Doxazocin

Pharmacologic Category

Alpha 1 Blocker; Antihypertensive

Dosing: Adult

BPH: Oral:

Immediate release: Initial: 1 mg once daily; may titrate (by doubling the daily dose [eg, to 2 mg, then 4 mg, then 8 mg]) at 1- to 2-week intervals up to 8 mg once daily based on patient response and tolerability (maximum: 8 mg/day).

Reinitiation of therapy: If therapy is discontinued for several days, restart at 1 mg dose and titrate using initial dosing regimen.

Extended release: 4 mg once daily; may titrate based on response and tolerability every 3 to 4 weeks to 8 mg once daily (maximum: 8 mg/day).

Reinitiation of therapy: If therapy is discontinued for several days, restart at 4 mg dose and titrate using initial dosing regimen.

Note: 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.

Hypertension (alternative agent): Oral: Immediate release: Initial: 1 mg once daily; titrate as needed based on patient response up to a dose of 16 mg once daily (ACC/AHA [Whelton 2017]); maximum: 16 mg/day.

Reinitiation of therapy: If therapy is discontinued for several days, restart at 1 mg dose and titrate using initial dosing regimen.

Ureteral calculi expulsion (off-label use): Oral: Immediate release: 4 mg once daily in evening (Gurbuz 2011; Resorlu 2011). Note: Patients with stones >10 mm were excluded from studies.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Avoid use for hypertension treatment (alternative agents have superior risk-benefit profiles) (Beers Criteria [AGS 2019]).

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (however, limited data suggest renal impairment does not significantly alter pharmacokinetic parameters).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Severe impairment (Child-Pugh class C): Use is not recommended.

Dosing: Pediatric

Note: If drug is discontinued for greater than several days, consider beginning with initial dose and retitrate as needed.

Dysfunctional voiding: Limited data available, efficacy results variable: Children ≥3 years and Adolescents: Oral: Immediate release: Initial: 0.5 mg once daily at bedtime; some trials maintained a fixed dose; others titrated at weekly or biweekly intervals to effect as tolerated (maximum daily dose: 2 mg/day) (Austin 1999; Cain 2003; El-Hefnawy 2012; Yucel 2005). In some trials, a larger initial dose (1 mg/day) was used in patients weighing >40 to 50 kg (Austin 1999; Yucel 2005).

Hypertension: Limited data available: Children and Adolescents: Oral: Immediate release: Initial: 1 mg/day; maximum daily dose: 4 mg/day (NHBPEP 2004; NHLBI 2011)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, limited data suggest renal impairment does not significantly alter pharmacokinetic parameters.

Dosing: Hepatic Impairment: Pediatric

Mild to moderate impairment (Child Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling, use with caution.

Severe impairment (Child-Pugh class C): There are no pediatric specific recommendations; however, based on experience in adult patients, use is not recommended.

Use: Labeled Indications

Benign prostatic hyperplasia: Treatment of signs and symptoms of benign prostatic hyperplasia (BPH).

Hypertension (immediate release only): Management of hypertension. Note: Alpha blockers are not recommended as first line therapy (ACC/AHA [Whelton 2017]).

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

​Ureteral calculi expulsionLevel of Evidence [B, G]

Use of alpha-1 adrenergic blockers, including doxazosin, for treating ureteral calculi is supported by data from a meta-analysis as well as numerous controlled trials. Tamsulosin has the most data, but doxazosin has also demonstrated efficacy in facilitating expulsion of ureteral stones (<10 mm) as medical therapy alone or as an adjunct to shock wave lithotripsy and ureteroscopy. Some trials indicate a class effect of alpha-1 adrenergic blockers, with doxazosin reported to be equally effective as terazosin, tamsulosin, and alfuzosin Ref

American Urological Association/Endourological Society guidelines and European Association of Urology guidelines recommend use of alpha-1 blockers, including doxazosin, for treating ureteral calculi Ref Access Full Off-Label Monograph

Level of Evidence Definitions

​Level of Evidence Scale

Class and Related Monographs

Alpha-1 Adrenergic Blockers

Clinical Practice Guidelines

Benign Prostatic Hyperplasia:

AUA, "Guideline: Management of Benign Prostatic Hyperplasia," 2010

CUA, “Guideline on Male Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia (MLUTS/BPH),” 2018

Hypertension:

"2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults," November 2017.

"ACCF/AHA Expert Consensus Document on Hypertension in the Elderly," 2011

AHA/ACC/CDC, “AHA/ACC/CDC Science Advisory: An Effective Approach to High Blood Pressure Control” November 2013

ASH/ISH “Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension,” January 2014

Eighth Joint National Committee (JNC 8), "2014 Evidence-based Guideline for the Management of High Blood Pressure in Adults," December 2013.

Administration: Oral

Extended release: Swallow tablets whole; do not crush, cut, chew, or divide. Administer with morning meal.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation.

Immediate release: Administer daily dose either in the morning or evening.

Administration: Pediatric

Oral: Immediate release: Administer without regard to meals at the same time each day

Dietary Considerations

Administer extended-release tablet with morning meal.

Storage/Stability

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat high blood pressure.

• In men, it is used to treat the signs of an enlarged prostate.

• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Loss of strength and energy

• Headache

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe dizziness

• Passing out

• Chest pain

• Shortness of breath

• Swelling of arms or legs

• Erection that lasts more than 4 hours

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Medication Safety Issues

​Sound-alike/look-alike issues:

​Geriatric Patients: High-Risk Medication:

Contraindications

Hypersensitivity to doxazosin, other quinazolines (eg, prazosin, terazosin), or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

Warnings/Precautions

Concerns related to adverse effects:

• Allergic reactions: May occur, including skin rash, urticaria, pruritus, angioedema, and respiratory symptoms.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Floppy iris syndrome: Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery. May require modifications to surgical technique.

• Hematologic effect: Decreases in white blood cells (WBC) and neutrophil count have been reported; WBC and neutrophils returned to normal after discontinuation.

• Orthostatic hypotension/syncope: May cause orthostatic hypotension and syncope within a few hours after dosing, but may occur later; anticipate a similar effect if therapy is interrupted for a few days, if dosage is increased, or if another antihypertensive drug, PDE-5 inhibitor, or nitrates are introduced. Use with caution in patients with symptomatic orthostatic hypotension.

• Priapism: Priapism has been associated with use (rarely); seek immediate medical assistance for erections lasting longer than 4 hours.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with heart failure, angina pectoris, or recent acute myocardial infarction (within the last 6 months). If symptoms of angina pectoris appear or worsen, discontinue use. In a scientific statement from the American Heart Association, doxazosin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

• Hepatic impairment: Use with caution in patients with mild to moderate impairment (Child-Pugh class A and B); monitor blood pressure and for symptoms of hypotension. Not recommended in severe impairment (Child-Pugh class C) (extensively metabolized).

• Prostate cancer: Rule out prostatic carcinoma before beginning therapy (many symptoms of BPH and prostate cancer are similar).

Dosage form specific issues:

• Extended release: 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.

Other warning/precautions:

• Appropriate use: Extended release: Not indicated for use in women or for the treatment of hypertension.

* See Cautions in AHFS Essentials for additional information.

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.

Pregnancy Considerations

Doxazosin crosses the placenta (Versmissen 2016).

Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).

Agents other than doxazosin are more commonly used to treat hypertension in pregnancy (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). Although rare, use of doxazosin for the treatment of hypertension due to a pheochromocytoma during pregnancy has been described; treatment was generally started after the first trimester (Lenders 2019; van der Weerd 2017).

Breast-Feeding Considerations

Doxazosin is present in breast milk.

Information is available from a single case report following a maternal dose of doxazosin 4 mg every 24 hours for 2 doses for urinary stones. Milk samples were obtained at various intervals over 24 hours, beginning ~17 hours after the first dose. Maternal serum samples were obtained at nearly the same times, beginning ~1 hour later. The highest serum and milk concentrations of doxazosin were observed ~1 hour after the dose. Using the highest milk concentration (4.15 mcg/L), the estimated dose to the breastfeeding infant was calculated to be <1% of the weight-adjusted maternal dose (Jensen, 2013). In general, breastfeeding is considered acceptable when the relative infant dose of a medication is <10% (Anderson 2016; Ito 2000).

In a second case report, doxazosin was not present in breast milk when sampled 30 hours after the last maternal dose. In this case, maternal doxazosin was administered for hypertension due to a pheochromocytoma, surgically removed after delivery. Doxazosin 4 mg once daily was used during pregnancy, increased to 6 mg/day prior to delivery, and 8 mg/day 3 days' postpartum prior to being discontinued (Versmissen 2016).

Briggs' Drugs in Pregnancy & Lactation

• Doxazosin

Adverse Reactions

>10%: Central nervous system: Dizziness (5% to 19%), malaise (≤12%), fatigue (8% to ≤12%), headache (6% to 10%)

1% to 10%:

Cardiovascular: Edema (3% to 4%), hypotension (1% to 2%), orthostatic hypotension (<1% to 2%), cardiac arrhythmia (1%), facial edema (1%), flushing (1%), palpitations (1%)

Central nervous system: Drowsiness (1% to 5%), vertigo (2% to 4%), pain (2%), anxiety (1%), ataxia (1%), hypertonia (1%), insomnia (1%), movement disorder (1%), myasthenia (1%)

