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  • CLASSES

    Alpha Adrenoreceptor Antagonists/Alpha Blockers
    Alpha-Blockers

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, alpha-blocker; used once daily for HTN and BPH; similar to prazosin and terazosin but longer-acting; the ALLHAT trial showed reduction of cardiac events in high-risk HTN patients treated with chlorthalidone vs. doxazosin, leading to discontinuation of the doxazosin group.

    COMMON BRAND NAMES

    Cardura, Cardura XL

    HOW SUPPLIED

    Cardura XL Oral Tab ER: 4mg, 8mg
    Cardura/Doxazosin/Doxazosin Mesylate Oral Tab: 1mg, 2mg, 4mg, 8mg

    DOSAGE & INDICATIONS

    For treatment of hypertension.
    Oral dosage (immediate-release)
    Adults

    1 mg PO once daily, initially. May double daily dose as needed if further control is needed. Max: 16 mg/day.

    For the treatment of benign prostatic hyperplasia (BPH).
    For treatment of BPH in combination with finasteride.
    Oral dosage
    Adult males

    The role of doxazosin for this purpose has not been established. Initially, 1 mg PO once daily; adjust based on response, up to 8 mg PO once daily. In a long-term, double-blind clinical trial of 3,047 men with BPH, combination therapy of doxazosin (4 to 8 mg/day PO) and finasteride (5 mg/day PO) was shown to significantly reduce the risk of overall clinical progression of BPH than either drug alone. However, based on a study of finasteride alone, more data are needed to confirm that finasteride has positive overall effects in delaying or reducing the incidence of prostate cancer.

    Oral dosage (immediate-release tablets)
    Adult males

    Initially, 1 mg PO once daily. Adjust dosage based on clinical response. Dosage may be increased up to 8 mg PO once daily.

    Oral dosage (extended-release tablets)
    Adult males

    Initially, 4 mg PO once daily, taken with breakfast. Adjust dosage in 3 to 4 weeks based on clinical response. Dosage may be increased up to 8 mg PO once daily. If therapy is interrupted for several days, initiate dosage at the starting dose of 4 mg PO once daily. If switching from immediate-release doxazosin tablets, initiate dosage with the extended-release tablets at the starting dose of 4 mg PO once daily. Prior to starting therapy with the extended-release tablets, the final evening dose of the immediate-release tablets should not be taken.

    MAXIMUM DOSAGE

    Adults

    16 mg/day PO for hypertension and 8 mg/day PO for benign prostatic hyperplasia (BPH).

    Elderly

    16 mg/day PO for hypertension and 8 mg/day PO for benign prostatic hyperplasia (BPH).

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No specific recommendations are available for hepatic disease. Since doxazosin is extensively metabolized, it is prudent to start with the lowest initial adult dosage (1 mg PO once daily in the morning or at bedtime). Adjust dosage based on response.

    Renal Impairment

    No dosage adjustment is needed.
     
    Intermittent hemodialysis
    No dosage adjustment is needed; doxazosin is highly protein bound and is not removed during hemodialysis.

    ADMINISTRATION

    Oral Administration

    Observe for postural hypotension, particularly with first dose.

    Oral Solid Formulations

    Immediate-release tablets: May be administered orally without regard to meals.
    Extended-release tablets: Administer once daily with breakfast. Prior to starting therapy with the extended-release tablets, the final evening dose of the immediate-release tablets should not be taken.

    STORAGE

    Cardura:
    - Store between 68 to 77 degrees F
    Cardura XL:
    - Avoid excessive humidity
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Doxazosin is contraindicated in patients with a hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any of its components.

    Angina, hypotension, orthostatic hypotension, syncope

    Doxazosin may cause orthostatic hypotension with or without symptoms (e.g., dizziness) and syncope. Postural or orthostatic hypotension may occur within a few hours after administration; however, symptomatic postural hypotension has infrequently been reported more than a few hours after doxazosin dosing. Maximum reductions in blood pressure occur within 2 to 6 hours after administration of immediate-release doxazosin. Similar to other alpha-blockers, the potential for syncope may be more likely after the initial dose (also known as the first-dose effect) or after an increase in dose. Dosages should be adjusted as necessary depending on patient symptomatic response and tolerability. Utilize caution when doxazosin is administered to any patient with symptomatic hypotension or who had a hypotensive response to other medications. The potential for hypotension is higher in elderly patients and patients taking concomitant PDE-5 inhibitors. Advise patients to use caution when driving, operating machinery, or performing hazardous tasks until the medication's effect has been determined. Doxazosin may worsen angina. Discontinue doxazosin if angina develops or worsens during therapy.

