Sonirid Duo Set, 0.4 mg+5 mg capsules 30 pcs

Sonirid Duo is intended to treat and control symptoms of benign prostatic hyperplasia (BPH) when combined treatment with tamsulosin and finasteride is necessary in order to:

– to achieve regression of prostate size, improve urination and reduce lower urinary tract symptoms caused by BPH;

– to slow the clinical progression of the disease and reduce the incidence of acute urinary retention and the need for surgical treatment, including transurethral resection of the prostate (TURP) and prostatectomy.

Sonirid Duo can only be used in cases of enlarged prostate (prostate volume greater than 40 cm3). At such enlargement of prostate the combined treatment relieves symptoms of BPH and slows down clinical progression of disease more effectively than monotherapy with finasteride or alpha 1-adrenoreceptor blocker.

The drug may be used only for treatment of men.

Pharmacodynamics

Pharmacodynamics of tamsulosin

Tamsulosin selectively and competitively blocks postsynaptic alpha-1-adrenoreceptors located in the smooth muscle of the prostate, bladder neck and prostatic urethra (alpha-1 A subtype) as well as alpha-1-adrenoreceptors mainly located in the bladder body (alpha-ID subtype).

This leads to a decrease in the tone of the smooth muscles of the prostate, bladder neck and prostatic part of the urethra and improvement of detrusor function. This decreases symptoms of obstruction and irritation associated with benign prostatic hyperplasia.

Therapeutic effect usually develops 2 weeks after initiation of the drug, although some patients show reduction of symptoms after the first dose. The ability of tamsulosin to affect alpha-1A-adrenoreceptors is 20 times greater than its ability to interact with alpha-1B-adrenoreceptors which are located in vascular smooth muscle.

This high selectivity ensures that the drug does not cause any clinically significant reduction in systemic arterial blood pressure (BP) in both patients with arterial hypertension and patients with normal baseline BP.

Pharmacodynamics of finasteride

Finasteride is a synthetic 4-azasteroid, a specific inhibitor of the intracellular 5-alpha reductase type II enzyme. The latter converts testosterone to the more active androgen, 5-alpha-dihydrotestosterone (DHT).

The normal function and growth of the prostate gland, including its hypertrophic tissue, is dependent on the conversion of testosterone to DHT. Finasteride does not act on androgen receptors. In healthy volunteers prostate cell proliferation and apoptosis are balanced by the interaction of growth-inhibiting and growth-promoting factors.

While the etiological factors that cause prostatic hyperplasia at the molecular level are not yet known, it is likely that DHT plays a role in this process. Specific inhibitors of 5-alpha reductase type II reduce the concentration of DHT in the prostate and promote regression of prostatic hyperplasia.

According to clinical studies, treatment with finasteride rapidly reduces plasma concentrations of DHT by 70%, resulting in a reduction in prostate volume. At continuous use statistically significant effects are registered after 3 months (reduction in the volume of the gland by approximately 20%) and 7 months, (reduction in the severity of symptoms associated with prostatic hyperplasia).

In the human body there are 2 types of 5-alpha reductase: I and P. Their distribution in tissues varies: type II isoenzyme is found in the prostate, testicles and their appendages, penile head, scrotum, seminal vesicles, liver and chest; type I is found mainly in the scalp, back and chest, sebaceous glands, liver, adrenal glands and kidneys.

Finasteride primarily inhibits the type II isoenzyme responsible for most of the DHT in the blood. A single dose of finasteride rapidly and significantly changes plasma concentrations of DHT. A single dose of 5 mg of finasteride reduces plasma DHT concentrations by 75%, which reaches its lowest level at 24 hours, then returns to baseline within 7 days.

Finasteride remains effective when taken multiple times. Finasteride reduces the concentration of DHT in the prostate itself by Finasteride has no affinity for androgen receptors and has no other hormonal action.

After the discovery of 5-alpha reductase and the description of 5-alpha reductase deficiency syndrome type II (male hermaphroditism), the role of androgens in benign prostatic hyperplasia has been revisited.

The development of the prostate depends on DHT, a strong androgen. When 5-alpha reductase deficiency occurs against a background of normal or high testosterone levels in adulthood, prostatic atrophy is observed.

DHT activates androgen receptors to form dimers that bind to DNA and directly or indirectly promote cell proliferation by altering expression of genes responsible for proliferation and apoptosis.

In intact prostate, the processes of apoptosis and proliferation are in equilibrium. Although the factors provoking prostatic hyperplasia at the molecular level are unknown, the role of DHT in this is highly probable. Specific type II 5-alpha reductase inhibitors can reduce the concentration of DHT in the prostate and promote the reversal of prostatic hyperplasia.

