Sonirid Duo (Tablets) Instructions for Use

Marketing Authorization Holder

Gedeon Richter, Plc. (Hungary)

Manufactured By

Gedeon Richter, Plc. (Hungary)

Or

Gedeon Richter Romania, S.A. (Romania)

Contact Information

GEDEON RICHTER JSC (Hungary)

ATC Codes

G04CA02 (Tamsulosin)

G04CB01 (Finasteride)

Active Substances

Tamsulosin (Rec.INN registered by WHO)

Finasteride (Rec.INN registered by WHO)

Dosage Form

Sonirid Duo

Tablet and capsule kit, the kit contains: caps. with modif. release 400 mcg: 30 pcs. in a pack; film-coated tab., 5 mg: 30 pcs. in a pack

Dosage Form, Packaging, and Composition

Tablet and capsule kit.

Modified-release capsules hard gelatin, size No. 2, cap: opaque, brown; body: opaque, brownish-yellow; capsule contents – pellets white or almost white.

Excipients : calcium stearate, triethyl citrate, talc, methacrylic acid and ethyl acrylate copolymer (1:1), also containing polysorbate 80, sodium lauryl sulfate, microcrystalline cellulose (type 101).

Composition of the hard gelatin capsule cap iron oxide yellow, titanium dioxide, iron oxide black, iron oxide red, gelatin.

Composition of the hard gelatin capsule body iron oxide red, iron oxide black, iron oxide yellow, titanium dioxide, gelatin.

Film-coated tablets white or almost white, rounded triangular shape, slightly biconvex, on one side – engraving “GR”, almost odorless.

Excipients : magnesium stearate, talc, sodium carboxymethyl starch (type A), pregelatinized starch, microcrystalline cellulose (type 101), lactose monohydrate.

Coating composition: titanium dioxide, lactose monohydrate, macrogol 6000, hypromellose.

10 pcs. (5 caps. + 5 tab.) – blisters (6) – cartons.

Clinical-Pharmacological Group

Drug for the treatment and control of symptoms of benign prostatic hyperplasia. Combination of a 5α-reductase inhibitor with an alpha₁-adrenergic blocker

Pharmacotherapeutic Group

Drugs for the treatment of benign prostatic hyperplasia: alpha-adrenergic blocker (tamsulosin) and 5-alpha-reductase inhibitor (finasteride)

Pharmacological Action

Tamsulosin

Tamsulosin selectively and competitively blocks postsynaptic α₁-adrenoceptors located in the smooth muscle of the prostate gland, bladder neck, and prostatic part of the urethra (subtype α_1A). Tamsulosin reduces the tone of the smooth muscle of the urethra and prostate gland, resulting in an increase in the maximum urinary flow rate; this is accompanied by easier urination and a reduction in symptoms associated with bladder obstruction and emptying. Tamsulosin also significantly alleviates symptoms associated with bladder filling due to its instability.

The effect on the severity of bladder filling and emptying symptoms persists during long-term therapy. The need for surgical intervention or catheterization is significantly reduced.

Alpha-1-adrenergic blockers can lower blood pressure by reducing peripheral vascular resistance. No reduction in blood pressure was observed with the use of tamsulosin.

Finasteride

Finasteride is a competitive inhibitor of type II 5-alpha-reductase, an intracellular enzyme that converts testosterone to the more active androgen, dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), prostate enlargement depends on the conversion of testosterone to DHT in the prostate. Finasteride effectively reduces DHT concentration in both serum and prostate tissue. Finasteride has no affinity for androgen receptors.

The use of finasteride reduces the incidence of acute urinary retention in patients with moderate or severe BPH symptoms, with an enlarged prostate gland (according to digital rectal examination) and with a low volume of residual bladder urine. A sustained reduction in prostate volume of approximately 20% and a stable increase in urinary flow rate were observed.

Combination therapy

The drug Sonirid Duo is intended for use only with significant prostate enlargement (volume more than 40 ml).

With such prostate enlargement, combination therapy is more effective in reducing BPH symptoms and slowing the clinical progression of the disease than monotherapy with finasteride or an alpha-1-adrenergic blocker.

Pharmacokinetics

Tamsulosin

Absorption

Tamsulosin is absorbed in the small intestine, bioavailability on an empty stomach is almost complete. When tamsulosin is taken with food, its absorption decreases. To achieve the same level of absorption, the drug should be taken daily at the dose indicated in the instructions, after breakfast. The kinetics are linear. C_max is reached approximately 6 hours after oral administration after a meal. After multiple doses, C_ss is reached by day 5, and C_max in blood plasma is approximately 2/3 higher than C_max after a single dose. Although these data were obtained in elderly patients, similar values are expected in young people. Interindividual differences in tamsulosin plasma concentrations are possible with both single and multiple doses.

