Lioresal intrathecal 10 mg/5 ml

Package leaflet: Information for the user

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Lioresal Intrathecal 10 mg/5 ml, solution for infusion
For use in adult patients and children aged 4 years and older
Active substance: baclofen
Please read this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Lioresal Intrathecal 10 mg/5 ml is and what it is 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 pack and other information

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

Lioresal Intrathecal 10 mg/5 ml contains the active substance baclofen. Lioresal Intrathecal
10 mg/5 ml is a medicine used to treat excessive muscle stiffness.
Lioresal Intrathecal is used in the treatment of severe, chronic spasticity (increased muscle
tone) that cannot be effectively managed with standard medications:

• in multiple sclerosis – a progressive neurological disease affecting the central nervous system, brain and spinal cord, with physical and psychological symptoms
• following spinal cord injuries or brain injuries
• in other spinal cord disorders

During the qualification phase 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 care. The dosage, possible adverse 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/5 ml

When not to use Lioresal Intrathecal 10 mg/5 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 treatment-resistant 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 interruption in section 3 "How to use Lioresal Intrathecal 10 mg/5 ml").
If any of the following apply to the patient, they must inform their doctor before starting treatment with Lioresal Intrathecal 10 mg/5 ml:

• disturbances in cerebrospinal fluid circulation due to flow obstruction
• treatable epilepsy or other convulsive seizures 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 states of 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 caused by previous head trauma. Long-term treatment of increased muscle tone should be initiated only 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 must inform their doctor immediately:

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

Children
In children, certain requirements regarding appropriate body weight must be met to allow implantation of the infusion pump. Lioresal Intrathecal 10 mg/5 ml is intended for use in children aged 4 years and older. The safety of intrathecal administration of Lioresal Intrathecal 10 mg/5 ml in children under 4 years of age has not yet been established.

Patients over 65 years of age
In 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 tablets shows that this group of patients may be more susceptible to adverse effects. Therefore, elderly patients should be closely monitored for the occurrence of adverse effects.

Lioresal Intrathecal 10 mg/5 ml and other medicines
Tell your doctor or pharmacist about any medicines the patient is currently taking, has recently taken, or plans to take.
The following medicines may affect the action of Lioresal Intrathecal 10 mg/5 ml, or Lioresal Intrathecal 10 mg/5 ml may affect them. Dose adjustments of Lioresal Intrathecal 10 mg/5 ml or one of the other concomitantly used medicines may be necessary:

• medicines used in Parkinson's disease
• medicines relieving severe muscle spasms
• medicines with a depressant 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/5 ml with food, drink, and alcohol
When using Lioresal Intrathecal 10 mg/5 ml, alcohol should be avoided, as it may cause undesirable, intensified, or unpredictable effects of the medicine.

Pregnancy and breastfeeding
Due to lack of experience, women who are pregnant or breastfeeding should use Lioresal Intrathecal 10 mg/5 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/5 ml may significantly affect these functions.

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

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

This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult the
doctor or pharmacist.
Available in commerce are: Lioresal Intrathecal 10 mg/5 ml, Lioresal Intrathecal 10 mg/20 ml.
Method of administration
Lioresal Intrathecal 10 mg/5 ml may be administered by direct injection or infusion into the intrathecal space only by a qualified specialist and using appropriate equipment.
For this reason, hospitalization is required at the beginning of treatment.
At the start of treatment, the doctor will determine whether a single injection of a lower dose – Lioresal Intrathecal 0.05 mg/1 ml, solution for injection – will alleviate 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 doctor refills the pump .
If the patient receives too low a dose of Lioresal Intrathecal 10 mg/5 ml, increased muscle tone may return. Muscle spasms may also worsen.
Inform the doctor immediately if there is no relief from muscle spasms or if they recur.
The doctor 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 doctor.
Use of a higher than recommended dose of Lioresal Intrathecal 10 mg/5 ml
Contact the doctor immediately if the patient or caregiver notices symptoms of overdose, which may occur suddenly or gradually:

• excessively low muscle tone
• drowsiness
• dizziness or 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 discontinuation of the medicine is necessary, it must be performed solely by the treating physician, who will gradually reduce the dose to avoid adverse effects. Sudden discontinuation of Lioresal Intrathecal 10 mg/5 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 discontinuation of Lioresal Intrathecal 10 mg/5 ml. This is particularly important when continued administration via pump is planned.

• worsening of 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 may result in death if treatment is not initiated immediately.

It should be remembered that pump malfunctions, such as battery problems, catheter issues, 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 doctor.

4. Possible adverse effects

* Adverse effects marked with an asterisk occur more frequently in patients with
cerebral palsy.
Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
Adverse effects are more common when treatment is initiated in hospital, but they may also
occur later. Many of the adverse effects 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 of treatment in section 3 "How to use Lioresal Intrathecal 10 mg/5 ml").
The following adverse effects and their frequency of occurrence have been reported:

Very common: may affect more than 1 in 10 people

• decreased muscle tone
• drowsiness

Common: may affect up to 1 in 10 people

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

Uncommon: may affect up to 1 in 100 people

• decreased body fluids (dehydration)
• pale skin
• high blood pressure
• intestinal obstruction due to blockage
• memory loss / distractibility
• mood disturbances
• hair loss
• false sensory perceptions not caused by external stimuli (hallucinations)
• redness of the skin
• low body temperature
• difficulty swallowing
• problems with movement coordination
• suicidal thoughts and attempts
• excessive sweating
• nystagmus
• slowed 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 people

• life-threatening withdrawal symptoms caused by problems with drug delivery

Some adverse effects occur at an unknown frequency:

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

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

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

Keep this medicine out of the 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 Lioresal Intrathecal 10 mg/5 ml after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

• The active substance is baclofen. Lioresal Intrathecal 10 mg/5 ml solution for infusion: 1 ml of infusion solution contains 2.0 mg of baclofen. One 5 ml ampoule contains 10 mg of baclofen.
• Other components: sodium chloride, water for injections.

