Lioresal Intrathecal 10 mg/5 ml

Leaflet accompanying 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/5 ml, solution for infusion

For use in adult and pediatric patients 4 years of age and older.
The active substance is baclofen

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

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If any side effects occur, including any possible side effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Lioresal Intrathecal 10 mg/5 ml and what is it used for

Lioresal Intrathecal 10 mg/5 ml contains the active substance baclofen. Lioresal Intrathecal is
a medicine used for excessive muscle tension.
Lioresal Intrathecal 10 mg/5 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.

In the qualification phase for treatment and in 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 personnel care. Regular assessment will be subject to dosing, possible side effects, or signs of infection. 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/5 ml

When not to use Lioresal Intrathecal 10 mg/5 ml

• if the patient is allergic to baclofenor 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.
• if the patient has untreatable epilepsy.

Consult a doctor immediately if the patient thinks 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/5 ml").
If any of the following points apply to the patient, they should tell their doctor before starting treatment with Lioresal Intrathecal 10 mg/5 ml:

• circulation disorders of cerebrospinal fluid due to flow difficulties;
• treatable epilepsy or other seizures affecting the brain;
• neurological disorders caused by damage to cranial nerves in the spinal cord (symptoms of foot drop) 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 due to a previous head injury. Long-term treatment of increased muscle tone should be started when spasticity symptoms are stable and can be reliably assessed.

If any of these symptoms occur during treatment with Lioresal Intrathecal 10 mg/5 ml, the patient should immediately inform their doctor:

• 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 immediately talk to a doctor or go to the hospital. They should also ask a relative or close friend to inform them if they notice changes in their behavior and read this leaflet.

Children
Children should meet certain requirements regarding appropriate body weight to allow for the implantation of an infusion pump.
Lioresal Intrathecal 10 mg/5 ml is intended for use in children 4 years of age and older.
The safety of intrathecal use of Lioresal Intrathecal 10 mg/5 ml in children under 4 years of age has not been established yet.
Patient over 65 years of age
During clinical trials, Lioresal Intrathecal 10 mg/5 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/5 ml and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
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The following medicines may affect the action of Lioresal Intrathecal 10 mg/5 ml or Lioresal Intrathecal 10 mg/5 ml may interact with them. It may be necessary to adjust the dose of Lioresal Intrathecal 10 mg/5 ml or one of the other medicines taken at the same time:

• medicines used in Parkinson's disease;
• medicines that relieve severe muscle spasms;
• medicines with a depressant effect on the functions of 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/5 ml with food, drink, and alcohol

When using Lioresal Intrathecal 10 mg/5 ml, you should 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/5 ml only if the doctor considers it absolutely necessary.

Driving and using machines

Do not drive vehicles, operate machinesor perform other hazardous activities, as Lioresal Intrathecal 10 mg/5 ml may significantly affect these activities.

Lioresal Intrathecal 10 mg/5 ml contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per 5 ml, i.e., the medicine is considered "sodium-free".
If the doctor needs to dilute Lioresal Intrathecal 10 mg/5 ml with a saline solution, the resulting sodium dose will be higher.

3. How to use Lioresal Intrathecal 10 mg/5 ml

This medicine should always be used as directed by your doctor. If you are unsure, consult your 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/5 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/5 ml, increased muscle tone may return. Muscle spasms may also worsen.
Tell your doctor 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

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The duration of treatment will be decided by your doctor.

Using a higher dose of Lioresal Intrathecal 10 mg/5 ml than recommended

Immediately contact your 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/5 ml

If it is necessary to discontinue the medicine, this can only be done by the attending physician, who will gradually reduce the dose of the medicine to avoid side effects. Sudden discontinuation of Lioresal Intrathecal 10 mg/5 ml may cause severe side effects, which in several cases have been fatal.
Immediately contact your doctorif the patient or caregiver notices the following symptoms and signs of discontinuationof Lioresal Intrathecal 10 mg/5 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 of the penis (priapism). The above symptoms can cause more severe side effects, which can lead to death if not treated immediately.

Remember that pump malfunctions, such as battery problems or catheter defects, alarm signal defects, or device malfunctions, can lead to overdose or underdose of the medicine.
If you have any doubts about using the medicine, consult your 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.
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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/5 ml").
The following side effects have been reported, along with their frequency:

• Very common: may occur in more than 1 in 10 patients
• low muscle tone,
• drowsiness.

Common: may occur in no 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 no more than 1 in 100 patients

• decreased fluid in the body (dehydration),
• pale skin,
• high blood pressure,
• intestinal obstruction due to blockage,
• memory loss/distractibility,
• mood disorders,
• hair loss,
• false sensory perceptions not caused by an external stimulus,
• skin redness,
• low body temperature,
• difficulty swallowing,

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• 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 no more than 1 in 1,000 patients

• life-threatening withdrawal symptoms due to problems with the administration of the medicine.