Distribution

In men, approximately 99% of tamsulosin is bound to plasma proteins; V_d is small (about 0.2 l/kg).

Metabolism

Tamsulosin is metabolized slowly, the “first-pass” effect is insignificant. Most of the tamsulosin is present in the blood plasma unchanged. The drug is metabolized in the liver. Results of in vitro studies suggest that the cytochrome P450 system isoenzymes CYP3A4, as well as CYP2D6, are involved in the metabolism of tamsulosin. In rats, tamsulosin was found to slightly induce the activity of liver microsomal enzymes. None of the metabolites are more active than tamsulosin.

Excretion

Tamsulosin and its metabolites are predominantly excreted by the kidneys, approximately 9% of the administered dose of the drug is excreted unchanged. After a single dose of 0.4 mg, with food and at steady state, T_1/2 from blood plasma is from 10 to 13 hours.

Pharmacokinetics in special clinical cases

In case of kidney disease, dose adjustment is not required.

Finasteride

Absorption

Rapidly absorbed from the gastrointestinal tract. C_max in blood plasma is reached approximately 2 hours after oral administration and absorption is completely completed within 6-8 hours. Oral bioavailability is approximately 80% of the reference dose and depends on food intake.

Distribution

Binding to plasma proteins is approximately 90%. The plasma clearance of finasteride is 165 ml/min, V_d is 76 L. Finasteride has been found to cross the blood-brain barrier. Finasteride is found in small amounts in the seminal fluid of patients.

Metabolism

Two metabolites of finasteride are known, which have weak activity against type II 5-alpha-reductase.

Excretion

In men after a single oral dose of ¹⁴C-labeled finasteride, 39% of the administered dose is excreted by the kidneys as metabolites (finasteride is practically not excreted unchanged by the kidneys), 57% of the total dose is excreted through the intestine.

Pharmacokinetics in special clinical cases

In elderly patients, finasteride is excreted slightly more slowly. In men over 70 years of age, T_1/2 increases to 8 hours, while in men aged 18 to 60 years, the T_1/2 period is approximately 6 hours. No dose reduction is required, as this difference is not clinically significant.

In patients with chronic renal failure (creatinine clearance from 9 to 55 ml/min), the distribution of ¹⁴C-labeled finasteride after a single dose did not differ from that in healthy volunteers. Protein binding in patients with impaired renal function also did not differ. Some metabolites that are usually excreted by the kidneys were excreted through the intestine. Thus, with a decrease in the renal excretion of metabolites, there is a proportional increase in excretion through the intestine. In patients with impaired renal function not on hemodialysis, no dose adjustment is required.

There are no data on the use of the drug in patients with hepatic insufficiency.

Indications

• Treatment and control of symptoms of benign prostatic hyperplasia.

ICD codes

Dosage Regimen

The combined drug Sonirid Duo contains 2 drugs: tamsulosin capsules at a dose of 0.4 mg and finasteride tablets 5 mg.

The drugs should be taken daily, once a day.

The daily dose of Sonirid Duo is: 0.4 mg (1 capsule) of tamsulosin and 5 mg (1 tablet) of finasteride.

The tamsulosin capsule should be taken at the same time of day, after breakfast or the first meal. The capsules should be swallowed whole, not broken or chewed, as this may disrupt the modified release of the active substance.

The finasteride tablet is taken regardless of food intake. The tablet should be swallowed whole, without breaking.

Long-term use of Sonirid Duo is necessary for maximum therapeutic effect. If adverse reactions occur, the patient can be switched to finasteride monotherapy, but it is recommended to return to the combination regimen if BPH symptoms worsen.

Special patient groups

Patients with renal insufficiency. In patients with renal insufficiency, no dose adjustment is required, but special caution should be exercised when treating patients with end-stage renal disease (creatinine clearance <10 ml/min), as clinical data on the use of the drug in this category of patients are insufficient.

Patients with hepatic insufficiency. In patients with mild to moderate hepatic insufficiency, no dose adjustment is required. In severe hepatic insufficiency, the use of this drug is contraindicated.

Elderly patients (over 65 years). No dose adjustment is required.

