Lioresal intrathecal 10 mg/20 ml

Package leaflet: Information for the user

Warning! Keep the leaflet. 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.
Active substance: baclofen
Please read all of this leaflet carefully before using this medicine because it contains
important information for you.

• Keep this leaflet. 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 person only. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If you experience any side effects, including any possible side effects not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

1. What Lioresal Intrathecal 10 mg/20 ml is and what it is 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. Contents of the pack and other information

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

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

• in multiple sclerosis. This is a progressive neurological disease affecting the brain and spinal cord, with physical and mental symptoms.
• after spinal cord injuries or brain injuries.
• in other spinal cord disorders.

During the patient's qualification for treatment and during the dose escalation phase, immediately after pump implantation, the patient will be closely monitored under conditions ensuring access to appropriate equipment and medical staff. The dosage, possible side effects, or signs of infection will be regularly assessed. The functioning of the drug delivery system will also be checked.
If there is no improvement or if the patient feels worse, 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 to 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 refractory epilepsy.

Warnings and precautions
Consult a doctor immediately if the patient thinks the device is not working properly or if they notice symptoms of withdrawal (see symptoms of discontinuation in section 3 “How to use Lioresal Intrathecal 10 mg/20 ml”).
If any of the following apply to the patient, they should inform their doctor before starting treatment with Lioresal Intrathecal 10 mg/20 ml:

• disturbances in cerebrospinal fluid circulation due to flow obstruction;
• treatable epilepsy or other seizure disorders involving the brain;
• neurological disorders caused by cranial nerve damage in the brainstem (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;
• history of autonomic reflex disorders (uncontrolled);
• insufficient blood flow to the brain;
• breathing difficulties;
• bladder sphincter hyperactivity;
• heart diseases;
• kidney function disorders;
• gastric and intestinal ulcers;
• severe liver function impairment;
• increased muscle tone due to previous head injury. Long-term treatment of increased muscle tone should be initiated only when spasticity symptoms are stable and can be reliably assessed.

If any of the following symptoms occur during treatment with Lioresal Intrathecal 10 mg/20 ml, inform the doctor immediately:

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

Children
In children, certain body weight requirements must be met to allow implantation of the infusion pump. Lioresal Intrathecal 10 mg/20 ml is intended for use in children aged 4 years and older. The safety of intrathecal administration of Lioresal Intrathecal 10 mg/20 ml in children under 4 years of age has not yet been established.

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 tablets shows that this patient group may be more susceptible to adverse reactions. Therefore, elderly patients should be carefully monitored for the occurrence of adverse effects.

Lioresal Intrathecal 10 mg/20 ml and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
The following medicines may affect the action of Lioresal Intrathecal 10 mg/20 ml or Lioresal Intrathecal 10 mg/20 ml may affect them. Dose adjustment of Lioresal Intrathecal 10 mg/20 ml or one of the other concomitantly used medicines may be necessary:

• medicines used in Parkinson's disease;
• medicines used to relieve severe muscle spasms;
• medicines with a central nervous system depressant effect;
• medicines used in the treatment of 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, avoid consuming alcohol simultaneously, as this may cause undesirable intensification or unpredictable changes in the drug's effects.

Pregnancy and breastfeeding
Due to 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 machinery
Do not drive, operate machinery or perform other hazardous activities, as Lioresal Intrathecal 10 mg/20 ml may significantly affect these functions.

Lioresal Intrathecal 10 mg/20 ml contains sodium
This medicine contains 70.81 mg of sodium (the main component of table salt) per 20 ml. This corresponds to 3.5% of the maximum recommended daily dietary sodium intake for adults.

