Uroflex (Tablets) Instructions for Use

ATC Code

G04BD07 (Tolterodine)

Active Substance

Tolterodine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug reducing the tone of the smooth muscles of the urinary tract

Pharmacotherapeutic Group

M-cholinoblocker

Pharmacological Action

Blocker of m-cholinergic receptors located in the bladder and salivary glands. Tolterodine and its active 5-hydroxymethyl metabolite are highly specific for m-cholinergic receptors and exhibit selectivity for these receptors in the bladder compared to the salivary glands.

It reduces the contractile function of the bladder and decreases salivation. It causes incomplete emptying of the bladder, increases the amount of residual urine, and reduces detrusor pressure.

The time to achieve a therapeutic effect is 4 weeks.

Pharmacokinetics

Absorption is rapid and high. C_max in blood plasma increases proportionally to the dose in the range of 1-4 mg. It is metabolized by the polymorphic enzyme CYP2D6 to form a pharmacologically active 5-hydroxymethyl metabolite, which is then metabolized to 5-carboxylic acid and N-dealkylated 5-carboxylic acid.

Bioavailability in individuals with reduced metabolism (lacking CYP2D6) is 65%, in individuals with increased metabolism it is 17%. Food does not affect the exposure of unbound tolterodine and the active 5-hydroxymethyl metabolite in individuals with increased metabolism, although its concentration increases when taken with food.

Tolterodine and the 5-hydroxymethyl metabolite bind predominantly to orosomucoid. The unbound fractions are 3.7% and 36%, respectively. V_d of tolterodine is 113 L. In individuals with increased metabolism, T_1/2 and systemic clearance are higher than in individuals with reduced metabolism.

It is excreted by the kidneys – 77% (51% as 5-carboxylic acid, 29% as N-dealkylated 5-carboxylic acid), through the intestines – 17%, with less than 1% excreted unchanged and about 4% as the active metabolite.

Indications

Overactive bladder, manifested by frequent urgent urges to urinate or urinary incontinence.

ICD codes

Dosage Regimen

Administer orally twice daily with a full glass of water. The standard adult dosage is one 2 mg tablet taken twice daily, for a total of 4 mg per day.

Reduce the total daily dose to 2 mg for patients with significant hepatic impairment or moderate to severe renal impairment (creatinine clearance ≤30 mL/min). Administer one 1 mg tablet twice daily in these populations.

Initiate a reduced dosage of 1 mg twice daily (2 mg/day total) for patients concurrently taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, clarithromycin, or ritonavir.

Swallow tablets whole; do not chew or crush. Dosing may be taken with or without food. The therapeutic effect on urinary symptoms may take up to 4 weeks to become fully apparent.

Discontinue treatment if therapeutic benefit is not achieved or if adverse effects become intolerable. Do not exceed the maximum recommended daily dose of 4 mg.

Adverse Reactions

From the digestive system: dryness of the oral mucosa, constipation, abdominal pain, dyspepsia, flatulence, vomiting, gastroesophageal reflux.

From the CNS: headache, dizziness, drowsiness, nervousness, confusion, hallucinations.

From the organ of vision: dryness of the sclera, visual disturbances (including accommodation disorders).

From the respiratory system: bronchitis, sinusitis.

From the urinary system: dysuria, urinary retention.

Allergic reactions: anaphylactic reactions, including angioedema.

Other: weakness, fatigue, chest pain, dry skin, weight gain, flushing, tachycardia, palpitations, peripheral edema.

Contraindications

Urinary retention, angle-closure glaucoma (untreatable), myasthenia gravis, severe ulcerative colitis, megacolon, pregnancy, lactation period, hypersensitivity to tolterodine.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and the lactation period.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Currently, the safety and efficacy of the drug in children have not been studied.

Special Precautions

Use with caution in severe obstruction of the lower urinary tract, obstructive lesions of the gastrointestinal tract (including pyloric stenosis), hepatic and/or renal insufficiency, in neuropathy, hiatal hernia, in children and adolescents under 18 years of age.

Before starting treatment, organic causes of frequent and urgent urges to urinate should be excluded.

Currently, the safety and efficacy of the drug in children have not been studied.

Influence on the ability to drive vehicles and mechanisms

During the treatment period, patients should exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased concentration, speed of psychomotor reactions, and good vision (may cause accommodation disorders and reduced speed of psychomotor reactions).

Drug Interactions

With simultaneous use with drugs that have anticholinergic properties, the effect of tolterodine is enhanced and the risk of side effects increases.

M-cholinergic receptor agonists reduce the effectiveness of tolterodine.

Tolterodine reduces the effect of prokinetics.

Pharmacokinetic interaction with drugs metabolized by CYP2D6 or CYP3A4 isoenzymes, which are inducers or inhibitors of these isoenzymes, is possible. Simultaneous use with strong CYP3A4 inhibitors, such as macrolide antibiotics (erythromycin and clarithromycin), or antifungal azole derivatives (ketoconazole, itraconazole and miconazole), should be avoided.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.