There was significant lethality in mice and rats of both sexes when a single dose of finasteride equal to 1500 mg/m2 (500 mg/kg) mg/m2 (400 mg/kg for females) and 5900 mg/m2 (1000 mg/kg for males) was fed. Low doses of the drug fed to pregnant rats caused genital malformations in male offspring.

Pharmacokinetics

Tamsulosin

Intake: Tamsulosin is absorbed in the small intestine with a fasting bioavailability of almost 100%. When tamsulosin is taken with food its absorption decreases. In order to achieve the same level of absorption, the drug should be taken daily in the dose indicated in the instructions after breakfast.

If a single long-acting capsule of 0.4 mg is taken after a meal, the maximum plasma concentration (Cmax) of the drug is reached approximately 6 hours later.

In multiple dosing, the equilibrium concentration is reached by day 5, when the maximum plasma concentration of the drug is approximately 2-3 times higher than in single dosing. Although these values were evaluated in elderly patients, they are assumed to be similar in younger patients. Individual fluctuations in plasma concentrations may occur with single and multiple dosing.

Distribution: Approximately 99% of tamsulosin is bound to plasma proteins; the volume of distribution is small (about 0.2 L/kg).

Metabolism: Tamsulosin is metabolized slowly; the “first pass” effect is insignificant. Tamsulosin is slowly biotransformed in the liver to form pharmacologically active metabolites that remain highly selective to alpha-1 A-adrenoreceptors.

Most of the active substance is present in the blood unchanged. Minor microsomal induction induced by tamsulosin has been detected in rats. None of the metabolites is more active than tamsulosin.

Elimation: Tamsulosin and its metabolites are primarily excreted by the kidneys, approximately 9% of the drug dose taken is unchanged. Plasma elimination half-life of the drug was 10 hours after a single use of 0.4 mg capsule, after repeated use – 13 hours, final elimination half-life – 22 hours. No dose adjustment is required in case of renal diseases. Finasteride

Intake: Rapidly absorbed from the gastrointestinal tract, within 2 hours it reaches a maximum plasma concentration of 37 ng/ml. Absorption in the gastrointestinal tract is completed 6-8 hours after intake. Food intake has no effect on absorption of finasteride. Bioavailability of finasteride when taken orally is approximately 80%.

Distribution: 90% of circulating finasteride is bound to plasma proteins and has no damaging effect in renal disease. Finasteride penetrates the blood-brain barrier and is distributed in small amounts in the seminal fluid of patients. The volume of distribution is 76±14 l.

Metabolism: Finasteride is actively metabolized in the liver by oxidative biotransformation. Two of the 5 metabolites of finasteride have weak activity and are responsible for 20% of the total inhibition of 5-alpha reductase.

Evacuation: The average half-life of finasteride is 6 hours (4-12 hours), in men over 70 years of age it is 8 hours (6-15 hours). When labeled finasteride was used, approximately 39% (32-49%) of the administered dose was excreted by the kidneys as metabolites.

Unlabeled finasteride was virtually undetectable in the urine. Approximately 57% (51-64%) of the total dose was excreted through the intestine. In patients with impaired renal function (creatinine clearance > 9 ml/min) no differences in finasteride excretion were observed. Concentrations of finasteride in semen range from undetectable ( Long-term, 3-7 months of administration at a dose of 5 mg/day, reduces serum DHT concentrations by 70%.

Pharmacokinetics in selected patient groups:

In elderly patients, finasteride is excreted slightly slower, but this has no clinical significance and does not require dose adjustment. This also applies to patients with renal insufficiency, as the decrease in renal excretion of metabolites is compensated for by increased excretion of the drug through the intestine.

The pharmacokinetics of finasteride in patients with hepatic impairment have not been studied. Since finasteride is actively metabolized in the liver, additional monitoring is required in patients with liver disease.

Indications

Treatment and control of symptoms of benign prostatic hyperplasia (BPH).

Composition

Finasteride

Composition per tablet:

the active ingredient:

Finasteride, 5 mg;

auxiliary substances:

Pill kernel:

Magnesium stearate 0.7500 mg; talc 4.5000 mg; sodium carboxymethyl starch (type A) 7.5000 mg; pregelatinized starch 15.0000 mg; microcrystalline cellulose 15.0000 mg; lactose monohydrate 102.2500 mg.

Shell:

Titanium dioxide SL.77891 EEC 171 0.1881 mg; lactose monohydrate 0.3809 mg; macrogol-6000 0.6214 mg; hyprolose 1.9048 mg; hypromellose 1.9048 mg.

