Oxybutynin genheim

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Oxybutynin Geneym (Oxybutynin Geneym)

Composition:

Active substance: oxybutynin hydrochloride;

1 tablet contains 5 mg of oxybutynin hydrochloride;

Excipients: microcrystalline cellulose; Celactose 80 (lactose monohydrate; microcrystalline cellulose); talc; magnesium stearate.

Pharmaceutical form. Tablets.

Basic physico-chemical properties: white or almost white, round, biconvex, uncoated tablets, odorless, 7.9 mm in size, with the inscriptions “B” and “R” on opposite sides of the break line on one side and flat on the other side.

Pharmacotherapeutic group. Drugs affecting the genitourinary system and sex hormones. Drugs used in urology. Drugs for the treatment of urinary urgency and urinary incontinence. Oxybutynin. ATC code G04BD04.

Pharmacological Properties

Pharmacodynamics

Oxybutynin is a synthetic tertiary amine with direct anticholinergic and spasmolytic effects on smooth muscle, including that of the urinary bladder.

The clinical effect of the medicinal product Oxybutynin Geneim manifests as an increase in bladder volume and a reduction in the frequency of spontaneous contractions of the unstable (overactive) detrusor muscle of the urinary bladder. As a result, urinary incontinence symptoms are reduced.

Pharmacokinetics

Absorption

After oral administration, oxybutynin is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration is reached within 60–90 minutes and demonstrates wide interindividual variability. Concomitant food intake, especially high-fat meals, delays absorption of oxybutynin but increases its overall bioavailability. The duration of action of oxybutynin is approximately 6–10 hours.

Oxybutynin is 83–95% bound to plasma albumin.

Metabolism

Due to pronounced first-pass metabolism, bioavailability is low, ranging from 2–11%. Oxybutynin hydrochloride is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, particularly CYP3A4. Individual predisposition may lead to significant interindividual variations in oxybutynin metabolism.

Its main metabolites are 2,2-diphenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin, which is pharmacologically active and has comparable pharmacological activity to oxybutynin, but reaches significantly higher plasma concentrations than the parent compound.

Elimination

Elimination of oxybutynin occurs in a biphasic manner, whereas the metabolite N-desethyloxybutynin is eliminated monophasically. The elimination half-life of both the drug and its active metabolite is 2–3 hours. A very small amount of unchanged oxybutynin is excreted in urine.

In elderly patients, particularly those with compromised health, the elimination half-life may be prolonged due to higher bioavailability. This may lead to an increased risk of adverse effects and may require dose reduction.

Clinical Characteristics

Indications

Adults

Urinary incontinence, urgency, or frequency due to overactive bladder caused by neurogenic bladder dysfunction (detrusor hyperreflexia) or idiopathic detrusor overactivity.

Children

Oxybutynin hydrochloride is indicated for use in children aged 5 years and older for:

• urinary incontinence, urgency, or frequency due to overactive bladder caused by idiopathic overactivity or neurogenic bladder dysfunction (detrusor overactivity);
• nocturnal enuresis associated with detrusor overactivity, in combination with non-pharmacological treatment, when other therapies have been ineffective.

Contraindications

• hypersensitivity to the active substance or to any of the excipients;
• urinary tract obstruction / impaired bladder emptying which may lead to urinary retention;
• gastrointestinal obstruction, including paralytic ileus or intestinal atony;
• toxic megacolon;
• severe ulcerative colitis;
• myasthenia gravis;
• narrow-angle glaucoma or shallow anterior chamber of the eye;
• polyuria or nocturia due to cardiac or renal failure;
• hiatal hernia complicated by reflux esophagitis.

Interaction with other medicinal products and other forms of interaction

Enhanced effect when used with other anticholinergic agents

Oxybutynin Genehm should be used with caution in combination with other anticholinergic agents due to the potential for potentiation of anticholinergic effects, such as:

• amantadine and other anticholinergic antiparkinsonian agents (e.g., biperiden, levodopa);
• antihistamines;
• antipsychotics (e.g., phenothiazines, butyrophenones, clozapine);
• quinidine;
• digitalis preparations;
• tricyclic antidepressants;
• atropine and related compounds (e.g., atropine-containing spasmolytics);
• dipyridamole.

Reduced effect due to oxybutynin

Due to decreased gastric motility, oxybutynin may impair the absorption of other medicinal products from the gastrointestinal tract (GI tract).

Modulation of mutual effects

Oxybutynin is metabolized by the CYP3A4 isoenzyme of cytochrome P450. Concomitant use with CYP3A4 inhibitors may inhibit oxybutynin metabolism and increase its exposure. This should be taken into account when co-administering with azole antifungal agents (e.g., ketoconazole) or macrolide antibiotics (e.g., erythromycin).

