Tamsulosin

Mechanism

Mechanism of Action

Highly selective competitive antagonist of postsynaptic α_1A and α_1D adrenergic receptors. α_1A receptors represent approximately 70% of all α₁ receptors present in the smooth muscle of the stroma of the prostate gland, the prostatic urethra and the neck of the urinary bladder. Its selective blockade specifically decreases the smooth muscle tone of the lower urinary tract, reducing mechanical urethral resistance to urinary flow and facilitating urination without inducing clinically relevant changes in mean systemic arterial pressure (which depends on the subtypes of α_1B receptors located in the peripheral resistance vessels).

Pharmacokinetics

Key Pharmacokinetics

• Routes: Oral (modified release capsules). It is advisable to take it constantly approximately 30 minutes after the same main meal each day.
• Bioavailability: Excellent, greater than 90% under fasting conditions.
• Metabolism: Extensive oxidative hepatic mediated by CYP3A4 and CYP2D6 isoenzymes.
• Elimination half-life: 9 to 15 hours in healthy volunteers, extending to 16-19 hours in the elderly.
• Excretion: Renal, eliminating less than 10% of the unchanged drug directly.

Indicators and dose

Approved and Off-label Indications

Approved: Symptomatic treatment of lower urinary obstruction secondary to benign prostatic hyperplasia (BPH).

Off-label: Facilitation of passage and spontaneous expulsion of distal ureteral stones smaller than 10 mm (renal medical expulsive therapy); voiding dysfunction of the lower urinary tract in women.

Dosage and Adjustments

Benign Prostatic Hyperplasia (Oral): Standard dose of 0.4 mg orally once daily. In case of suboptimal response after a period of 2 to 4 weeks, the dose may be increased to 0.8 mg once daily.

Renal adjustment: Does not require differentiated dosing guidelines in mild to moderate renal insufficiency. Insufficient data are available for patients with creatinine clearance < 10 mL/min.

Hepatic adjustment: No adjustment is required in mild or moderate hepatic insufficiency. Absolutely contraindicated in Child-Pugh Class C.

Security

Contraindications

Absolute: Hypersensitivity to the active substance or history of clinically documented orthostatic hypotension, severe decompensated liver failure (Child-Pugh C).

Relative: Concomitant use of strong CYP3A4 inhibitors, impending planned cataract surgery or other major ophthalmic intervention.

Adverse Effects (ADR)

Common: Orthostatic dizziness, abnormal ejaculation (retrograde ejaculation due to blockade of α₁ receptors of the vas deferens), congestive rhinitis, mild headache, physical asthenia.

Serious: Severe postural hypotension with syncope (rare), priapism, intraoperative floppy iris syndrome (IFIS) during surgical cataract extraction, which may complicate the intervention due to persistent miosis.

Interactions

Potent inhibitors of CYP3A4 (e.g., ketoconazole, ritonavir) or CYP2D6 (e.g., paroxetine): Disproportionately increase plasma levels of tamsulosin, multiplying the risk of syncope and postural hypotension.

PDE-5 antagonists (e.g., sildenafil, tadalafil): Added risk of antihypertensive synergy with induction of severe symptomatic hypotension.

Pregnancy and Breastfeeding

Tamsulosin is not indicated for routine clinical use in the female population. However, preclinical reproductive toxicology studies in animals do not reveal specific teratogenic risks.

Intraoperative floppy iris syndrome (IFIS)

Prolonged blockade of α_1A receptors in the iris dilator muscle by chronic use of tamsulosin causes a permanent loss of tone of said muscle. During ophthalmic cataract surgery, the surgeon may observe progressive miosis, prolapse and flaccidity of the iris due to the passage of fluid currents. It is advisable to suspend the drug a minimum of 1 to 2 weeks before scheduled ophthalmic cataract surgery, always warning the surgeon of the history of consumption.