    Hepatic disease

    Doxazosin should be used with caution in patients with hepatic disease because the drug is primarily metabolized by the liver. Exaggerated effects could occur after normal doses of drug in these patients.

    Pregnancy

    There are insufficient data regarding the use of doxazosin in pregnant women to determine if a drug-associated risk for major birth defects and miscarriage exists. However, untreated hypertension during pregnancy can result in increased maternal risks including pre-eclampsia, gestational diabetes, premature delivery, and delivery complications. Hypertension also increases the risk for fetal intrauterine growth restriction and intrauterine death. In animal reproduction studies, no adverse developmental effects were observed when doxazosin was orally administered at doses 4 to 10 times the human AUC exposures.

    Breast-feeding

    There are no data regarding the effects of doxazosin on the breast-fed infant or on milk production. Although the data are insufficient to confirm the presence of doxazosin in human milk, a single case study involving a breast-feeding mother receiving doxazosin reports an infant exposure of doxazosin of < 1% of the maternal weight-adjusted dosage and a milk:plasma ratio of 0.1.

    Ocular surgery

    Patients receiving or who have previously received treatment with doxazosin or other alpha-1 blockers may be at risk for intraoperative floppy iris syndrome during ocular surgery for cataracts. Intraoperative floppy iris syndrome is a small pupil syndrome variant that is characterized by a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery, but ophthalmologists should be prepared for possible modifications to their surgical technique such as the use of iris hooks, iris dilator rings, or viscoelastic substances.

    Priapism

    Rarely, doxazosin, like other alpha adrenergic antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.

    Geriatric

    Insufficient data are available from hypertension clinical trials to determine a difference between the effects of doxazosin in geriatric vs. younger patients. Geriatric patients may be more likely to be susceptible to hypotensive effects at the usual adult dosage, particularly with initial dosing or an increase in dose, when postural hypotensive effects and orthostasis are more likely to occur (e.g., first-dose effect). The safety and effectiveness profile of doxazosin for benign prostatic hypertrophy (BPH) was similar in older male patients (65 years and older) and younger adult males.[50858] According to the Beers Criteria, doxazosin is considered a potentially inappropriate medication (PIM) in geriatric patients and is not recommended as routine treatment of hypertension due to the high risk of orthostatic hypotension and the availability of alternative agents with a superior benefit to risk profile in the elderly. The Beers panel also recommends avoiding doxazosin in geriatric patients whose syncope may be due to orthostasis. Also, avoid use in geriatric females with urinary incontinence of any type because the aggravation of incontinence may occur.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); antihypertensive regimens should be individualized to achieve the desired outcome while minimizing adverse effects. Alpha-blockers may cause dizziness, postural hypotension, fatigue, and there is an increased risk for falls. Doxazosin can cause significant hypotension and syncope during the first few doses; therefore, the dose should be administered at bedtime initially, and the drug slowly titrated as needed. Alpha-blockers are infrequently used as a treatment for urinary incontinence; these drugs have specific and limited uses for incontinence and are not approved for this indication. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.[60742]

    Constipation, GI obstruction

    Rare reports of obstructive symptoms have been associated with use of another medication with a non-deformable extended-release formulation in patients with known strictures. Since doxazosin extended-release tablets contain non-deformable material, caution is recommended in patients with severe pathologic or iatrogenic gastrointestinal narrowing due to the potential risk for GI obstruction. Patients with chronic constipation may experience an increase in doxazosin-related adverse reactions due to an increase in doxazosin systemic exposure related to markedly increased GI retention times.

    Prostate cancer

    Prostate cancer and benign prostatic hyperplasia (BPH) cause many of the same symptoms, and frequently, they coexist. Patients should be evaluated prior to starting doxazosin therapy to rule out the presence of prostate cancer.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 1.4-2.0
    myocardial infarction / Delayed / Incidence not known
    bradycardia / Rapid / Incidence not known
    stroke / Early / Incidence not known
    GI obstruction / Delayed / Incidence not known
    bronchospasm / Rapid / Incidence not known

    Moderate

    edema / Delayed / 2.7-4.0
    dyspnea / Early / 1.2-2.6
    orthostatic hypotension / Delayed / 0.3-2.2
    hypotension / Rapid / 1.0-1.8
    chest pain (unspecified) / Early / 1.2-1.2
    palpitations / Early / 1.2-1.2
    impotence (erectile dysfunction) / Delayed / 1.1-1.1
    ataxia / Delayed / 1.0-1.0
    hypertonia / Delayed / 1.0-1.0
    urinary incontinence / Early / 1.0-1.0
    myasthenia / Delayed / 1.0-1.0
    sinus tachycardia / Rapid / 0.9-0.9
    hematuria / Delayed / Incidence not known
    priapism / Early / Incidence not known
    cholestasis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    floppy iris syndrome / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known