As an anticholinergic agent, oxybutynin may act antagonistically to the effect of prokinetic agents (e.g., metoclopramide, domperidone).

Concomitant use with acetylcholinesterase inhibitors may reduce their efficacy.

Other interactions

Sedative effects may be enhanced when used concomitantly with medicinal products acting on the central nervous system (see section "Ability to influence reaction speed when driving or operating machinery").

Patients should be informed that alcohol consumption may enhance drowsiness caused by anticholinergic agents such as oxybutynin.

Concomitant alcohol intake may cause dizziness, drowsiness, and visual disturbances.

The ability of sublingual tablets to dissolve under the tongue may be impaired due to dry mouth; therefore, patients using sublingual nitrates are advised to moisten the oral cavity with the tongue or a small amount of water before taking a sublingual tablet.

Special precautions for use

The medicinal product should be used with caution in patients with Parkinson's disease, as they have a higher risk of adverse effects associated with oxybutynin (see sections "Posology and method of administration" and "Pharmacokinetics"), as well as in patients with autonomic neuropathy, severe gastrointestinal disorders (e.g., motility disorders), or hepatic or renal impairment.

A dose reduction may be required in such patients. In patients with hepatic or renal impairment, appropriate laboratory parameters should be monitored during long-term therapy.

Oxybutynin may exacerbate cognitive disorders, symptoms of benign prostatic hyperplasia, and clinical manifestations of tachycardia (therefore, caution is advised in hyperthyroidism, congestive heart failure, arrhythmias, ischemic heart disease, and arterial hypertension).

Caution is recommended in patients with fever or when exposed to high environmental temperatures. Treatment may potentially cause heat stroke due to reduced sweating as a result of decreased sweat gland secretion (see section "Adverse reactions").

Nervous system

Anticholinergic effects on the central nervous system (e.g., hallucinations, restlessness, confusion, somnolence) have been reported. Monitoring is recommended, particularly during the first few months of treatment or following a dose increase. If anticholinergic effects on the central nervous system (CNS) occur, discontinuation of treatment or dose reduction should be considered.

The medicinal product should also be used with caution in patients with Parkinson's disease or other central nervous system disorders associated with cognitive impairment, as they are at higher risk of developing psychiatric and CNS-related adverse effects. A dose reduction may be required in such patients.

Infections

If urinary tract infections occur during treatment with oxybutynin, appropriate therapy should be initiated.

Prolonged use of oxybutynin may lead to reduced salivation, which in turn may promote the development of dental caries, periodontitis, or candidal stomatitis.

Eye disorders

Since oxybutynin may cause acute angle-closure glaucoma, patients should have visual acuity and intraocular pressure monitored during treatment. Patients should be advised to seek immediate medical attention if they experience sudden loss of visual acuity or eye pain.

Gastrointestinal disorders

Anticholinergic medicinal products may reduce gastrointestinal motility; therefore, oxybutynin should not be used in patients with obstructive gastrointestinal disorders such as severe ulcerative colitis, toxic megacolon, intestinal atony, or intestinal obstruction (see section "Contraindications").

Anticholinergic agents such as oxybutynin should be used with caution in patients with severe gastrointestinal motility disorders, other gastrointestinal diseases, hiatal hernia, gastroesophageal reflux disease (GERD), reflux esophagitis, and in patients concurrently taking other medicinal products (e.g., bisphosphonates) that may cause or exacerbate esophagitis.

Dependence

Dependence on oxybutynin has been observed in patients with a history of substance or psychotropic drug abuse (see section "Adverse reactions").

Elderly patients

Anticholinergic agents should be used with caution in elderly patients due to the risk of cognitive impairment.

Oxybutynin should be used cautiously in elderly patients, as they may be more sensitive to its effects. Therefore, a dose reduction may be required in elderly patients (see section "Posology and method of administration"). Plasma concentrations of the medicinal product are generally higher in elderly individuals.

Children under 5 years of age

The use of oxybutynin in children under 5 years of age is not recommended; safety has not been established in this age group.

There is only limited experience supporting the use of oxybutynin in children with monosymptomatic nocturnal enuresis (not associated with detrusor overactivity).

Children aged 5 to 18 years

Oxybutynin should be used with caution in children aged 5 years and older, as they may be more sensitive to the drug's effects, particularly CNS- and psychiatric-related adverse effects.

Information on excipients with known effects

The medicinal product Oxybutynin Genheim contains lactose. Patients with rare hereditary forms of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption syndrome should not take Oxybutynin Genheim due to its lactose content.

Use during pregnancy or breastfeeding

Pregnancy

There are no adequate data on the use of oxybutynin in pregnant women. Animal studies are insufficient to assess effects on pregnancy, embryonal/foetal development, parturition, or postnatal development. The potential risk to humans is unknown. Oxybutynin should not be used during pregnancy unless clearly necessary.

