Tamsulosin (with ADS Technology) for the Treatment of BPH

Benign prostatic hyperplasia: An introduction

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate gland and is one of the most common conditions affecting the elderly males.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.  ²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  Prostrate enlargement can produce voiding symptoms that can lead to pathological changes in the urinary bladder and the kidney.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

BPH refers to stromal and glandular epithelial hyperplasia that occurs in the periurethral transition zone of the prostate that surrounds the urethra. BPH clinically manifest as lower urinary tract symptoms (LUTS) that consist of irritative symptoms (urgency, frequency, nocturia) and obstructive symptoms (hesitancy, a weak and interrupted urinary stream, straining to initiate urination, a sensation of incomplete bladder emptying). Prolonged obstructions may eventually lead to acute urinary retention (AUR), recurrent urinary tract infection (UTI), haematuria, bladder calculi, and renal insufficiency.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.

BPH is a quality of life disorder, and affects man’s ability to initiate or terminate urine flow stream and reduces the feeling of well being. The overgrowth of smooth muscle tissue and glandular epithelial tissue in BPH is attributed to a number of different causes such as aging, late activation of cell growth, genetic factors, and hormonal changes.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.

Epidemiology

Half of the men by the age of 60 exhibit histological evidence of BPH and by 90 years 90% of men develop histology of BPH.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.
Age and normal androgenic factors are postulated to be the two well established factors that cause BPH. The prevalence of LUTS increases steadily with increasing age. A community-based survey in UK reported 41% overall prevalence of LUTS.³Roehrborn CG. Benign Prostatic Hyperplasia: An overview. Rev Urol. 2005; 7(Suppl 9): S3–S14.

The high prevalence of histologic BPH, bothersome LUTS, benign prostatic enlargement (BPE), and bladder outlet obstruction (BOO) has been emphasised. Over the next few decades the number of patients presenting with these symptoms to health care providers will probably increase significantly.³Roehrborn CG. Benign Prostatic Hyperplasia: An overview. Rev Urol. 2005; 7(Suppl 9): S3–S14.

Estimates from the United Nations demonstrate that the percentage of the population aged 65 years or older increased significantly between 2000 and 2005, both in underdeveloped and more developed regions, and from 7% to 11% worldwide. In addition, life expectancy has changed from 56 years for the observation period 1965 to 1970 to 65 years for 2000 to 2005. Although developed regions have a longer life expectancy, but the incremental increase is greater in Africa, Asia, and Latin America and the Caribbean regions.³Roehrborn CG. Benign Prostatic Hyperplasia: An overview. Rev Urol. 2005; 7(Suppl 9): S3–S14.

Diagnosis and evaluation

Men commonly fail to seek help for LUTS associated with BPH. Therefore, it is imperative that primary care physicians routinely inquire about urinary function with men over the age of 50.⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

All patients presenting with LUTS should undergo physical examination including a careful digital rectal examination (DRE).⁵. Shrivastava A, Gupta VB. Various treatment options for benign prostatic hyperplasia: A current update. J Midlife Health. 2012 Jan;3(1):10–9.

Diagnostic tests

International prostatic symptom score

This is a questionnaire that was developed by a committee of American Urological Association. An indexing tool called the International Prostate Symptoms Score (IPSS) can help to evaluate the key lower urinary tract symptoms. Unlike laboratory tests or other objective tests, this scoring system measures the patient’s own experience. The higher the score, the more severe is the condition. Patients score on this test gives a highly accurate assessment of the effect of lower urinary tract symptoms on the quality of a man’s life.

Other indexing systems

In addition to IPSS, other indexing systems that are being used to help assess the patient are Madsen-Iversen point system, the Boyarsky guidelines, Maine Medical Assessment Score, Symptom Problem Index (SPI) and the BPH Impact Index (BII), which gauge different quality-of-life and disease issues.