    Mild

    dizziness / Early / 5.3-19.0
    fatigue / Early / 8.0-12.0
    headache / Early / 5.1-9.9
    asthenia / Delayed / 3.9-6.9
    drowsiness / Early / 1.2-5.0
    vertigo / Early / 1.5-4.1
    rhinitis / Early / 3.0-3.0
    abdominal pain / Early / 1.8-2.4
    diarrhea / Early / 2.3-2.3
    nausea / Early / 1.2-2.3
    polyuria / Early / 2.0-2.0
    infection / Delayed / 0-1.4
    dyspepsia / Early / 1.2-1.4
    xerostomia / Early / 1.4-1.4
    myalgia / Early / 0.5-1.4
    insomnia / Early / 1.2-1.2
    anxiety / Delayed / 1.1-1.1
    hyperhidrosis / Delayed / 1.1-1.1
    influenza / Delayed / 1.1-1.1
    tinnitus / Delayed / 1.0-1.0
    epistaxis / Delayed / 1.0-1.0
    arthralgia / Delayed / 1.0-1.0
    muscle cramps / Delayed / 1.0-1.0
    flushing / Rapid / 1.0-1.0
    libido decrease / Delayed / 0.8-0.8
    syncope / Early / 0.5-0.5
    agitation / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    nocturia / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    rash / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    malaise / Early / Incidence not known
    purpura / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Sympathomimetics can antagonize the antihypertensive effects of adrenergic agonists when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Acetaminophen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Acrivastine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Aldesleukin, IL-2: (Moderate) Doxazosin may potentiate the hypotension seen with aldesleukin, IL-2.
    Alemtuzumab: (Moderate) Alemtuzumab may cause hypotension. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischemic heart disease and in patients on antihypertensive agents.
    Alfuzosin: (Major) Alfuzosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between alfuzosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Alprostadil: (Minor) The concomitant use of systemic alprostadil injection and antihypertensive agents, such as doxazosin, may cause additive hypotension. Caution is advised with this combination. Systemic drug interactions with the urethral suppository (MUSE) or alprostadil intracavernous injection are unlikely in most patients because low or undetectable amounts of the drug are found in the peripheral venous circulation following administration. In those men with significant corpora cavernosa venous leakage, hypotension might be more likely. Use caution with in-clinic dosing for erectile dysfunction (ED) and monitor for the effects on blood pressure. In addition, the presence of medications in the circulation that attenuate erectile function may influence the response to alprostadil. However, in clinical trials with alprostadil intracavernous injection, anti-hypertensive agents had no apparent effect on the safety and efficacy of alprostadil.
    Amifostine: (Major) Patients receiving alpha-blockers should be closely monitored during amifostine infusions due to additive effects. Patients receiving amifostine at doses recommended for chemotherapy should have antihypertensive therapy interrupted 24 hours preceding administration of amifostine. If the antihypertensive cannot be stopped, patients should not receive amifostine.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Amphetamines: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed in patients receiving doxazosin and amphetamines. Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents, such as doxazosin.
    Amyl Nitrite: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Apomorphine: (Moderate) Use of doxazosin and apomorphine together can increase the hypotensive effects of apomorphine. Monitor blood pressure regularly during use of this combination.
    Apraclonidine: (Minor) Alpha blockers as a class may reduce heart rate and blood pressure. While no specific drug interactions have been identified with systemic agents and apraclonidine during clinical trials, it is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with the use of antihypertensive agents. Patients using cardiovascular drugs concomitantly with apraclonidine should have their pulse and blood pressure monitored periodically.
    Aripiprazole: (Minor) Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
    Articaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Asenapine: (Moderate) Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of asenapine and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Atazanavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with atazanavir. Atazanavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Atazanavir; Cobicistat: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with atazanavir. Atazanavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution. (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Avanafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and alpha-blockers.
    Baclofen: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Beta-blockers: (Moderate) Orthostatic hypotension may be more likely if beta-blockers are coadministered with alpha-blockers.
    Bortezomib: (Moderate) Patients on antihypertensive agents receiving bortezomib treatment may require close monitoring of their blood pressure and dosage adjustment of their medication. During clinical trials of bortezomib, hypotension was reported in roughly 12 percent of patients.
    Brexpiprazole: (Moderate) Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Brompheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Brompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Bupivacaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Cabergoline: (Moderate) Cabergoline should be used cautiously with antihypertensive agents, including alpha-blockers. Cabergoline has been associated with hypotension. Initial doses higher than 1 mg may produce orthostatic hypotension. It may be advisable to monitor blood pressure.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbetapentane; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbetapentane; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Carbidopa; Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Carbinoxamine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Carbinoxamine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Cariprazine: (Moderate) Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents. Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
    Cetirizine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Chloramphenicol: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with chloramphenicol. Chloramphenicol is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Chlorpheniramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Chlorpheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Clarithromycin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Clozapine: (Moderate) Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug.
    Cobicistat: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Codeine; Phenylephrine; Promethazine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Co-Enzyme Q10, Ubiquinone: (Moderate) Co-enzyme Q10, ubiquinone (CoQ10) may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring. Patients should be advised to inform their prescriber of their use of CoQ10.
    Darunavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with darunavir. Darunavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Darunavir; Cobicistat: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution. (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with darunavir. Darunavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution. (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with darunavir. Darunavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with ritonavir. Ritonavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Delavirdine: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with delavirdine. Delavirdine is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Desloratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Desogestrel; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Dextromethorphan; Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Diazoxide: (Moderate) Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agents. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving other antihypertensive agents.
    Diethylpropion: (Major) Diethylpropion has vasopressor effects and may limit the benefit of alpha-blockers. Although leading drug interaction texts differ in the potential for an interaction between diethylpropion and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications.
    Diphenhydramine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Dobutamine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Dopamine: (Major) In general, alpha-blockers should not be used during dopamine infusion. The undesired peripheral vasoconstriction observed with high-dose dopamine is opposed by alpha-adrenergic blockers. The renal, mesenteric, or cerebral vasodilatory properties resulting from dopaminergic-receptor stimulation are not affected by alpha-blockers .
