Doxazosin: Uses, Side Effects, and Interactions

Benign prostatic hyperplasia and hypertension are both common as we age. These conditions tend to increase as we grow older.

According to estimates in men over 60 years, around 25% of them are likely to suffer from hypertension and benign prostatic hyperplasia at the same time (1).

We don’t always need to use multiple drugs in these patients. Instead, certain medications may improve both conditions.

One of them is doxazosin, an alpha-blocker used for BPH and other diseases.

n what clinical settings is doxazosin useful? Are there any side effects we should know about? What about drug interactions?

In this article, we are going to answer all of these questions. We are also going to provide a few alternative treatments for doxazosin.

What is doxazosin?

Doxazosin is an alpha-blocker medication to treat symptoms of benign prostatic hyperplasia. It is also used to reduce blood pressure readings in hypertensive patients.

While doing so, it does not cause hypotension in patients with normal blood pressure readings (2). One of the most commonly available forms of doxazosin is doxazosin mesylate.

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What is doxazosin used for?

Along with other medications, doxazosin is commonly used to treat benign prostatic hyperplasia. It can be used to treat hypertension, as well.

It relaxes the blood vessels to promote blood flow in various target tissues. However, not all patients with hypertension and cardiovascular problems are recommended to use this drug (1).

In benign prostatic hyperplasia, doxazosin does not reduce the size of the prostate. Instead, it relaxes the muscles of the prostatic gland. It does a similar job with bladder muscle and provides some relief from the urinary symptoms of BPH.

As we will further address, doxazosin can be found in different forms and dosages. Among them, the extended-release presentations are specifically designed for prostate issues. They are not to be used in patients with hypertension (1).

Among other less frequent uses, doxazosin can promote the elimination of kidney stones (3). It is also useful to treat urinary bladder issues in women (4).

Moreover, new studies suggest that doxazosin might also be useful in post-traumatic stress disorders and other psychiatric conditions (5). It is also helpful in cases of erectile dysfunction (6). However, these applications warrant further research before using them in the general public.

When should you consider doxazosin treatment?

The guidelines to use doxazosin treatment in hypertension and BPH are very specific. They detail the exact moment when doxazosin treatment should be considered.

In hypertension, it is used only in cases of resistant hypertension. In other words, it is not the first medication patients will try. Moreover, according to the National Institute for Health and Clinical Effectiveness (NICE), there are more effective drugs than doxazosin.

NICE guidelines place alpha-blockers like doxazosin as the fourth-line therapy for resistant hypertension. In other words, it is used only in cases when patients do not tolerate other drugs, or they are ineffective. This decision was made to avoid side effects of doxazosin we will review in further sections of this article (7).

The clinical guidelines paint a completely different picture in cases of lower urinary tract symptoms.

Doxazosin is more recommended for patients with BPH than patients with hypertension. That is because it is a first-line treatment for lower urinary tract symptoms (LUTS). (8).

What are the different forms and doses of doxazosin?

Doxazosin tablets come in different doses and forms. Tablets are usually 1, 2, 4, or 8 milligrams. In extended-release formulations, you may only find 4 and 8-milligram tablets, but that’s only for patients with BPH. There is also a long-acting, controlled-release formulation called GITS.

It stands for the gastrointestinal therapeutic system. This formulation normalizes drug concentration in the blood, and it is useful in both conditions (1).

Doses range from 1mg to 16mg daily for patients with hypertension. Benign prostatic hyperplasia patients may benefit from 1mg to 8mg daily. It depends on the clinical response of the patient and the severity of the symptoms.

Since doxazosin is administered only once a day, many patients worry about missing a dose. If you forgot a dose of doxazosin, take it as soon as you remember.

If you forgot for a whole day and you’re near the next dose, skip the last dose. If you forgot your medication for several days, contact your doctor. You might need a dose adjustment to resume your treatment.

What groups of people respond best to doxazosin?

Similar to other alpha-blockers, doxazosin does the job by relaxing blood vessels and improving circulation.

