Lioresal Intrathecal 10 mg/20 ml

Leaflet attached to the packaging: information for the user

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Lioresal Intrathecal 10 mg/20 ml, solution for infusion

For use in adult patients and children aged 4 years and older.
The active substance is baclofen

Table of contents of the leaflet

• 1. What is Lioresal Intrathecal 10 mg/20 ml and what is it used for
• 2. Important information before using Lioresal Intrathecal 10 mg/20 ml
• 3. How to use Lioresal Intrathecal 10 mg/20 ml
• 4. Possible side effects
• 5. How to store Lioresal Intrathecal 10 mg/20 ml
• 6. Package contents and other information

1. What is Lioresal Intrathecal 10 mg/20 ml and what is it used for

Lioresal Intrathecal 10 mg/20 ml contains the active substance baclofen. Lioresal Intrathecal 10 mg/20 ml is a medicine used for excessive muscle tension.
Lioresal Intrathecal 10 mg/20 ml is used to treat severe, chronic spasticity (increased muscle tone) that cannot be effectively treated with standard medicines:

• in multiple sclerosis. This is a progressive disease of the nervous system, brain, and spinal cord with physical and mental symptoms.
• after spinal cord injuries or injuries with brain damage.
• in other spinal cord diseases.

During the qualification phase for treatment and during the dose escalation phase, immediately after the pump is implanted, the patient will be closely monitored in conditions that ensure access to appropriate equipment and staff care. The dosage, possible side effects, or signs of infection will be regularly evaluated. The functioning of the drug delivery system will also be checked.
If there is no improvement or the patient feels worse, they should consult a doctor.

2. Important information before using Lioresal Intrathecal 10 mg/20 ml

When not to use Lioresal Intrathecal 10 mg/20 ml

• if the patient is allergic to baclofen or any of the other ingredients of this medicine (listed in section 6). If the patient thinks they may be allergic, they should consult a doctor.

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• The leaflet should be kept so that it can be re-read if necessary.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If any side effects occur, including any possible side effects not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. See section 4.
• if the patient has epilepsy that is resistant to treatment.

Warnings and precautions

The doctor should be consulted immediately if the patient thinks that the device is not working properly or if they observe withdrawal symptoms (see discontinuation symptoms in section 3 "How to use Lioresal Intrathecal 10 mg/20 ml").
If any of the following points apply to the patient, they should inform their doctor before starting treatment with Lioresal Intrathecal 10 mg/20 ml:

• circulatory disorders of cerebrospinal fluid due to impaired flow;
• treatable epilepsy or other seizures affecting the brain;
• neurological disorders caused by damage to cranial nerves in the spinal cord (symptoms of bulbar palsy) or partial paralysis of respiratory muscles;
• acute or chronic confusion;
• psychiatric and (or) psychological disorders, such as schizophrenia;
• Parkinson's disease;
• autonomic reflex disorders (uncontrolled) in history;
• insufficient blood flow to the brain;
• breathing difficulties;
• overactive bladder sphincter;
• heart disease;
• kidney function disorders;
• stomach and intestinal ulcers;
• severe liver function disorders;
• increased muscle tone caused by a previous head injury. Long-term treatment of increased muscle tone should be started when the symptoms of spasticity are stable and can be reliably assessed.

If any of these symptoms occur during treatment with Lioresal Intrathecal 10 mg/20 ml, the doctor should be informed immediately:

• If the patient experiences back, arm, neck, and buttock pain during treatment (a type of spinal deformity called scoliosis).
• If the patientever thinks about self-harm or suicide, they should talk to a doctor immediately or go to the hospital. They should also ask a relative or close friend to inform the patient if they are concerned about changes in their behavior and read this leaflet.

Children
Children should meet certain requirements regarding adequate body weight to allow for the implantation of an infusion pump. Lioresal Intrathecal 10 mg/20 ml is intended for use in children aged 4 years and older. The safety of intrathecal use of Lioresal Intrathecal 10 mg/20 ml in children under 4 years of age has not been established yet.
Patients over 65 years of age
During clinical trials, Lioresal Intrathecal 10 mg/20 ml was administered to several elderly patients and did not cause particular problems. However, experience with the use of Lioresal in tablet form shows that this group of patients may be more prone to side effects. Therefore, elderly patients should be closely monitored for side effects.

Lioresal Intrathecal 10 mg/20 ml and other medicines

The doctor or pharmacist should be informed about all medicines currently being used by the patient or recently used, as well as medicines that the patient plans to use.
The following medicines may affect the action of Lioresal Intrathecal 10 mg/20 ml or Lioresal Intrathecal 10 mg/20 ml may interact with them. It may be necessary to adjust the dose of Lioresal Intrathecal 10 mg/20 ml or one of the other medicines used at the same time:

• medicines used in Parkinson's disease;
• medicines that relieve severe muscle spasms;
• medicines with a sedating effect on the central nervous system;
• medicines used to treat depression, such as imipramine, doxepin, amitriptyline, opipramol;
• medicines used to treat high blood pressure.

Lioresal Intrathecal 10 mg/20 ml with food, drink, and alcohol

When using Lioresal Intrathecal, it is recommended to avoid consuming alcohol at the same time, as this may cause undesirable intensification or unpredictable changes in the action of the medicine.

Pregnancy and breastfeeding

Due to the lack of experience, pregnant and breastfeeding women may use Lioresal Intrathecal 10 mg/20 ml only if the doctor considers it absolutely necessary.

Driving and operating machines

Do not drive vehicles, operate machinesor perform other hazardous activities, as Lioresal Intrathecal 10 mg/20 ml may significantly affect these activities.

Lioresal Intrathecal 10 mg/20 ml contains sodium

The medicine contains 70.81 mg of sodium (main component of table salt) per 20 ml. This corresponds to 3.5% of the maximum recommended daily sodium intake in the diet for adults.

3. How to use Lioresal Intrathecal 10 mg/20 ml

This medicine should always be used as directed by the doctor. In case of doubts, consult a doctor or pharmacist.
Lioresal Intrathecal 10 mg/20 ml (10 mg/20 ml) and Lioresal Intrathecal 10 mg/5 ml (10 mg/5 ml) are available on the market.

Method of administration

Lioresal Intrathecal 10 mg/20 ml can be administered by direct injection or infusion into the spinal canalonly by a qualified specialist and with the help of appropriate equipment.
Therefore, hospitalization is necessary at the beginning of treatment.
At the beginning of treatment, the doctor will determine whether a single injection of the medicine in a smaller dose - Lioresal Intrathecal, 0.05 mg/1 ml, solution for injection - will relieve muscle spasms. If possible, a special pump will be implanted under the patient's skin, which will allow for continuous dosing tailored to the patient.
It is very important for the patient to attend scheduled visits, during which the doctor will refill the pump.
If the patient receives too small a dose of Lioresal Intrathecal 10 mg/20 ml, increased muscle tone may return. Muscle spasms may also worsen.
The doctor should be informed immediatelyif muscle spasms do not improve or worsen.
The doctor must regularly monitor the patient's condition and the pump's function - at least once a month.

Duration of treatment

The duration of treatment will be decided by the doctor.

Use of a higher than recommended dose of Lioresal Intrathecal 10 mg/20 ml

Immediately contact a doctorif the patient or caregiver notices symptoms of overdose, which may occur suddenly or gradually:

• too little muscle tone;
• drowsiness;
• dizziness or a feeling of emptiness in the head;
• excessive salivation;
• nausea or vomiting;
• breathing difficulties or even respiratory arrest;
• seizures;
• reduced consciousness or even coma;
• low body temperature.

Discontinuation of Lioresal Intrathecal 10 mg/20 ml

If it is necessary to discontinue the medicine, it can only be done by the attending doctor, who will gradually reduce the dose of the medicine to avoid side effects. Abrupt discontinuation of Lioresal Intrathecal 10 mg/20 ml may cause severe side effects, which in several cases have been fatal.
Immediately contact a doctorif the patient or caregivers notice the following symptoms and signs of discontinuationof Lioresal Intrathecal 10 mg/20 ml. This is especially important for further administration through the pump.

• increased spasticity, too much muscle tone;
• difficulty moving muscles;
• increased heart rate and faster pulse;
• itching;
• tingling, burning, or numbness of hands and feet;
• palpitations;
• anxiety;
• fever;
• low blood pressure;
• changes in the patient's mental state, such as agitation, disorientation, hallucinations, abnormal thinking, and behavior;
• seizures;
• prolonged painful erection (priapism). The above symptoms can cause more severe side effects, which can lead to death if not treated immediately.

It should be remembered that pump failures, such as battery problems or catheter defects, alarm signal defects, or device malfunctions, can lead to overdose or underdose of the medicine.
In case of any doubts related to the use of the medicine, consult a doctor.

4. Possible side effects

*Side effects marked with an asterisk occur more frequently in patients with
cerebral palsy.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Side effects are more common during the initiation of treatment in the hospital, but they can also occur later. Many of the listed side effects may also be related to the underlying disease being treated.
Malfunction of the implanted device delivering the medicine or the infusion system can lead to withdrawal symptoms, which can be life-threatening (see discontinuation symptoms in section 3 "How to use Lioresal Intrathecal 10 mg/20 ml").
The following side effects have been reported, along with their frequency:

• low muscle tone
• drowsiness

Very common:may occur in more than 1 in 10 patients

• anxiety
• decreased appetite
• shortness of breath, slow or shallow breathing
• decreased alertness
• decreased blood pressure when sitting and standing
• depression
• disorientation
• diarrhea, even incontinence of feces
• increased muscle tone
• fever
• increased restlessness
• urinary retention*
• itchy skin swelling, similar to an insect bite
• itching
• headache*, pain
• seizures*
• pneumonia
• strange skin sensations with tingling of hands and feet
• dry mouth
• muscle weakness
• coma
• chills
• swelling of the face, hands, and feet
• dizziness
• sexual disorders
• vision disturbances with blurred or double vision
• apathy
• involuntary urination
• nausea or vomiting*
• excessive salivation
• constipation
• slurred speech
• confusion
• respiratory depression

Uncommon:may occur in fewer than 1 in 100 patients

• decreased amount of fluids in the body (dehydration)
• pale skin
• high blood pressure
• intestinal obstruction due to blockage
• memory loss/confusion
• mood disorders
• hair loss
• false sensory perceptions not caused by an external stimulus
• skin redness
• low body temperature
• difficulty swallowing
• coordination problems
• suicidal thoughts and attempts
• excessive sweating
• nystagmus
• slow heart rate
• reduced sense of taste
• blockage of a blood vessel due to a blood clot in the deep veins
• hallucinations
• euphoria

Rare:may occur in fewer than 1 in 1,000 patients

• life-threatening withdrawal symptoms due to administration problems

Some side effects occur with an unknown frequency:

• increase in lateral curvature of the spine (scoliosis)
• inability to achieve or maintain an erection (erectile dysfunction)

Reporting side effects

If any side effects occur, including any possible side effects not listed in the leaflet, the doctor, pharmacist, or nurse should be informed. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Aleje Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Lioresal Intrathecal 10 mg/20 ml

The medicine should be stored in a place that is invisible and inaccessible to children.

Storage conditions

Do not store above 30°C.
Do not freeze. Do not sterilize with high temperature.
The medicine should be used immediately after opening. Unused solution should be discarded.
The solution must be clear and colorless. Do not use this medicine if cloudiness or discoloration is observed.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the specified month.
Medicines should not be disposed of in the sewage system or household waste containers. Ask a pharmacist how to dispose of unused medicines. This will help protect the environment.