Adverse Reactions

Adverse reactions (ARs) are distributed by system-organ classes in accordance with MedDRA, indicating the frequency of their occurrence according to WHO recommendations: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000), frequency unknown (insufficient data to estimate frequency).

The following ARs have been registered with monotherapy with tamsulosin and finasteride preparations.

Tamsulosin

Nervous system disorders common – dizziness; uncommon – headache; rare – syncope.

Eye disorders: frequency unknown – blurred vision, visual impairment.

Cardiac disorders uncommon – palpitations.

Vascular disorders uncommon – orthostatic hypotension.

Respiratory system disorders uncommon – rhinitis; frequency unknown – epistaxis.

Gastrointestinal disorders uncommon – constipation, diarrhea, nausea, vomiting; frequency unknown – dry mouth.

Skin and subcutaneous tissue disorders uncommon – skin rash, pruritus, urticaria; very rare – Stevens-Johnson syndrome; frequency unknown – exfoliative dermatitis.

Immune system disorders: rare – angioedema.

Reproductive system and breast disorders common – ejaculation disorders; very rare – priapism; frequency unknown – retrograde ejaculation, inability to ejaculate.

General disorders and administration site conditions : uncommon – asthenia.

Cases of intraoperative floppy iris syndrome (IFIS) during cataract and glaucoma surgery in patients taking tamsulosin have been described.

Use of the drug in the post-registration surveillance period: in addition to the ARs described above, atrial fibrillation, arrhythmia, tachycardia and dyspnea have been observed with the use of tamsulosin. Since these data were obtained by spontaneous reporting in the post-registration period, determining the frequency and causal relationship of these phenomena with tamsulosin intake seems difficult.

Finasteride

Among the side effects, impotence and decreased libido were most frequently observed. These ARs occur at the beginning of therapy and disappear during treatment in most patients. The frequency of adverse reactions registered during post-registration use cannot be determined, as the information is obtained from spontaneous reports.

Immune system disorders frequency unknown – hypersensitivity reactions, angioedema, including swelling of the lips, tongue, larynx and face.

Psychiatric disorders common – decreased libido; frequency unknown – depression, decreased libido that may persist after discontinuation of treatment.

Cardiac disorders: frequency unknown – palpitations.

Hepatobiliary disorders frequency unknown – increased activity of liver transaminases.

Skin and subcutaneous tissue disorders: uncommon – skin rash; frequency unknown – pruritus, urticaria.

Reproductive system and breast disorders: common – impotence; uncommon – ejaculation disorder, breast tenderness, breast enlargement; frequency unknown – testicular pain, sexual dysfunction (erectile dysfunction and ejaculation disorders), sometimes persisting after discontinuation of therapy, male infertility and/or deterioration of semen quality. After discontinuation of finasteride, semen quality normalized or improved.

Laboratory and instrumental data: common – decreased ejaculate volume.

In addition, cases of breast cancer in men have been reported during clinical trials and in the post-registration period.

When assessing the concentration of prostate-specific antigen (PSA) in the blood serum, its decrease in patients taking finasteride should be taken into account.

Adverse reactions with combination therapy

In patients receiving combination treatment (finasteride and an alpha₁-adrenergic blocker), the same adverse reactions have been described, occurring with the same frequency as with monotherapy with finasteride and an alpha₁-adrenergic blocker. However, the following exceptions have been identified: erectile dysfunction and ejaculation disorder were detected more often with combination treatment, while disease progression (including worsening of BPH symptoms or the need for surgical treatment) was noted more often with monotherapy.

Contraindications

• Hypersensitivity to the active or excipients in the drug, including the occurrence of angioedema while taking the drug;
• Use in women;
• History of orthostatic hypotension;
• Severe hepatic insufficiency;
• Age under 18 years (due to lack of data on the efficacy and safety of the drug in this population);
• Lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

With caution

• Patients with end-stage renal disease (creatinine clearance <10 ml/min);
• Mild and moderate hepatic insufficiency;
• Elderly patients;
• When planning surgical treatment of cataract.

Use in Pregnancy and Lactation

The use of Sonirid Duo in women is not indicated.

Pregnant women and women of reproductive age should avoid contact with crushed or damaged finasteride tablets, and should also avoid contact with the semen of a man taking finasteride (use a condom).

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency. Use with caution in patients with mild and moderate hepatic insufficiency.

Use in Renal Impairment

Contraindicated in renal impairment (plasma creatinine concentration >2 mg/dl).