Physical examination

Digital rectal examination

The DRE is used to detect an enlarged prostate. The doctor inserts a gloved and lubricated finger into the patient’s rectum and feels the prostate to estimate its size and to detect nodules or tenderness. Although the examination is quick and painless, it is embarrassing for some. The test helps to rule out prostate cancer, but it is generally underestimates the prostate size. The examination is not considered accurate for diagnosing prostatic hyperplasia, and is never the primary diagnostic tool for either BPH or cancer.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Uroflowmetry

Uroflowmetry is used to measure the speed of urine flow in order to determine obstruction in bladder. To perform this test, the patient is asked to urinate into a special toilet equipped with an uroflowmeter. It is important that the patient remains still while urinating to help ensure accuracy, and that he urinates normally and does not exert strain to empty his bladder or attempt to retard his urine flow. Many factors like straining or holding back because of self-consciousness can affect urine flow. Hence, experts recommend that the test be repeated at least twice. The values more than 15 mL per second and voiding volume of 150 mL or more is considered to be the normal range.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Urine analysis

A urinalysis involves a physical and chemical examination of urine and is performed to detect signs of bleeding or infection. Urine is examined under a microscope. Although urinary infection is uncommon in younger men, it occurs more frequently in older men, particularly those with BPH. A urinalysis also helps rule out bladder cancer.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Prostate specific antigen (PSA)

A PSA test measures the level of PSA in the patient’s blood and is the standard screening test for prostate cancer. A PSA is recommended annually for all men over 50-years-old and for men over 40 who are at high risk for prostate cancer. BPH itself can also raise PSA levels, but the test has generally been optional for men with suspected BPH. The decrease in the prostate size corresponds to the decrease in the PSA levels. Every 19% decrease in the PSA levels there is a decrease of prostate volume by 10%.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Postvoid residual urine

Postvoid residual urine (PVR) volume is one of the important tests for urinary incontinence, the amount of urine left after urination. Normally, about 50 mL or less of urine is left. Urine more than 200 mL is a definite sign of abnormalities. The most common method for measuring PVR is by transabdominal ultrasonography. PVR can also be measured using a catheter, a soft tube that is inserted into the urethra within a few minutes of urination.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Management

The Canadian Urological Association (CUA) has established treatment algorithm for BPH and is based primarily on a combination of the degree of symptoms, the amount of bother, and the size of the prostate.⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

BPH rarely causes serious complications and men usually have a choice between treating it than opting for watchful waiting treatment options: The primary goals of treatment for BPH are to improve urinary flow and to reduce symptoms.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Options are available are¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.:

• Watchful waiting
• Medical treatment
• Surgical treatment

Watchful waiting

For patients with a low IPSS symptom score (zero to seven) watchful waiting is an appropriate treatment. However, follow-up monitoring is important. Patients with higher IPSS symptom scores should be given information on appropriate treatment options.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  Despite a high American Urological Association Symptom Index (AUA-SI) or IPSS score, watchful waiting remains to be a patient’s choice as the level of symptom distress that a patient can tolerate varies greatly. A variety of lifestyle changes like restricting fluid intake, avoiding foods or beverages that cause irritation (e.g., caffeine or alcohol), monitoring some medications (e.g., diuretics, decongestants, antihistamines, and antidepressants), timed voiding (bladder retraining), pelvic floor exercises, and treatment for constipation.⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

Medical treatment

Common symptoms of BPH are due to increased resistance to the flow of urine through the bladder neck and compressed prostatic urethra. Medical treatments have been devised to decrease the size of the prostate, and thereby decrease the resistance to urinary flow.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.  Efficacy of medical therapies may not match the efficacy of surgical therapies, but they can provide adequate symptom relief.⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

Non-selective alpha-1 blockers

Doxazosin and terazosin, second-generation alpha blockers, are recommended as treatment options for patients with LUTS secondary to BPH. They act by reducing prostatic smooth muscle tone and thus, have an immediate effect on urinary flow. First-generation alpha-blockers and prazosin are not recommended. The side effects reported with alpha blockers are dizziness, postural hypotension, fatigue, asthenia and retrograde ejaculation. These side effects can be reduced by bedtime administration and slow titration of the dosage. Alpha blockers can be used with other therapies as needed.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  ⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

Selective alpha-1 blocker

Alfuzosin and tamsulosin, third-generation alpha blockers, are more selective in relaxing prostatic smooth muscle and therefore does not affect blood pressure. Tamsulosin, a highly selective alpha-1 adrenergic antagonist was developed to avoid the side effects of non-selective agents. Patients who do not respond to non-selective alpha blockers may respond to tamsulosin and it may also have fewer side effects because of the selectivity, including hypotension. Compared to second-generation agents the risk of dizziness is lower with tamsulosin and alfuzosin. Initial dosage of tamsulosin is 0.4 mg once-daily, with a maximum dosage of 0.8 mg/day. Tamsulosin shows no antihypertensive effect and is more expensive than non- selective alpha blockers.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  ⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