6. Package contents and other information

• The active substance of the medicine is baclofen. 1 ml of Lioresal Intrathecal 10 mg/20 ml solution for infusion contains 0.5 mg of baclofen. 1 ampoule with 20 ml of solution for infusion contains 10 mg of baclofen.
• The other ingredients are: sodium chloride, water for injections.

What Lioresal Intrathecal 10 mg/20 ml looks like and what the package contains

Lioresal Intrathecal 10 mg/20 ml is a clear, colorless solution in a transparent, colorless ampoule.
Lioresal Intrathecal 10 mg/20 ml solution for infusion is available in packages containing 1, 2, or 5 ampoules.
For more detailed information, consult the marketing authorization holder or parallel importer.

Marketing authorization holder in Germany, the country of export:

Novartis Pharma GmbH
Roonstr. 25
D-90429 Nuremberg
Germany

Manufacturer:

Novartis Pharma GmbH
Roonstr. 25
D-90429 Nuremberg
Germany

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
License number in Germany, the country of export: 39917.01.01

Parallel import license number: 207/17

This medicinal product has been authorized in the Member States of the European Economic Area under the following names:

Germany
Lioresal Intrathecal 10 mg/20 ml Infusionslösung
Poland
Lioresal Intrathecal 10 mg/20 ml, solution for infusion
Date of leaflet approval: 24.06.2022
[Information about the trademark]

Information intended only for healthcare professionals:

How to prepare and administer Lioresal Intrathecal 10 mg/20 ml?

The administration of a test dose, the implantation of an infusion pump, and the escalation of the dose of the medicinal product administered intrathecally should be performed in a hospital setting, in centers with appropriate experience and under the close supervision of qualified physicians. Immediate access to an intensive care unit should be ensured due to the possibility of severe or life-threatening side effects of the medicinal product.
Before administering Lioresal Intrathecal 10 mg/20 ml, the clarity and colorlessness of the solution should be checked. If the solution is cloudy or discolored, the medicinal product should not be administered.
Each ampoule is intended for single use only. The solution it contains is stable, isotonic, free of pyrogens and antioxidants, with a pH of 5.0-7.0.

Implantation of the infusion pump/dose escalation phase (in a hospital setting)

After confirming the patient's response to treatment with Lioresal Intrathecal 10 mg/20 ml during the trial phase, intrathecal infusion of the medicinal product can be started using the aforementioned infusion pump. The antispastic effect of baclofen begins within 6 to 8 hours after the start of continuous infusion, and the maximum effect of the medicine is observed after 24 to 48 hours.
The initial total daily dose of Lioresal Intrathecal 10 mg/20 ml is calculated as follows: if the effect of the medicine after administration of the test dose lasts more than 12 hours, this dose is considered the initial dose. If the effect of the medicine after administration of the test dose lasts less than 12 hours, the test dose should be doubled and administered as the initial dose. The dose of the medicine should not be increased during the first 24 hours of treatment.
After the first day of treatment, the dose of the medicine can be gradually increased to achieve the desired therapeutic effect. The daily dose of the medicinal product should not be increased by more than 10% to 30% of the previous dose in patients with spinal cord spasticity and 5% to 15% in patients with cerebral spasticity. In the case of programmable pumps, it is recommended to modify the dose only once every 24 hours. In the case of non-programmable pumps equipped with a 76 cm catheter, delivering 1 ml of solution per day, it is recommended to assess the patient's response to the new dose of the medicine after a period of 48 hours. If a significant increase in the daily dose does not cause an increase in the clinical effect, the proper functioning of the pump and the patency of the catheter should be checked.
Essentially, the dose of the medicinal product is increased to achieve a maintenance dose in the range of 300 μg to 800 μg per day in patients with spinal cord spasticity. Patients with cerebral spasticity usually require smaller doses (see below).

