1. DOXAZOSIN HISTORY
(How was Doxazosin discovered?)

Doxazosin contains the active ingredient Doxazosin, which is a type of medicine called an alpha-blocker. Doxazosin works by blocking alpha-receptors in certain areas of the body. 

The US FDA approved Doxazosin in October 2000.

2. DOXAZOSIN FACTS

Alpha-receptors are found on the muscle in the walls of blood vessels. When Doxazosin blocks these receptors it causes the muscle in the blood vessel to relax and the blood vessel to widen. This lets the blood pass more easily through the blood vessels and hence reduces the pressure in the blood vessels. Doxazosin can therefore be used to treat high blood pressure.

Alpha-receptors are also found on the muscle in the prostate gland. This gland is found only in men and lies at the top of the tube connecting the bladder to the outside (urethra).

The prostate gland often enlarges with advancing age (benign prostatic hyperplasia), pressing on the urethra and obstructing the flow of urine from the bladder. This can cause various urinary symptoms such as difficulty passing urine.

By blocking the alpha-receptors, Doxazosin causes the muscle in the prostate gland to relax. This allows urine to flow freely past the prostate and relieves the urinary symptoms of this condition. 

3.ABOUT DOXAZOSIN MEDICATION

What is benign prostatic hyperplasia?

Benign prostatic hyperplasia (BPH) is a condition that affects the prostate gland in men.

The prostate is a gland found between the bladder (where urine is stored) and the urethra (the tube urine passes through). As men age, the prostate gland slowly grows bigger (or enlarges). As the prostate gets bigger, it may press on the urethra and cause the flow of urine to be slower and less forceful.

"Benign" means the enlargement isn't caused by cancer or infection. "Hyperplasia" means enlargement.

What are the symptoms of BPH?

Most symptoms of BPH start gradually. One symptom is the need to get up more often at night to urinate. Another symptom is the need to empty the bladder often during the day. Other symptoms include difficulty in starting the urine flow and dribbling after urination ends. The size and strength of the urine stream may decrease.

These symptoms can be caused by other things besides BPH. They may be signs of more serious diseases, such as a bladder infection or bladder cancer. Tell your doctor if you have any of these symptoms, so he or she can decide which tests to use to find the possible cause.

How will my doctor know if I have BPH?

After your doctor takes a complete history of your symptoms, a rectal exam is the next step. This exam allows your doctor to actually feel the size of the prostate gland.

It might not be possible for your doctor to be sure that your prostate problem is benign just by taking a history and performing a physical exam. Your doctor might need to look at a sample of your urine for signs of infection. Your doctor may also do a blood test. An ultrasound exam or a biopsy of the prostate may help your doctor make the diagnosis.

How will my doctor treat my BPH?

Once your doctor is sure that your symptoms are caused by benign growth of the prostate gland, treatment can be recommended. However, your doctor may suggest that you wait to see if your symptoms get better because sometimes-mild symptoms get better on their own. If your symptoms get worse, your doctor may suggest another treatment option.

Surgery is considered the most effective treatment and is used in men with strong symptoms. This is also the best way to diagnose and cure early cancer of the prostate. Surgery is usually done through the urethra, leaving no scars. Surgery does have risks, such as bleeding, infection or impotence. These risks are generally small.

Are there any drugs I can take?

Drug treatments are available. Finasteride and dutasteride blocks a natural hormone that makes the prostate enlarge, but it does not help all patients. The side effects of finasteride are rare and mild, but they usually have to do with sexual function. They go away when the medicine is stopped. The prostate will enlarge again when the medicine is stopped, so another treatment may have to be tried.

Another kind of medicine, called alpha blockers, also can help the symptoms of BPH. Some of these drugs are terazosin, doxazosin, tamsulosin and alfuzosin . Alpha blockers have been used for a long time to treat high blood pressure, but they can also help the symptoms of BPH, even in men with normal blood pressure. These medicines may not work in all men. The side effects of alpha blockers are mild and go away if you stop taking the medicine. The side effects include dizziness, fatigue and lightheadedness. 

4.DOXAZOSIN EFFECTIVENESS
(When is Doxazosin best taken?)

After oral administration of therapeutic doses, peak plasma levels of Doxazosin occur at about 2-3 hours. Bioavailability is approximately 65%, reflecting first pass metabolism of Doxazosin by the liver. The effect of food on the pharmacokinetics of Doxazosin was examined in a crossover study with twelve hypertensive subjects. Reductions of 18% in mean maximum plasma concentration and 12% in the area under the concentration-time curve occurred when doxazosin mesylate was administered with food. Neither of these differences was statistically or clinically significant. 

Doxazosin is extensively metabolized in the liver, mainly by O-demethylation of the quinazoline nucleus or hydroxylation of the benzodioxan moiety. Although several active metabolites of Doxazosin have been identified, the pharmacokinetics of these metabolites have not been characterized. In a study of two subjects administered radiolabelled Doxazosin 2 mg orally and 1 mg intravenously on two separate occasions, approximately 63% of the Doxazosin dose was eliminated in the feces and 9% of the dose was found in the urine. On average only 4.8% of the dose was excreted as unchanged drug in the feces and only a trace of the total radioactivity in the urine was attributed to unchanged drug. At the plasma concentrations achieved by therapeutic doses approximately 98% of the circulating drug is bound to plasma proteins.