Endocrine & metabolic: Sexual disorder (2%)

Gastrointestinal: Abdominal pain (2%), nausea (1% to 2%), dyspepsia (1%), xerostomia (1%)

Genitourinary: Urinary incontinence (1%), urinary tract infection (1%)

Neuromuscular & skeletal: Weakness (4% to 7%), muscle cramps (1%), myalgia (1%), arthralgia (≤1%), arthritis (≤1%)

Ophthalmic: Visual disturbance (2%)

Otic: Tinnitus (1%)

Renal: Polyuria (2%)

Respiratory: Respiratory tract infection (5%), rhinitis (3%), dyspnea (1% to 3%), epistaxis (1%)

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, abnormal lacrimation, abnormality in thinking, agitation, alopecia, altered sense of smell, amnesia, angina pectoris, anorexia, back pain, blurred vision, bradycardia, bronchospasm (aggravated), cerebrovascular accident, chest pain, cholestasis, cholestatic hepatitis, confusion, cough, decreased libido, depersonalization, diaphoresis, diarrhea, dysgeusia, dysuria, eczema, emotional lability, fecal incontinence, fever, flu-like symptoms, gastroenteritis, gastrointestinal obstruction, gout, gynecomastia, hematuria, hepatitis, hot flash, hypersensitivity reaction, hypoesthesia, hypokalemia, impotence, increased appetite, increased thirst, infection, intraoperative floppy iris syndrome (cataract surgery), jaundice, lack of concentration, leukopenia, lymphadenopathy, mastalgia, migraine, myocardial infarction, nephrolithiasis, nervousness, neutropenia, nocturia, orthostatic dizziness, otalgia, pallor, paranoia, paresis, paresthesia, peripheral ischemia, pharyngitis, photophobia, priapism, pruritus, purpura, rigors, sinusitis, skin rash, syncope, tachycardia, thrombocytopenia, tremor, twitching, urinary frequency, urination disorder, urticaria, vomiting, weight gain, weight loss, xeroderma

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Alpha-Blocker, Piperazinyl Quinazoline Allergy

Toxicology

• Alpha Adrenergic Blockers

Metabolism/Transport Effects

Substrate of CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Abametapir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Alpha-/Beta-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy

Alpha1-Agonists: Alpha1-Blockers may diminish the vasoconstricting effect of Alpha1-Agonists. Similarly, Alpha1-Agonists may antagonize Alpha1-Blocker vasodilation. Risk C: Monitor therapy

Alpha1-Blockers: May enhance the antihypertensive effect of other Alpha1-Blockers. Risk X: Avoid combination

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Risk D: Consider therapy modification

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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 C: Monitor therapy

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Calcium Channel Blockers: Alpha1-Blockers may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination. Some combinations are specifically contraindicated by manufacturers; others may have recommended dose adjustments. If combined, monitor for increased substrate effects. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Dapoxetine: May enhance the orthostatic hypotensive effect of Alpha1-Blockers. Risk C: Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Alpha1-Blockers (Nonselective). 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 Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Rilmenidine: Alpha1-Blockers may enhance the hypotensive effect of Rilmenidine. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Genes of Interest

• Cytochrome P450 3A4

Monitoring Parameters

Blood pressure routinely and for at least 6 hours after initial dose and with each dose increase (standing and sitting/supine); monitor patients with mild-to-moderate impairment for symptoms of hypotension.

Hypertension: The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%: Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk: Target blood pressure <130/80 mm Hg may be reasonable

Advanced Practitioners Physical Assessment/Monitoring

Obtain CBC and liver function tests; not recommended in patients with severe liver impairment. Assess blood pressure and monitor for hypotension routinely prior to and throughout the duration of therapy. Assess for cardiovascular disease. Consider assessing cardiac function and structure with echocardiogram prior to initiation of therapy; may exacerbate underlying myocardial dysfunction. Assess other medication patient is taking; alternative therapy or dosage adjustment may be needed. Assess for urinary retention prior to treatment and routinely. Assess for prostatic carcinoma prior to beginning therapy. Order dose tapering over 1 week or more when discontinuing therapy.

