Doxazosin (Cardura) - Uses, Dosage, Warnings, Side effects, MOA

Doxazosin (Cardura) is an alpha-1 adrenergic receptor blocker that is used to treat patients with symptoms of BPH (benign prostatic hyperplasia) and hypertension.

Doxazosin (Cardura) Uses:

  • Benign prostatic hyperplasia:

    • For 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.
  • Off Label Use of Doxazosin in Adults:

    • Ureteral calculi (distal)

Adult dose:

Doxazosin (Cardura) Dose in the treatment of BPH: Oral:

  • Immediate-release tablets:

    • Initial: 1 mg once day; may be increased to 2 mg, 4 mg, and finally 8 mg at 1- to 2-week intervals, up to a maximum of 8 mg once daily, depending on the patient's reaction and tolerability.
    • Re-initiation of therapy:

      • If the medication is stopped for a few days, restart it at a dose of 1 mg and titrate using the original dosing schedule.
  • Extended-release tablets:

    • 4 mg once a day;
    • Every 3 to 4 weeks, the dose may be increased to 8 mg once a day (maximum: 8 mg/day) depending on response and tolerability.
    • Re-initiation of therapy:

      • Restart medication at a dose of 4 mg and titrate using the initial dosing regimen if it has been stopped for a few days.

Note:

  • Conversion to extended-release from the immediate-release:

    • Do not take the final evening dose of immediate-release before starting morning dosing with the extended-release product;
    • initiate the extended-release product using 4 mg once a day.

Doxazosin (Cardura) dose as an alternative agent in the treatment of Hypertension: Oral:

  • Immediate-release:

    • Initial: 1 mg once a day;
    • titrate based on the patient's response as necessary, up to a dose of 16 mg once per day;
    • maximum dose: 16 mg/day.
    • Re-initiation of therapy:

      • Restart medication at a dose of 1 mg and titrate using the initial dosing regimen if it has been stopped for a few days.

Doxazosin (Cardura) Dose in the treatment of Distal Ureteral calculi expulsion (off-label): Oral:

  • Immediate release:

    • 4 mg once a day in the evening.
    • Note: Patients with stones >10 mm were excluded from studies.

Dose in children:

  • Note: If the drug is discontinued for more than several days, re-initiate with initial dose and titrate as needed.

Doxazosin (Cardura) Dose in the treatment of Dysfunctional voiding:

  • Children ≥3 years and Adolescents: Oral:

    • Immediate release:
      • Initial: 0.5 mg once every day at bedtime; some trials continued with a fixed-dose; others titrated at weekly or biweekly intervals to effect as tolerated (maximum daily dose: 2 mg/day).
      • In some trials, a larger initial dose (1 mg/day) was used in patients whose weight >40 to 50 kg.

Doxazosin (Cardura) Dose in the treatment of Hypertension:

  • Children and Adolescents: Oral:

    • Immediate release:
      • Initial: 1 mg/day;
      • The maximum daily dose: 4 mg/day

Pregnancy Risk Category: C

  • In some studies on animal reproduction, adverse events were reported.
  • Doxazosin crosses over the placenta (Versmissen 2016,
  • Chronic maternal hypertension, if not treated, can lead to adverse outcomes in the infant, mother, and fetus.
  • Other agents are preferred if hypertension is a concern during pregnancy.

Doxazosin use during breastfeeding:

  • Breast milk contains doxazosin. A single case report describing a maternal dose (doxazosin 4mg every 24 hours) of doxazosin for two doses is available.
  • Samples of milk were taken at different times over 24 hours starting approximately 17 hours after the first dose.
  • The maternal serum samples were taken at the same time as the father's, starting approximately one hour later.
  • After the first dose, the highest levels of doxazosin in serum and milk were seen within one hour.
  • The highest milk concentration (4.15 mg/L) was used to calculate the infant's estimated dose. It was 1% of weight-adjusted maternal dosage.

Renal dose:

Doxazosin (Cardura) Dose in Liver disease: 

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

Doxazosin (Cardura) Dose in Liver disease:

  • Mild to moderate impairment (Child-Pugh class A or B):

    • There are no dosage adjustments provided in the drug manufacturer’s labeling;
    • use with caution.
  • Severe impairment (Child-Pugh class C):

    • Use is not recommended.

