Doxazosin
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Alpha Adrenergic blockers, Therapy Class:
Antihypertensive, Doxazosin is an Antihypertensive agent belonging to Alpha Adrenergic blockers.
Doxazosin is used in the treatment of Hypertension (immediate release only) and Benign prostatic hyperplasia. It is also used to treat Ureteral stone(s) and expulsion.
It is well absorbed from the gastrointestinal tract. Its bioavailability is approx 65%, and it Crosses the placenta; enters breastmilk (in small amounts). The Plasma protein binding is approx 98%. It is metabolized in the liver primarily by CYP3A4 and to a lesser extent by CYP2D6 and CYP2C9 isoenzymes via O-demethylation or hydroxylation and gets excreted mainly via feces (approx 63% mainly as metabolites, 4.8% as unchanged drug); urine (9% mainly as metabolites) with an elimination half-life of approx 22 hours (conventional tab); 15-19 hours (extended-release tab).
The onset of Action of Doxazosin is within 2-6 hours.
The Duration of action of Doxazosin is >24 hours.
The Tmax of Doxazosin was within 2-3 hours (conventional tab); 8 ± 3.7 to 9 ± 4.7 hours (extended-release tab), and Cmax of Doxazosin was found within 10.1 ± 5.6 ng/ml
The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.
Doxazosin is available in a dosage form, such as tablets.
Doxazosin is available in the USA, Austria, Colombia, the UK, and India.
Doxazosin, a quinazoline derivative, selectively and competitively blocks the postsynaptic α1-adrenergic receptors resulting in venous and arterial vasodilation and reduction in total peripheral resistance and blood pressure. It also competitively inhibits the postsynaptic α1-adrenergic receptors in the prostatic and bladder neck tissues, thereby decreasing the sympathetic tone-induced urethral stricture in BPH.
Doxazosin is available in the form of a dosage form, such as tablets.
Doxazosin tablet is taken by mouth. It is usually taken once or twice a day with or without food.
Doxazosin is used in the treatment of Hypertension (immediate release only) and Benign prostatic hyperplasia. It is also used to treat Ureteral stone(s), expulsion.
Doxazosin selectively inhibits the postsynaptic alpha-1 receptors on vascular smooth muscle by nonselectively blocking the alpha-1a, alpha-1b, and alpha-1d subtypes. This action on blood vessels decreases systemic peripheral vascular resistance, reducing blood pressure, exerting minimal effects on the heart rate due to its receptor selectivity.
Doxazosin is approved for its use in following clinical indication:-
- Hypertension (immediate release only)
The immediate-release formulation can a second-line agent for the management of Hypertension in patients with concomitant BPH.If combination therapy is needed to achieve blood pressure control, the recommendation is to combine it with a diuretic for optimal effectiveness. There is a sentiment that Doxazosin can be used as monotherapy for Hypertension in a patient with LUTS or BPH; however, the American Urologic Society states that monotherapy with Doxazosin is not optimal and Hypertension should have separate management.
- Benign Prostatic Hyperplasia
Doxazosin is an alpha1 antagonist that is FDA approved to treat the signs and symptoms of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS). In the USA, alpha1 antagonists are the most commonly used treatment for the signs and symptoms of BPH. Though drug therapy for the management of symptoms of BPH or LUTS may not be as effective as surgery, it may be sufficient for symptom management and avoid the more serious adverse effects of surgery.
There is also an extended-release formulation of Doxazosin. It utilizes the gastrointestinal therapeutic system (GITS). It is FDA-approved for the treatment of BPH and LUTS but does not have approval for the treatment of Hypertension. One benefit of the extended-release formulation is stable drug concentrations throughout the day and decreased incidence of orthostatic hypotension/syncope.
Although not approved there have been certain off label use documented for Doxazosin which includes:
- Ureteral stone(s)
The use of alpha1-antagonists, including Doxazosin, for the treatment of ureteral calculi is recommended by US and European guidelines. Tamsulosin has the most evidence, but Doxazosin has demonstrated efficacy in the expulsion of ureteral calculi less than 10 mm as medical therapy alone or in combination with shockwave lithotripsy.
- Expulsion
Like Prazosin, Doxazosin has an off-label use for the treatment of PTSD-associated nightmares. There have been numerous small studies and case reports that have shown that Doxazosin is effective in treating PTSD-related nightmares.
The benefits of Doxazosin over Prazosin are a longer half-life and a gastrointestinal therapeutic availability system (in the extended-release form), allowing for a more gradual absorption of the drug, thereby reducing the peak to trough concentration ratio. This characteristic permits higher initial doses without the risk of hypotension. Extended-release doxazosin dosing initially starts at 4 mg daily.
Doxazosin is available in various dosage strengths: 1 mg, 2 mg, 4 mg, 8 mg
Doxazosin is available in the form of a dosage form such as tablets.
Dose Adjustment in Kidney patient:
- Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction.
- Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed: No supplemental dose or dosage adjustment necessary.
- Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound): No dosage adjustment necessary.
- CRRT: No dosage adjustment necessary.
- PIRRT (eg, sustained, low-efficiency defiltration): No dosage adjustment necessary.
Dose Adjustment in Hepatic Impairment Patient
- Mild to moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
- Severe impairment (Child-Pugh class C): Use is not recommended.
Dose Adjustment in Pediatric Patients.
- Dysfunctional voiding:
Children ≥3 years and Adolescents: Oral: Immediate release: Initial: 0.5 mg once daily at bedtime; some trials maintained a fixed dose; others titrated at weekly or biweekly intervals to effect as tolerated (maximum daily dose: 2 mg/day) . In some trials, a larger initial dose (1 mg/day) was used in patients weighing >40 to 50 kg
- Hypertension:
Children and Adolescents: Oral: Immediate release: Initial: 1 mg/day; maximum daily dose: 4 mg/day
Doxazosin is approved for the treatment of Hypertension.
