Tamsulosin

Tamsulosin is an antagonist of α1-adrenoceptors.

Tamsulosin is used in the treatment of Benign prostatic hyperplasia. It is also used in the treatment of Chronic prostatitis/chronic pelvic pain syndrome in males; Lower urinary tract infection symptoms in males; Ureteral stone(s), expulsion; Ureteral stent-related urinary infection symptoms.

It is rapidly absorbed from the gastrointestinal tract. Bioavailability: 30% increase in fasting state. Food reduces the rate and extent of absorption. The Volume of distribution is Approx 0.2 L/kg (prolonged-release); 16 L (immediate-release), with plasma protein binding of approx 99%, mainly to α₁-acid glycoprotein. It is extensively metabolized in the liver by CYP3A4 and CYP2D6 to metabolites and further undergoes extensive conjugation to glucuronide or sulfate and gets excreted via urine (76%, <10% as unchanged drug); feces (21%).The elimination half-life: 5-7 hours (immediate-release); 9-13 hours (prolonged-release).

The onset of Action of Tamsulosin is within 4 to 8 hours.

The Duration of action of Tamsulosin is within 3-4 days

The Tmax of Tamsulosin was approx 1 hour (immediate-release)and approx 6 hours (prolonged-release)., and the Cmax of Tamsulosin was found within 1.2 to 65.1 ng ml−1.

The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.

Tamsulosin is available in the form of a dosage forms, such as capsules and tablets.

Tamsulosin is available in the USA, UK, Canada, Japan, India

Tamsulosin is an antagonist of α₁-adrenoceptors, which mediate smooth muscle tone in the prostate. This leads to the relaxation of smooth muscle in the bladder neck and prostate thereby improving urine flow and reducing the symptoms of benign prostatic hyperplasia (BPH).

Tamsulosin is available in the form of a dosage forms, such as capsules and tablets.

Tamsulosin Tablets and capsules are taken orally with or without food.

Tamsulosin is used in the treatment of Benign prostatic hyperplasia. It is also used in the treatment of Chronic prostatitis/chronic pelvic pain syndrome in males; Lower urinary tract symptoms in males; Ureteral stone(s), expulsion; Ureteral stent-related urinary symptoms, treatment.

Tamsulosin is a blocker of alpha-1A and alpha-1D adrenoceptors. About 70% of the alpha-1 adrenoceptors in the prostate are of the alpha-1A subtype. By blocking these adrenoceptors, smooth muscle in the prostate is relaxed and urinary flow is improved. The blocking of alpha-1D adrenoceptors relaxes the bladder's detrusor muscles, which prevents storage symptoms. The specificity of Tamsulosin focuses on the effects on the target area while minimizing effects in other areas.

Tamsulosin is approved for its use in the following clinical indications:-

● Benign prostatic hyperplasia: Treatment of signs and symptoms of benign prostatic hyperplasia (BPH)

Although not approved, there has been certain label use documented for Tamsulosin which includes:

Chronic prostatitis/pelvic pain syndrome in males; Lower urinary tract symptoms in males; Ureteral stone(s), expulsion; Ureteral stent-related urinary symptoms, treatment.

Tamsulosin is available in various dosage strengths: 0.4mg.

Tamsulosin is available in the form of dosage forms such as capsules and tablets.

Dose Adjustment in Kidney Patients:

● ≥10 mL/minute: No dosage adjustment necessary.

● CrCl <10 mL/minute: No dosage adjustment likely to be necessary (has not been studied); use with caution (expert opinion).

● Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): No dosage adjustment likely to be necessary (has not been studied); use with caution (expert opinion).

● Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment likely to be necessary (has not been studied); use with caution (expert opinion).

Dose Adjustment in Hepatic Impairment Patient

● Mild-to-moderate impairment: No dosage adjustment is necessary.

● Severe impairment: There are no dosage adjustments.

Dose Adjustment in Pediatric Patients.

Diagnosis of Pheochromocytoma (Tamsulosin blocking test):

Nephrolithiasis, distal stones:

• Children 2 to 4 years: Oral: 0.2 or 0.4 mg once daily at bedtime

• Children >4 years and Adolescents: Oral: 0.4 mg once daily at bedtime

• Dosing based on two studies. The larger was a multi-institutional retrospective cohort study of pediatric patients with stones up to 10 mm; patients received either Tamsulosin 0.4 mg once daily (n=99, median age: 14.8 years) or analgesics alone (n=175). The spontaneous stone passage was higher in the treatment group (55% vs 44%, p=0.03); the treatment group was older and had smaller, more distal stones. When adjusted for stone size and location as part of the analysis of 99 case-matched pairs, success was also higher in the treatment group (OR 3.31, 95% CI: 1.49 to 7.34).