Moreover, studies suggest there’s also another pathway contributing to relieve urinary symptoms. (1). But regardless of the mechanism of action, there’s a group of people that respond best to this treatment.

Doxazosin mesylate is an option for this type of patients:

  • Patients with coexisting hypertension and BPH: These patients may benefit from the pressure-lowering and the improvements in urinary symptoms at the same time.

  • Patients with coexisting hypertension and dyslipidemia: According to recent clinical trials, doxazosin might also reduce fat levels in the blood.

  • Patients with elevated cardiovascular risk: Not all cardiovascular problems, though. Heart failure patients are not recommended to use doxazosin.

  • Older adults: 25% of older adults have coexisting hypertension. It is often asymptomatic.

We can use doxazosin tablets in many ways. However, it is currently recommended for hypertension and benign prostatic hyperplasia (1).

Hypertension: The efficacy of doxazosin to treat hypertension is well-established. Additionally, it has other effects that improve our cardiovascular health.

It helps patients control their blood lipids. It is also known to improve the sensitivity to insulin. However, it was discontinued after the Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial.

According to this trial, alpha-blockers, in general, increase the incidence of heart failure. Thus, other antihypertensive agents should replace them (9).

However, the clinical trials of doxazosin were interrupted after the release of this report. Thus, there’s no way to confirm or deny these claims. Still today, there’s an ongoing debate about this topic.

For this reason, it is not commonly used in hypertension resistant to treatment. Still, it is suggested in patients with high blood pressure readings and lower urinary tract symptoms.

Benign prostatic hyperplasia: In benign prostatic hyperplasia, alpha-blockers do not reduce the size of the prostate gland but improve urinary tract symptoms in men.

It is possible to measure these symptoms through the International Prostate Symptom Score (IPSS).

Clinical trials show that doxazosin in all formulations reduces up to 34% of symptoms (10, 11). In the clinical trials, half of the patients improved their symptoms with a starting dose of 4 mg.

Doxazosin mesylate works similarly to other alpha-blockers commonly used in BPH. According to a randomized, double-blind clinical trial, doxazosin is better than tamsulosin. It produces more significant improvements in the patient’s symptoms, and it is better well-tolerated (12).

How quickly do diseases respond to doxazosin treatment?

Diseases may respond quite fast to doxazosin treatment. You don’t need to wait for too long for the drug to take effect.

The majority of clinical trials use a time interval of 8 weeks or more to evaluate symptoms. However, that is not because doxazosin takes months to relieve symptoms. Instead, it is because they are clinical trials that evaluate the long-term effect of doxazosin.

What are the most common side effects of doxazosin?

We are always at risk of something, and we have a chance of experiencing the consequences of every decision we make.

There are common side effects, which are not usually very severe. On the other hand, there are severe and often life-threatening side effects, which are not very common.

The most common side effects of doxazosin are not life-threatening or concerning patients. The most commonly reported in clinical trials include (15):

  • Dizziness: Doxazosin has a role in brain function, and may cause dizziness. Talk to your doctor if you work as a driver or any other job that requires your full attention.

  • Tiredness and sleepiness: Doxazosin mesylate may reduce your energy levels for the reasons stated above.

  • Weight changes: More commonly, weight increases. It is probably associated with physical activity reductions due to lower energy levels. If you experience significant weight gain, talk to your doctor. You may need to rule out several causes, including prostate cancer.

  • Transient hypotension: Patients may feel dizzy when they change posture or stand up violently. That’s because they experience transient postural hypotension.

  • Headache: Blood pressure changes cause it, and it is not usually severe.

What are the most dangerous side effects of doxazosin?

A wrong dose or incorrect use of doxazosin tablets may cause side effects. This medication may cause life-threatening conditions such as (15):

  • Allergic reactions: They can be very severe and cause swelling of the eyes, tongue, and throat. You should look for urgent medical attention if you have an allergic reaction with respiratory symptoms.