Nursing Physical Assessment/Monitoring

Check ordered labs and tests and report any abnormalities. Monitor heart rate and blood pressure routinely prior to and throughout the duration of therapy. Monitor and educate patient to report any dizziness, passing out, chest pain, or shortness of breath. Educate patient to not stop taking medication abruptly.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Cardura: 1 mg [scored]

Cardura: 2 mg [scored; contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]

Cardura: 4 mg [scored; contains fd&c yellow #6 (sunset yellow)]

Generic: 1 mg, 2 mg, 4 mg

Tablet, Oral, as mesylate:

Cardura: 8 mg [scored; contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]

Generic: 8 mg

Tablet Extended Release 24 Hour, Oral:

Cardura XL: 4 mg, 8 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Cardura-1: 1 mg [DSC]

Cardura-2: 2 mg [DSC]

Cardura-4: 4 mg [DSC]

Generic: 1 mg, 2 mg, 4 mg

Anatomic Therapeutic Chemical (ATC) Classification

• C02CA04

Generic Available (US)

May be product dependent

Pricing: US

Tablet, 24-hour (Cardura XL Oral)

4 mg (per each): $6.74

8 mg (per each): $7.08

Tablets (Cardura Oral)

1 mg (per each): $5.86

2 mg (per each): $5.86

4 mg (per each): $6.15

8 mg (per each): $6.46

Tablets (Doxazosin Mesylate Oral)

1 mg (per each): $0.26 - $3.76

2 mg (per each): $0.26 - $3.76

4 mg (per each): $0.29 - $3.94

8 mg (per each): $0.29 - $1.49

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

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

Duration: >24 hours

Protein binding: ~98%

Metabolism: Extensively hepatic to active metabolites; primarily via CYP3A4; secondary pathways involve CYP2D6 and 2C9

Bioavailability: Immediate release: ~65%; Extended release relative to immediate release: 54% to 59%

Half-life elimination: Immediate release: ~22 hours; Extended release: 15 to 19 hours

Time to peak, serum: Immediate release: 2 to 3 hours; Extended release: 8 ± 3.7 to 9 ± 4.7 hours

Excretion: Feces (~63%, primarily as metabolites [4.8% as unchanged]); urine (9%, primarily as metabolites)

Pharmacodynamics/Kinetics: Additional Considerations

Hepatic function impairment: Immediate release: 40% increase in exposure in mild impairment (Child-Pugh class A).

Geriatric: Extended release: Cmax and AUC increased 27% and 34% respectively in elderly patients.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation); Patients may experience orthostatic hypotension as they stand up after treatment; especially if lying in dental chair for extended periods of time. Use caution with sudden changes in position during and after dental treatment.

Effects on Bleeding

No information available to require special precautions

Related Information

• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Oral Medications That Should Not Be Crushed or Altered

Pharmacotherapy Pearls

First-dose hypotension occurs less frequently with doxazosin as compared to prazosin; this may be due to its slower onset of action.

Index Terms

Doxazosin Mesylate

FDA Approval Date

November 02, 1990

References

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Brand Names: International

Alfadil (SE); Alfadil XL (PH); Alfamedin (DE); Barova 4 (TH); Cadex (IL); Cadil (KR); Cadlin (KR); Cardenalin (JP); Cardolin-2 (TH); Cardular (DE, LB); Cardular PP (DE); Cardular Uro (DE); Cardura (AE, AR, BB, BG, BH, CL, CO, CR, CY, CZ, DO, EG, GB, GR, GT, HK, HN, HU, ID, IE, IQ, IR, JO, KW, LT, LU, LY, MT, MX, MY, NI, NL, OM, PA, PK, PT, QA, RU, SA, SG, SV, SY, TH, TR, UA, UY, VE, YE, ZA, ZM); Cardura CR (CH); Cardura XL (CL, CN, CO, CR, DO, EE, GT, HK, HN, LT, LU, MT, MY, NI, PA, PE, PL, RO, SI, SK, SV, TH, ZW); Cardura-XL S.R. (KR); Carduran (AU, NO); Carduran Neo (ES); Carduran Retard (DK, IS); Carduran XL (BR); Cazosin (TH); Curcard (BH, LB); Dalgen (CO); Dedralen (IT); Diblocin (DE); Diblocin PP (DE); Diblocin Uro (DE); Doka (HR); Dophilin (TW); Dorbantil (PY); Dosabin (TW); Dosan (NZ); Dosin (BH, EG); Dovozin (TH); Doxaben (TW); Doxaben XL (TW); Doxacar (IE); Doxacard (IN); Doxacin (LB); Doxacor (EG, PE); Doxagamma (DE); Doxan (TW); Doxane (IE); Doxatan (IE, MT); Doxazone XL SR (KR); Doxino (HK); Doxolbran (AR); Genzosin (TW); Jutalar (DE); Kamiren (HR, RO); Kamiren XL (HK, MY, RO); Kinxaben (TW); Maguran (GR); Magurol (JO, LK, MT, MY); Mahurol (UA); Pencor (HK, MY, SG, TH); Progandol (ES); Prostasin (TH); Pzocin XL (KR); Saxobin (TW); Supressin (AT); Tarzos (EG); Tonocardin (HR); Tonokardin (HR); Uriduct (DE); Xadosin (TW); Xadosin XL (TW); Zoxan (VN); Zoxan LP (FR); Zoxon (UA)

Last Updated 10/9/20