5-alpha reductase inhibitors (ARIs)

Dutasteride and finasteride, 5-ARIs, act by blocking the conversion of testosterone to dihydrotestosterone (DHT). DHT is an androgen that is believed to be responsible for prostate enlargement. The 5-ARI class is the sole hormonal therapy to date that demonstrates both efficacy and acceptable safety for the treatment of BPH. Finasteride, which inhibits type 2 5-AR, suppresses serum DHT by 70.8% ± 18.3% at 24 weeks but not to castrate levels. Finasteride treatment led to significant improvements in urinary symptoms and flow rates. According to the Prospect study, the improvements with finasteride are significantly less than those with any alpha blocker or surgery. Adverse effects of finasteride include decreased libido, ejaculatory disorder, and impotence. Dutasteride has sexual side effects similar to finasteride.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  ⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

The CUA and AUA guidelines recommend dutasteride and finasteride as appropriate treatment for patients with LUTS associated with demonstrable prostatic enlargement, but should not be used to treat men with LUTS without prostatic enlargement. Finasteride and dutasteride both reduces PSA levels by approximately 50% after 6 months and this PSA suppression is maintained over time. If PSA rises while on a 5-ARI, drug compliance should be checked.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.  ⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

Combination therapy

Combination therapy of 5-ARI and an alpha-blocker is helpful in managing static and dynamic component in patients with an enlarged prostate gland having symptoms of BOO. The underlying principle for this recommendation is that alpha blocker provides rapid relief of symptoms without targeting the underlying disease process and 5-ARI provides mid or more sustained relief of symptoms. Also, ARI reduces the risk of serious complications like acute urinary retention (AUR) and/or the need for BPH-related surgery. According to the Medical Therapy of Prostatic Symptoms (MTOPS) trial combination therapy (finasteride and doxazosin) reduced the risk of progression by 66% compared to placebo and with either drug by itself (34% for finasteride and 39% for doxazosin).¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.   ⁴. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.

Surgical treatment

If medical treatment fails, surgery should be considered as treatment. Surgery should be performed if patients who have refractory urinary retention, fail catheter removal, or have recurrent urinary tract infections, persistent haematuria, bladder stones, or renal insufficiency. For patients with high IPSS who want surgical treatment and are good candidates for it, surgery can be the initial treatment. Surgical procedures that can be performed are described below.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Open prostatectomy

In this method the inner portion of the prostate is surgically removed using a suprapubic or retropubic approach. It is the oldest and most effective treatment for relieving the symptoms of BPH and increasing maximum urinary flow. In patients who undergo this procedure symptomatic improvement rate is 98%, while the treatment rate is only 2%. However, this procedure is the most invasive treatment for BPH and is associated with the most morbidity. Hence, this procedure is typically used in patients with a very large prostate gland or structural problems such as a large median lobe that protrudes into the bladder or a large bladder calculus or urethral diverticulum.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Transurethral resection of the prostate (TURP)

TURP is the most commonly employed surgical procedure for BPH, and it reduces symptoms in 88% of patients. Approximately 10% of patients require retreatment within five years. The procedure results in complications, the most frequent complications being inability to void, clot retention, and secondary infection. Bleeding, the most morbid complication occurs in only 1% of patients. Long-term complications include retrograde ejaculation, impotence, partial incontinence, and total incontinence.²Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.

Transurethral electrovaporization (TUVP)

A modification of TURP, TUVP utilises high electrical current to vaporise and coagulate the obstructing prostate tissue. Although long-term efficiency of TUVP is comparable with TURP, many patients experience irritative side effects.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.

Transurethral microwave thermotherapy (TUMT)

TUMT destruct malignant cells without affecting normal cells by raising the temperature of the cells using low-level radiofrequency (microwave) in the prostate up to 40°-45°C (hyperthermia), 46°-60°C (thermotherapy), and 61° to 75°C (transrectal thermal ablation). TUMT is safe and cost-effective treatment, with reasonable improvement in urine flow rate and minimal impairment on sexual function.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.

High-intensity focused ultrasound (HIFU)

Effective protein denaturation and coagulative necrosis of prostatic tissue have been achieved by using HIFU frequencies of 4 MHZ. Although significant increase in uroflow and a decrease in postvoid residual volume have been observed, the cost is three times higher than that of TURP.¹Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.

