Product Overview
Composition
Composition per capsule:
Active substance:
silodosin 4 mg or 8 mg.
Excipients:
mannitol
pregelatinized starch (1500 ™ starch),
pregelatinized starch (PCS ™ PC-10 starch),
sodium lauryl sulfate,
magnesium stearate.
The composition of the gelatin capsule:
gelatin,
titanium dioxide
iron oxide yellow oxide (E-172)
pharmachologic effect
Pharmacodynamics
Mechanism of action
Silodosin, a highly selective competitive antagonist of alpha 1a-adrenergic receptors, blocks postsynaptic alpha 1a-adrenergic receptors located in the smooth muscles of the prostate gland, bladder neck and prostatic urethra.
Reduces the tone of the smooth muscles of the prostate gland, bladder neck and prostatic urethra, improving urine outflow. At the same time, the symptoms of obstruction and irritation associated with benign prostatic hyperplasia are reduced.
Affinity for alpha | 1a-adrenergic receptors located in the bladder are 162 times greater than its ability to interact with alpha-1b-adrenoreceptors, which are located in the smooth muscles of blood vessels. Due to its high selectivity, it does not cause a clinically significant decrease in blood pressure (BP) in patients with initially normal blood pressure.
Pharmacokinetics
When administered, silodosin is well absorbed. Absolute bioavailability is 32%. Food reduces the maximum concentration (Cmax) by about 30%, increasing the time to reach the maximum concentration (tmax) to about 1 hour and has a minimal effect on the area under the concentration-time curve (AUC).
Cmax87 ± 51 mg / ml, tmax - 2.5 hours, the average concentration in the urine of 433 ± 286 ng * h / ml. The volume of distribution of silodosin is 0.81 l / kg and binds to plasma proteins by 96.6%. The binding of silodosin to carbamoylglucuronide by plasma proteins is 91%. Silodosin is metabolized via glucuronidation (involving UGT2B7), involving alcohol dehydrogenase and aldehyde dehydrogenase, oxidative pathways, mainly involving CYP3A4.
The main active metabolite in plasma carbamoyl glucuronide (K.MD-3213G) reaches a plasma concentration 4 times higher than silodosin itself. Silodosin does not have the potential to induce or inhibit cytochrome P450 isoenzymes.
33.5% of silodosin is excreted through the kidneys and 54.9% through the intestines. The clearance of silodosin is about 23.1 l / h. Silodozin is excreted mainly in the form of metabolites and in a very small amount unchanged in the urine. T1 / 2 of silodosin and carbamoyl glucuronide is 11 hours and 18 hours, respectively.
Pharmacokinetics in various patient groups
Elderly patients: the pharmacokinetics of silodosin and metabolites were not significantly dependent on age. Silodozin clearance did not change in patients older than 75 years. Patients with impaired liver function: In patients with moderate impaired liver function (7-9 points on the Child-Pugh scale), the pharmacokinetics of silodosin does not significantly change. In patients with severe hepatic insufficiency, the pharmacokinetics of silodosin have not been studied.
Patients with impaired renal function: For patients with moderate renal failure, no dose reduction was required. For patients with severe renal failure, the use of silodosin is not recommended.
Indications
Contraindications
- Hypersensitivity to the active substance or any of the excipients
- components or their intolerance
- Children under 18
- Severe renal failure (creatinine clearance less than 30 ml / min)
- Severe liver failure (insufficient clinical data)
In mild to moderate renal failure (creatinine clearance from 30 to 50 ml / min).
Side effects
Adverse reactions with frequency are shown below: very often:> 10, often: from> 1/100 to <1/10, infrequently: from> 1/1000 to <1/100, rarely: from> 1/10 000 to < 1/1000, the frequency is unknown (the available data do not allow determining the frequency).
Nervous system
Often: dizziness.
Unknown frequency: syncope
The cardiovascular system
Often: orthostatic hypotension.
Respiratory system
Often: nasal congestion.
Gastrointestinal tract
Often: diarrhea.
Infrequently: nausea, dry mouth.
Reproductive system
Very often: retrograde ejaculation, anejaculation
Infrequently; decreased libido, erectile dysfunction
Intraoperative Cider
Unknown frequency:
Intraoperative flaccid iris syndrome during cataract surgery.
Interaction
Combination with other alpha-blockers is not recommended because of the possible potentiation of the action.
The combined use of inhibitors of the CYP3A4 isoenzyme (ketoconazole, clarithromycin, itraconazole, ritonavir) is not recommended, since it increases the concentration of silodosin in the plasma.
Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) when used together may increase the risk of dizziness.
Antihypertensive drugs beta-blockers, calcium antagonists, drugs acting on the renin-angiotensin-aldosterone system, diuretics when combined, enhance orthostatic hypotension.
How to take, course of administration and dosage
The recommended dose is 8 mg once, at the same time as eating, preferably at the same time of the day. It is necessary to swallow the whole capsule, preferably with a glass of water.
For the treatment of patients with moderate renal failure (creatinine clearance> 30 - <50 ml / min), it is recommended to take an initial dose of 4 mg per day during the first week, with good individual tolerance, then the dose can be increased to 8 mg per day.
Overdose
Symptoms: marked decrease in blood pressure, compensatory tachycardia.
Treatment: gastric lavage, taking activated charcoal or an osmotic laxative, symptomatic therapy aimed at increasing the volume of circulating blood (BCC), vasoconstrictor drugs. Monitoring kidney function. Dialysis is ineffective due to the intense binding of the drug to plasma proteins.