Plasma elimination of Doxazosin is biphasic, with a terminal elimination half-life of about 22 hours. Steady-state studies in hypertensive patients given Doxazosin doses of 2-16 mg once daily showed linear kinetics and dose proportionality. In two studies, following the administration of 2 mg orally once daily, the mean accumulation ratios (steady-state AUC vs. first dose AUC) were 1.2 and 1.7. Enterohepatic recycling is suggested by secondary peaking of plasma Doxazosin concentrations. 

5.DOXAZOSIN EFFECTS ON SPECIAL POPULATION
(How do different people react to Doxazosin?)

Nursing Mothers

Studies in lactating rats given a single oral dose of 1 mg/kg of [2-14C]- Doxazosin indicate that Doxazosin accumulates in rat breast milk with a maximum concentration about 20 times greater than the maternal plasma concentration. It is not known whether Doxazosin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Doxazosin is administered to a nursing mother.

Pediatric Use

The safety and effectiveness of Doxazosin as an antihypertensive agent have not been established in children.

Geriatric Use

The safety and effectiveness profile of Doxazosin in BPH was similar in the elderly (age 65 years) and younger (age <65 years) patients.

6.DOXAZOSIN EFFECTS ON MEDICAL CONDITIONS
(How does Doxazosin affect your existing condition/ailment?)

Impaired Liver Function

Doxazosin should be administered with caution to patients with evidence of impaired hepatic function or to patients receiving drugs known to influence hepatic metabolism.

7.OTHER/ALTERNATE USES OF DOXAZOSIN
(What else does Doxazosin treat?)

Doxazosin is also indicated for the treatment of hypertension. Doxazosin may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers or angiotensin-converting enzyme inhibitors.

8.ADVERSE/SIDE EFFECTS of DOXAZOSIN
(What are the side effects of Doxazosin?)

The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented in the table below are based on combined data from seven placebo-controlled trials involving once daily administration of doxazosin mesylate in doses of 1-16 mg in hypertensives and 0.5-8 mg in normotensives. The adverse events when the incidence in the doxazosin mesylate group was at least 1% are summarized in table below. No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema and dyspnea. Dizziness and dyspnea appeared to be dose-related.

Adverse Reactions During Placebo-Controlled Studies Benign Prostatic Hyperplasia
Body System	Doxazosin Mesylate (N=665)	Placebo (N=300)
Body as a Whole
Back Pain	1.8%	2.0%
Chest Pain	1.2%	0.7%
Fatigue	8.0%	1.7%
Headache	9.9%	9.0%
Influenza-Like Symptoms	1.1%	1.0%
Pain	2.0%	1.0%
Cardiovascular System
Hypotension	1.7%	0.0%
Palpitation	1.2%	0.3%
Digestive System
Abdominal Pain	2.4%	2.0%
Diarrhea	2.3%	2.0%
Dyspepsia	1.7%	1.7%
Nausea	1.5%	0.7%
Metabolic and Nutritional Disorders
Edema	2.7%	0.7%
Nervous System
Dizziness†	15.6%	9.0%
Mouth Dry	1.4%	0.3%
Somnolence	3.0%	1.0%
Respiratory System
Dyspnea	2.6%	0.3%
Respiratory Disorder	1.1%	0.7%
Special Senses
Vision Abnormal	1.4%	0.7%
Urogenital System
Impotence	1.1%	1.0%
Urinary Tract Infection	1.4%	2.3%
Skin & Appendages
Sweating Increased	1.1%	1.0%
Psychiatric Disorders
Anxiety	1.1%	0.3%
Insomnia	1.2%	0.3%

Cardiovascular System: Angina pectoris (0.6% vs. 0.7%), postural hypotension (0.3% vs. 0.3%), syncope (0.5% vs. 0.0%), tachycardia (0.9% vs. 0.0%).

Urogenital System : Dysuria (0.5% vs. 1.3%).

Psychiatric Disorders : Libido decreased (0.8% vs. 0.3%).

The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies.

The majority of adverse experiences with Doxazosin were mild.

Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin. The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight. The following additional adverse reactions were reported by <0.5% of 3960 patients who received Doxazosin in controlled or open, short- or long-term clinical studies; including international studies.

Cardiovascular System: Angina pectoris, myocardial infarction, cerebrovascular accident.

Autonomic Nervous System: Pallor.

Metabolic: Thirst, gout, hypokalemia.

Hematopoietic: Lymphadenopathy, purpura.

Reproductive System: Breast pain.

Skin Disorders: Alopecia, dry skin, eczema.

Central Nervous System: Paresis, tremor, twitching, confusion, migraine, impaired concentration.

Psychiatric: Paroniria, amnesia, emotional lability, abnormal thinking, depersonalization.

Special Senses: Parosmia, earache, taste perversion, photophobia, abnormal lacrimation.

Gastrointestinal System: Increased appetite, anorexia, fecal incontinence, gastroenteritis.

Respiratory System: Bronchospasm, sinusitis, coughing, pharyngitis.

Urinary System: Renal calculus.

General Body System: Hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms.

Doxazosin has not been associated with any clinically significant changes in routine biochemical tests. No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine or liver function tests. Doxazosin mesylate has been associated with decreases in white blood cell counts (see PRECAUTIONS).

In post-marketing experience the following additional adverse reactions have been reported:

Autonomic Nervous System: priapism;

Central Nervous System: hypoesthesia;

Endocrine System: gynecomastia;

Gastrointestinal System: vomiting;

General Body System: allergic reaction;

Heart Rate/Rhythm: bradycardia;

Hematopoietic: leukopenia, thrombocytopenia;

Liver/Biliary System: hepatitis, hepatitis cholestatic;

Respiratory System: bronchospasm aggravated;

Skin Disorders: urticaria;

Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.