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

  • Re-initiation of therapy:

    • If therapy is discontinued for a few days, re-initiate at 1 mg dose and titrate using the initial dosing regimen.

• Extended-release tablets:

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

  • Re-initiation of therapy:

    • If therapy is discontinued for several days, re-initiate at 4 mg dose and titrate using the initial dosing regimen.

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 as needed based on patient response up to a dose of 16 mg once a day;
  • maximum dose: 16 mg/day.

  • Re-initiation of therapy:

    • If therapy is discontinued for several days, re-initiate at 1 mg dose and titrate using the initial dosing regimen.

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

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: