Vesoxx

Package leaflet: Information for the user

Vesoxx
1 mg/ml, solution for bladder instillation
Oxybutynin hydrochloride
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Vesoxx is and what it is used for
2. Important information before using Vesoxx
3. How to use Vesoxx
4. Possible side effects
5. How to store Vesoxx
6. Contents of the pack and other information

1. What Vesoxx is and what it is used for

What Vesoxx contains
Vesoxx is a solution containing a medicine called oxybutynin hydrochloride. It works by
reducing the tone of the bladder muscles and preventing sudden muscle contractions.
This helps control urination.
The Vesoxx solution is intended for direct instillation into the bladder (administration into
the urinary bladder) via a tube called a catheter.

What Vesoxx is used for
Vesoxx is used in children aged 6 years and above and in adults for the treatment of
neurogenic detrusor overactivity (due to neurological disease, such as spinal cord injury or
spina bifida, a congenital malformation of the spinal cord).
Vesoxx should only be used when symptoms of detrusor overactivity are not well controlled,
or when severe side effects occur with oral treatment of this type of medicine, and when the
patient empties the bladder using a catheter.
Treatment with Vesoxx must be initiated and supervised by a physician specialized in the
management of neurogenic detrusor overactivity.

2. Important information before using Vesoxx

The following information should be read before starting treatment with
this medicine.
When not to use Vesoxx

• If the patient is allergic to oxybutynin hydrochloride or any of the other ingredients of this medicine (listed in section 6).
• If the patient has a rare autoimmune disease called myasthenia gravis, which causes muscle weakness and fatigue.
• If the patient has a severe stomach or intestinal disorder, e.g. severe ulcerative colitis or toxic megacolon (acute dilation of the large intestine).
• If the patient has glaucoma (increased pressure in the eyeballs, sometimes sudden and painful, with blurred vision or loss of vision). If there is a family history of glaucoma, the patient should inform the doctor.
• If the patient has difficulty passing urine or incomplete emptying of the bladder when urinating.
• If the patient frequently passes urine at night due to heart or kidney disease.
• If the patient is receiving oxygen therapy.

Warnings and precautions
Before starting treatment with Vesoxx, consult a doctor if:

• the patient has a urinary tract infection. Antibiotics may be required.
• the patient is over 65 years of age, as they may be more sensitive to Vesoxx.
• the patient is taking sublingual nitrates (medicines placed under the tongue used to treat chest pain).
• the patient has gastrointestinal obstruction, as Vesoxx may slow down gastric and intestinal motility.
• the patient has hiatus hernia (hiatus hernia) or heartburn (gastroesophageal reflux).
• the patient has a neurological disorder called autonomic neuropathy, which affects involuntary body functions such as heart rate, blood pressure, sweating and digestion.
• the patient has problems with memory, speech or thinking abilities.
• the patient has hyperthyroidism, which may cause increased appetite, weight loss or sweating.
• the patient has narrowing of the blood vessels supplying blood and oxygen to the heart.
• the patient has heart problems which may cause shortness of breath or ankle swelling.
• the patient has irregular and/or rapid heartbeat.
• the patient has high blood pressure.
• the patient has an enlarged prostate gland.

Vesoxx may reduce saliva production, leading to tooth decay, gum disease,
or fungal infection of the mouth (oral candidiasis).
Oxybutynin may cause a certain type of glaucoma. If blurred vision, vision loss or eye pain occurs, the patient should contact a doctor immediately. During treatment, visual acuity and intraocular pressure should be checked periodically.
Caution should be exercised when using Vesoxx during hot weather or if the patient has a fever. The patient should stay in the shade and avoid physical activity during the hottest part of the day.
This is because Vesoxx reduces sweating, which may lead to heat exhaustion or heat stroke.
Children and adolescents
Vesoxx is not recommended for use in children under 6 years of age.
Vesoxx and other medicines
The patient should inform their doctor or pharmacist about all medicines currently used, recently used, or planned for use.
Concurrent use of Vesoxx with other medicines that have similar side effects, such as dry mouth, constipation and drowsiness, may increase the frequency and severity of these side effects.
The active substance in Vesoxx is oxybutynin hydrochloride, which may slow gastrointestinal motility and thereby affect the absorption of other oral medicines.
Using this medicine together with other medicines may intensify the effects of oxybutynin hydrochloride.
In particular, the doctor should be informed if the patient is taking any of the following
medicines:

• bisphosphonates (used to treat osteoporosis) and other medicines that may cause or worsen oesophageal inflammation.
• ketoconazole, itraconazole or fluconazole (used to treat fungal infections).
• erythromycin, a macrolide antibiotic (used to treat bacterial infections).
• biperiden, levodopa or amantadine (used to treat Parkinson's disease).
• antihistamines (used to treat allergies such as hay fever).
• phenothiazines, butyrophenones or clozapine (used to treat psychiatric disorders).
• tricyclic antidepressants (used to treat depression).
• dipyridamole (used to treat blood clotting disorders).
• quinidine (used to treat heart rhythm disorders).
• atropine and other anticholinergic medicines (used to treat gastrointestinal disorders such as irritable bowel syndrome).
• cholinesterase inhibitors (used to treat dementia or certain muscle diseases).

Medicines used to treat angina (chest pain due to reduced blood flow to the heart), which should dissolve under the tongue, may dissolve less effectively due to dry mouth. Therefore, it is recommended to moisten the mouth before taking Vesoxx.
Vesoxx and alcohol
Vesoxx may cause drowsiness or blurred vision. Alcohol may increase drowsiness.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor before using this medicine.
Pregnancy
Vesoxx should not be used during pregnancy unless specifically advised by a doctor.
Breastfeeding
Vesoxx is not recommended during breastfeeding.
Driving and operating machinery
Vesoxx may cause drowsiness or blurred vision. Extreme caution should be exercised when driving or operating machinery.
Vesoxx contains sodium
This medicine contains 3.56 mg of sodium (the main component of table/food salt) per millilitre. This corresponds to 0.18% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Vesoxx

This medicine should always be used as directed by the physician. In case of doubt, consult your doctor.

Dosage
The physician will determine the correct dose of Vesoxx required to treat overactive bladder in the patient. Do not change the dose on your own.
At the beginning of treatment, the doctor will regularly monitor bladder function and, if necessary, adjust the dose of the medicine.

Adolescents (aged 12 years and older), adults, and elderly patients (aged over 65 years)
The usual recommended starting dose is typically 10 ml of Vesoxx per day.

Children (6–12 years)
The usual recommended starting dose of Vesoxx is generally 0.1 mg/kg body weight, administered in the morning.
For example: in children weighing 20 kg, the starting dose is 2 mg (2 ml).

If the patient has liver or kidney disease
Inform the doctor if the patient has any kidney or liver disease.

Method of administration
The doctor will prescribe Vesoxx only if the patient or a family member (caregiver) has been trained in a procedure called "clean intermittent catheterization" (CIC). This procedure must be performed at least six times daily to help empty the bladder using a catheter.

The acronym CIC stands for "Clean Intermittent Catheterisation":

• Clean: as germ-free as possible
• Intermittent: performed regularly several times a day
• Catheterisation: using a catheter (a type of thin tube) to remove urine from the bladder

The doctor will train the patient and/or a family member (caregiver) in performing the CIC procedure and in administering Vesoxx.