Common Side Effects of Doxazosin (Cardura):

  • Central nervous system:

    • Dizziness
    • Malaise
    • Fatigue
    • Headache

Less Common Side Effects of Doxazosin (Cardura):

  • Cardiovascular:

    • Edema
    • Hypotension
    • Orthostatic Hypotension
    • Cardiac Arrhythmia
    • Facial Edema
    • Flushing
    • Palpitations
  • Central Nervous System:

    • Drowsiness
    • Vertigo
    • Pain
    • Anxiety
    • Ataxia
    • Hypertonia
    • Insomnia
    • Movement Disorder
    • Myasthenia
  • Endocrine & Metabolic:

    • Sexual Disorder
  • Gastrointestinal:

    • Abdominal Pain
    • Nausea
    • Dyspepsia
    • Xerostomia
  • Genitourinary:

    • Urinary Incontinence
    • Urinary Tract Infection
  • Neuromuscular & Skeletal:

    • Weakness
    • Muscle Cramps
    • Myalgia
    • Arthralgia
    • Arthritis
  • Ophthalmic:

    • Visual Disturbance
  • Otic:

    • Tinnitus
  • Renal:

    • Polyuria
  • Respiratory:

    • Respiratory Tract Infection
    • Rhinitis
    • Dyspnea
    • Epistaxis

Contraindications to Doxazosin:

  • Hypersensitivity/Allergy 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 defect, or
    • glucose-galactose malabsorption.

Warnings and precautions

  • Allergy reactions:

    • It can cause skin rash, urticaria and pruritus as well as respiratory symptoms such as angioedema and pruritus.
  • CNS depression:

    • CNS depression can lead to mental or physical impairments.
    • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.
  • Floppy iris syndrome:

    • Patients undergoing cataract surgery who had been previously treated with alpha-1 blocking drugs have shown intraoperative floppy-iris syndrome.
    • There is no benefit to stopping alpha-blocker treatment before surgery.
    • Modifications to surgical procedures may be necessary.
  • Hematologic effect

    • There have been reports of a decrease in white blood cell count (WBC), and neutrophil count. WBC and neutrophil counts returned to normal following discontinuation.
  • Orthostatic hypotension, syncope

    • Orthostatic hypotension or syncope may occur within hours of dosing.
    • However, it is possible to experience the same effect after therapy has been stopped for a few more days or if another antihypertensive drug is introduced, such as a PDE-5 inhibitor or nitrates.
    • Patients with orthostatic hypotension symptoms should be supervised.
  • Priapism

    • Rarely, priapism was associated with drug use.
    • For erections that last more than four hours, seek immediate medical attention.
  • Cardiovascular disease

    • Patients with angina pectoris, heart failure, and recent acute myocardial injury (within the past 6 months) should be cautious.
    • Stop using the medication if you experience angina pectoris symptoms or worsening.
    • The American Heart Association has stated that doxazosin may be an agent that can exacerbate myocardial dysfunction.
  • Hepatic impairment

    • Patients with mild or moderate impairment (Childugh class A/B) should be used with caution. Monitor blood pressure and look for signs of hypotension.
    • Not recommended for severe impairment (Child Puugh class C).
  • Prostate cancer:

    • Before starting therapy, make sure you rule out prostate cancer. There are many symptoms that can be similar to BPH.

Doxazosin: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).

