)
Ocular: Abnormal vision (1% to 2%), conjunctivitis (1%)
Otic: Tinnitus (1%)
Respiratory: Respiratory tract infection (5%), rhinitis (3%), dyspnea (1% to 3%), respiratory disorder (1%), epistaxis (1%)
Miscellaneous: Diaphoresis increased (1%), flu-like syndrome (1%)
<1% (Limited to important or life-threatening): Abnormal lacrimation, abnormal thinking, agitation, alopecia, amnesia, angina, anorexia, appetite increased, breast pain, bronchospasm, cerebrovascular accident, confusion, cough, depersonalization, dry skin, earache, eczema, emotional lability, fecal incontinence, fever, gastroenteritis, gout, hot flashes, hypoesthesia, hypokalemia, impaired concentration, infection, leukopenia, lymphadenopathy, migraine, MI, neutropenia, pallor, paranoia, paresis, parosmia, peripheral ischemia, purpura, renal calculus, rigors stroke, syncope, tachycardia
Postmarketing and/or case reports: Allergic reaction, bradycardia, cholestasis, gynecomastia, hematuria, hepatitis, intraoperative floppy iris syndrome (cataract surgery), jaundice, liver function tests increased, micturition abnormality, nocturia, paresthesia, priapism, purpura, thrombocytopenia, urticaria, vomiting
Metabolism/Transport Effects
None known.
Drug Interactions
Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Risk X: Avoid combination
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Beta-Blockers: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Exceptions: Levobunolol; Metipranolol. Risk D: Consider therapy modification
Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Alpha1-Blockers. Management: Ensure patient is stable on one agent prior to initiating the other, and always initiate combination using the lowest possible dose of the drug being added. When tadalafil is used for treatment of BPH, concurrent alpha 1-blockers are not recommended. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid saw palmetto when used for BPH (due to limited experience with this combination). Avoid garlic (may have increased antihypertensive effect).
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Mechanism of Action
Hypertension: Competitively inhibits postsynaptic alpha1-adrenergic receptors which results in vasodilation of veins and arterioles and a decrease in total peripheral resistance and blood pressure; ~50% as potent on a weight by weight basis as prazosin.
BPH: Competitively inhibits postsynaptic alpha1-adrenergic receptors in prostatic stromal and bladder neck tissues. This reduces the sympathetic tone-induced urethral stricture causing BPH symptoms.
Pharmacodynamics/Kinetics
Not significantly affected by increased age
Duration: >24 hours
Protein binding: ~98%
Metabolism: Extensively hepatic to active metabolites; primarily via CYP3A4; secondary pathways involve CYP2D6 and 2C19
Bioavailability: Immediate release: ~65%; Extended release relative to immediate release: 54% to 59%
Half-life elimination: Immediate release: ~22 hours; Extended release: 15-19 hours
Time to peak, serum: Immediate release: 2-3 hours; Extended release: 8-9 hours
Excretion: Feces (63%, primarily as metabolites); urine (9%, primarily as metabolites)
Dosage
Oral:
Children (unlabeled use): Hypertension: Immediate release: Initial: 1 mg once daily; maximum: 4 mg/day
Adults:
Immediate release: 1 mg once daily in morning or evening; may be increased to 2 mg once daily. Thereafter titrate upwards, if needed, over several weeks, balancing therapeutic benefit with doxazosin-induced postural hypotension.
BPH: Goal: 4-8 mg/day; maximum dose: 8 mg/day
Hypertension: Maximum dose: 16 mg/day
Reinitiation of therapy: If therapy is discontinued for several days, restart at 1 mg dose and titrate as before
Extended release: BPH: 4 mg once daily with breakfast; titrate based on response and tolerability every 3-4 weeks to maximum recommended dose of 8 mg/day
Reinitiation of therapy: If therapy is discontinued for several days, restart at 4 mg dose and titrate as before.
