赛洛多辛(Silodosin)的注意事项与药物相互作用

Silodosin is a highly selective α-1A adrenergic receptor antagonist designed for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia.

Precautions for the use of Silodosin

1. Contraindications and absolute contraindications

The following patients are strictly prohibited from use:

(1) Patients with severe renal insufficiency: creatinine clearance (CCr) <30mL/min.

(2) Patients with severe hepatic insufficiency: Child-Pugh score ≥10.

(3) Those who use strong CYP3A4 inhibitors in combination: such as ketoconazole, clarithromycin, itraconazole, ritonavir, etc. Therefore, such combination will cause the plasma concentration of silodosin to rise sharply, which is extremely risky.

(4) Those who are allergic to any component of silodosin.

2. Dose adjustment for special groups

(1) For patients with moderate renal insufficiency (CCr30-50mL/min): the dose must be reduced to 4 mg, once a day. Its plasma drug concentration can reach about 3 times that of people with normal renal function.

(2) Elderly patients: Although there is no need to adjust the dose uniformly, you need to be alert that the risk of orthostatic hypotension increases with age, especially for patients over 75 years old.

3. Safety warning

(1) Orthostatic hypotension: Dizziness, dizziness or even fainting may occur in the early stage of treatment. Patients should be advised to avoid driving or operating dangerous machinery and to rise slowly.

(2) Rule out prostate cancer: The symptoms of BPH are similar to those of prostate cancer. Necessary examinations must be conducted to rule out malignant tumors before taking medicine.

(3) Risks of eye surgery: Patients who plan to undergo cataract surgery must inform their ophthalmologist in advance that they are using or have used silodosin, because it may increase the risk of "intraoperative iris floppy syndrome".

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.

Silodosin drug interactions

Silodosin is mainly metabolized by the CYP3A4 enzyme and is a substrate of P-glycoprotein, so it interacts with a variety of drugs.

1. Absolutely contraindicated interactions

Powerful CYP3A4 inhibitors: As mentioned above, drugs such as ketoconazole will increase the plasma concentration and exposure of silodosin by more than three times, and their combined use is strictly prohibited.

2. Drugs that need to be avoided or used with caution

(1) Other α-blockers (such as terazosin): combined use will have superimposed antihypertensive effects and increase the risk of hypotension, so combined use should be avoided.

(2) PDE5 inhibitors (such as sildenafil, tadalafil): Both have vasodilatory effects, and combined use may cause symptomatic hypotension, so extra caution is required.

(3) Potent P-glycoprotein inhibitors (such as cyclosporine): may increase the absorption of silodosin and are not recommended for combined use.

(4) Antihypertensive drugs: combined use may increase the incidence of hypotension and dizziness, and blood pressure needs to be closely monitored.

(5) Moderate CYP3A4 inhibitors (such as verapamil, diltiazem, erythromycin): may increase the concentration of silodosin, so caution is required when used together and adverse reactions should be monitored.

3. Drugs without significant interactions

Digoxin: Studies have shown that silodosin does not affect the pharmacokinetics of digoxin, and no dose adjustment is required when used together.

Pharmacokinetic properties of Silodosin

The pharmacokinetic properties of Silodosin directly determine its dosage regimen and risk of interaction.

1. Absorption

The absolute bioavailability after oral administration is approximately 32%.

Food effects: Taking it with a moderate-fat meal can reduce the peak blood concentration (Cmax) by 18%-43% and reduce the exposure (AUC) by 4%-49%. Therefore, it is recommended to take it with food to reduce the incidence of adverse reactions.

For those who have difficulty swallowing, the contents of the capsule can be sprinkled on applesauce and taken. Its bioavailability is equivalent to that of the whole capsule.

2. Distribution and protein binding

The distribution volume is 49.5 liters, indicating that it is widely distributed in tissues. The plasma protein binding rate is as high as 97%, which means that dialysis has little effect on overdose.

3. Metabolism

(1). The metabolic pathways are complex: mainly metabolized through three pathways: glucuronidation (UGT2B enzyme), alcohol/aldehyde dehydrogenase and CYP3A4.

(2) Active metabolite: Its main metabolite KMD-3213G (glucuronic acid conjugate) is pharmacologically active, has a longer half-life (about 24 hours), and the plasma exposure is 4 times that of the prototype drug, which explains the sustained effect of the drug to a certain extent.

4. Excretion

After oral administration, approximately 33.5% of the radioactive dose is excreted through urine and 54.9% is excreted through feces.

5. Pharmacokinetics in special populations

(1) Renal insufficiency: The clearance rate of patients with moderate renal impairment decreases significantly, resulting in a significant increase in AUC and half-life, and the dose must be reduced.

(2) Liver dysfunction: Mild to moderate liver damage has no significant impact on pharmacokinetics, but severe liver damage is contraindicated.

(3) Elderly patients: AUC and half-life increased slightly, but the difference was not significant, suggesting that age itself is not a key factor in dose adjustment.