Pediatric Use

Contraindicated in children.

Geriatric Use

In elderly patients, finasteride is excreted slightly more slowly, but this has no clinical significance and does not require dose adjustment.

Special Precautions

Before starting therapy with Sonirid Duo, the patient should be examined to rule out other diseases characterized by symptoms resembling those of BPH. Before starting treatment and regularly during therapy, a digital rectal examination of the prostate gland should be performed, and if necessary, PSA determination.

Precautions for the use of tamsulosin

As with the use of other α₁-adrenoceptor blockers, blood pressure may decrease during treatment with tamsulosin, which in rare cases leads to fainting. At the first signs of orthostatic hypotension (e.g., dizziness, weakness), the patient should be seated or laid down until the symptoms completely disappear.

Special caution should be exercised when treating patients with end-stage renal disease (creatinine clearance less than 10 ml/min), as the use of tamsulosin in this patient population has not been studied.

During cataract or glaucoma surgery, some patients taking tamsulosin (at the time of surgery or previously) developed intraoperative floppy iris syndrome (a type of small pupil syndrome). The occurrence of this syndrome increases the risk of complications during surgery and in the postoperative period. It is not recommended to prescribe tamsulosin to patients who are scheduled for cataract or glaucoma surgery. It is advisable to discontinue tamsulosin 1-2 weeks before surgery; however, the benefit and duration of discontinuing tamsulosin treatment before cataract surgery have not been determined. Cases of intraoperative floppy iris syndrome have been known to occur in patients who discontinued tamsulosin earlier before surgery. During the preoperative examination, the operating surgeon and members of the ophthalmology team should take into account whether the patient is taking (or has taken) tamsulosin. This is necessary to prepare for the possible occurrence of the syndrome during surgery.

Tamsulosin should be used with caution in combination with strong and moderate inhibitors of the CYP3A4 isoenzyme.

Tamsulosin and active inhibitors of the CYP3A4 isoenzyme (e.g., ketoconazole) should not be used in poor metabolizers of the CYP2D6 isoenzyme.

Precautions for the use of finasteride

General

To avoid obstructive complications, patients with a large volume of residual urine and a sharp decrease in urine flow rate should be carefully monitored. The possibility of surgical intervention should be evaluated.

Effect of finasteride on PSA and diagnosis of prostate cancer (PCa)

The clinical efficacy of finasteride at a dose of 5 mg in patients with PCa has not been established. Before starting treatment with finasteride and during subsequent therapy, digital rectal examination of the prostate and other tests to exclude PCa should be performed regularly. Serum PSA determination is also used for the diagnosis of PCa. As a rule, with initial PSA values above 10 ng/ml, further examination and biopsy are indicated; if initial PSA values are from 4 to 10 ng/ml, additional examination is recommended. In men, PSA values can vary widely, regardless of the presence of PCa. Thus, normal PSA values do not exclude PCa in men with BPH, regardless of treatment with finasteride 5 mg. PCa cannot be ruled out even with an initial PSA value below 4 ng/ml.

In patients with BPH using finasteride 5 mg, serum PSA concentration decreases by approximately 50%, even in the presence of PCa. This fact must be taken into account when assessing the PSA level in patients with BPH receiving finasteride treatment, since a decrease in PSA concentration is not a basis for excluding concomitant PCa. A decrease in PSA concentration is expected in any range of values, but there are individual characteristics. In patients receiving finasteride 5 mg for 6 months or longer, the obtained PSA value must be doubled and only then compared with normal values. Using this correction allows maintaining the sensitivity and specificity of the PSA test and taking the result into account when diagnosing PCa.

If there is a persistent increase in PSA concentration in patients receiving finasteride 5 mg, an examination should be performed. At the same time, possible non-compliance with the therapy regimen by the patient cannot be ruled out.

Effect on laboratory test results

Effect on PSA. Serum PSA concentration correlates with the patient’s age and prostate volume, and prostate volume correlates with the patient’s age. When interpreting the result of a PSA laboratory test, it must be taken into account that patients receiving finasteride 5 mg experience a decrease in PSA levels. Most patients experience a rapid decrease in PSA levels during the first months after starting treatment, after which its concentration stabilizes at a new level. The PSA value after treatment is approximately half of the value obtained before the start of therapy. Thus, in patients receiving finasteride 5 mg for six months or longer, the obtained PSA value must be doubled and only then compared with normal values.