  • Priapism: It is the clinical name of a painful penile erection that is maintained over a prolonged period. It is not life-threatening but an emergency that should be attended as soon as possible. This side effect is quite rare, but it has been documented.

  • Major hepatic toxicity: Patients with a susceptibility may experience significant hepatic toxicity. Thus, it is important to inform your doctor if you have a baseline hepatic condition (16).

  • Heart failure: Alpha-blockers, in general, are thought to cause heart failure or worsen the condition. This is debatable in the case of doxazosin but should be considered as a possibility.

What other drugs and supplements interact with doxazosin?

Any drug that works in the blood vessels and the central nervous system may interact with doxazosin. Interactions reported by the scientific literature include:

  • Certain antibiotics, such as clarithromycin

  • Certain antifungal drugs, such as ketoconazole and itraconazole

  • Antidepressant drugs

  • VIH medications

  • Sildenafil and other drugs for erectile dysfunction or pulmonary hypertension

  • Other alpha-blocker medications, such as tamsulosin

If your doctor does not have your medical records, it is essential to list all the medications you take.

Include medications for benign prostatic hyperplasia and other conditions.

That includes over-the-counter medications and any herbal products or alternative treatments you are using.

Do not start or change the dose of medications without your doctor’s approval. This may reduce the incidence of drug interaction.

When should you consider an alternative to doxazosin treatment?

There is always an alternative, and patients have the last call when it comes to their health. Certain patients are not recommended to use doxazosin, and other drugs and alternatives may be considered.

We all want to reduce enlarged prostate symptoms in BPH. Improving benign prostatic hyperplasia (BPH) naturally would be ideal.

People look for alternative drugs and herbal treatments in fear of adverse events. There are other pressing reasons to consider an alternative:

  • Patients with allergies to similar products: For example, allergies to tamsulosin or prazosin. You should use another drug for BPH if you have experienced allergies to similar medications.

  • Patients with severe gastrointestinal symptoms: Especially if you have severe constipation or a significant blockade in your gastrointestinal system.

  • Baseline liver disease: Patients with liver disease and BPH symptoms should look for an alternative. Doxazosin can have considerable liver toxicity for susceptible patients.

  • Heart disease: Doctors should be careful with patients who suffered a heart attack within 6 months. An alternative is recommended for patients with heart failure, angina, and other cardiac problems.

  • Low blood pressure readings: Patients with hypotension should be evaluated very closely. Doxazosin can be used as a blood pressure medication. Effects are not clinically significant in patients with normal blood pressure readings. But patients with hypotension may need an alternative.

  • Patients with cataracts and glaucoma: You need an alternative if you have eye problems or need to undergo surgery in your eyes.

  • Patients under treatment for erectile dysfunction: Because doxazosin may interact with erectile dysfunction drugs such as sildenafil.

What are the best natural treatments to consider in place of doxazosin treatment?

The best natural treatments and remedies for BPH include at least three herbal products. They are as follows:

  • Pygeum africanum: Studies show that Pygeum africanum slows down the process of enlargement of the prostate gland. It also improves the flow of urine in BPH. Thus, it can be used instead of doxazosin to treat these patients (17).

  • Secale cereal: Another alternative extract is Secale cereal. This is an extract of plant pollen digested by bacteria. It works by relaxing the muscles of the urethra and the bladder. It has been found to improve the symptoms of urgency and nocturia in BPH (17).

  • Saw palmetto: This herbal treatment works similarly to doxazosin and other alpha-blockers. It promotes relaxation in the prostate and bladder muscles. Additionally, saw palmetto has an anti-inflammatory effect, which contributes to improving the blood flow (18)

It is also essential to maintain a few lifestyle changes that will help in improving your symptoms.

For example, reduce your intake of alcohol and caffeine. They irritate your bladder and produce more urine. Eat healthily and control your weight to slow down prostate growth. And do not drink too much water before going to bed.

The same supplements listed above may be used along with doxazosin. Saw palmetto, Pygeum africanum, and Secale cereal reduces BPH symptoms. In many patients, using these medications may reduce the need for larger doses.

