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Doxazosin Mesylate

Pronunciation

Class: alpha-Adrenergic Blocking Agents
VA Class: CV150
Chemical Name: 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-[(2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl]piperazine monomethanesulfonate
Molecular Formula: C23H25N5O5•CH4O3S
CAS Number: 77883-43-3
Brands: Cardura

Introduction

Postsynaptic α1-adrenergic blocking agent; quinazoline derivative.1 2 3 4 5 6 7

Uses for Doxazosin Mesylate

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).1 2 3 4 6 7

Current antihypertensive and urology guidelines (e.g., JNC 7) no longer recommend α1-blockers as preferred first-line therapy for patients with hypertension.66 70 82

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May have potential favorable effects in hypertensive patients with benign prostatic hyperplasia or other urinary outflow obstruction.70 82

Benign Prostatic Hyperplasia (BPH)

Reduction of urinary obstruction and relief of associated manifestations in hypertensive or normotensive patients with symptomatic BPH.1 21 33 35 37 40 41 42 43 44 46

Although drug therapy usually is not as effective as surgical therapy, it may provide adequate symptomatic relief with fewer and less serious adverse effects compared with surgery.66

May consider combined therapy with an α1-adrenergic blocker and 5α-reductase inhibitor for men with bothersome moderate to severe BPH and demonstrable prostatic enlargement.66 84 85 Has been more effective than therapy with either drug alone in preventing long-term BPH symptom progression.66 Men at risk for BPH progression are most likely to benefit from combination therapy.66 84

Doxazosin Mesylate Dosage and Administration

Administration

Oral Administration

Administer orally once daily in the morning or evening.1 Effect of food on maximum plasma concentration and AUC is not clinically important.1

Dosage

Available as doxazosin mesylate; dosage expressed in terms of doxazosin.1

Individualize dosage according to patient response and tolerance.1 7 Initiate at low dosage to minimize frequency of postural hypotension and syncope.1

Postural effects are most likely to occur 2–6 hours after a dose; monitor BP during this period after first dose and with any dosage increases.1

If therapy is interrupted for several days, restart using initial dosage regimen.1

Pediatric Patients

Hypertension
Oral

Initially, 1 mg once daily.106 Increase dosage as necessary up to a maximum of 4 mg once daily.106

Adults

Hypertension
Oral

Initially, 1 mg once daily.1 7 70 Do not initiate with higher dosages.1

Depending on patient response (standing BP 2–6 and 24 hours after initial dose), may increase dosage to 2 mg once daily; make subsequent dosage adjustments by doubling dose at intervals of 2 weeks–1 month until desired BP control is achieved, drug is not tolerated, or maximum daily dosage of 16 mg is reached.1 7 70

Increased likelihood of excessive postural effects (e.g., syncope, postural dizziness/vertigo, postural hypotension) with dosages >4 mg daily; substantial risk of postural effects with dosages >16 mg daily.1

Careful monitoring of BP is recommended during initial titration or subsequent upward dosage adjustment;53 70 avoid large or abrupt reductions in BP.53

BPH
Oral

Initially, 1 mg once daily in the morning or evening;1 41 44 some clinicians recommend administration at bedtime to minimize postural effects.35 36 Do not initiate with higher dosages.1

To achieve desired improvement in symptoms and urodynamics, may increase dosage in a stepwise manner to 2, 4, and 8 mg daily as necessary, at intervals ≥1–2 weeks.1 41 42 43 44 Do not exceed 8 mg daily.

