LIORESAL 0.5 mg/mL SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Lioresal 0.5 mg/ml Solution for Infusion

Baclofen

Read all of this leaflet carefully before this medicine is administered to you 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.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What Lioresal 0.5 mg/ml Solution for Infusion is and what it is used for
2. What you need to know before you are given Lioresal 0.5 mg/ml Solution for Infusion
3. How to use Lioresal 0.5 mg/ml Solution for Infusion
4. Possible side effects
5. Storage of Lioresal 0.5 mg/ml Solution for Infusion
6. Contents of the pack and further information

1. What Lioresal 0.5 mg/ml Solution for Infusion is and what it is used for

The active substance of Lioresal is baclofen.

Lioresal administered intrathecally is used in adults and children from 4 years of age to reduce and relieve excessive muscle stiffness (spasms) caused by certain diseases such as cerebral palsy, multiple sclerosis, stroke, spinal cord diseases, and certain disorders of the nervous system.

Due to muscle relaxation and subsequent pain relief, Lioresal promotes mobility, helps with self-care in daily activities, and facilitates physiotherapy.

It is used in people who have not responded to oral medications, including baclofen, or who have developed unacceptable side effects when taking baclofen orally.

The ampoules contain a solution that is injected or infused into your back (around your spinal column) through a special pump implanted under the skin of your abdomen. There is a constant administration of the medication into your spinal cord through a thin tube.

2. What you need to know before you are given Lioresal 0.5 mg/ml Solution for Infusion

Lioresal must not be administered intrathecally:

• if you are allergic to baclofen or any of the other components of this medicine (listed in section 6).

Warnings and Precautions

Seek urgent medical help if you notice that the implanted device is not working and you observe any withdrawal symptoms (see "If you stop treatment with Lioresal intrathecally").

Consult your doctor or pharmacist before you are given Lioresal intrathecally if you have:

• • any infection,
  • a reduced circulation of the fluid that contains the brain and spinal cord due to an obstruction caused, for example, by inflammation or injury,
  • inadequate blood flow to the brain (cerebrovascular insufficiency),
  • acute or chronic confusional states,
  • a psychotic or schizophrenic disorder (mental illness),
  • if you have Parkinson's disease,
  • if you suffer from epilepsy (seizures),
  • if you have ever had heart problems,
• if you have acute stomach pain (ulcer) or intestine problems, breathing difficulties, liver disease, or cerebral circulation disorders,
• if you have kidney disease. Your doctor will decide if Lioresal is the right treatment for you.
• before taking Lioresal, inform your doctor if you are taking medications for arthritis or pain (see section: Use of Lioresal with other medications),
• if you have difficulty urinating,
• if you are diabetic,
• if you have experienced a sudden increase in blood pressure, anxiety, excessive sweating, chills, sharp headaches, and abnormal heart rhythm due to overstimulation of your nervous system caused by having a full bladder or intestine, skin irritation, and pain,
• if you have had a head injury: in patients with spasticity due to head injury, it is recommended not to start long-term therapy with Lioresal intrathecally until the symptoms of spasticity are stable (i.e., at least one year after the injury),
• it is essential to monitor cardiovascular function during the initial test phase, especially if you have respiratory or cardiac problems,
• before undergoing any surgical procedure (including dental procedures) or emergency treatment, inform your doctor that you are being treated with Lioresal intrathecally.

If you are in any of these circumstances, inform your doctor before you are given Lioresal intrathecally.

After the pump is implanted, you will be closely monitored in an equipped environment with trained personnel during the test and dose selection phase. You will undergo regular assessments of side effects or suspected infections according to your needs. The system's functioning will be evaluated periodically. It is crucial to check that there are no problems with the pump.

Consult your doctor immediatelyif you experience any of these symptoms during treatment with Lioresal intrathecally:

• if you have back, shoulder, neck, and buttock pain during treatment (a type of spinal deformity called scoliosis). If at any time you think about self-harm or suicide, talk to your doctor or go to the hospital immediately. Also, ask a family member or close friend to inform you if they observe any worrying changes in your behavior and ask them to read this leaflet.

Children and Adolescents

The intrathecal formulation of baclofen is indicated in children aged 4 years and older.

The use of Lioresal intrathecally is not recommended in children under 4 years of age.

Children must have sufficient body mass to allow the implantation of the infusion pump.

The administration of Lioresal intrathecally in the pediatric population should only be performed by specialist doctors.