Tamsulosin in BPH

Tamsulosin, a sulfamoylphenthylamine is a new uroselective alpha-1 A adrenoreceptor subtype antagonist. It is approximately 99% protein-bound and undergoes hepatic metabolism. Most of the parent drug and metabolites are excreted in urine; up to 14% is excreted as unchanged drug.⁶Mohanty NK, Arora RP, Nayak RL, Malhotra V. A randomized comparative study of tamsulosin vs placebo in the treatment of benign prostatic hyperplasia. Indian J Urol. 2003; 20(1):40–45.  Role of tamsulosin in the treatment of BPH has been demonstrated in many clinical studies.

Clinical studies

Milicevic S and Bijelic R conducted a study to establish the efficacy and safety of a daily dose of tamsulosin 0.4 mg in patients with functional symptoms of BPH through an evaluation of reduction of subjective symptoms, quantified through the IPSS.⁷Milicevic S, Bijelic R. Efficacy and safety of tamsulosin in the treatment of benign prostatic hyperplasia. Med Arch. 2012;66(3):173–6.

The study reported reduction in symptoms after 4 weeks (35.51%) and 12 weeks (55.11%) of treatment (Table 1). The Quality of Life Index showed marked improvement of 44.54% after 4 weeks and 68.82% after 12 weeks.⁷Milicevic S, Bijelic R. Efficacy and safety of tamsulosin in the treatment of benign prostatic hyperplasia. Med Arch. 2012;66(3):173–6.

In a randomised placebo-controlled trial conducted by Mohanty NK et al., efficacy, safety and advantages of tamsulosin in the management of BPH was evaluated. The study results showed tamsulosin to be very effective in the management of BPH cases, not requiring surgery, with few side effects and good patient compliance. A significant change in IPSS was seen in the tamsulosin group as compared to the placebo group at the end of the study. The improvement with tamsulosin was significantly greater as compared to the placebo group at all time intervals and for all the three parameters (Table 2).⁶Mohanty NK, Arora RP, Nayak RL, Malhotra V. A randomized comparative study of tamsulosin vs placebo in the treatment of benign prostatic hyperplasia. Indian J Urol. 2003; 20(1):40–45.

Rahardjo D et al., conducted an open-label, randomised, multicenter study, to compare the efficacy and safety of tamsulosin hydrochloride and doxazosin in patients with LUTS due to BPH. The study reported that tamsulosin is more effective than doxazosin in the treatment of LUTS due to BPH. Tamsulosin group had a significant improvement in Qmax and Qave compared to the doxazosin group (Table 3).⁸Rahardjo D, Soebadi DM, Sugandi S, et al. Efficacy and safety of tamsulosin hydrochloride compared to doxazosin in the treatment of Indonesian patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Int J Urol. 2006 Nov;13(11):1405–9.

Tamsulosin with ADS technology: Advantages

After its introduction in 1990’s, tamsulosin has been most commonly used in the treatment of BPH; but the available tamsulosin modified release (MR) capsule formulation has been associated with some drawbacks. The current capsule is food dependent and if it is taken in the fasting state, maximum plasma concentration (Cmax) and the area under the curve (AUC) increases by about 70% and 30%, respectively, compared to when it is taken after breakfast. Hence, the labelling information recommends that tamsulosin MR should be dosed after breakfast or the first meal of the day. Non-compliance with this recommendation will lead to increased exposure to tamsulosin, which can lead to a higher risk for vasodilatation-related adverse events like dizziness, headache, etc.⁹Michel MC, Korstanje C, Krauwinkel W, Kuipers M. The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS1). European Urology Supplements. 2005;4:15–24.

It is important to develop new pharmaceutical formulations to improve the convenience and/or risk/benefit ratio of well established medicinal products. By controlling the release and absorption of drugs in the gastrointestinal (GI) tract and specifically in the colon, improved safety and/or efficacy can be achieved. This will enable once-daily administration resulting in a continuous 24-hour pharmacological effect. Technologies like multi-unit membrane-coated pellets, osmotic pump technology (OROS) and GeoMatrix have been developed and used for tamsulosin MR. However, these technologies are water-dependant and require water in GI to release the active ingredient.⁹Michel MC, Korstanje C, Krauwinkel W, Kuipers M. The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS1). European Urology Supplements. 2005;4:15–24.

