Silodosin (Capsules) Instructions for Use

ATC Code

G04CA04 (Silodosin)

Active Substance

Silodosin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug used for urination disorders associated with benign prostatic hyperplasia. Alpha₁-adrenergic blocker

Pharmacotherapeutic Group

Drugs used in urology; drugs for the treatment of benign prostatic hyperplasia; alpha-adrenergic blockers

Pharmacological Action

A highly selective competitive antagonist of α_1A-adrenergic receptors, it blocks postsynaptic α_1A-adrenergic receptors located in the smooth muscle of the prostate gland, bladder neck, and prostatic part of the urethra.

It reduces the tone of the smooth muscle of the prostate gland, bladder neck, and prostatic part of the urethra, improving urine outflow. Simultaneously, it reduces the symptoms of obstruction and irritation associated with benign prostatic hyperplasia.

The affinity of silodosin for α_1A-adrenergic receptors located in the bladder is 162 times greater than its ability to interact with α_1B-adrenergic receptors, which are located in vascular smooth muscles.

Due to its high selectivity, Silodosin does not cause a clinically significant decrease in blood pressure in patients with initially normal blood pressure.

Pharmacokinetics

When taken orally, Silodosin is well absorbed. The absolute bioavailability is 32%.

Food intake reduces C_max by approximately 30%, increases the time to reach C_max to approximately 1 hour, and has a minimal effect on AUC. C_max 87±51 ng/ml, T_max – 2.5 hours, mean urinary concentration 433±286 ng×h/ml.

The V_d of silodosin is 0.81 L/kg. Silodosin is 96.6% bound to plasma proteins.

Silodosin is metabolized via glucuronidation (involving UGT2B7), with the participation of alcohol dehydrogenase and aldehyde dehydrogenase, and oxidative pathways, mainly involving CYP 3A4.

The main active metabolite in plasma, carbamoyl glucuronide (KMD-3213G), reaches a plasma concentration 4 times greater than Silodosin itself. Silodosin does not have the potential to induce or inhibit cytochrome P450 isoenzymes.

33.5% of silodosin is excreted by the kidneys and 54.9% via the intestines. The clearance of silodosin is about 23.1 L/h.

Silodosin is excreted mainly as metabolites and in very small amounts unchanged in the urine. The T_1/2 of silodosin and carbamoyl glucuronide is 11 hours and 18 hours, respectively.

Indications

Benign prostatic hyperplasia.

ICD codes

Dosage Regimen

Capsules

The recommended dose is 8 mg once daily, simultaneously with food intake, preferably at the same time of day. The capsule should be swallowed whole, preferably with a glass of water.

When treating patients with moderate renal impairment (creatinine clearance from 30 to 50 ml/min), it is recommended to take the drug at a dose of 4 mg/day for the first week; if well tolerated individually, the dose can then be increased to 8 mg/day.

In severe renal impairment, the use of silodosin is not recommended.

Adverse Reactions

From the central nervous system common – dizziness; frequency unknown – syncope.

From the cardiovascular system: common – orthostatic hypotension.

From the respiratory system: common – nasal congestion.

From the digestive system common – diarrhea; uncommon – nausea, dry mouth.

From the reproductive system: very common – retrograde ejaculation, anejaculation; uncommon – decreased libido, erectile dysfunction.

Other frequency unknown – intraoperative floppy iris syndrome during cataract surgery.

Contraindications

Severe renal failure (creatinine clearance <30 ml/min); severe hepatic impairment; children and adolescents under 18 years of age; hypersensitivity to silodosin.

Special Precautions

Use with caution in moderate renal failure (creatinine clearance from 30 to 50 ml/min).

As with the use of other alpha₁-adrenergic blockers, treatment with silodosin may lead to a decrease in blood pressure and orthostatic hypotension. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in this position until the symptoms of orthostatic hypotension disappear.

Since benign prostatic hyperplasia and prostate tumors have similar symptoms and can develop concurrently, patients suspected of having benign prostatic hyperplasia should be examined to rule out prostate tumors before prescribing the drug.

In patients taking or having taken alpha₁-adrenergic blockers, floppy iris syndrome may occur during cataract surgery, which can lead to complications during the operation. Treatment with alpha₁-adrenergic blockers should be discontinued 1-2 weeks before such surgery. Patients scheduled for cataract surgery are not recommended to start treatment with silodosin.

Effect on the ability to drive vehicles and operate machinery

The appearance of symptoms associated with orthostatic hypotension (e.g., dizziness) is possible, so until the individual tolerance to silodosin is determined, patients should refrain from driving vehicles and other potentially hazardous activities.

Drug Interactions

Combination with other alpha-adrenergic blockers is not recommended due to possible potentiation of the effect.

Concomitant use with inhibitors of the CYP3A4 isoenzyme (ketoconazole, clarithromycin, itraconazole, ritonavir) is not recommended, as it increases the plasma concentration of silodosin.

PDE5 inhibitors (sildenafil, tadalafil) when used concomitantly may increase the risk of dizziness.

Hypotensive drugs (beta-blockers, calcium antagonists, drugs acting on the RAAS, diuretics) when used concomitantly may enhance orthostatic hypotension.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.