赛洛多辛(Silodosin)中文说明书

Silodosin is an α1-adrenergic blocker that is selective for α1A-adrenergic receptors and is a trifluoroethoxy-phenoxyethylamine derivative.

Indications for Silodosin

Benign prostatic hyperplasia (BPH)

It is used to reduce urinary tract obstruction and relieve related symptoms in patients with symptomatic BPH, such as urinary hesitation, weak urine flow, feeling of incomplete bladder emptying, frequent urination, urgency, and nocturia.

It may be a useful alternative to surgery for patients awaiting surgery to correct growths or who are not candidates for such surgery.

Silodosin usage and dosage

1. Dosage method

Oral administration with meals.

2. Dosage

Once a day, 8 mg each time.

3. Special groups

(1) Hepatic insufficiency

Patients with mild or moderate hepatic insufficiency (Child-Pugh class A or B) do not need to adjust the dosage.

Not recommended for patients with severe hepatic insufficiency (Child-Pugh C class).

(2), Renal insufficiency

Patients with mild renal insufficiency (creatinine clearance 50–80 mL/min) do not need to adjust the dosage.

In patients with moderate renal impairment (creatinine clearance 30–50 mL/min), the dose should be reduced to 4 mg once daily.

Not recommended for patients with severe renal insufficiency (creatinine clearance <30mL/minute).

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Contraindications of Silodosin

1. Severe liver insufficiency (Child-Pugh C grade).

2. Severe renal insufficiency (creatinine clearance <30mL/minute).

3. It is prohibited to use this product simultaneously with strong CYP3A4 inhibitors (such as clarithromycin, itraconazole, ketoconazole, ritonavir).

Precautions for Silodosin

1. Orthostatic hypotension

Silodosin may cause orthostatic hypotension, dizziness or syncope.

2. Rule out prostate cancer

Before starting treatment, the possibility of prostate cancer needs to be ruled out.

3. Intraoperative floppy iris syndrome

Intraoperative floppy iris syndrome (IFIS) has been observed during phacoemulsification cataract surgery in some patients who are currently receiving or have previously received α1-adrenergic blockers.

Male patients scheduled to undergo cataract surgery should be specifically questioned to determine whether they have been treated with silodosin or other alpha1-adrenergic blockers.

If the patient has been treated with α1-adrenergic blockers, the ophthalmologist should consider modifying the surgical technique by using an iris hook or iris dilation ring, or pharmacological intervention with intracameral phenylephrine or preoperative atropine to minimize complications of IFIS. The benefit of discontinuing α1-blockers before cataract surgery has not been established.

Silodosin (Silodosin) Medication for Special Populations

1. Pregnancy

Silodosin is classified as pregnancy category B and is not suitable for women.

2. Lactation period

Silodoxin is not suitable for women.

3. Pediatric medication

Silodosin is not suitable for children.

4. Medication for the elderly

It is reported that the incidence of orthostatic hypotension in patients aged ≥65 years is higher than that in young adults. There were no other significant differences in safety and efficacy compared with young adults.

5. Hepatic insufficiency

It is not recommended for patients with severe hepatic insufficiency.

6. Renal insufficiency

Not recommended for patients with severe renal insufficiency. Use with caution and dose reduction in patients with moderate renal impairment.

Common adverse reactions of Silodosin

Retrograde ejaculation, dizziness, diarrhea, orthostatic hypotension, headache, nasopharyngitis, and nasal congestion.

Silodosin drug interactions

1. Drugs that affect liver microsomal enzymes

There is a pharmacokinetic interaction with potent CYP3A4 inhibitors (increased silodosin plasma concentration), and simultaneous use is prohibited.

2. Drugs that affect or are affected by P-glycoprotein transport

Silodosin is a substrate of the P-glycoprotein transport system. Potential pharmacokinetic interaction with P-glycoprotein transport inhibitors (increased silodosin plasma concentrations). Concomitant use with strong P-glycoprotein inhibitors is not recommended.

3. Drugs that affect uridine diphosphate glucuronosyltransferase (UGT) 2B7

There is a potential pharmacokinetic interaction with UGT2B7 inhibitors (increased silodosin exposure).

Silodosin pharmacokinetics

1. Absorption

Bioavailability: After oral administration under eating conditions, the absolute bioavailability is about 32%, and the peak plasma concentration is reached in about 2.6 hours.

Food effects: Compared with administration in the fasting state, when administered with a medium-fat, medium-calorie meal, the area under the drug curve (AUC) and peak plasma concentration were reduced by 4%–49% and 18%–43%, respectively. Concomitant use with high-fat, high-calorie meals has not been evaluated.

2. Distribution

The plasma protein binding rate is about 97%.

3. Metabolism

Mainly in the liver, it is extensively metabolized through glucuronidation, alcohol dehydrogenase, aldehyde dehydrogenase and CYP3A4 isoenzyme. The major active metabolite, KMD-3213G, is formed through UGT2B7-mediated glucuronidation. Another major metabolite, KMD-3293, is formed by alcohol dehydrogenase and aldehyde dehydrogenase. KMD-3293 is not expected to contribute significantly to the overall pharmacological activity of silodosin.

4. Elimination pathway

Excreted through urine (33.5%) and feces (54.9%), with a half-life of approximately 13.3 hours.

Special population pharmacokinetics of silodosin

1. In patients with moderate hepatic insufficiency, the pharmacokinetics of silodosin did not change significantly after a single dose. The pharmacokinetics of silodosin have not been evaluated in patients with severe hepatic impairment.

2. In patients with moderate renal insufficiency, the AUC, peak plasma concentration and elimination half-life were 3.2 times, 3.1 times and 2 times higher respectively than in healthy individuals.

3. In elderly individuals, AUC and elimination half-life are increased by approximately 15% and 20% respectively compared with young individuals.

Silodosin (Silodosin) mechanism of action

By blocking α1-adrenergic receptors in the lower urinary tract, it causes smooth muscle relaxation in the bladder neck and prostate, thereby improving urinary flow rate and reducing BPH symptoms.

Having higher affinity for α1A-adrenergic receptors in nonvascular smooth muscle (e.g., prostate) than for α1B-adrenergic receptors in vascular smooth muscle; this may result in a reduced incidence of cardiovascular effects (e.g., syncope, dizziness, hypotension).

Storage of Silodosin

Silodosin is stored at 25°C (can be exposed to 15–30°C), protected from moisture and light.