Breastfeeding

Small amounts of oxybutynin pass into breast milk. Therefore, the use of oxybutynin during breastfeeding is not recommended.

Fertility

There are no data on the effect of oxybutynin on human fertility. Animal studies have shown reduced fertility in females.

Ability to affect performance of skilled tasks such as driving vehicles or operating machinery

Some adverse effects (e.g., dizziness, somnolence, blurred vision) of the medicinal product Oxybutynin Genheim may impair a patient's ability to concentrate and react quickly, thereby posing a risk in situations where these abilities are particularly important (e.g., driving a car, operating machinery, or performing hazardous activities).

Dosage and Administration

The tablet should be swallowed with an adequate amount of liquid (e.g., 1 glass of water).

The duration of treatment is determined by the onset of symptoms.

Adults

The dosage should be individualized. The initial dose is 2.5 mg three times daily. Subsequently, the lowest effective dose should be selected. The daily dose may range from 5 mg twice or three times daily (10 to 15 mg per day), and the maximum dose is 5 mg four times daily (maximum daily dose 20 mg).

Elderly patients (aged 65 years and older)

Dosage should be reduced in elderly patients (see sections "Special Warnings and Precautions for Use" and "Pharmacokinetics"). The recommended dose for these patients is 2.5 mg twice daily, particularly in frail patients. If a clinical effect is not achieved and side effects are well tolerated, this dose may be titrated up to 5 mg twice daily.

Children aged 5 years and older

The initial dose is 2.5 mg twice daily. Subsequently, the lowest effective dose should be selected. The maximum dose, based on body weight (0.3–0.4 mg/kg/day), is specified in the table:

Children.

The use of the drug is contraindicated in children under 5 years of age (see section "Special precautions").

Overdose

Symptoms of oxybutynin overdose manifest as enhanced parasympathetic effects in the central nervous system: restlessness, excitement, confusion, hallucinations including psychotic behavior, ataxia, disorientation, nervousness. Cardiovascular system disorders (e.g., sensation of warmth, decreased arterial pressure, dizziness, circulatory disturbances, arrhythmia, tachycardia, facial flushing, respiratory arrest, paralysis, and coma).

Signs of anticholinergic intoxication (e.g., mydriasis, fever, flushing, increased skin temperature, and dry mucous membranes).

Treatment of overdose:

1. Immediate gastric lavage and administration of activated charcoal;
2. In severe cases, administer physostigmine by slow intravenous injection.

Adults – 0.5–2 mg of physostigmine intravenously; if necessary, repeated doses may be administered up to a maximum daily dose of 5 mg.

Children – 30 mcg/kg body weight administered intravenously (if necessary, repeated doses may be administered up to a maximum daily dose of 2 mg).

Symptomatic treatment of fever.

In cases of pronounced restlessness or agitation, administer diazepam 10 mg as an intravenous injection. In cases of tachycardia, administer propranolol intravenously. In cases of urinary retention, bladder catheterization is indicated.

In the event of curare-like effects leading to paralysis of respiratory muscles, perform artificial ventilation of the lungs.

Adverse Reactions

The adverse effects of oxybutynin are primarily due to its anticholinergic activity, are dose-dependent, and may be reduced or eliminated by decreasing the dose.

The adverse reactions listed below are classified according to frequency of occurrence: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (frequency cannot be estimated from available data).

Adverse reactions in patients receiving oxybutynin hydrochloride therapy

Table 1

Reporting of Suspected Adverse Reactions

Reporting of adverse reactions after marketing authorization of a medicinal product is of significant importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: http://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions

Store at a temperature not exceeding 30 °C. Keep in the original packaging to protect from moisture. Keep out of reach and sight of children.

Packaging

10 tablets per blister; 3 blisters per carton.

Prescription status

Prescription only.

Manufacturer. Accord Healthcare Polska Sp. z o.o. Importer's Warehouse / Accord Healthcare Polska Sp. z o.o. Magazyn Importera.

Manufacturer's address and place of business.

ul. Lutomierska 50, Pabianice, 95-200, Poland / ul. Lutomierska 50, Pabianice, 95-200, Poland.

Marketing Authorization Holder. Accord Healthcare Polska Sp. z o.o. / Accord Healthcare Polska Sp. z o.o.

Inquiries regarding poor quality of the medicinal product; questions related to safety of use, incorrect use, or complaints are accepted 24/7 via telephone: +380993100335 or by email at: [email protected].

Address of the Marketing Authorization Holder. 7 Tasmowa St., Warsaw, 02-677, Poland / 7 Tasmowa St., Warsaw, 02-677, Poland.