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

This medicine should always be used exactly as directed by the physician. If in doubt, consult the doctor or pharmacist.
The following products are available on the market: Lioresal Intrathecal 10 mg/20 ml (10 mg/20 ml), Lioresal Intrathecal 10 mg/5 ml (10 mg/5 ml).
Method of administration
Lioresal Intrathecal 10 mg/20 ml may be administered by direct injection or infusion into the intrathecal space only by a qualified specialist and using appropriate equipment.
Therefore, hospitalization is required at the beginning of treatment.
At the start of treatment, the physician will determine whether a single injection of a lower dose – Lioresal Intrathecal, 0.05 mg/1 ml, solution for injection – reduces muscle spasms. If possible, a special pump will be implanted under the patient's skin, which will allow continuous, patient-tailored dosing.
It is very important that the patient attends scheduled appointments during which the physician refills the pump .
If the patient receives too low a dose of Lioresal Intrathecal 10 mg/20 ml, increased muscle tone may return. Muscle spasms may also worsen.
Inform the doctor immediately if muscle spasms do not improve or recur.
The physician must regularly monitor the patient's condition and pump function—at least once a month.
Duration of treatment
The duration of treatment will be determined by the physician.
Use of a higher than recommended dose of Lioresal Intrathecal 10 mg/20 ml
Contact the doctor immediately if the patient or caregiver notices symptoms of overdose, which may appear suddenly or gradually:

• excessively low muscle tone;
• drowsiness;
• dizziness or feeling faint;
• 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 discontinuation of the medicine is necessary, it must be performed only by the treating physician, who will gradually reduce the dose to avoid adverse effects. Sudden discontinuation of Lioresal Intrathecal 10 mg/20 ml may cause severe adverse reactions, which in several cases have resulted in death.
Contact the doctor immediately if the patient or caregivers notice the following symptoms of withdrawal from Lioresal Intrathecal 10 mg/20 ml. This is particularly important when continued administration via pump is planned.

• increased spasticity, excessive muscle tone;
• difficulty moving muscles;
• increased heart rate and rapid pulse;
• itching;
• tingling, burning, or numbness in hands and feet;
• palpitations;
• anxiety;
• fever;
• low blood pressure;
• changes in the patient's mental state, e.g. agitation, disorientation, hallucinations, abnormal thinking and behavior;
• seizures;
• prolonged painful penile erection (priapism).

The above symptoms may lead to severe adverse reactions, which can be fatal if treatment is not initiated immediately.

It should be noted that pump malfunctions, such as battery or catheter problems, alarm signal failure, or device malfunction, may lead to overdose or underdosing of the medicine.
In case of any doubts regarding the use of the medicine, consult the physician.

4. Possible adverse reactions

* Adverse reactions marked with an asterisk occur more frequently in patients with
cerebral palsy.
Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
Adverse reactions are more common when treatment is initiated in hospital, but they may also
occur later. Many of the adverse reactions listed may also be related to the underlying disease being treated.
Malfunction of the implanted drug delivery device or infusion system may lead to withdrawal symptoms, which may result in death (see symptoms of interruption in section 3 "How to use Lioresal Intrathecal 10 mg/20 ml").
The following adverse reactions and their frequency have been reported:

Very common: may affect more than 1 in 10 patients

• decreased muscle tone
• somnolence

Common: may affect up to 1 in 10 patients

• anxiety
• decreased appetite
• shortness of breath, slow or shallow breathing
• reduced alertness
• low blood pressure upon sitting or standing
• depression
• disorientation
• diarrhoea, even faecal incontinence
• increased muscle tone
• fever
• increased motor restlessness
• urinary retention*
• itchy skin swelling, similar to an insect bite
• pruritus
• headache*, pain
• seizures*
• pneumonia
• unusual skin sensations with tingling in hands and feet
• dry mouth
• muscle weakness
• coma
• chills
• facial, hand and foot swelling
• dizziness
• sexual dysfunction
• visual disturbances with blurred or double vision
• apathy
• urinary incontinence
• nausea or vomiting*
• excessive salivation
• constipation
• slurred speech
• confusion
• respiratory depression

Uncommon: may affect up to 1 in 100 patients

• decreased body fluids (dehydration)
• pallor
• high blood pressure
• intestinal obstruction due to constipation
• memory loss/distractibility
• mood disturbances
• alopecia
• false sensory perceptions not caused by external stimuli (hallucinations)
• skin redness
• low body temperature
• difficulty swallowing
• problems with coordination
• suicidal thoughts and attempts
• excessive sweating
• nystagmus
• slow heart rate
• reduced sense of taste
• blockage of a blood vessel due to deep vein thrombosis
• hallucinations
• euphoria