Tamsulosin

Composition per 1 capsule:

acting substance:

Tamsulosin hydrochloride, 0.4 mg;

accompanies:

calcium stearate 0.800 mg; triethylcitrate 1.100 mg; talc 2.500 mg; methacrylic acid and ethylacrylate copolymer (1:1) 43.800 mg, also containing polysorbate-80 1.000 mg, sodium lauryl sulfate 0.300 mg; microcrystalline cellulose 281.400 mg.

Composition of the hard gelatin capsule Capsule:

Iron oxide yellow dye SL. 77492 E172 0.2000%, titanium dioxide SL. 77891 E171 0.3333%, iron oxide black dye SL. 77499 E172 0.5300% iron oxide red dye SL. 77491 E172 0,9300 %, gelatin up to 100,000 %.

Corpus:

Iron oxide red dye SL 77491 E172 0.010 %, iron oxide black dye SL. 77499 E172 0.0100%, iron oxide yellow dye SL. 77492 E172 0.1714 %, titanium dioxide SL 77891 E171 3.000 %, gelatin up to 100.000 %.

How to take, the dosage

Sonyrid Duo contains tamsulosin 400 mcg in modified-release capsules and finasteride 5 mg in film-coated tablets.

The drugs are intended to be taken daily.

The daily dose of Sonirid Duo includes 1 tamsulosin 400 mcg modified-release capsule and 1 film-coated tablet of finasteride 5 mg.

Tamsulosin 400 mcg modified-release capsules should be taken at the same time of day, after meals. The capsules should be swallowed whole and should not be crushed or chewed as this may interfere with the slow release of the active substance.

Long-term use of Sonirid Duo is necessary for full therapeutic effect.

If adverse reactions occur, the patient can be switched to finasteride monotherapy; however, it is recommended to return to the combination regimen if symptoms of BPH increase.

Interaction

In in vitro studies of hepatic microsomal fractions (a model of drug metabolism by the cytochrome P450 enzyme system) have determined that tamsulosin does not interact pharmacokinetically with finasteride during hepatic metabolism.

Additional Interactions of Tamsulosin with Other Medicinal Products and Other Interactions

No interactions have been found with tamsulosin and atenololol, enalapril, nifedipine or theophylline concomitantly.

The co-administration with cimetidine may increase the plasma concentration of tamsulosin, whereas furosemide decreases it. However, there is no need to change the dose of the drug as tamsulosin concentrations are within normal limits.

In vitro diazepam, propranolol, trichloromethiazide, chlormadinone, amitriptyline, diclofenac, glibenclamide, simvastatin and warfarin do not change the plasma free fraction of tamsulosin.

In addition, tamsulosin does not change the free fraction content of diazepam, propranololol, trichloromethiazide and chlormadinone.

In in vitro studies of hepatic microsomal fractions (cytochrome P450 enzyme system model of drug metabolism) no interaction with amitriptyline, salbutamol, glibenclamide and finasteride was observed at the hepatic metabolism level.

Contraindications

With caution: if there is a risk of obstructive uropathy; in liver disease; when planning the surgical treatment of cataracts.

Side effects

Adverse reactions of tamsulosin monotherapy

Nervous system disorders: frequent – dizziness; infrequent – headache; rare – fainting.

Cardiovascular system: infrequent – postural hypotension, tachycardia.

Respiratory system disorders: infrequent – rhinitis.

Digestive system disorders: infrequent – constipation, diarrhea, nausea, vomiting.

Skin and subcutaneous fatty tissue: infrequent – rash, pruritus, urticaria; rare – angioedema.

Reproductive system disorders: infrequent – retrograde ejaculation; rare – priapism.

Unwanted reactions of finasteride monotherapy

Immune system: infrequent – hypersensitivity.

An organ of vision: infrequent – clouding of the lens.

Digestive system disorders: frequent – abdominal pain.

Skin and subcutaneous fatty tissue: infrequent – rash.

Reproductive system and mammary glands: frequent – erectile dysfunction, impaired ejaculation, decreased ejaculate volume, decreased libido; infrequent – pain in the mammary glands, breast enlargement, pain in the testicles.

The following additional adverse reactions have been described during post-marketing monitoring (data on the frequency of adverse reactions are not available): hypersensitivity reactions, including itching, urticaria, and swelling of the lips and face.

Unwanted reactions of combination treatment

In patients receiving combination treatment (finasteride and α1-adrenoblocker) have described the same adverse reactions occurring with the same frequency as with monotherapy with finasteride and α1-adrenoblocker. However, the following exceptions were found: erectile dysfunction and ejaculatory dysfunction were detected more frequently with combination therapy, while disease progression (including increased symptoms of BPH or the need for surgical treatment) was noted more frequently with monotherapy.