What Lioresal Intrathecal looks like and contents of the pack
Lioresal Intrathecal 10 mg/5 ml is a clear, colourless solution in a transparent, colourless ampoule.
Lioresal Intrathecal 10 mg/5 ml solution for infusion is available in packs containing 1, 2 or 5 ampoules.
For further information, contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation 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:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing Authorisation number in Germany, the country of export: 39917.00.01
Parallel Import licence number: 281/19
This medicinal product has been authorised 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

Information intended exclusively for medical professionals:

How to prepare and administer Lioresal Intrathecal 10 mg/5 ml?
Administration of a test dose, implantation of an infusion pump, and dose escalation of the intrathecally administered medicinal product must be performed in hospital settings within centers possessing appropriate expertise and under the close supervision of adequately qualified physicians. Immediate access to an intensive care unit must be ensured due to the potential for severe or life-threatening adverse reactions.

To determine the optimal dosing regimen for Lioresal Intrathecal 10 mg/5 ml, each patient should first receive a trial dose prior to initiating long-term treatment: Lioresal Intrathecal 0.05 mg/1 ml administered intrathecally as a bolus injection via an intrathecal catheter or lumbar puncture. Subsequently, the dose must be carefully and individually adjusted for each patient, due to considerable inter-individual variability in therapeutically effective doses.

For long-term therapy, Lioresal Intrathecal 10 mg/5 ml is administered via an implanted pump enabling continuous infusion of baclofen solution into the cerebrospinal fluid.

The efficacy of Lioresal Intrathecal 10 mg/5 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 tissue) connected to an intrathecal catheter extending from the subcutaneous implantation site into the intrathecal space. Experience with other implanted infusion systems is currently lacking.

Prior to initiating treatment with Lioresal Intrathecal 10 mg/5 ml, myelography of the intrathecal space should be performed in patients with traumatic spasticity. If radiological signs of arachnoiditis are detected, treatment with Lioresal Intrathecal 10 mg/5 ml should not be initiated.

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

Each ampoule is intended for single use only. The solution it contains is stable, isotonic, pyrogen-free, and free from 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/5 ml during the trial 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 starting continuous infusion, with maximal effect observed after 24 to 48 hours.

The initial total daily dose of Lioresal Intrathecal 10 mg/5 ml is calculated as follows: if the effect of the test dose lasts longer 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 administered as the initial dose. Dose escalation should not occur 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-origin spasticity, and by 5% to 15% in patients with cerebral-origin 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 per day, the patient's response to a new dose should be evaluated after 48 hours. If a significant increase in daily dose does not enhance clinical effect, the proper functioning of the pump and catheter patency should be verified.

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

Long-term therapy phase
The goal of treatment is to use the lowest effective dose providing adequate control of spasticity without unacceptable adverse effects. Since therapeutic efficacy may diminish over time and spasticity severity may fluctuate, dose adjustments in a hospital setting are typically required during long-term therapy.

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

The need for sudden dose escalation to achieve therapeutic effect suggests possible pump malfunction or catheter kinking, fracture (abrasion), or displacement.

The maintenance dose of Lioresal Intrathecal 10 mg/5 ml in long-term treatment of patients with spinal-origin spasticity typically ranges from 300 μg to 800 μg of baclofen per day. The lowest and highest recorded daily doses administered to individual patients during the titration phase were 12 μg and 2003 μg, respectively (data from U.S. studies). Experience with doses exceeding 1000 μg per day is limited. During the first several months of treatment, the dose should be verified and modified frequently.

In patients with cerebral-origin spasticity, maintenance doses during long-term continuous infusion therapy with Lioresal Intrathecal 10 mg/5 ml range from 22 μg to 1400 μg of baclofen per day. Mean daily doses were 276 μg after one year and 307 μg after two years of observation. 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 pump's technical parameters 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 hourly infusion rate may be required. Changes in infusion rate should be programmed to occur two hours before the desired clinical effect is needed.

Throughout the treatment period, regular monitoring (at least monthly) at the treating center is essential to assess tolerance to Lioresal Intrathecal 10 mg/5 ml and to detect possible signs of infection. The proper functioning of the infusion system must be regularly checked. Local infection or catheter malfunction may interrupt intrathecal delivery of Lioresal Intrathecal 10 mg/5 ml, potentially leading to 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/5 ml should be diluted under aseptic conditions using sterile sodium chloride for injection, free from 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 introducing a 10- to 14-day interruption in baclofen administration, during which preservative-free morphine sulfate should be administered. After this period, patients may again respond to treatment with Lioresal Intrathecal 10 mg/5 ml. Therapy should be resumed with the initial dose used in 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/5 ml solution for infusion must not be mixed with other injectable or infusion solutions except sterile sodium chloride solution free from preservatives, diluted under aseptic conditions.

Chemical incompatibility between dextrose and baclofen has been demonstrated.

Do not freeze. Do not sterilize by high temperature.