Vezomni (Tablets) Instructions for Use

Marketing Authorization Holder

Astellas Pharma Europe B.V. (Netherlands)

Manufactured By

Avara Pharmaceutical Technologies, Inc. (USA)

Packaging and Quality Control Release

ASTELLAS PHARMA EUROPE, B.V. (Netherlands)

ATC Code

G04CA53 (Tamsulosin and Solifenacin)

Active Substances

Tamsulosin (Rec.INN registered by WHO)

Solifenacin (Rec.INN registered by WHO)

Dosage Form

Vezomni

Modified-release tablets, film-coated, 6 mg+0.4 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Modified-release tablets, film-coated brownish-red, round, biconvex, with the engraving “6/0.4” on one side.

* each bilayer tablet contains one layer of solifenacin succinate (6 mg) and one layer of tamsulosin hydrochloride (0.4 mg).

Excipients: mannitol – 83 mg, maltose – 10 mg, magnesium stearate – 2.2 mg, macrogol 7 000 000 – 200 mg, macrogol 8000 – 40 mg.

Shell composition opadry red 03F45072 (hypromellose 6 mPa·s – 69.536%, iron oxide red dye – 17.44%, macrogol 8000 – 13.024%) – 10.2 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment and control of symptoms of benign prostatic hyperplasia. Combination of an m-cholinoblocker with an alpha₁-adrenoblocker

Pharmacotherapeutic Group

Benign prostatic hyperplasia treatment agent

Pharmacological Action

A combined medicinal product containing two active substances, Solifenacin and Tamsulosin. These active substances have independent and complementary mechanisms of action in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia, in the presence of storage symptoms.

Solifenacin is a selective competitive inhibitor of muscarinic bladder receptors, predominantly the m₃-subtype, and has low or no affinity for other receptors, enzymes, and ion channels.

Tamsulosin is an alpha₁-adrenoblocker. It is a selective competitive blocker of postsynaptic α₁-adrenoceptors, especially the α_1A and α_1D subtypes, responsible for the relaxation of the smooth muscles of the lower urinary tract.

Pharmacokinetics

Solifenacin

After multiple doses, T_max for solifenacin varied between 4.27 h and 4.76 h in different studies, for tamsulosin – between 3.47 h and 5.65 h, respectively. C_max in plasma for solifenacin varied between 26.5 ng/ml and 32.0 ng/ml, for tamsulosin – between 6.56 ng/ml and 13.3 ng/ml. The AUC value for solifenacin varied from 528 ng×h/ml to 601 ng×h/ml, for tamsulosin – between 97.1 ng×h/ml and 222 ng×h/ml. The absolute bioavailability for solifenacin is about 90%, while Tamsulosin is absorbed at 70-79%.

After a single dose, T_1/2 for solifenacin varies from 49.5 h to 53 h, for tamsulosin – from 12.8 h to 14 h.

C_max is reached in 3-8 h. T_max is dose-independent. C_max and AUC increase proportionally with dose escalation from 5 to 40 mg. Absolute bioavailability is 90%. The V_d of solifenacin after IV administration is approximately 600 L. Solifenacin is largely (about 98%) bound to plasma proteins, predominantly to α₁-acid glycoprotein.

Solifenacin is actively metabolized in the liver, mainly by the CYP3A4 isoenzyme. However, there are alternative metabolic pathways through which solifenacin metabolism can occur. The systemic clearance of solifenacin is about 9.5 L/h, and the terminal T_1/2 is 45-68 h. After oral administration of the drug, the following metabolites were identified in plasma besides solifenacin: one pharmacologically active (4R-hydroxysolifenacin) and three inactive (N-glucuronide, N-oxide and 4R-hydroxy-N-oxide of solifenacin).

After a single administration of 10 mg of ¹⁴C-labeled solifenacin, after 26 days, about 70% of the radioactivity was found in the urine and 23% in the feces. In urine, approximately 11% of the radioactivity was found as unchanged active substance, about 18% as the N-oxide metabolite, 9% as the 4R-hydroxy-N-oxide metabolite, and 8% as the 4R-hydroxy metabolite (active metabolite).