    Drospirenone; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Duloxetine: (Moderate) Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of antihypertensive agents and duloxetine may increase the risk of hypotension. Monitor blood pressure if the combination is necessary.
    Dutasteride; Tamsulosin: (Major) Tamsulosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between tamsulosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with cobicistat. Cobicistat is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Ephedrine: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and alpha-blockers; alpha-blockers antagonize the pressor effect of ephedrine.
    Ephedrine; Guaifenesin: (Moderate) Carefully monitor blood pressure in patients who have received both ephedrine and alpha-blockers; alpha-blockers antagonize the pressor effect of ephedrine.
    Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Epoprostenol: (Minor) Epoprostenol can have additive effects when administered with other antihypertensive agents, including alpha-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Estradiol: (Minor) Estrogens can induce fluid retention and may increase blood pressure in some patients; patients who are receiving antihypertensive agents concurrently with hormonal contraceptives should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking alpha-blockers. Concomitant use may increase the risk for hypotension.
    Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethinyl Estradiol; Norgestrel: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Etomidate: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Etonogestrel; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Fexofenadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Finasteride; Tadalafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest recommended dose of tadalafil. Conversely, patients already receiving an optimized dose of tadalafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in stepwise fashion. When tadalafil is used for benign prostatic hypertrophy (BPH), discontinue alpha-blocker therapy at least 1 day prior to initiating tadalafil therapy. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of tadalafil and an alpha-blocker.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Fosamprenavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with fosamprenavir. Fosamprenavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    General anesthetics: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Grapefruit juice: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with grapefruit juice. Grapefruit juice is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Guaifenesin; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Guaifenesin; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Haloperidol: (Moderate) In general, haloperidol should be used cautiously with antihypertensive agents due to the possibility of additive hypotension.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Hydrocodone; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Ibuprofen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Idelalisib: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with idelalisib. Idelalisib is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Iloperidone: (Moderate) Secondary to alpha-blockade, iloperidone can produce vasodilation that may result in additive effects during concurrent use with antihypertensive agents. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope. If concurrent use of iloperidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Iloprost: (Moderate) Further reductions in blood pressure may occur when inhaled iloprost is administered to patients receiving other antihypertensive agents.
    Indinavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with indinavir. Indinavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Intravenous Lipid Emulsions: (Moderate) High doses of fish oil supplements may produce a blood pressure lowering effect. It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents.
    Isocarboxazid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Isoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Isoproterenol: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Isosorbide Dinitrate, ISDN: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Isosorbide Mononitrate: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Itraconazole: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with itraconazole. Itraconazole is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Ketamine: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Ketoconazole: (Moderate) Monitor blood pressure and for symptoms of hypotension if coadministration of doxazosin and ketoconazole is necessary. Concurrent use may result in increased doxazosin exposure. Doxazosin is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
    Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Levodopa: (Moderate) Concomitant use of antihypertensive agents with levodopa can result in additive hypotensive effects.
    Levoketoconazole: (Moderate) Monitor blood pressure and for symptoms of hypotension if coadministration of doxazosin and ketoconazole is necessary. Concurrent use may result in increased doxazosin exposure. Doxazosin is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Lidocaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Lofexidine: (Major) Because the central alpha-2 agonist effects of lofexidine can cause hypotension and orthostasis, the drug should be avoided, if possible, in combination with other medications that can significantly decrease blood pressure such as the antihypertensive alpha-blockers. If coadministration is required, blood pressure should be monitored, particularly after dose changes of either agent. Adjustments should be made as clinically indicated. Patients being given lofexidine in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine should be reduced in amount, delayed, or skipped.
    Lopinavir; Ritonavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with ritonavir. Ritonavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Loratadine; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Lovastatin; Niacin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Lurasidone: (Moderate) Due to the antagonism of lurasidone at alpha-1 adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. If concurrent use of lurasidone and antihypertensive agents is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known.
    Mestranol; Norethindrone: (Minor) Estrogen containing oral contraceptives can induce fluid retention and may increase blood pressure in some patients; monitor patients receiving concurrent therapy to confirm that the desired antihypertensive effect is being obtained.
    Methohexital: (Moderate) Concurrent use of methohexital and alpha-blockers increases the risk of developing hypotension and hypothermia.
    Methylphenidate Derivatives: (Moderate) Periodic evaluation of blood pressure is advisable during concurrent use of methylphenidate derivatives and antihypertensive agents, particularly during initial coadministration and after dosage increases of methylphenidate. Methylphenidates can reduce the hypotensive effect of antihypertensive agents such as alpha-blockers.
    Midodrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Milrinone: (Moderate) Concurrent administration of antihypertensive agents could lead to additive hypotension when administered with milrinone. Titrate milrinone dosage according to hemodynamic response.
    Naproxen; Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Nefazodone: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with nefazodone. Nefazodone is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Nelfinavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with nelfinavir. Nelfinavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with antihypertensive agents.
    Niacin, Niacinamide: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Niacin; Simvastatin: (Moderate) Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents. This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise.
    Nicotine: (Moderate) Nicotine use may reduce the clinical effects of the alpha-blockers. If significant changes in nicotine intake occur, the dosages of these drugs may need adjustment.
    Nirmatrelvir; Ritonavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with ritonavir. Ritonavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Nitrates: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroglycerin: (Moderate) Concomitant use of nitrates with other antihypertensive agents can cause additive hypotensive effects. Dosage adjustments may be necessary.