Elderly Patients

During clinical trials, some patients over 65 years of age have been treated with intrathecal baclofen without specific problems being observed. However, experience with oral baclofen tablets indicates that this group of patients may have a greater tendency to suffer from side effects. Therefore, elderly patients should be kept under close surveillance to rule out the occurrence of side effects.

Use of Lioresal with Other Medications

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medications.

Concomitant treatment with Lioresal intrathecally requires special attention in the following cases:

• other medications for treating muscle spasms; if possible, your doctor will slowly discontinue the other medications for treating muscle spasms,
• medications for treating depression,
• medications that lower blood pressure, including medications for treating high blood pressure (hypertension),
• levodopa, carbidopa: medications for treating Parkinson's disease,
• potent analgesics, such as morphine,
• medications that slow down the functioning of the central nervous system, such as those used for inducing sleep,
• other medications administered into the spinal column,
• it is not recommended to administer other medications into the spinal column during treatment with Lioresal solution for infusion.

The concomitant use of general anesthetics may increase the risk of cardiac disorders and seizures.

Your doctor may decide to change the dose or sometimes interrupt one of the medications or take other precautions if deemed necessary.

Use of Lioresal with Food, Drinks, and Alcohol

Avoid drinking alcohol during treatment with Lioresal, as this may lead to an undesirable intensification or unpredictable change in the effects of the medication.

Pregnancy, Breastfeeding, and Fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication.

Pregnancy

There are limited or no data on the use of baclofen in pregnant women.

Your doctor will assess the possible risk of using Lioresal intrathecally during pregnancy.

As a precaution, it is preferable to avoid the use of Lioresal intrathecally during pregnancy.

Breastfeeding

Lioresal intrathecally passes into breast milk in very small amounts.

No effects in breastfed children/infants are expected since the systemic exposure to baclofen in breastfeeding mothers is negligible. You can breastfeed your child if your doctor allows it and always monitors the child for possible side effects.

Baclofen may decrease milk production if used for a prolonged period.

Fertility

Animal studies have shown that intrathecal baclofen is unlikely to produce adverse effects on fertility.

Driving and Using Machines

Lioresal intrathecally may cause drowsiness, dizziness, vision problems, or clumsiness or instability in some people. If this happens, do not drive or use tools or machinery.

Lioresal Contains Sodium

This medicine contains 70.81 mg of sodium (the main component of table/cooking salt) per ampoule (20 ml). This is equivalent to ≥ 3.5% of the maximum recommended daily intake of sodium for an adult.

3. How to Use Lioresal 0.5 mg/ml Solution for Infusion

Lioresal intrathecally should only be administered by a specially qualified doctor.

Lioresal intrathecally is administered only in the hospital through a pump placed under the skin of the abdomen. It can only be administered into the spinal canal (intrathecally). It must not be administered intravenously, intramuscularly, epidurally, or subcutaneously.

Lioresal is designed to be administered chronically by intrathecal infusion through a continuous release pump located in the abdomen. Through a prior test phase, the suitable dose of Lioresal for this chronic phase will have been determined. For the prior test phase, another formulation of Lioresal (Lioresal 0.05 mg/ml) is used, which is administered in a single bolus through a spinal catheter or lumbar puncture intrathecally. Determining a suitable dose for you may take several days, under the supervision of a doctor.

If your muscle spasms improve with the test dose, a pump will be implanted under the skin of your abdomen, allowing the continuous release of small amounts of the medication to control your symptoms.

Once the pump is implanted, the reservoir refill should be monitored to prevent it from emptying. The refill should always be done under aseptic conditions to avoid possible microbial contamination.

It is very important that your doctor checks the functioning of the pump during regular visits.

It is essential that you keep the appointments for the pump refill, as otherwise, the spasms may recur due to not receiving a sufficient dose of Lioresal.As a result, muscle spasticity may not improve and may even worsen.

The duration of treatment will be decided by your doctor. During long-term treatment, some patients observe a decrease in the efficacy of baclofen. Your doctor may recommend occasional breaks from treatment to counteract this phenomenon.

If your muscle spasticity does not improve or if you start having spasms again, either gradually or suddenly, contact your doctor immediately.

If you are given more Lioresal intrathecally than you should

You may experience an overdose. It is crucial that you and your caregivers are able to recognize the symptoms of an overdose. These may appear suddenly or gradually because the pump is not working correctly.