Tamsulosin

Tamsulosin is characterized by linear pharmacokinetics. At steady state, C_max of tamsulosin in plasma is reached in 4-6 h. Plasma protein binding is about 99%, V_d is small (about 0.2 L/kg).

Tamsulosin is slowly metabolized in the liver to form less active metabolites. Most of tamsulosin is present in the blood plasma unchanged. Tamsulosin is mainly metabolized in the liver, primarily with the participation of CYP3A4 and CYP2D6 isoenzymes.

After a single dose of 0.2 mg of ¹⁴C-labeled tamsulosin, after 1 week, about 76% of the radioactivity was detected in the urine and 21% in the feces. In urine, about 9% of the radioactivity was found as unchanged active substance; about 16% as O-desethyl tamsulosin sulfate, and 8% as O-ethoxyphenoxyacetic acid.

In clinical pharmacology and bioavailability studies, the age of patients ranged from 19 to 79 years. After administration, the highest concentration levels were found in elderly patients, although there was almost complete overlap with individual levels in younger patients. Can be used in elderly patients.

AUC and C_max of solifenacin in patients with mild and moderate renal impairment differ slightly from those in healthy volunteers. In patients with severe renal impairment (CrCl ≤30 ml/min), the exposure of solifenacin is significantly higher – an increase in C_max of about 30%, AUC – more than 100% and T_1/2 – more than 60%. A statistically significant correlation between CrCl and solifenacin clearance was noted.

Indications

Treatment of storage symptoms (irritative symptoms), from moderate to severe (urgent urination, frequent urination), and voiding symptoms (obstructive symptoms), associated with benign prostatic hyperplasia in men.

ICD codes

Dosage Regimen

Take one tablet orally once daily.

Swallow the tablet whole; do not crush, split, or chew.

Take the dose after the same meal each day to ensure consistent absorption.

The recommended dose is one tablet containing solifenacin succinate 6 mg and tamsulosin hydrochloride 0.4 mg.

This is a fixed-dose combination; do not adjust the individual components.

Re-evaluate therapy periodically to assess the need for continued treatment.

Do not use in patients with severe renal impairment (CrCl ≤30 ml/min).

Use with caution in patients with severe renal impairment who are at risk of urinary retention.

Contraindicated in patients with severe hepatic impairment (Child-Pugh score >9).

Use with caution in patients with moderate hepatic impairment (Child-Pugh score 7-9).

Avoid concomitant use with potent CYP3A4 inhibitors (e.g., ketoconazole).

Adverse Reactions

Metabolism and nutrition disorders: decreased appetite, hyperkalemia.

Nervous system disorders: dizziness, drowsiness, dysgeusia, headache, fainting, hallucinations, psychosis, delirium.

Eye disorders: blurred vision, intraoperative floppy iris syndrome, dry eyes, glaucoma.

Skin and subcutaneous tissue disorders: itching, dry skin, rash, Stevens-Johnson syndrome, angioedema, erythema multiforme, exfoliative dermatitis.

Cardiac disorders: palpitations, torsades de pointes tachycardia, QT interval prolongation, atrial fibrillation, arrhythmia, tachycardia, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: rhinitis, dyspnea, dry nose, dysphonia.

Gastrointestinal disorders: dry mouth, dyspepsia, constipation, nausea, abdominal pain, GERD, diarrhea, dry throat, vomiting, colonic obstruction, coprostasis, intestinal obstruction, abdominal discomfort, impaired liver function, increased activity of “liver” enzymes.

Musculoskeletal and connective tissue disorders: muscle weakness.

Reproductive system and breast disorders: ejaculation disorders, priapism.

Renal and urinary disorders: urinary tract infections, cystitis, urinary retention, difficulty urinating, renal failure.

Other: anaphylactic reaction

Contraindications

Hypersensitivity to the active substances; hemodialysis; severe hepatic impairment; severe renal impairment or moderate hepatic impairment with simultaneous treatment with strong inhibitors of the CYP3A4 isoenzyme, for example, ketoconazole; severe gastrointestinal diseases (including toxic megacolon); myasthenia gravis; angle-closure glaucoma; orthostatic hypotension; children under 18 years of age.