Long-term therapy phase

The goal of treatment is to use the smallest dose that provides good control of spasticity without unacceptable side effects. Since the therapeutic effect may decrease during treatment, and the severity of spasticity may change, it is usually necessary to adjust the dose in a hospital setting during long-term therapy.
Also, in this case, the daily dose of the medicinal product can be increased by 10% to 30% in patients with spinal cord spasticity and 5% to 20% (upper limit) in patients with cerebral spasticity by changing the infusion rate or changing the concentration of baclofen in the pump reservoir. And vice versa, if side effects occur, the daily dose of the medicinal product can be decreased by 10% to 20%.
The need for rapid dose escalation to achieve the desired therapeutic effect suggests the possibility of pump failure or catheter kinking, cracking (abrasion), or displacement.
The maintenance dose of Lioresal Intrathecal 10 mg/20 ml in long-term therapy in patients with spinal cord spasticity is usually 300 μg to 800 μg of baclofen per day. The lowest and highest registered daily doses administered to individual patients during the loading phase were 12 μg and 2003 μg (studies conducted in the United States). Experience with doses exceeding 1000 μg per day is limited. During the first few months of treatment, the dose of the medicinal product should be verified and modified, especially frequently.
In the case of patients with cerebral spasticity, the maintenance doses used during long-term therapy with continuous infusion of Lioresal Intrathecal 10 mg/20 ml are in the range of 22 μg to 1400 μg of baclofen per day, and the average daily doses of the medicinal product are 276 μg after 1 year of observation and 307 μg after 2 years.
Children under 12 years of age usually require smaller doses (range: 24 μg to 1199 μg per day; average: 274 μg per day).
If the technical parameters of the pump allow, after determining the daily dose of the medicinal product and stabilizing the antispastic effect, it is possible to try to adjust the administration of the medicinal product to the daily rhythm of spasticity. For example, if spasms occur more frequently at night, this may require a 20% increase in the infusion rate for one hour. Changes in the infusion rate should be programmed to occur 2 hours before the desired clinical effect.
Throughout the treatment period, regular, at least monthly, monitoring of tolerance to Lioresal Intrathecal 10 mg/20 ml and possible signs of infection is necessary in the treatment center. The proper functioning of the infusion system should be regularly checked. The development of local infection or improper catheter function can lead to a break in intrathecal administration of Lioresal Intrathecal 10 mg/20 ml with life-threatening consequences for the patient.
The concentration of baclofen required during pump filling depends on the total daily dose of the medicinal product and the infusion rate of the pump. If it is necessary to administer baclofen in concentrations other than 0.05 mg/ml, 0.5 mg/ml, or 2 mg/ml, Lioresal Intrathecal 10 mg/20 ml should be diluted under aseptic conditions using a sterile sodium chloride solution forinjectionwithout preservatives. In this case, the instructions provided by the pump manufacturer should be followed.
About 5% of patients may require a higher dose of the medicinal product due to decreased efficacy of treatment ("development of tolerance") during long-term treatment. As described in the literature, the development of tolerance is prevented by maintaining a 10 to 14-day break in baclofen administration, during which sodium morphine without preservatives is administered. After this period, the patient may respond to treatment with Lioresal Intrathecal 10 mg/20 ml again.
Treatment should be resumed by administering the initial dose used in continuous infusion, and then gradually increasing the dosage again to avoid side effects due to overdose. This procedure should be performed in a hospital setting.

Incompatibilities

Lioresal Intrathecal 10 mg/20 ml solution for infusion should not be mixed with other solutions for injection or infusion, except for sterile, preservative-free sodium chloride solution, diluted under aseptic conditions.
A chemical incompatibility has been demonstrated between dextrose and baclofen.
Do not freeze. Do not sterilize with high temperature.