The main symptoms of overdose are:

• excessive muscle weakness (too low muscle tone),
• drowsiness,
• dizziness or vertigo,
• excessive salivation,
• nausea or vomiting,
• breathing difficulties,
• seizures,
• loss of consciousness,
• abnormal decrease in body temperature,
• rapid heart rate (tachycardia),
• ringing in the ears (tinnitus).

If you experience any of these symptoms, inform your doctor immediately.

If you stop treatment with Lioresal intrathecally

If you need to stop treatment with this medication for any reason, your doctor will gradually reduce the dose to avoid the occurrence of side effects.

Sudden interruption or reduction of Lioresal intrathecally can cause withdrawal symptoms, which in some cases have been fatal. It is crucial that you and your caregivers are able to recognize the symptoms of Lioresal intrathecally withdrawal. These may appear suddenly or gradually due to, for example, battery problems, catheter problems, alarm malfunction, or device malfunction.

For this reason:

• Attend the scheduled appointments regularly with your doctor for the pump refill.
• Do not stop taking Lioresal suddenly.

The withdrawal symptoms are:

• uncontrolled and severe muscle spasms (too high muscle tone),
• difficulty performing muscle movements,
• rapid heart rate (tachycardia),
• low blood pressure,
• numbness or tingling in your hands or feet,
• anxiety,
• high fever,
• altered mental conditions such as agitation, confusion, hallucinations, abnormal behavior, or seizures.
• persistent and painful erection of the penis (priapism)
• infection (sepsis)

If you experience any of the above symptoms, go to the doctor immediately. These symptoms may be followed by more severe side effects (including death) if you do not receive immediate treatment.

If you have any further questions about the use of this medication, ask your doctor or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can have adverse effects, although not all people suffer from them.

Adverse effects occur more frequently at the start of treatment during your hospital stay, but they could also occur later. Many of these adverse effects are associated with the medical condition for which you are being treated.

If you experience any of the following adverse effects, you should consult your doctor:

Some adverse effects can be serious

If you suffer from any of the adverse effects indicated below, inform your doctor immediately:

• malfunction of the implanted device or infusion system that can produce withdrawal symptoms, including death (see “If you interrupt treatment with Lioresal Intrathecal”)
• suicidal ideas or attempts,
• confusion, disorientation,
• feeling of extreme happiness (euphoria),
• mood or mental changes (paranoia),
• feeling of sadness,
• muscle coordination disorder (ataxia),
• hallucinations (seeing or hearing things that are not real),
• blurred vision, visual disturbances,
• shortness of breath or abnormally slow breathing or breathing problems,
• pneumonia,
• fever,
• sedation and lethargy (excessive drowsiness),
• low blood pressure (hypotension),
• high blood pressure (hypertension),
• seizures,
• muscle tone that is too low or too high.

If you experience any of these adverse effects, inform your doctor immediately.

Some adverse effects are very common(may affect more than 1 in 10 patients):

• drowsiness,
• muscle tone that is too low.

If you experience any of these adverse effects in a severe manner, inform your doctor.

Some adverse effects are common(may affect up to 1 in 10 patients):

• feeling of sadness,
• feeling of anxiety,
• sedation or exhaustion (fatigue),
• dizziness or vertigo,
• headache,
• tingling of hands and feet,
• insomnia,
• blurred vision, visual disturbances, double vision,
• low blood pressure,
• pneumonia,
• agitated or very slow breathing or breathing problems,
• weakness, sedation, fatigue,
• pain,
• too much muscle tone,
• dry mouth,
• skin rash or itching,
• swelling of ankles, feet, lower legs, swelling of the face,
• unusual nervousness or restlessness,
• speech disorder,
• confusion, disorientation,
• nausea and/or vomiting,
• constipation,
• diarrhea,
• decreased appetite,
• excessive salivation,
• fever/chills,
• urinary problems,
• sexual disorders.

If you experience any of the aforementioned adverse effects in a severe manner, inform your doctor.

Some adverse effects are uncommon(may affect up to 1 in 100 patients):

• suicidal ideas, attempts,
• hallucinations (seeing or hearing things that do not exist),
• mood or mental changes (paranoia),
• feeling of extreme happiness (euphoria),
• muscle coordination disorder (ataxia),
• abnormal decrease in body temperature,
• memory disorders,
• uncontrolled and continuous eye movements,
• unusually slow heartbeat,
• decreased sense of taste,
• difficulty swallowing,
• abdominal pain,
• hair loss,
• increased sweating.