With caution

Severe renal impairment; risk of urinary retention; gastrointestinal obstructive diseases; risk of reduced gastrointestinal motility; hiatal hernia, gastroesophageal reflux and patients simultaneously taking medications that may cause or exacerbate esophagitis (for example, bisphosphonates); autonomic neuropathy; presence of risk factors such as long QT syndrome and hypokalemia (QT interval prolongation and torsades de pointes tachycardia have been observed).

Use in Pregnancy and Lactation

Intended for use only in males.

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

With caution in patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale).

Use in Renal Impairment

Contraindicated: in severe renal impairment or moderate hepatic impairment with simultaneous treatment with strong inhibitors of the CYP3A4 isoenzyme, for example, ketoconazole.

With caution in patients with severe renal impairment; risk of urinary retention.

Pediatric Use

Contraindicated use of the drug in children and adolescents under 18 years of age.

Geriatric Use

The drug is approved for use in elderly patients

Special Precautions

As with the use of other alpha₁-adrenoblockers, treatment with tamsulosin may in some cases lead to a decrease in blood pressure, which in rare cases can lead to fainting. At the first signs of orthostatic hypotension (dizziness, weakness), the patient should sit or lie down and remain in this position until the symptoms disappear.

In some patients taking or having previously taken tamsulosin hydrochloride, the development of intraoperative floppy iris syndrome (IFIS) was noted during surgery for cataract and glaucoma, which can lead to complications during surgery or in the postoperative period. It is not recommended to start therapy in patients who are scheduled for cataract or glaucoma surgery.

Should be used with caution in combination with strong and moderate CYP3A4 inhibitors, for example, verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole. Should not be used in patients with impaired metabolism of the CYP2D6 isoenzyme in combination with strong CYP3A4 inhibitors or strong CYP2D6 inhibitors, for example, paroxetine.

Can be used in patients with mild and moderate renal impairment, but should be prescribed with caution to patients with severe renal impairment.

Can be used in patients with mild hepatic impairment (≤7 points on the Child-Pugh scale). Patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale) should take the drug with caution. Use is contraindicated in patients with severe hepatic impairment (above 9 points on the Child-Pugh scale).

Influence on the ability to drive vehicles and mechanisms

The patient should be informed about the possible occurrence of dizziness, blurred vision, fatigue and less often drowsiness, which may adversely affect the ability to drive a car and operate machinery.

Drug Interactions

Concomitant use of solifenacin and ketoconazole (200 mg/day), a potent inhibitor of the CYP3A4 isoenzyme, caused a twofold increase in the AUC of solifenacin, and at a dose of 400 mg/day – a threefold increase.

Concomitant use of tamsulosin with ketoconazole at a dose of 400 mg/day leads to an increase in C_max and AUC of tamsulosin by 2.2 and 2.8 times, respectively.

Concomitant administration with verapamil (a moderate CYP3A4 inhibitor) leads to an increase in C_max and AUC of tamsulosin by 2.2 times and an increase in C_max and AUC of solifenacin by approximately 1.6 times.

Concomitant administration of tamsulosin with the strong CYP2D6 inhibitor paroxetine (20 mg/day) leads to an increase in C_max and AUC of tamsulosin by 1.3 and 1.6 times, respectively.

Since Solifenacin and Tamsulosin are metabolized by the CYP3A4 isoenzyme, pharmacokinetic interactions with inducers of the CYP3A4 isoenzyme (for example, rifampicin) are possible.

Solifenacin may reduce the effect of drugs that stimulate gastrointestinal motility, for example, metoclopramide and cisapride.

Concomitant use of tamsulosin with other α₁-adrenoceptor blockers may lead to a hypotensive effect.

When tamsulosin was used concomitantly with furosemide, some decrease in concentration was noted, but this does not require a dose change, since the drug concentration remains within the normal range.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.