Evaluate BP routinely, particularly with initiation of therapy and subsequent dosage adjustment.1

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Maximum 4 mg daily.76

Adults

Hypertension
Oral

Maximum 16 mg daily.1

BPH
Oral

Maximum 8 mg daily.1

Special Populations

Geriatric Patients

Hypertension

Select dosage carefully, usually initiating therapy at the low end of the dosage range, because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy;1 generally, increase dosage more slowly in geriatric patients than in younger adults.7

Cautions for Doxazosin Mesylate

Contraindications

  • Known hypersensitivity to doxazosin, quinazolines (e.g., prazosin, terazosin), or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Postural Hypotension

Marked hypotension, especially in the upright position, can occur; may be accompanied by syncope and other postural effects (e.g., dizziness, lightheadedness, vertigo).1

Postural effects are most common after initial dose but may also occur when dosage is increased or when therapy is resumed after an interruption exceeding a few days.1

To decrease risk of excessive hypotension and syncope, initiate therapy at a low dosage (i.e., 1 mg daily) and titrate slowly; initiate concomitant antihypertensive agents with caution.1

If syncope or hypotension occurs, place patient in a recumbent position and institute supportive therapy as necessary; a transient hypotensive response is not a contraindication to further doses.1

Use with particular caution in patients in occupations in which orthostatic hypotension could be dangerous.1

Priapism

Priapism reported rarely; may lead to permanent impotence if not treated promptly.1

General Precautions

Prostate Cancer

Exclude possibility of prostate cancer before initiation of therapy for BPH.1

Hematologic Effects

Possible decreases in leukocyte and neutrophil counts in patients receiving α1-adrenergic blocking agents, including doxazosin.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1

Geriatric Use

Geriatric patients may be particularly susceptible to postural effects.7

BPH: Safety and efficacy were similar in those ≥65 years of age compared with younger patients.1

Hypertension: Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; other clinical experience has not revealed age-related differences in response.1 Select dosage with caution.1 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with hepatic impairment and those who are receiving other agents known to influence hepatic metabolism.1 (See Interactions.)

Common Adverse Effects

Dizziness, headache, drowsiness, fatigue, edema, nausea, dyspnea, somnolence, abdominal pain, diarrhea.1 2 3 4 6 7

Interactions for Doxazosin Mesylate

No formal drug interaction studies to date, but no interactions observed in patients receiving various agents concomitantly during clinical trials.1 (See Specific Drugs and Laboratory Tests.)

Antihypertensive Agents

Potential pharmacodynamic interaction (additive hypotensive effects; initiate additional antihypertensive agents with caution).1

Drugs Affecting Hepatic Metabolism

Potential pharmacokinetic interaction; use concomitantly with caution.1

Protein-bound Drugs

Potential pharmacokinetic interaction (displacement of doxazosin or other protein-bound drug); no information available to date on effect of other highly protein-bound drugs on doxazosin binding.1 Doxazosin has no effect on protein binding of certain drugs in vitro.1 (See Specific Drugs and Laboratory Tests.)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Acetaminophen

No interaction observed in clinical trials1

Amoxicillin

No interaction observed in clinical trials1

Antacids

No interaction observed in clinical trials1

β-Adrenergic blocking agents (e.g., atenolol, propranolol)

No interaction observed in clinical trials1

Chlorpheniramine

No interaction observed in clinical trials1

Cimetidine

Increased AUC (10%) of doxazosin1

Clinical importance unknown1

Codeine

No interaction observed in clinical trials1

Corticosteroids

No interaction observed in clinical trials1

Co-trimoxazole

No interaction observed in clinical trials1

Diazepam

No interaction observed in clinical trials1

Digoxin

No effect on digoxin protein binding in vitro1

Diuretics, thiazide (e.g., hydrochlorothiazide)

No interaction observed in clinical trials1

Erythromycin

No interaction observed in clinical trials1

Finasteride

Adverse effects with concomitant use generally reflect combined toxicity profile of each drug alone66 84

Hypoglycemic

No interaction observed in clinical trials1

NSAIAs (e.g., aspirin, ibuprofen, indomethacin)

No interaction observed in clinical trials; no effect on indomethacin protein binding in vitro1

Phenytoin

No effect on phenytoin protein binding in vitro1

Test for prostate specific antigen (PSA)

No effect on plasma PSA concentrations in patients receiving doxazosin for up to 3 years1

Warfarin

No effect on warfarin protein binding in vitro1

Doxazosin Mesylate Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained within about 2–3 hours.1