Alpha-/Beta Agonists The vasoconstricting effects of Alpha/BetaAgonists may be lessened by Alpha1-Blockers. Alpha-/Beta Agonists may also lessen the vasodilation caused by Alpha1-Blockers.
Alpha1-Agonists The vasoconstrictive effects of alpha1-1 agonists may be lessened by alpha1-blockers.
Amphetamines Alpha1-Agonists may also have an impact on Alpha1-Blocker vasodilation.
Antipsychotic Agents, Second Generation (Atypical) May lessen the effects of antihypertensive medications in treating hypertension.
Antipsychotic drugs can have a greater hypotensive effect when blood pressure-lowering medications are used (Second Gen [Atypical]).
Aprepitant High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Barbiturates May intensify blood pressure lowering medications' hypotensive effects.
Benperidol May intensify blood pressure lowering medications' hypotensive effects.
Beta-Blockers Alpha1-Blockers may increase orthostatic hypotensive effects. Ophthalmic products are less likely to be a risk than systemic ones. Levobunolol and Metipranolol are exceptions.
Bosentan Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Brigatinib May lessen the effects of antihypertensive medications in treating hypertension.
Brimonidine (Topical) The bradycardic effects of antihypertensive medications may be exacerbated by brutinib.
Calcium Channel Blockers May intensify blood pressure lowering medications' hypotensive effects.
Clofazimine High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Moderate CYP3A4 Inducers Calcium channel blockers' hypotensive effects could be amplified by alpha1-blockers.
Moderate CYP3A4 inhibitors Could decrease serum levels of CYP3A4 substrates (High Risk with Inducers).
Dapoxetine Could possibly reduce the metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Deferasirox Alpha1-Blockers might make the effects of orthostatic hypotension worse.
Dexmethylphenidate Alpha1-Blockers might make the effects of orthostatic hypotension worse.
Diazoxide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
DULoxetine DULoxetine may increase hypotensive effects by lowering blood pressure.
Duvelisib High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Erdafitinib Could decrease serum levels of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosaprepitant High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosnetupitant High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Herbs (Hypertensive Properties) May decrease the antihypertensive effects of Antihypertensive Drugs.
Herbs (Hypotensive properties) Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Hypotension-Associated Agents Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Ivosidenib Could decrease serum levels of CYP3A4 substrates (High Risk with Inducers).
Larotrectinib High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Levodopa-Containing Products Blood Pressure Lowering Agents can increase the hypotensive effects of Levodopa - Containing Products.
Lormetazepam Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Methylphenidate May decrease the antihypertensive effects of Antihypertensive Drugs.
Molsidomine Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Netupitant High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Nicorandil Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Nitroprusside The hypotensive effects of Nitroprusside may be enhanced by blood pressure lowering agents.
Palbociclib High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Pentoxifylline Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Pholcodine Pholcodine may increase hypotensive effects by lowering blood pressure.
Prostacyclin Analogues Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Quinagolide Might increase the hypotensive effects of Blood Pressure Lowering Agents.
Rilmenidine Rilmenidine may have a hypotensive effect that Alpha1-Blockers might enhance.
Sarilumab Could decrease serum levels of CYP3A4 substrates (High Risk with Inducers).
Siltuximab Could decrease serum levels of CYP3A4 substrates (High Risk with Inducers).
Simeprevir High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Tocilizumab Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Yohimbine May decrease the antihypertensive effects of Antihypertensive Drugs.

Risk Factor D (Regard therapy modification)

Amifostine Amifostine's hypotensive effects may be enhanced by blood pressure lowering agents. Treatment: Blood pressure lowering drugs should be stopped 24 hours before amifostine administration. Amifostine should be avoided if blood pressure lowering medication cannot be withheld.
Strong CYP3A4 Inducers May speed up CYP3A4 substrate metabolism (High Risk with Inducers). Management: You might think about switching out one of the interfering medications with another medication. Contraindications may apply to specific combinations. the relevant manufacturer's label.
Strong CYP3A4 inhibitors Could possibly reduce the metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Dabrafenib High chance that inducers will lower serum CYP3A4 substrate levels.
Management: If at all possible, look for CYP3A4 substrate substitutes.
It is best to avoid concurrent therapy wherever possible. Keep a close eye on the substrate's clinical effects (especially therapeutic effects).
Enzalutamide High chance that inducers will lower serum levels of CYP3A4 substrates.
Management: Steer clear of using enzalutamide and CYP3A4 substrates simultaneously. When utilising enzalutamide or any other CYP3A4 sub-substance, you should use caution.
Lorlatinib High chance that inducers will lower serum levels of CYP3A4 substrates. Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates. A therapeutic failure or negative clinical outcomes could result from even a modest drop in serum concentrations.
MiFEPRIStone High chance that inhibitors will raise serum levels of CYP3A4 substrates.
Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity.
Avoid ergotamine and dihydroergotamine.
Mitotane High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
Obinutuzumab This may increase the hypotensive effects of Blood Pressure Lowering Agents. Management: You may temporarily withhold blood pressure lowering medication beginning 12 hours before obinutuzumab injection and continuing for 1 hour after infusion.
Phosphodiesterase 5 Inhibitors Alpha1-Blockers (Nonselective) may increase the hypotensive effects. Management: Before initiating any combination, ensure that the patient is stable on the first agent. Concurrent alpha 1-blockers should not be used when tadalafil treatment is being administered for BPH.
Pitolisant High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
St John's Wort High chance that inducers will lower serum CYP3A4 substrate levels.
Management: You might think about switching out one of the interfering medications with another medication. Contraindications may apply to specific combinations. the relevant manufacturer's label.
Stiripentol High chance that inhibitors will raise serum levels of CYP3A4 substrate. Treatment: Steer clear of using stiripentol with CYP3A4 substrates that have a limited therapeutic index. This is done to prevent negative consequences and toxicity. Any CYP3A4 substrate that is administered in conjunction with stiripentol should be strictly monitored.