Finasteride 5 mg does not significantly reduce the free PSA fraction (the ratio of free PSA to total). The ratio of free PSA to total remains unchanged even while taking finasteride 5 mg. When determining the free PSA fraction for the diagnosis of PCa, no correction of values is required.

Male breast cancer

Cases of male breast cancer have been reported during clinical trials and in the post-marketing period in men taking finasteride 5 mg. The specialist should warn the patient to immediately report any changes in the breasts (lumps, pain, gynecomastia, or nipple discharge).

Mood changes

Mood changes, including depression and suicidal ideation, have been observed in patients taking finasteride 5 mg. The emergence of psychopathological symptoms should be monitored, and if they appear, the patient should be referred for consultation with a specialist.

Hepatic insufficiency

Studies on changes in the pharmacokinetics of finasteride in hepatic insufficiency have not been conducted.

Effect on the ability to drive vehicles and operate machinery

There are no data on the effect of finasteride on the ability to drive vehicles and operate machinery. No effect of tamsulosin on the ability to drive vehicles and operate machinery has been reported. However, patients should be aware that dizziness may occur when taking the drug.

Overdose

No cases of simultaneous overdose of finasteride and tamsulosin have been described.

Overdose of tamsulosin may lead to the development of arterial hypotension, which may lead to cardiovascular disorders. To restore blood pressure and heart rate, the patient should be placed on their back; if necessary, plasma-substituting drugs should be used and, depending on the patient’s condition, vasopressor drugs. Renal function should be monitored. Dialysis is not indicated due to the significant binding of tamsulosin to plasma proteins. To reduce drug absorption, it is advisable to induce vomiting. Gastric lavage after taking a large amount of the drug should be performed along with the administration of activated charcoal and an osmotic laxative (e.g., sodium sulfate).

Overdose of finasteride: a single dose of 400 mg of finasteride and multiple doses of up to 80 mg/day for 3 months did not reveal adverse reactions. In case of overdose, no specific treatment is required.

Drug Interactions

Tamsulosin does not enter into pharmacokinetic interaction with finasteride during metabolism in the liver.

Interaction of tamsulosin with other medicinal products and other forms of interaction

No interaction was found with simultaneous use of tamsulosin and atenolol, enalapril, nifedipine, or theophylline.

Concomitant use with cimetidine may cause an increase in tamsulosin plasma concentration, while furosemide causes its decrease. However, no dose adjustment of the drug is required, as the tamsulosin concentration remains within the normal range.

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

Also, tamsulosin does not change the free fraction content of diazepam, propranolol, trichlormethiazide, and chlormadinone.

Diclofenac and warfarin may increase the elimination rate of tamsulosin.

Tamsulosin should be used with caution in combination with moderate inhibitors of the CYP3A4 isoenzyme (e.g., erythromycin).

Tamsulosin should not be used in combination with potent inhibitors of the CYP3A4 isoenzyme (e.g., ketoconazole) in poor metabolizers of CYP2D6.

When tamsulosin and potent inhibitors of the CYP3A4 isoenzyme are used concomitantly, an increase in tamsulosin exposure may be observed. With concomitant use of ketoconazole, an increase in the C_max of tamsulosin by 2.2 times and the area under the concentration-time pharmacokinetic curve (AUC) by 2.8 times is observed.

With concomitant use of tamsulosin and paroxetine, a potent inhibitor of the CYP2D6 isoenzyme, an increase in the C_max and AUC of tamsulosin by 1.3 and 1.6 times, respectively, is observed; however, this increase is not clinically significant.

There is a possibility of arterial hypotension developing with the simultaneous use of tamsulosin with other alpha-1-adrenergic blockers.

Interaction of finasteride with other medicinal products and other forms of interaction

No clinically significant drug interactions have been identified. Finasteride is metabolized primarily by the CYP3A4 isoenzyme of the cytochrome P450 system, without significantly affecting the function of this system. Although the risk of finasteride affecting the pharmacokinetics of other drugs is considered low, there is a possibility that inhibitors or inducers of the CYP3A4 isoenzyme will affect the plasma concentration of finasteride. However, based on available safety data, it is unlikely that an increase in finasteride concentration occurring with the concomitant use of such inhibitors will have clinical significance.

In studies of the use of finasteride with propranolol, digoxin, glibenclamide, warfarin, theophylline, and phenazone, no clinically significant interaction was identified.

Storage Conditions

The drug should be stored out of the reach of children at a temperature between 15°C (59°F) and 30°C (86°F).

Shelf Life

The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.