• The smaller study was a prospective, randomized controlled trial of pediatric patients with stones up to 12 mm; patients received either Tamsulosin 0.4 mg once daily (0.2 mg if ≤4 years old) (n=33, age: 2 to 15 years) or placebo (n=28). In this study, 45% of the treatment group had previously received either extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy, but none in the control group had received these therapies; however, stone size at the start of treatment was similar between groups. Treatment resulted in higher expulsion rate (87.8% vs 64.2%, p<0.01), less days to expulsion (mean: 8.2 vs 14.5 days, p<0.001), less pain episodes (mean: 1.4 vs 2.2, p<0.02) and less need for analgesia (mean: 0.7 vs 1.4, p<0.02) . In both studies, Tamsulosin was well tolerated and there were no reported adverse effects.

Primary bladder neck dysfunction:

Children ≥3 years and Adolescents:

Oral:

• Initial dose: 0.2 mg once daily, increase by 0.2 mg increments based on response (symptoms and urodynamic studies) and tolerability. Mean effective dose: 0.4 mg daily; maximum reported daily dose: 0.8 mg/day.

• Dosing based on two trials evaluating treatment with alpha-blockers, including over 50 pediatric patients who received Tamsulosin. Treatment resulted in improved urine flow rates and decreased post-void residual urine volume; values returned to pretreatment levels when therapy was discontinued. Tamsulosin was well tolerated with no major adverse effects and benefits continued for at least 3 years.

Tamsulosin is approved for the treatment of Benign prostatic hyperplasia.

Eat a low-fat diet. Eat a large variety of vegetables each day. Eat a few servings of fruit daily, and be sure to include citrus fruits. Participate in moderate to vigorous physical activity most days of the week.

Tamsulosin may be in the following

• Hypersensitivity (eg, angioedema, rash, urticaria, pruritus, respiratory symptoms) to Tamsulosin or any component of the formulation.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

Concerns related to adverse effects:

• Angina: Discontinue if symptoms of angina occur or worsen.

• Sulfonamide allergy: Rarely, patients with a sulfa allergy have also developed an allergic reaction to Tamsulosin; avoid use when the previous reaction has been severe or life-threatening.

Disease-related concerns:

• Heart failure: In a scientific statement from the American Heart Association, Tamsulosin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate)

Avoid taking alcohol with Tamsulosin as it may result in side effects like headache, dizziness, and faintness.

Teratogenic Effects

Pregnancy Category B.

Administration of tamsulosin hydrochloride to pregnant female rats at dose levels up to approximately 50 times the human therapeutic AUC exposure (300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of tamsulosin hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. Tamsulosin capsules are not indicated for use in women.

Salt Substitutes: Those taking Tamsulosin should avoid sodium, calcium, and magnesium-rich foods. The salts may reduce the blood-pressure-lowering effect of Tamsulosin.

The adverse reactions related to the molecule Tamsulosin can be categorized as

• Common Adverse effects: Orthostatic hypotension, postural hypotension, syncope, floppy iris syndrome in cataract and glaucoma surgery, hypersensitivity reactions, and MI exacerbations.
• Less Common adverse effects: Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower, hoarseness, lightheadedness, fainting, rash, yellowing of the skin or eyes, fever, sore throat, chills, and other signs of infection.
• Rare Adverse effects: Pruritus, urticaria, skin desquamation including erythema multiforme, dermatitis exfoliative, and rarely, Stevens-Johnson syndrome.

The clinically relevant drug interactions of Tamsulosin are briefly summarized here.

Symptoms: Severe hypotensive effects, vomiting, diarrhea.

Management: Supportive and symptomatic treatment. CV support may be given in case of acute hypotension. Lie the patient down to restore blood pressure and normalize the heart rate. For severe cases, volume expanders and vasopressors may be given. Administer activated charcoal and osmotic laxative or perform gastric lavage for ingestion of large doses.

Pharmacodynamics:

Tamsulosin is an alpha-adrenoceptor blocker with specificity for the alpha-1A and alpha-1D subtypes, which are more common in the prostate and submaxillary tissue. The final subtype, alpha-1B, is most common in the aorta and spleen. Tamsulosin binds to alpha-1A receptors 3.9-38 times more selectively than alpha-1B and 3-20 times more selectively than alpha-1D. This selectivity allows for a significant effect on urinary flow with a reduced incidence of adverse reactions like orthostatic hypotension.

Pharmacokinetics:

• Absorption:

They are rapidly absorbed from the gastrointestinal tract. Bioavailability: 30% increase in fasting state. Food reduces the rate and extent of absorption. Time to peak plasma concentration: Approx 1 hour (immediate-release); approx 6 hours (prolonged-release).

• Distribution:

Volume of distribution: Approx 0.2 L/kg (prolonged-release); 16 L (immediate-release). Plasma protein binding: Approx 99%, mainly to α1-acid glycoprotein.

• Metabolism:

Extensively metabolized in the liver by CYP3A4 and CYP2D6 to metabolites and further undergoes extensive conjugation to glucuronide or sulfate.

• Excretion:

Via urine (76%, <10% as unchanged drug); faeces (21%). Elimination half-life: 5-7 hours (immediate-release); 9-13 hours (prolonged-release).

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