Hypertension: It has been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.
Doxazosin may be contraindicated in the following
- Hypersensitivity to Doxazosin or other quinazolines.
- Pregnancy
- Doxazosin is Pregnancy Category C, meaning that there is no adequate data on the safety of Doxazosin in pregnant women.
The treating physician must closely monitor the patient and keep pharmacovigilance as follows.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• Hematologic effect: Decreases in WBC and neutrophil count have been reported; WBC and neutrophils returned to normal after discontinuation.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with heart failure, angina pectoris, or recent acute myocardial infarction (within the last 6 months). If symptoms of angina pectoris appear or worsen, discontinue use. In a scientific statement from the American Heart Association, Doxazosin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate).
• Hepatic impairment: Use with caution in patients with mild to moderate impairment (Child-Pugh class A and B); monitor blood pressure and for symptoms of hypotension. Not recommended in severe impairment (Child-Pugh class C) (extensively metabolized).
Alcohol Warning
Avoid taking alcohol with Doxazosin as it may result in side effects like headache, dizziness and faintness.
Pregnancy Warning
Teratogenic Effects
Pregnancy
Doxazosin is Pregnancy Category C, meaning that there is no adequate data on the safety of Doxazosin in pregnant women.
Food Warning
Salt Substitutes: Those who are taking Doxazosin should avoid sodium, calcium and magnesium-rich foods. The salts may reduce the blood-pressure lowering effect of Doxazosin.
The adverse reactions related to molecule Doxazosin can be categorized as
● Common Adverse effect:
Cough ,headache, dizziness, drowsiness
● Less Common adverse effects:
Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower, hoarseness, difficulty breathing or swallowing, lightheadedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.
The clinically relevant drug interactions of Doxazosin is briefly summarized here.
May result in symptomatic hypotension with phosphodiesterase-5 (PDE-5) inhibitors (e.g. sildenafil, tadalafil, vardenafil). Strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ritonavir, nelfinavir, telithromycin) may increase the serum concentration of Doxazosin. It may potentiate the hypotensive effects of other α1-blockers and antihypertensive agents.
Symptom: Hypotension.
Management: Supportive treatment. Place the patient in a supine, head down position. If inadequate, treat shock with volume expanders. May give vasopressors if needed. Monitor renal function.
Pharmacodynamics:
Doxazosin decreases standing and supine blood pressure5 and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. Doxazosin may cause hypotension due to its pharmacological actions. This frequently occurs in the upright position, leading to a feeling of dizziness or lightheadedness. The first dose of Doxazosin may lead to such effects, however, subsequent doses may also cause them. The risk of these effects is particularly high when dose adjustments occur or there are long intervals between doxazosin doses.
Doxazosin, a quinazoline derivative, selectively and competitively blocks the postsynaptic α1-adrenergic receptors resulting in venous and arterial vasodilation, and reduction in total peripheral resistance and blood pressure. It also competitively inhibits the postsynaptic α1-adrenergic receptors in the prostatic and bladder neck tissues, thereby decreasing the sympathetic tone-induced urethral stricture in BPH.
Pharmacokinetics:
- Absorption: Doxazosin is rapidly absorbed in the gastrointestinal tract and peak concentrations are achieved within 2-3 hours after administration. The bioavailability is about 60%-70%. The intake of food with Doxazosin is not expected to cause clinically significant effects.
- Distribution: The volume of distribution of Doxazosin is 1.0-1.9 L/kg.7,11 In a study of radiolabeled Doxazosin administered to pregnant rats, Doxazosin was found to cross the placenta.
- Metabolism: Hepatic metabolism of Doxazosin produces inactive O-demethylated and C-hydroxylated metabolites. Metabolism occurs via O-demethylation of the quinazoline nucleus of Doxazosin or via hydroxylation of its benzodioxan portion. The enzymes involved in the metabolism of Doxazosin include CYP2C1923, CYP2D6, CYP2C19, and CYP3A4, which is the primary metabolizing enzyme. Doxazosin itself is considered to be mainly responsible for its pharmacological action, however, some active metabolites have been Identified whose pharmacokinetics have not been adequately characterized.
- Excretion: Mainly via feces (approx. 63% mainly as metabolites, 4.8% as unchanged drug); urine (9% mainly as metabolites). Elimination half-life: Approx. 22 hours (conventional tab); 15-19 hours (extended-release tab).
There are some clinical studies of the drug Doxazosin mentioned below:
- https://clinicaltrials.gov/ct2/show/NCT00532493
- https://pubmed.ncbi.nlm.nih.gov/29414272/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538493/
- https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.17080913
- https://www.mims.com/india/drug/info/doxazosin?type=full&mtype=generic
- https://www.uptodate.com/contents/doxazosin-drug-information?search=doxazosin-drug-in&usage_type=panel&kp_tab=drug_general&source=search_result&selectedTitle=1~37&display_rank=1#F162889
- https://go.drugbank.com/drugs/DB00590
- https://www.rxlist.com/consumer_doxazosin_cardura/drugs-condition.htm
- https://reference.medscape.com/drug/cardura-xl-doxazosin-342343
- Fulton B, Wagstaff AJ, et.al,. Doxazosin. Drugs. 1995 Feb;49(2):295-320
- Young RA, Brogden RN. Doxazosin. Drugs. 1988 May;35(5):525-41
Published on: 21 Oct 2022 5:21 PM GMT