Bioavailability is approximately 65%.1

Onset

In patients with hypertension, maximum reduction in BP usually occurs 2–6 hours after administration.1

In patients with BPH, decreased severity of symptoms and improved urinary flow rate observed within 1–2 weeks.1

Food

Food decreases mean maximum plasma concentrations and AUC by 18 and 12%, respectively; not statistically or clinically significant.1

Distribution

Extent

Crosses the placenta and is distributed into milk in animals; not known whether distributed into human milk.1

Plasma Protein Binding

Approximately 98%.1

Elimination

Metabolism

Extensively metabolized, principally in the liver by O-demethylation of quinazoline nucleus or hydroxylation of benzodioxan moiety, to several active metabolites; pharmacokinetics of metabolites not characterized.1

Elimination Route

Excreted in feces (63%) and urine (9%) mainly as metabolites; only 4.8% and trace amounts excreted unchanged in feces and urine, respectively.1

Half-life

Biphasic; terminal half-life is approximately 22 hours.1

Special Populations

In patient with cirrhosis (Child-Pugh class A), systemic exposure was increased by 40% after a single 2-mg dose.1 Effect of hepatic impairment on disposition not established in controlled clinical studies.1

In geriatric patients and patients with renal impairment, clinically important alterations in pharmacokinetics not observed to date.1

Stability

Storage

Oral

Tablets

<30°C.1

Actions

  • Reduces peripheral vascular resistance and BP as a result of vasodilating effects; produces both arterial and venous dilation.1 2 3 4 6 7

  • Binds to α-adrenergic receptors on the prostate capsule, prostate adenoma, and the bladder trigone, resulting in decreased urinary outflow resistance in men.1 5

  • May improve to limited extent the serum lipid profile (e.g., small increases in HDL and HDL/total cholesterol ratio; small decreases in LDL, total cholesterol, and triglyceride concentrations).1 2 3 7

Advice to Patients

  • Possible syncopal and orthostatic symptoms, especially at initiation of therapy; importance of avoiding driving or other hazardous tasks where injury could occur for 24 hours after first dose, a dosage increase, or when resumed after therapy interruption.1

  • Importance of sitting or lying down when symptoms of lowered BP occur, and of rising carefully from a sitting or lying position.1

  • Importance of informing clinician if bothersome dizziness, lightheadedness, or palpitations occur.1

  • Possible drowsiness or somnolence; use caution when operating machinery or driving a motor vehicle until effects on individual are known.1

  • Importance of men seeking immediate medical attention if painful or sustained (for hours) erection occurs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Doxazosin Mesylate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

1 mg (of doxazosin)*

Cardura (scored)

Pfizer

2 mg (of doxazosin)*

Cardura (scored)

Pfizer

4 mg (of doxazosin)*

Cardura (scored)

Pfizer

8 mg (of doxazosin)*

Cardura (scored)

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Cardura 1MG Tablets (PFIZER U.S.): 30/$55.63 or 90/$166.90

Cardura 2MG Tablets (PFIZER U.S.): 30/$55.99 or 90/$159.96

Cardura 4MG Tablets (PFIZER U.S.): 30/$66.49 or 90/$167.36

Cardura 8MG Tablets (PFIZER U.S.): 30/$66.49 or 90/$181.12

Cardura XL 4MG 24-hr Tablets (PFIZER U.S.): 30/$69.99 or 90/$189.97

Cardura XL 8MG 24-hr Tablets (PFIZER U.S.): 30/$67.20 or 90/$184.79

Doxazosin Mesylate 1MG Tablets (MYLAN): 30/$17.99 or 90/$47.97

Doxazosin Mesylate 2MG Tablets (MYLAN): 30/$20.99 or 90/$44.97

Doxazosin Mesylate 4MG Tablets (MYLAN): 30/$21.99 or 90/$59.97

Doxazosin Mesylate 8MG Tablets (MYLAN): 30/$23.99 or 90/$71.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions May 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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