The most commonly recommended supplement for this purpose is Saw palmetto. It has anti-inflammatory potential and relaxes smooth muscle at the same time.

Sources

  1. . Boyle, P., & Napalkov, P. (1995). The epidemiology of benign prostatic hyperplasia and observations on concomitant hypertension. Scandinavian journal of urology and nephrology. Supplementum, 168, 7-12.
  2. Kirby, R. S. (1995). Efficacy of doxazosin in normotensive and hypertensive patients with benign prostatic hyperplasia. Scandinavian journal of urology and nephrology. Supplementum, 168, 29-33.
  3. Lipkin, M., & Shah, O. (2006). The use of alpha-blockers for the treatment of nephrolithiasis. Reviews in urology, 8(Suppl 4), S35.
  4. Lo, T. S. (2010). Alpha blockers in the clinical treatment of female lower urinary tract dysfunction. Incont Pelvic Floor Dysfunct, 4, 69-71.
  5. Smith, C., & Koola, M. M. (2016). Evidence for using doxazosin in the treatment of posttraumatic stress disorder. Psychiatric annals, 46(9), 553-555.
  6. Kaplan, S. A., De Rose, A. F., Kirby, R. S., O’LEARY, M. P., & McVARY, K. T. (2006). Beneficial effects of extended‐release doxazosin and doxazosin standard on sexual health. BJU international, 97(3), 559-566.
  7. NICE, U. (2011). Hypertension in adults: diagnosis and management. Clinical guideline
  8. National Institute for Health and Care Excellence. (2015). Lower urinary tract symptoms in men: management.
  9. Einhorn, P. T., Davis, B. R., Massie, B. M., Cushman, W. C., Piller, L. B., Simpson, L. M., … & ALLHAT Collaborative Research Group. (2007). The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) heart failure validation study: diagnosis and prognosis. American heart journal, 153(1), 42-53.
  10. Kirby, R. S., Andersen, M., Gratzke, P., Dahlstrand, C., & Høye, K. (2001). A combined analysis of double‐blind trials of the efficacy and tolerability of doxazosin‐gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia. BJU international, 87(3), 192-200.
  11. Andersen, M., Dahlstrand, C., & Høye, K. (2000). Double–Blind Trial of the Efficacy and Tolerability of Doxazosin in the Gastrointestinal Therapeutic System, Doxazosin Standard, and Placebo in Patients with Benign Prostatic Hyperplasia. European urology, 38(4), 400-409.
  12. Kirby, R. S. (2003). A randomized, double‐blind crossover study of tamsulosin and controlled‐release doxazosin in patients with benign prostatic hyperplasia. BJU international, 91(1), 41-44.
  13. Kaplan, S. A., Meade-D’Alisera, P., Quinones, S., & Soldo, K. A. (1995). Doxazos1n in physiologically and pharmacologically normotensive men with benign prostat1c hyperplasia. Urology, 46(4), 512-517.
  14. Steers, W. D., & Kirby, R. S. (2005). Clinical ease of using doxazosin in BPH patients with and without hypertension. Prostate cancer and prostatic diseases, 8(2), 152.
  15. Janknegt, R. A., & Chapple, C. R. (1993). Efficacy and safety of the alpha-1 blocker doxazosin in the treatment of benign prostatic hyperplasia. European urology, 24, 319-326.
  16. National Institutes of Health. (2017). Livertox: clinical and research information on drug-induced liver injury. Bethesda, MD.: US National Library of Medicine.
  17. Keehn, A., & Lowe, F. C. (2015). Complementary and alternative medications for benign prostatic hyperplasia. Can J Urol, 22(Suppl 1), 18-23.
  18. Kao, C., Hsieh, C., Chen, C., & Liu, C. (2014). The pharmacological effects of natural products and herbs in benign prostatic hyperplasia. Austin J Nutri Food Sci, 2(10), 1054.

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