Conversion to extended release from immediate release: Omit final evening dose of immediate release prior to starting morning dosing with extended release product; initiate extended release product using 4 mg once daily
Elderly: Hypertension: Consider lower initial doses (eg, immediate release: 0.5 mg once daily) and titrate to response (Aronow, 2011)
Dosing adjustment in hepatic impairment: Use with caution in mild-to-moderate hepatic dysfunction. Do not use with severe impairment.
Administration: Oral
Cardura® XL: Tablets should be swallowed whole; do not crush, chew, or divide. Administer with morning meal.
Monitoring Parameters
Blood pressure, standing and sitting/supine; syncope may occur usually within 90 minutes of the initial dose
Dietary Considerations
Cardura® XL: Take with morning meal.
Patient Education
Do not crush or chew extended release forms, swallow whole. Tablet shell may be visible in the stool. Follow recommended diet and exercise program. May cause drowsiness, dizziness, postural hypotension, or nausea. Report increased nervousness or depression; sudden weight gain; unusual or persistent swelling of ankles, feet, or extremities; palpitations or rapid heartbeat; or muscle weakness, fatigue, or pain.
Geriatric Considerations
Adverse reactions such as orthostatic hypotension, dry mouth, and urinary problems can be particularly bothersome in the elderly. In studies of the extended-release tablets, the incidence of hypotension was higher in the elderly compared to younger patients.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: Quality of evidence - moderate; Strength of recommendation - strong).
Additional Information
First-dose hypotension occurs less frequently with doxazosin as compared to prazosin; this may be due to its slower onset of action.
Cardiovascular Considerations
Doxazosin may be used in combination with other agents for the treatment of hypertension or alone in select patients who fail to respond or have contraindications to other agents. Patients with BPH may derive an extra benefit from therapy. Recently, the doxazosin treatment arm of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) was prematurely stopped due to a significantly higher incidence (25%) of cardiovascular events, particularly heart failure events, compared to the diuretic (chlorthalidone) treatment arm. This unfavorable difference was also present when doxazosin was compared to the amlodipine and lisinopril treatment arms. This study does not address cardiovascular outcomes when doxazosin is combined with other antihypertensive medications.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and orthostatic hypotension
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common.
Mental Health: Effects on Psychiatric Treatment
Psychotropics may potentiate the hypotensive effects of doxazosin
Nursing: Physical Assessment/Monitoring
Assess blood pressure and monitor for hypotension, CNS changes, and urinary retention prior to treatment and on a regular basis. When discontinuing, blood pressure should be closely monitored and dose tapered slowly over 1 week or more.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 1 mg, 2 mg, 4 mg, 8 mg
Cardura®: 1 mg, 2 mg, 4 mg, 8 mg [scored]
Tablet, extended release, oral:
Cardura® XL: 4 mg, 8 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Cardura XL)
4 mg (30): $64.04
8 mg (30): $67.20
Tablets (Cardura)
1 mg (30): $55.63
2 mg (30): $55.99
4 mg (30): $66.49
8 mg (30): $66.49
Tablets (Doxazosin Mesylate)
1 mg (30): $17.99
2 mg (30): $20.99
4 mg (30): $21.99
8 mg (30): $23.99
References
"American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults," J Am Geriatr Soc, 2012 [epub ahead of print].
Aronow WS, Fleg JL, Pepine CJ, et al, “ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly: A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” Circulation, 2011, 123(21):2434-506.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Davis BR, Cutler JA, Gordon DJ, et al, “Rationale and Design for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group,” Am J Hypertens, 1996, 9(4 Pt 1):342-60.
“Major Cardiovascular Events in Hypertensive Patients Randomized to Doxazosin vs Chlorthalidone: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Collaborative Research Group,” JAMA, 2000, 283(15):1967-75.
McConnell JD, Roehrborn CG, Bautista OM, et al, “The Long-Term Effect of Doxazosin, Finasteride, and Combination Therapy on the Clinical Progression of Benign Prostatic Hyperplasia. Medical Therapy of Prostatic Symptoms (MTOPS) Research Group,” N Engl J Med, 2003, 349(25):2387-98.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
International Brand Names
Lexi-Comp.com
Last full review/revision April 2012
Content last modified April 2012
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