    Nitroprusside: (Moderate) Additive hypotensive effects may occur when nitroprusside is used concomitantly with other antihypertensive agents. Dosages should be adjusted carefully, according to blood pressure.
    Nonsteroidal antiinflammatory drugs: (Moderate) If nonsteroidal anti-inflammatory drugs (NSAIDs) and an antihypertensive drug are concurrently used, carefully monitor the patient for signs and symptoms of renal insufficiency and blood pressure control. Doses of antihypertensive medications may require adjustment in patients receiving concurrent NSAIDs. NSAIDs, to varying degrees, have been associated with an elevation in blood pressure. This effect is most significant in patients receiving concurrent antihypertensive agents and long-term NSAID therapy. NSAIDs cause a dose-dependent reduction in prostaglandin formation, which may result in a reduction in renal blood flow leading to renal insufficiency and an increase in blood pressure that are often accompanied by peripheral edema and weight gain. Patients who rely upon renal prostaglandins to maintain renal perfusion may have acute renal blood flow reduction with NSAID usage. Elderly patients may be at increased risk of adverse effects from combined long-term NSAID therapy and antihypertensive agents, especially diuretics, due to age-related decreases in renal function and an increased risk of stroke and coronary artery disease.
    Norepinephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. Also, because norepinephrine is an alpha-adrenergic agonist, drugs with alpha-blocking activity such as alpha-blockers directly counteract the vasopressor effects of norepinephrine.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Norethindrone; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Norgestimate; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Olanzapine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olanzapine; Fluoxetine: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Olanzapine; Samidorphan: (Moderate) Olanzapine may induce orthostatic hypotension and thus enhance the effects of antihypertensive agents.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with ritonavir. Ritonavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Oxymetazoline: (Major) Caution is advised when administering doxazosin with oxymetazoline. Doxazosin, an alpha adrenergic blocker, would likely antagonize the sympathomimetic effects of oxymetazoline, alpha adrenergic agonists; thereby reducing the effectiveness of oxymetazoline.
    Paliperidone: (Moderate) Paliperidone may cause orthostatic hypotension, thereby enhancing the hypotensive effects of antihypertensive agents. Orthostatic vital signs should be monitored in patients receiving paliperidone and doxazosin who are susceptible to hypotension.
    Pentoxifylline: (Moderate) Pentoxifylline has been used concurrently with antihypertensive drugs (beta blockers, diuretics) without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensives. If indicated, dosage of the antihypertensive agents should be reduced.
    Phendimetrazine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Phenelzine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phentermine: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Phentermine; Topiramate: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Posaconazole: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with posaconazole. Posaconazole is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Prilocaine; Epinephrine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure.
    Procainamide: (Moderate) Procainamide can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents. Intravenous administration of procainamide is more likely to cause hypotensive effects.
    Procaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Promethazine; Phenylephrine: (Major) Sympathomimetics can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly.
    Propofol: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Pseudoephedrine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Pseudoephedrine; Triprolidine: (Moderate) The cardiovascular effects of pseudoephedrine may reduce the antihypertensive effects produced by alpha-blockers. Monitor blood pressure and heart rate.
    Quinidine: (Moderate) Quinidine can decrease blood pressure and should be used cautiously in patients receiving antihypertensive agents due to the potential for additive hypotension.
    Rasagiline: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Risperidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ritonavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with ritonavir. Ritonavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Saquinavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with saquinavir. Saquinavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogen-containing oral contraceptives may induce fluid retention and may increase blood pressure in some patients taking antihypertensive agents. Such patients should be monitored to confirm that the desired antihypertensive effect is being obtained.
    Sevoflurane: (Moderate) General anesthetics can potentiate the hypotensive effects of antihypertensive agents.
    Sildenafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and an alpha-blocker.
    Silodosin: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Tadalafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest recommended dose of tadalafil. Conversely, patients already receiving an optimized dose of tadalafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in stepwise fashion. When tadalafil is used for benign prostatic hypertrophy (BPH), discontinue alpha-blocker therapy at least 1 day prior to initiating tadalafil therapy. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of tadalafil and an alpha-blocker.
    Tamsulosin: (Major) Tamsulosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between tamsulosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Telithromycin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with telithromycin. Telithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Tetrabenazine: (Moderate) Tetrabenazine may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of tetrabenazine may be necessary in patients receiving antihypertensive agents concomitantly.
    Tetracaine: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Use extreme caution with the concomitant use of tetracaine and antihypertensive agents.
    Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as alpha-blockers should be used cautiously due to the potential for additive bradycardia.
    Thiothixene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
    Tipranavir: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with tipranavir. Tipranavir is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Tizanidine: (Moderate) Concurrent use of tizanidine with antihypertensive agents can result in significant hypotension. Caution is advised when tizanidine is to be used in patients receiving concurrent antihypertensive therapy.
    Trandolapril; Verapamil: (Moderate) Monitor blood pressure if verapamil is used with other antihypertensive agents; an additive blood pressure lowering effect may occur. Using verapamil with agents that attenuate alpha-adrenergic function, such as doxazosin, may result in blood pressure reductions that are excessive in some patients.
    Tranylcypromine: (Contraindicated) The use of hypotensive agents and tranylcypromine is contraindicated by the manufacturer of tranylcypromine because the effects of hypotensive agents may be markedly potentiated.
    Trazodone: (Minor) Due to additive hypotensive effects, patients receiving antihypertensive agents concurrently with trazodone may have excessive hypotension. Decreased dosage of the antihypertensive agent may be required when given with trazodone.
    Vardenafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on alpha-blocker therapy before initiating therapy with the lowest dose of vardenafil. Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of vardenafil and an alpha-blocker.
    Verapamil: (Moderate) Monitor blood pressure if verapamil is used with other antihypertensive agents; an additive blood pressure lowering effect may occur. Using verapamil with agents that attenuate alpha-adrenergic function, such as doxazosin, may result in blood pressure reductions that are excessive in some patients.
    Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with clarithromycin. Clarithromycin is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Voriconazole: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with voriconazole. Voriconazole is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
    Ziprasidone: (Minor) Ziprasidone is a moderate antagonist of alpha-1 receptors and may cause orthostatic hypotension with or without tachycardia, dizziness, or syncope. Additive hypotensive effects are possible if ziprasidone is used concurrently with antihypertensive agents.