Hence, a novel technology, advanced delivery system (ADS) has been developed.¹⁰. Data on file.   This technology is a controlled release system of a gel matrix type that is composed of a gel-forming agent and a gel-enhancing agent as its major components. This technology has been shown to provide pH-independent drug release and GI-agitation resistant gel formation.⁹Michel MC, Korstanje C, Krauwinkel W, Kuipers M. The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS1). European Urology Supplements. 2005;4:15–24.

ADS technology was developed to overcome the drawbacks of existing tamsulosin MR formulation. The ADS technology has following benefits¹⁰. Data on file.:

• 24 hours consistent release in colon where water is poorly available
• Improved control of nocturia and IPSS
• It shows a steady plasma level after dosing with a improved Cmax/C24h ratio
• Better quality of sleep
• It can be taken with or without food
• Independent of food intake
• Reduced Cmax related side effects
• Reduced incidence of postural hypotension

Tamsulosin with ADS technology is a unique formulation. This technology ensures 24 hour consistent drug release throughout the entire GI tract. The drug gets sufficiently hydrated during its transit through the upper GI tract so that it is able to release sufficient amount of the drug even in the colon where water is poorly available. With conventional MR formulations of tamsulosin release of the drug occurs only in stomach and small intestine, thus providing suboptimal serum drug levels over 24 hour dosing interval, hence leading to poor control of symptoms, especially nocturia (Figure 1).¹⁰. Data on file.

ADS technology provides a continuous release of the drug in the GI tract even in colon, thus maintaining a constant 24 hour plasma drug levels and hence offers a better symptom control of the most bothersome symptom i.e., nocturia that affect the quality of life. There is slower release of tamsulosin which leads to a reduction in Cmax and hence there is lower risk of treatment-emergent adverse events, such as orthostatic hypotension.¹⁰. Data on file.

In conventional MR formulations, release of drug occurs in stomach and small intestine rather than the colon. Due to this, there is suboptimal serum drug level over 24 hour dosing interval and hence poor symptom control. Moreover, the conventional MR when taken on empty stomach increases the risk of unwanted cardiovascular effects (CVS) effects such as orthostatic hypotension, dizziness and syncope (fainting) (Figure 2).¹⁰. Data on file.

Conclusion

BPH is the most common disorder amongst the geriatric population. Patient evaluation and careful differential diagnosis are important steps in making an accurate clinical diagnosis. Tamsulosin have been found to be safe and effective in the treatment of BPH. Delivery of tamsulosin with ADS technology has improved the efficacy and safety of the drug and has surpassed the drawbacks of previous technologies.

References

1. Dhingra N and Bhagwat D Benign prostatic hyperplasia: An overview of existing treatment. Indian J Pharmacol. 2011 Feb; 43(1): 6–12.
2. Praveen R. Benign prostatic hyperplasia: Updated review. Res J Pharm. 2013;4 (8):45-50.
3. Roehrborn CG. Benign Prostatic Hyperplasia: An overview. Rev Urol. 2005; 7(Suppl 9): S3–S14.
4. Tanguay S, Awde M, Brock G, et al. Diagnosis and management of benign prostatic hyperplasia in primary care. Can Urol Assoc J. 2009 Jun; 3(3 Suppl 2): S92–S100.
5. Shrivastava A, Gupta VB. Various treatment options for benign prostatic hyperplasia: A current update. J Midlife Health. 2012 Jan;3(1):10–9.
6. Mohanty NK, Arora RP, Nayak RL, Malhotra V. A randomized comparative study of tamsulosin vs placebo in the treatment of benign prostatic hyperplasia. Indian J Urol. 2003; 20(1):40–45.
7. Milicevic S, Bijelic R. Efficacy and safety of tamsulosin in the treatment of benign prostatic hyperplasia. Med Arch. 2012;66(3):173–6.
8. Rahardjo D, Soebadi DM, Sugandi S, et al. Efficacy and safety of tamsulosin hydrochloride compared to doxazosin in the treatment of Indonesian patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Int J Urol. 2006 Nov;13(11):1405–9.
9. Michel MC, Korstanje C, Krauwinkel W, Kuipers M. The Pharmacokinetic Profile of Tamsulosin Oral Controlled Absorption System (OCAS1). European Urology Supplements. 2005;4:15–24.
10. Data on file.