The procedure is performed as follows:

1. Disinfect hands as instructed on the disinfectant packaging. Open the prefilled syringe package at the designated spot.
2. Remove the prefilled syringe from the packaging. Unscrew the cap by gently rotating it.
3. NOTE: If a dose smaller than the syringe content has been prescribed, expel the excess amount before administration, unless the user assumes responsibility for using the remaining amount in the syringe (see point 5). (Unused medicinal product or waste must be disposed of in accordance with national requirements. For environmental protection, do not dispose of medicines via wastewater.)
4. Place the syringe back into its packaging without touching the tip.
5. Disinfect hands and begin catheterization. (Instructions are available at: www.farco.de/isk).
6. Completely empty the bladder through the catheter and ensure the catheter remains in the bladder before starting administration.
7. Remove the prefilled syringe from its packaging and attach it to the catheter.
8. Administer the entire content of the prefilled syringe into the bladder by pressing the plunger. Remove the prefilled syringe together with the catheter for disposal.
9. Unused medicinal product or waste must be disposed of in accordance with national regulations. For environmental protection, do not dispose of medicines via wastewater.

The instilled solution remains in the bladder until the next catheterization.
Each syringe is for single use only. The urinary catheter and any unused medicine should be discarded.

Use of a higher than recommended dose of Vesoxx
If a dose larger than prescribed is accidentally administered, immediately empty the bladder using a catheter.
Overdose may cause symptoms such as: restlessness, dizziness, speech and vision disturbances, muscle weakness, or rapid heartbeat.
If any of these symptoms occur, contact a doctor or the nearest hospital immediately.

Missed dose of Vesoxx
If the patient forgets to administer the dose at the usual time, administer the normal dose at the next scheduled catheterization. However, if the next dose is due soon, skip the missed dose.
Do not administer a double dose to make up for a missed dose.
In case of doubt, always consult the doctor.

Stopping treatment with Vesoxx
If the patient stops taking Vesoxx, symptoms of overactive bladder may return or worsen. If the patient is considering stopping treatment, they should always consult the doctor.

If you have any further questions about the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like any medicine, this one may also cause adverse reactions, although not everyone will experience them.
The most commonly occurring adverse reactions are typical for this type of medicine and include dry mouth, drowsiness and constipation.
The following adverse reactions have been reported with the use of oxybutynin chloride, although not all have been reported in connection with intravesical administration. The frequency of these adverse reactions is unknown (cannot be estimated from available data):
The medicine Vesoxx should be discontinued and (or) the doctor should be contacted immediately if:

• the patient experiences a (severe) allergic reaction causing swelling of the face or throat (angioedema)*
• the patient has reduced sweating leading to overheating in hot conditions (heat stroke)*
• the patient experiences sudden eye pain with blurred vision or loss of vision (glaucoma)*

Patients should inform their doctor or pharmacist if any of the following adverse reactions worsen or persist for more than a few days:
Kidneys

• urinary tract infection
• presence of bacteria in urine without causing symptoms
• urgency (sudden need to urinate)
• presence of protein in urine
• presence of blood in urine
• pain during instillation of solution into the bladder
• disturbances in urination or difficulty initiating urination

Psychiatric disorders

• seeing or hearing non-existent stimuli (hallucinations)
• cognitive disturbances
• excessive restlessness and hyperactivity (hyperkinesis)
• agitation*
• loss of consciousness or confusion
• sleep disturbances
• agoraphobia (e.g. fear of leaving home, entering shops, being in crowds or public places)
• inability to concentrate
• anxiety*
• nightmares*
• excessive suspicion and distrust of others (paranoia)*
• symptoms of depression*
• dependence on oxybutynine (in patients with a history of drug or psychoactive substance abuse)*

General condition

• disorientation
• loss of consciousness
• apathy
• feeling of fatigue
• drowsiness
• sensation of dizziness or spinning

Eyes

• dry eye syndrome
• abnormal sensation in the eye
• inability of the eye to accommodate from distant to near objects, which may cause blurred vision, double vision, eye fatigue
• blurred vision*
• increased intraocular pressure*

Cardiac and vascular disorders

• regular but abnormally rapid heartbeat (supraventricular tachycardia)
• irregular heartbeat (arrhythmia)*
• low blood pressure