Risk Factor X (Avoid Combination)

Alpha1-Blockers This may increase the antihypertensive effects of Alpha1-Blockers.
Bromperidol The hypotensive effects of bromperidol may be strengthened by blood pressure-lowering medications. The hypotensive effects of blood pressure-lowering medications may be lessened by bromperidol.
Conivaptan High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fusidic Acid (Systemic). High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Idelalisib High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations

Monitoring parameters:

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

Hypertension: Follow The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults:

  • Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
    • Keep 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

How to administer Doxazosin (Cardura)?

Oral:

  • Extended-release:
    • Swallow tablets whole; do not crush, cut, chew, or divide. Administer with morning meal.
  • Immediate-release:
    • Administer daily dose either in the morning or evening.

Mechanism of action of Doxazosin (Cardura):

  • Hypertension: Competitively inhibits postsynaptic Alpha-1 adrenergic receptors, which causes vasodilation and arterioles to dilate and decreases total peripheral resistance and blood pressure.
  • It is about 50% as potent on a weight by weight basis as prazosin.

BPH:

  • Competitively inhibits postsynaptic beta-1 adrenergic receptors within the bladder neck and prostatic stromal tissues. 
  • This decreases the sympathetic tone-induced stricture in the urethral tract that causes BPH symptoms.

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)

International Brands of Doxazosin:

  • Cardura
  • Cardura XL
  • APO-Doxazosin
  • Cardura-1
  • Cardura-2
  • Cardura-4
  • DOM-Doxazosin
  • Doxazosin-1
  • Doxazosin-2
  • Doxazosin-4
  • MYLAN-Doxazosin
  • PMS-Doxazosin
  • TEVA-Doxazosin
  • Alfadil
  • Alfadil XL
  • Alfamedin
  • Cadex
  • Cadil
  • Cadlin
  • Cardenalin
  • Cardolin-2
  • Cardular
  • Cardular PP
  • Cardular Uro
  • Cardura
  • Cardura CR
  • Cardura XL
  • Cardura-XL S.R.
  • Carduran
  • Carduran Neo
  • Carduran Retard
  • Carduran XL
  • Cazosin
  • Curcard
  • Dalgen
  • Dedralen
  • Diblocin
  • Diblocin PP
  • Diblocin Uro
  • Doka
  • Dophilin
  • Dorbantil
  • Dosabin
  • Dosan
  • Dosin
  • Dovozin
  • Doxaben
  • Doxaben XL
  • Doxacar
  • Doxacard
  • Doxacin
  • Doxacor
  • Doxagamma
  • Doxan
  • Doxane
  • Doxatan
  • Doxazone XL SR
  • Doxino
  • Doxolbran
  • Genzosin
  • Jutalar
  • Kamiren
  • Kamiren XL
  • Kinxaben
  • Maguran
  • Magurol
  • Mahurol
  • Pencor
  • Progandol
  • Prostasin
  • Pzocin XL
  • Saxobin
  • Supressin
  • Tarzos
  • Tensidox
  • Tonocardin
  • Tonokardin
  • Uriduct
  • Xadosin
  • Xadosin XL
  • Zoxan
  • Zoxan LP
  • Zoxon

Doxazosin Brand Names in Pakistan:

Doxazosin 2 mg Tablets

Carducin Hamaz Pharmaceutical (Pvt) Ltd.
Cardura Pfizer Laboratories Ltd.
Caydor Caylex Pharmaceuticals (Pvt) Ltd.
Dozax Wilshire Laboratories (Pvt) Ltd.
Oxiz Noa Hemis Pharmaceuticals
Oxiz Noa Hemis Pharmaceuticals
Proalpha Obsons Pharmaceuticals
Prosdura Epla Laboratories (Pvt) Ltd.
Uripas Searle Pakistan (Pvt.) Ltd.

Doxazosin 4 mg Tablets

Cardura Pfizer Laboratories Ltd.
Caydor Caylex Pharmaceuticals (Pvt) Ltd.
Dozax Wilshire Laboratories (Pvt) Ltd.
Oxiz Noa Hemis Pharmaceuticals
Uripas Searle Pakistan (Pvt.) Ltd.