    PREGNANCY AND LACTATION

    Pregnancy

    There are insufficient data regarding the use of doxazosin in pregnant women to determine if a drug-associated risk for major birth defects and miscarriage exists. However, untreated hypertension during pregnancy can result in increased maternal risks including pre-eclampsia, gestational diabetes, premature delivery, and delivery complications. Hypertension also increases the risk for fetal intrauterine growth restriction and intrauterine death. In animal reproduction studies, no adverse developmental effects were observed when doxazosin was orally administered at doses 4 to 10 times the human AUC exposures.

    There are no data regarding the effects of doxazosin on the breast-fed infant or on milk production. Although the data are insufficient to confirm the presence of doxazosin in human milk, a single case study involving a breast-feeding mother receiving doxazosin reports an infant exposure of doxazosin of < 1% of the maternal weight-adjusted dosage and a milk:plasma ratio of 0.1.

    MECHANISM OF ACTION

    Doxazosin competitively inhibits alpha-1-adrenergic receptors in the sympathetic nervous system. Doxazosin causes peripheral vasodilation, reducing peripheral vascular resistance and blood pressure. It causes the blood pressure to decrease in both the standing and the supine positions. Standing heart rates increase slightly, and the drug's effects on blood pressure and heart rate are more pronounced while the patient is standing. Doxazosin also alters lipid metabolism, decreasing the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increasing the high-density lipoprotein/total cholesterol ratio. The implications of these changes are not known. As an antihypertensive, doxazosin does not worsen and may decrease LVH, does not worsen insulin resistance, and exerts mild to negligible effects on sexual dysfunction.

    PHARMACOKINETICS

    Doxazosin is administered orally.  The primary hypotensive effect is usually evident from 2 hours onward, with peak hypotensive effects occurring in 5—6 hours. Antihypertensive effects of a single dose of doxazosin last approximately 24 hours. The drug is extensively protein-bound (98%). Although it appears to cross the placenta, animal studies have not revealed evidence of drug-induced fetal harm. It is not known whether doxazosin is distributed in the breast milk of humans, but studies in rats suggest accumulation in breast milk does occur.
     
    Doxazosin is highly metabolized in the liver, with the majority of an oral dose being eliminated via the feces and the remainder (9%) excreted in the urine. Enterohepatic recycling is suggested by significant fecal elimination of drug and secondary peaking of doxazosin plasma concentrations. Elimination is biphasic, and terminal elimination half-life is approximately 22 hours.

    Oral Route

    Doxazosin is well absorbed orally; bioavailability is approximately 65%. Food minimally affects the bioavailability of doxazosin (reduced mean peak plasma concentrations by 18% and reduced AUC by 12% in one study).