Skin disorders

• sudden flushing of the face
• rash
• reduced sweating
• night sweats
• itchy rash with wheals (urticaria)*
• dry skin*
• increased sensitivity of the skin to sunlight (photosensitivity)*

Gastrointestinal disorders

• constipation
• dry mouth
• abdominal discomfort
• lower abdominal pain or stomach ache
• nausea
• dyspepsia
• diarrhoea
• vomiting*
• loss of appetite (anorexia)*
• decreased appetite*
• difficulty swallowing (dysphagia)*
• burning sensation in the oesophagus (heartburn)*
• abnormal distension (swelling) with accompanying pain, nausea or vomiting (pseudointestinal obstruction)*
• altered sense of taste
• increased thirst

General disorders

• chest discomfort
• feeling of cold
• headache
• nervous system disorder (anticholinergic syndrome)
• seizures
• elevated blood levels of a hormone called prolactin. In women, this may lead to menstrual cycle disturbances or spontaneous milk production from the breasts. In men, disturbances in sexual desire or erectile function and increased breast tissue may occur.

* The above adverse reactions have also been reported with this type of medicine. However, it is not known whether they will occur during treatment with the prescribed medicine Vesoxx.
In one patient, oxygen deficiency occurred during home oxygen therapy (see section 2 "When not to use Vesoxx").
Additional adverse reactions in children and adolescents
Children may be more sensitive to the effects of this medicinal product. They may experience adverse reactions, particularly affecting the central nervous system and psychiatric adverse reactions.
Reporting of adverse reactions
If any adverse reactions occur in patients, including any adverse reactions not listed in this leaflet, they should inform their doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 2-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to collect more information on the safety of the medicine.

5. How to store Vesoxx

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the syringe label and
the carton following the wording “Expiry date” (EXP). The expiry date refers to the last day
of the stated month.
No special precautions regarding storage temperature are required.
If the medicine is not used immediately, the user is responsible for the time and conditions of storage prior to administration.
Medicines must not be disposed of in household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the pack and other information

What Vesoxx contains

• The active substance is oxybutynin hydrochloride.

1 ml of solution contains 1 mg of oxybutynin hydrochloride.
One 10 ml pre-filled syringe containing a sterile solution has 10 mg of oxybutynin hydrochloride.

• Other ingredients are hydrochloric acid (10% diluted), sodium chloride and water for injections.

What Vesoxx looks like and contents of the pack
Vesoxx is a clear, colourless solution.
It is supplied as a ready-to-use solution in a 10 ml pre-filled syringe equipped with a plunger and a
closure made of synthetic bromobutyl rubber.
Pack contains 100 pre-filled syringes for direct connection to standard catheter systems.
Pack contains 12 pre-filled syringes for direct connection to standard catheter systems.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
FARCO-PHARMA GmbH
Gereonsmühlengasse 1-11
50670 Köln
Germany
E-mail: [email protected]

Manufacturer
Klosterfrau Berlin GmbH
Motzener Strasse 41
12277 Berlin
Germany

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria: Vesoxx 1 mg/ml Lösung zur intravesikalen Anwendung
Belgium: Vesoxx 1 mg/ml
Czech Republic: Vesoxx
Spain: VESOLOX 1 mg/ml solución intravesical
Netherlands: VESOLOX 1 mg/ml oplossing voor intravesicaal gebruik
Luxembourg: Vesoxx 1 mg/ml
Germany: Vesoxx 1 mg/ml Lösung zur intravesikalen Anwendung
Poland: Vesoxx
Portugal: Vesoxx 1 mg/ml
Slovakia: Vesoxx 1 mg/ml
Sweden: Vesoxx 1 mg/ml intravesikal lösning
United Kingdom (Northern Ireland): Vesoxx 1 mg/ml intravesical solution
Italy: Vesoxx 1 mg/ml, soluzione endovescicale

