Pharmacological action Rapaflo
Rapaflo Highly selective competitive antagonist α1A-adrenoceptor blocking postsynaptic α1A-adrenergic receptors located in the smooth muscle of the prostate, bladder neck and prostatic urethra. Reduces the tone of smooth muscles of the prostate, bladder neck and prostatic urethra, improving the flow of urine. At the same time reduces the symptoms of obstruction and irritation associated with benign prostatic hyperplasia.
Affinity α1A-adrenoreceptors located in the bladder, 162 times greater than its ability to interact with α1B-adrenoceptors located in vascular smooth muscle. Due to the high selectivity does not cause clinically significant reduction in blood pressure in patients with initially normal BP.
Pharmacokinetics Rapaflo
Absorption and distribution
If ingestion silodozin well absorbed. The absolute bioavailability of 32%. Food intake decreases the Cmax by approximately 30%, increasing the time to Cmax approximately 1 hour and has minimal effect on AUC. Cmax 87 ± 51 mg / ml, Tmax – 2.5 h, the average concentration in the urine of 433 ± 286 ng × h / ml.
Vd silodozina is 0 / 81 l / kg and bound to plasma proteins at 96.6%. Binding proteins silodozina karbamoilglyukuronida plaza is 91%.
Metabolism and Elimination
Silodozin metabolized by glyukuronirovaniya (involving UGT2B7), involving alcohol dehydrogenase and aldehyde dehydrogenase, oxidizing ways, mostly involving the CYP 3A4. The main active metabolite in plasma karbamoilglyukuronid (KMD-3213G) reaches the plasma concentration is 4 times greater than the silodozin. Silodozin not have the capacity induction or inhibition of cytochrome P450 isoenzymes.
33.5% silodozina eliminated via the kidneys and 54.9% through the intestines. Silodozina clearance is about 1.23 l / h. Silodozin excreted mainly as metabolites in very small quantities unchanged in the urine. T1 / 2 and silodozina karbamoilglyukuronida at 11 h and 18 h respectively.
Pharmacokinetics in special clinical situations
Pharmacokinetics silodozina and metabolites did not significantly depend on age. Silodozina clearance did not change in patients over 75 years.
In patients with moderate hepatic dysfunction (7-9 points on the Child-Pugh), pharmacokinetics silodozina not significantly changed. Patients with severe hepatic insufficiency pharmacokinetics silodozina not studied.
Indications Rapaflo
- Benign prostatic hyperplasia.
Dosing regimen
Recommended dose – 8 mg 1 time / simultaneously with food intake, preferably in the same time. Need to swallow the capsule whole, preferably with a glass of water.
When treating patients with renal failure secondary degree (QC from 30 to 50 ml / min) is recommended during the first week of taking the drug at a dose of 4 mg, with good individual tolerance can then increase the dose to 8 mg /
In renal insufficiency, severe appointment silodozina not recommended.
Side effects Rapaflo:
Adverse reactions with an indication of frequency are as follows: very common (≥ 1 / 10), often (from ≥ 1 / 100 to CNS: Frequently – dizziness; frequency is unknown – syncope.
With the cardiovascular system: often – orthostatic hypotension.
Part of the respiratory system: often – nasal congestion.
From the digestive system: often – diarrhea; infrequently – nausea, dry mouth.
From the reproductive system: Very common – retrograde ejaculation, aneyakulyatsiya; infrequently – decreased libido, erectile dysfunction.
Other: the frequency is unknown – intraoperative syndrome “flabby” iris during surgery for cataracts.
Contraindications
- Severe renal insufficiency (creatinine clearance – Severe hepatic insufficiency (insufficient clinical data);
- Children up to age 18 years;
- Hypersensitivity to active substance or to any of the auxiliary components or their intolerance.
Caution should be used in renal failure of moderate severity (QC from 30 to 50 ml / min).
Application Rapaflo with hepatic dysfunction
Contraindications: severe hepatic insufficiency (insufficient clinical data).
Application Rapaflo with renal impairment
When treating patients with renal failure secondary degree (QC from 30 to 50 ml / min) is recommended during the first week of taking the drug at a dose of 4 mg, with good individual tolerance can then increase the dose to 8 mg /
In renal insufficiency, severe appointment silodozina not recommended.
Cautions
As with other alpha1-blockers in the treatment of silodozinom may experience decreased blood pressure, orthostatic hypotension. At the first sign of orthostatic hypotension (dizziness, weakness) the patient must sit or lie down and stay in this position until the symptoms of orthostatic hypotension did not disappear.
Because benign prostatic hyperplasia and prostate tumor have similar symptoms and may occur together, patients with suspected benign prostatic hyperplasia before prescribing the drug to examination to exclude prostate tumors.
Treatment with Urorek reduces the allocated amount of seminal fluid that may affect male fertility. This effect disappears after discontinuation Urorek.
Patients receiving or taking alpha 1 blockers during surgery for cataracts may occur syndrome “flabby” Iris, which can lead to complications during surgery. Must stop treating alpha 1-adrenergic 1-2 weeks before the operation. Patients who are assigned to cataract surgery is not recommended to begin treatment with Urorek.
Effects on ability to drive vehicles and management mechanisms
Not conducted studies of the effect on the ability to drive vehicles and equipment. However, patients should be informed of the possible manifestations of the symptoms associated with orthostatic hypotension (eg dizziness), as well as to warn that one should refrain from driving vehicles and equipment to determine the individual tolerability Urorek patient.
Overdose Rapaflo
Symptoms: a marked reduction in blood pressure, compensatory tachycardia.
Treatment: gastric lavage, taking activated charcoal or osmotic laxatives, symptomatic therapy aimed at increasing the BCC, vasoconstrictor drugs. Monitor renal function. Dialysis is ineffective due to heavy drug binding to plasma proteins.
Drug Interactions Rapaflo
Not recommended combination with other alpha-blockers because of possible potentiation action.
Joint application of inhibitors of isoenzyme CYP3A4 (ketoconazole, clarithromycin, itraconazole, ritonavir) is not recommended as it increases the concentration of silodozina in plasma.
Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) for the combined application may increase the risk of dizziness.
Antihypertensive drugs (beta-blockers, calcium antagonists, drugs acting on the renin-aldosterone system angiotenzii, diuretics) for the joint application enhance orthostatic hypotension.