Some adverse effects have unknown frequency:

• agitation (restlessness),
• abnormally slow breathing rate (bradypnea),
• increased curvature of the spine (scoliosis),
• inability to achieve or maintain an erection (erectile dysfunction),
• allergic reaction (hypersensitivity).

Some of these adverse effects may be related to the delivery system of the pump.

For a description of withdrawal symptoms, see “If you interrupt treatment with Lioresal”.

For a description of overdose symptoms, see “If you are administered more Lioresal Intrathecal than you should”.

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Lioresal 0.5 mg/ml solution for intrathecal infusion

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Store below 30°C. Do not freeze.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Lioresal 0.5 mg/ml solution for intrathecal infusion

• The active ingredient is baclofen. Each 20 ml ampoule contains 10 mg of baclofen. Each ml contains 0.5 mg (500 micrograms) of baclofen.
• The other components (excipients) are: sodium chloride and water for injectable preparations.

Appearance of the product and package contents

Lioresal 0.5 mg/ml is presented as a clear and colorless solution for intrathecal infusion.

Each package contains 1 ampoule.

Other presentations

Lioresal 2 mg/ml solution for infusion. Package with 1 ampoule

Lioresal 0.05 mg/ml injectable solution. Package with 5 ampoules

Marketing Authorization Holder

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes 764

08013 Barcelona

Spain

Manufacturer

Novartis Pharma GmbH

Roonstrasse 25

90429 Nürnberg

Germany

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Spain

Date of the last revision of this prospectus: August 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es

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This information is intended only for healthcare professionals: Consult the technical sheet for more details on the medicine, its posology, and administration form.

Posology

Recommended dose:

Test phase:

Adults

In adults, the initial test dose is 25 or 50 micrograms, which can be increased by 25 micrograms every 24 hours until a response that lasts approximately 4-8 hours is observed. The dose will be pumped for at least 1 minute. For this test dose, 0.05 mg/ml ampoules are available.

Pediatric population

The initial lumbar puncture of the test phase in patients aged 4 years and under 18 years should be 25 to 50 micrograms per day, depending on the age and height of the child. Patients who do not respond to this dose may receive a dose increase of 25 micrograms every 24 hours. The maximum dose of the test phase should not exceed 100 micrograms/day in pediatric patients.

Dose determination phase:

The initial daily dose of Lioresal Intrathecal to be administered through the pump is determined by doubling the dose that was effective in the test phase, administered over a 24-hour period. If the effect of the test dose lasted more than 12 hours, the initial dose should be the same as the test dose but administered over a 24-hour period. No dose increases should be made during the first 24 hours of treatment. After the first 24 hours, the dose will be adjusted daily in a slow manner until the desired clinical effect is achieved. Experience is limited with doses above 1000 micrograms/day.

Maintenance phase:

The minimum dose that achieves an adequate response should be used. Many patients need gradual dose increases to maintain an optimal response during chronic therapy due to reduced response to treatment or disease progression.

Preparation and handling of the product

Lioresal Intrathecal is designed for continuous intrathecal injection and infusion as indicated by the administration specifications of the infusion system.

The specific concentration to be used depends on the total daily dose required and the pump's release rate. Consult the manufacturer's manual for specific recommendations.

For patients who require concentrations other than 50 micrograms/ml, 500 micrograms/ml, or 2000 micrograms/ml, Lioresal Intrathecal must be diluted, under aseptic conditions, with sterile sodium chloride for injection and free of preservatives.

As a general rule, Lioresal 0.5 mg/ml ampoules for intrathecal administration should not be mixed with other infusion or injection solutions.

Glucose (dextrose) has been shown to be incompatible due to a chemical reaction that occurs with baclofen.

Administration devices

Different administration systems have been used for the prolonged intrathecal application of Lioresal. These include the Medtronic SynchroMed? Programmable Infusion System, which is an implantable drug delivery system with refillable reservoirs, implanted in a subcutaneous cavity, generally in the abdominal wall.

This device is connected to an intrathecal catheter that passes subcutaneously to the subarachnoid space. More details can be obtained from the manufacturer.

Before using other systems, it should be confirmed that the technical specifications, including the chemical stability of baclofen in the reservoir, meet the requirements for the intrathecal use of Lioresal.

Each ampoule is intended for single use. Discard any unused portion. Do not freeze. Do not sterilize with heat.

Stability

Lioresal Intrathecal has been shown to be stable in the Medtronic SynchroMed? Programmable Infusion System for 11 weeks. There is no stability data available for Lioresal Intrathecal when using other infusion systems.