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 side effects not listed in the leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel.: +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/5 ml

Keep the medicine out of sight and reach of 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 you notice cloudiness or discoloration.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month stated.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

• The active substance of the medicine is baclofen. 1 ml of the solution for infusion contains 2.0 mg of baclofen.

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1 ampoule with 5 ml of the solution for infusion contains 10 mg of baclofen.

• The other ingredients are: sodium chloride, water for injections.

What Lioresal Intrathecal 10 mg/5 ml looks like and what the packaging contains

Lioresal Intrathecal 10 mg/5 ml is a clear, colorless solution in a transparent, colorless ampoule.
Lioresal Intrathecal 10 mg/5 ml, solution for infusion, is available in packaging 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
German authorization number: 39917.00.01

Parallel import authorization number: 12/13

This medicine has been authorized for marketing in the Member States of the European Economic Area under the following names:

Germany
Lioresal Intrathecal 10 mg/5 ml Infusionslösung
Poland
Lioresal Intrathecal 10 mg/5 ml, solution for infusion
Date of leaflet approval: 13.01.2023
[Information about the trademark]
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Information intended only for healthcare professionals:

How to prepare and administer Lioresal Intrathecal 10 mg/5 ml?

The test dose, implantation of the infusion pump, and dose escalation of the medicine administered intrathecally should be performed in a hospital setting, in centers with appropriate experience and under very close supervision of appropriately qualified physicians.
Immediate availability of an intensive care unit should be ensured due to the possibility of severe or life-threatening side effects of the medicine.
To determine the optimal dosing schedule for Lioresal Intrathecal 10 mg/5 ml, each patient first receives a test dose of Lioresal Intrathecal 0.05 mg/1 ml by intrathecal injection in a bolus through a spinal catheter or lumbar puncture. Then, the dose should be very carefully adjusted individually to the patient's needs. This is necessary due to significant differences in therapeutically effective doses for individual patients.
In long-term therapy, Lioresal Intrathecal 10 mg/5 ml is administered using an implanted pump, which allows for continuous infusion of the baclofen solution into the cerebrospinal fluid.
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 is calculated as follows: if the effect of the medicine after the test dose lasts more than 12 hours, this dose is used as the initial dose. If the effect of the medicine after the test dose lasts less than 12 hours, the test dose should be doubled and used 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 should not be increased by more than 10% to 30% of the previous dose in patients with spasticity of spinal origin and 5% to 15% in patients with spasticity of cerebral origin. When using a programmable pump, it is recommended to modify the dose only once every 24 hours. When using non-programmable pumps equipped with a 76 cm catheter, which delivers 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 increase the clinical effect, the proper functioning of the pump and the patency of the catheter should be checked.
Basically, the dose of the medicine is increased to achieve a maintenance dose in the range of 300 µg to 800 µg per day in patients with spasticity of spinal origin. Patients with spasticity of cerebral origin 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 the long-term therapy phase in a hospital setting.
Also, in this case, the daily dose can be increased by 10% to 30% in patients with spasticity of spinal origin and 5% to 20% (upper limit) in patients with spasticity of cerebral origin 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 medicine 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 in long-term therapy in patients with spasticity of spinal origin is usually 300 µg to 800 µg of baclofen per day. The smallest and largest 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 medicine should be verified and modified, especially frequently.
In the case of patients with spasticity of cerebral origin, the maintenance doses used during long-term therapy with continuous infusion of Lioresal Intrathecal are in the range of 22 µg to 1400 µg of baclofen per day, and the average daily doses of the medicine 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 it, after determining the daily dose and stabilizing the antispastic effect, it is possible to try to adjust the administration of the medicine 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 so that they occur 2 hours before the desired clinical effect.
Throughout the treatment period, regular, at least monthly, monitoring of tolerance to Lioresal Intrathecal 10 mg/5 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/5 ml with life-threatening consequences for the patient.
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The concentration of baclofen required during pump filling depends on the total daily dose of the medicine 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/5 ml should be diluted in aseptic conditions using a sterile sodium chloride injection solutionwithout preservatives. In this case, follow the instructions provided by the pump manufacturer.
About 5% of patients may require a higher dose of the medicine due to decreased treatment efficacy ("development of tolerance") during long-term treatment. As described in the literature, the development of tolerance is prevented by a 10- to 14-day break in baclofen administration, during which morphine sulfate without preservatives is administered. After this period, the patient may respond to treatment with Lioresal Intrathecal 10 mg/5 ml again. Treatment should be resumed by administering the initial dose used in continuous infusion, and then the dose should be gradually increased again to avoid side effects due to overdose. This procedure should be performed in a hospital setting.

Incompatibilities

Lioresal Intrathecal 10 mg/5 ml, solution for infusion, should not be mixed with other injection or infusion solutions except for sterile, preservative-free sodium chloride solution, diluted in aseptic conditions.
A chemical incompatibility has been demonstrated between dextrose and baclofen.
Do not freeze. Do not sterilize with high temperature.
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