SIDOPROS 8 CAPSULES

Indications

• Benign prostatic hyperplasia
• Lower urinary tract symptoms associated with benign prostatic hyperplasia

Dosage

Adults: The usual recommended dose for adults is 8 mg once daily, taken with food.

Mechanism of action

Silodosin functions as an antagonist to alpha-1 adrenergic receptors, specifically exhibiting the highest selectivity for the alpha-1A subtype. By blocking these receptors, silodosin reduces smooth muscle tone in the prostate and bladder neck, alleviating bladder outlet obstruction and improving urinary symptoms. It is believed to relieve both voiding and storage symptoms associated with BPH by modulating smooth muscle contraction through G protein-coupled receptor signaling pathways.

Pharmacodynamics

Silodosin has a high affinity for alpha-1A adrenergic receptors, being 162-fold more selective than for the alpha-1B subtype and approximately 50-fold more than for the alpha-1D subtype. Clinical trials have demonstrated that silodosin enhances maximum urinary flow rate and improves both voiding and storage symptoms of BPH. Its onset of action occurs within two to six hours of oral administration. While it inhibits the human ether-a-go-go-related gene (HERG) tail current, its cardiovascular effects remain minimal. However, it may lead to intraoperative floppy iris syndrome (IFIS) in patients undergoing cataract surgery.

Pharmacokinetics

Silodosin is well absorbed after oral administration, with a rapid onset of action. It undergoes extensive hepatic metabolism, primarily via the cytochrome P450 system, resulting in various metabolites. The elimination half-life is approximately 13 hours, and it is predominantly excreted via the fecal route. Renal clearance is also significant, but dose adjustments may be necessary in patients with renal impairment due to altered pharmacokinetic profiles.

Contra-indications

• Severe hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors

Adverse effects

• Ejaculation disorders
• Orthostatic hypotension
• Dizziness
• Nasal congestion
• Fatigue
• Diarrhea

Interactions

• Caution with other antihypertensive agents
• Caution with PDE5 inhibitors
• Strong CYP3A4 inhibitors may increase silodosin levels

Precautions

• Use with caution in patients with a history of orthostatic hypotension
• Consider risk of intraoperative floppy iris syndrome (IFIS) in cataract surgery
• Monitor for signs of hypotension

Pregnancy

Silodosin is not indicated for use in women and its safety during pregnancy has not been established.

Breast-feeding

Silodosin is not indicated for use in women and its safety during breastfeeding has not been established.

Storage

Store below 30°C in a dry place. Keep out of reach of children.

Formulations

• Capsules 4 mg
• Capsules 8 mg

Mechanism of action

The pathogenesis of benign prostatic hyperplasia is not fully understood: it is believed to involve several pathways, including inflammation, apoptosis, and cellular proliferation. Most drug therapies aim to alleviate symptoms of benign prostatic hyperplasia, silodosin included. Lower urinary tract symptoms of benign prostatic hyperplasia are categorized into three main groups: voiding or obstructive (hesitancy, slow stream, intermittency, incomplete emptying), storage or irritative (frequency, urgency, nocturia, urge urinary incontinence), and postmicturition (postvoid dribbling). Prostate contraction is the main contributor to lower urinary tract symptoms of benign prostatic hyperplasia. The smooth muscle tone of the prostate is regulated by α_1A-adrenoceptors, which are the most highly expressed subtype of α₁adrenoceptors in the human prostate tissue. It has been reported that blockade of α_1A-adrenoceptors relieves bladder outlet obstruction. Blockade of α_1D-adrenoceptors, another subtype found in prostate tissue, is believed to alleviate storage symptoms due to detrusor overactivity. α₁-adrenoceptors are G protein-coupled receptors: upon binding of its natural ligand, norepinephrine and epinephrine, leads to the activation of phospholipase C and downstream signalling molecules, including inositol triphosphate and diacylglycerol. Ultimately, there is an increase in intracellular calcium levels and, consequently, smooth muscle contraction. Silodosin is an antagonist of α₁-adrenoceptors, with the highest selectivity for the α_1A-adrenoceptor subtype. By blocking the α_1A-adrenoceptor signalling pathway, silodosin promotes prostatic and urethral smooth muscle relaxation, thereby improving lower urinary tract symptoms such as voiding. Silodosin also targets afferent nerves in the bladder, relieving bladder overactivity and storage symptoms.

Pharmacodynamics

Silodosin is an antagonist of α₁-adrenoceptors. It has the highest selectivity for the α_1A-adrenoceptor subtype, with a 162-fold greater affinity than α_1B-adrenoceptor and about a 50-fold greater affinity than for α_1D-adrenoceptor. In clinical trials, silodosin improved maximum urinary flow rate, voiding symptoms, and storage symptoms of benign prostatic hyperplasia. Following oral administration, silodosin had a rapid onset of effect in men, with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose. Silodosin inhibited the human ether-a-go-go-related gene (HERG) tail current; however, it has weak cardiovascular effects. As with all α₁-adrenoceptor antagonists blocking α₁-adrenoceptors in the iris dilator muscle, silodosin may cause intraoperative floppy iris syndrome (IFIS), which is characterized by small pupils and iris billowing during cataract surgery in patients taking α1-AR antagonists.