Rare: may affect up to 1 in 1,000 patients

• life-threatening withdrawal symptoms due to problems with drug administration

Some adverse reactions occur with unknown frequency:

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

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Aleje Jerozolimskie 181C
PL-02 222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

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

Keep this medicine out of sight and reach of children.
Storage conditions
Do not store above 30°C.
Do not freeze. Do not sterilize by heat.
The solution should be used immediately after opening. Any unused solution must be discarded.
The solution must be clear and colourless. Do not use this medicine if cloudiness or discoloration is observed.
Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
Medicines must 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 pack and other information

• The active substance is baclofen. 1 ml of Lioresal Intrathecal 10 mg/20 ml infusion solution contains 0.5 mg of baclofen. One 20 ml vial of infusion solution contains 10 mg of baclofen.
• Other ingredients are: sodium chloride, water for injections.

What Lioresal Intrathecal 10 mg/20 ml looks like and contents of the pack
Lioresal Intrathecal 10 mg/20 ml is a clear, colourless solution in a transparent, colourless vial.
Lioresal Intrathecal 10 mg/20 ml infusion solution is available in packs containing 1, 2 or 5 vials.
For more detailed information, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Germany, 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 in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
German, country of export, Marketing Authorisation number: 39917.01.01
Parallel Import Licence number: 207/17
This medicinal product has been authorised 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, infusion solution

Information intended exclusively for healthcare professionals:

How to prepare and administer Lioresal Intrathecal 10 mg/20 ml?
Administration of a test dose, implantation of an infusion pump, and dose escalation of the medicinal product administered intrathecally must be performed in a hospital setting, within centers with appropriate experience and under the close supervision of suitably qualified physicians. Immediate access to an intensive care unit must be ensured due to the potential for severe or life-threatening adverse reactions to the medicinal product.

To determine the optimal dosing regimen for Lioresal Intrathecal 10 mg/20 ml, each patient should first receive a test dose prior to initiating long-term therapy with Lioresal Intrathecal 0.05 mg/1 ml administered as an intrathecal bolus injection via an intrathecal catheter or lumbar puncture. The dose must then be carefully and individually adjusted for each patient, due to considerable inter-patient variability in therapeutically effective doses.

For long-term therapy, Lioresal Intrathecal 10 mg/20 ml is administered via an implanted pump that enables continuous infusion of baclofen solution into the cerebrospinal fluid. The efficacy of Lioresal Intrathecal 10 mg/20 ml has been demonstrated in clinical trials using the SynchroMed infusion system. This drug delivery system includes refillable reservoirs implanted subcutaneously in the patient (usually in the abdominal wall tissues). The device is also connected to an intrathecal catheter, which runs from the subcutaneous implantation site into the intrathecal space. Experience with other implanted infusion systems for this medicinal product is currently lacking.

Prior to administering Lioresal Intrathecal 10 mg/20 ml, a myelographic examination of the intrathecal space should be performed in patients with traumatic spasticity. If radiological signs of meningitis are observed, therapy with Lioresal Intrathecal 10 mg/20 ml should not be initiated.

Before administration, the solution should be inspected visually for clarity and colorlessness. The medicinal product must not be administered if the solution is cloudy or discolored.

Each ampoule is intended for single use only. The solution contained therein is stable, isotonic, pyrogen-free, and free of antioxidants, with a pH of 5.0–7.0.

Implantation of the infusion pump / dose escalation phase (in hospital setting)
After confirming the patient's response to Lioresal Intrathecal 10 mg/20 ml during the test phase, intrathecal infusion of the medicinal product may be initiated using the aforementioned infusion pump. The antispastic effect of baclofen begins 6 to 8 hours after the start of continuous infusion, with maximum effect observed after 24 to 48 hours.

The total initial daily dose of Lioresal Intrathecal 10 mg/20 ml is calculated as follows: if the effect of the test dose lasts more than 12 hours, this dose is used as the initial dose. If the effect lasts less than 12 hours, the test dose should be doubled and used as the initial dose. The dose should not be increased during the first 24 hours of therapy.