Information intended for healthcare professionals only:

Dosage

Initial dose titration should be performed by a neuro-urologist under precise urodynamic control.
There are no fixed dosage regimens, as there are considerable inter-individual differences regarding bladder pressure and the dose required to relieve symptoms of neurogenic detrusor overactivity. Therefore, the dosing regimen (doses and timing) must be individually tailored according to the patient's needs.
Individual doses should be sufficient to adequately control urodynamic parameters (maximum detrusor pressure < 40 cm H₂O), aiming to completely suppress neurogenic detrusor overactivity.
During intravesical treatment with oxybutynin, urodynamic parameters should be monitored at regular intervals as recommended by the treating physician.

Children and adolescents

The safety and efficacy of oxybutynin hydrochloride have not been established in children aged 0 to 5 years.

Recommended doses in the following age groups

Dosage recommendations are based on body weight percentiles in different age groups (Table 1).

Table 1: Recommended doses in the following age groups

| Age group | Age [years] | Recommended initial daily dose [mg] | Recommended total daily dose [mg] | |---------------|-----------------|-----------------------------------------|----------------------------------------| | Children | 6 - 12 | Individually titrated, see below | 2 - 30 | | Adolescents | 12 - 18 | 10 | 10 - 40 | | Adults | 19 - 65 | 10 | 10 - 40 | | Elderly patients | > 65 | 10 | 10 - 30 |

If doses higher than the initial dose are required, the dose should be gradually increased until neurogenic detrusor overactivity is adequately controlled, allowing careful monitoring of both efficacy and safety. The required daily maintenance doses may be divided into several administrations (Tables 2 and 3). Assuming six intermittent catheterisations per day (clean intermittent catheterization, CIC), the following dosing schedules are recommended:

Table 2: Recommended dosing schedule (children aged 6 to 12 years)

| Daily dose [mg] | CIC 1 [mg] | CIC 2 [mg] | CIC 3 [mg] | CIC 4 [mg] | CIC 5 [mg] | CIC 6 [mg] | |---------------------|----------------|----------------|----------------|----------------|----------------|----------------| | 2 | 2 | - | - | - | - | - | | 5 | 5 | - | - | - | - | - | | 10 | 5 | - | 5 | - | - | - | | 15 | 5 | - | 5 | - | 5 | - | | 20 | 10 | - | 10 | - | - | - | | 30 | 10 | - | 10 | - | 10 | - |

Table 3: Recommended dosing schedule for initial doses of 10 mg (adolescents aged 12 years and older, adults and elderly patients)

| Daily dose [mg] | CIC 1 [mg] | CIC 2 [mg] | CIC 3 [mg] | CIC 4 [mg] | CIC 5 [mg] | CIC 6 [mg] | |---------------------|----------------|----------------|----------------|----------------|----------------|----------------| | 10 | 5 | - | 5 | - | - | - | | 20 | 10 | - | 10 | - | - | - | | 30 | 10 | - | 10 | - | 10 | - | | 40 | 10 | 10 | 10 | - | 10 | - |

Children (aged 6 to 12 years)

Dosing is individually adjusted. The initial dose is 0.1 mg/kg body weight administered intravesically in the morning. The dose may be adjusted after one week of treatment. The lowest effective dose should be selected. The daily dose may be increased up to 30 mg to achieve adequate therapeutic effect, provided that adverse effects are tolerable. A single dose should not exceed 10 mg.

The safety and efficacy of oxybutynin hydrochloride have not been established in children under 6 years of age.

Elderly patients (over 65 years)

As with other anticholinergic drugs, caution should be exercised in frail and elderly patients, especially if doses higher than 30 mg per day are required.

Hepatic or renal impairment

Vesoxx should be used with caution in patients with hepatic or renal impairment. Treatment with Vesoxx in these patients should be closely monitored and dose reduction may be necessary.