After the first day of treatment, the dose may 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 spinal spasticity, and by 5% to 15% in patients with cerebral spasticity. When using a programmable pump, dose adjustments should be made no more than once every 24 hours. For non-programmable pumps equipped with a 76 cm catheter delivering 1 ml of solution per day, the patient's response to the new dose should be evaluated after 48 hours. If a significant increase in the daily dose does not enhance clinical effect, the proper function of the pump and catheter patency should be verified.

In general, the dose of the medicinal product is escalated until a maintenance dose of 300 μg to 800 μg per day is reached in patients with spinal spasticity. Patients with cerebral spasticity usually require lower doses (see below).

Long-term therapy phase
The goal of treatment is to use the lowest dose that provides adequate control of spasticity without unacceptable adverse effects. Since therapeutic efficacy may decrease over time and the severity of spasticity may change, dose adjustments in the hospital setting are often required during long-term therapy.

In this phase, the daily dose may be increased by 10% to 30% in patients with spinal spasticity and by 5% to 20% (upper limit) in patients with cerebral spasticity, by adjusting the infusion rate or the baclofen concentration in the pump reservoir. Conversely, if adverse effects occur, the daily dose may be reduced by 10% to 20%.

The need for a sudden dose increase to achieve adequate therapeutic response may indicate pump malfunction or catheter kinking, fracture (abrasion), or displacement.

The maintenance dose of Lioresal Intrathecal 10 mg/20 ml in long-term therapy for patients with spinal spasticity is typically 300 μg to 800 μg of baclofen per day. The lowest and highest recorded daily doses administered to individual patients during the dose-escalation phase were 12 μg and 2003 μg, respectively (studies conducted in the United States). Experience with doses exceeding 1000 μg per day is limited. During the first several months of treatment, the dose should be verified and modified particularly frequently.

In patients with cerebral spasticity, maintenance doses used during long-term continuous infusion of Lioresal Intrathecal 10 mg/20 ml range from 22 μg to 1400 μg of baclofen per day, with mean daily doses of 276 μg after 1 year of observation and 307 μg after 2 years.

Children under 12 years of age generally require lower doses (range: 24 μg to 1199 μg per day; mean: 274 μg per day).

If the technical parameters of the pump allow, after establishing the daily dose and stabilizing the antispastic effect, attempts may be made to adjust drug delivery to the patient's circadian spasticity pattern. For example, if spasms occur more frequently at night, a 20% increase in the hourly infusion rate may be required. Changes in infusion rate should be programmed to occur 2 hours before the desired clinical effect is expected.

Throughout the treatment period, regular monitoring (at least monthly) at the treating center is essential to assess tolerance to Lioresal Intrathecal 10 mg/20 ml and to detect any signs of infection. The proper function of the infusion system should be regularly checked. Local infection or catheter malfunction may interrupt intrathecal delivery of Lioresal Intrathecal 10 mg/20 ml, with potentially life-threatening consequences.

The baclofen concentration required for pump refilling depends on the total daily dose of the medicinal product and the pump's infusion rate. If baclofen administration at concentrations other than 0.05 mg/ml, 0.5 mg/ml, or 2 mg/ml is necessary, Lioresal Intrathecal 10 mg/20 ml should be diluted under aseptic conditions using sterile sodium chloride for injection, free of preservatives. In such cases, the manufacturer's instructions for the infusion pump must be followed.

Approximately 5% of patients may require higher doses due to reduced treatment efficacy ("development of tolerance") during long-term therapy. As described in the literature, tolerance development may be prevented by a 10- to 14-day interruption of baclofen administration, during which preservative-free morphine sulfate should be administered. After this period, the patient may again respond to treatment with Lioresal Intrathecal 10 mg/20 ml. Therapy should be resumed with the initial dose used for continuous infusion, followed by gradual dose escalation to avoid adverse effects due to overdose. This procedure must be performed in a hospital setting.

Pharmaceutical incompatibilities
Lioresal Intrathecal 10 mg/20 ml infusion solution must not be mixed with other injectable or infusion solutions except sterile sodium chloride solution free of preservatives, diluted under aseptic conditions.

Chemical incompatibility between dextrose and baclofen has been demonstrated.

Do not freeze. Do not sterilize at high temperature.