Leaflet: information for the user

Lioresal 0.5 mg/ml infusion solution

baclofen

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

- If you have any questions, consult your doctor or pharmacist.

- If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isLioresal 0.5 mg/ml infusion solutionand what it is used for

2. What you need to know before you start usingLioresal 0.5 mg/ml infusion solution

3. How to useLioresal 0.5 mg/ml infusion solution

4. Possible side effects

5. Storage ofLioresal 0.5 mg/ml infusion solution

6. Contents of the pack and additional information

The active ingredient of Lioresal is baclofen.

Lioresal administered via the intrathecal route is used in adults and children aged 4 years and above to reduce and alleviate excessive muscle stiffness (spasms) produced in certain diseases such as cerebral palsy, multiple sclerosis, cerebrovascular accidents, spinal cord diseases, and certain alterations of the nervous system.

Due to muscle relaxation and the consequent relief of pain, Lioresal promotes mobility, helps to perform daily activities independently, and facilitates physical therapy.

It is used in individuals 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) via a special pump implanted under the skin of your abdomen. There is a constant administration of the medication in your spinal cord through a thin tube.

You should not administer Lioresal via intrathecal:

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

Warnings and precautions

Seek immediate medical help if you observe that the implanted device does not function and you notice any withdrawal symptoms (see “If you interrupt treatment with Lioresal via intrathecal”).

Consult your doctor or pharmacist before starting Lioresal via intrathecal if you have:

• • any infection,
  • reduced cerebrospinal fluid circulation due to obstruction, for example, caused by inflammation or injury,
  • insufficient cerebral blood flow,
  • acute or chronic confusion states,
  • psychotic disorder or schizophrenia (mental illness),
  • if you have Parkinson's disease,
  • if you have epilepsy (seizures),
  • if you have had heart problems,
• if you have acute stomach or intestinal pain (ulcer), breathing problems, liver disease, or cerebral circulation disorders,
• if you have kidney disease. Your doctor will decide if Lioresal is the appropriate treatment for you.
• before taking Lioresal, inform your doctor if you are taking medications for arthritis or pain (see section: Using Lioresal with other medications),
• if you have difficulty urinating,
• if you are diabetic,
• if you have experienced sudden increases in blood pressure, anxiety, excessive sweating, chills, stabbing headaches, and abnormally slow heart rate due to overstimulation of your nervous system caused by a full bladder or bowel, skin irritation, and pain,
• if you have suffered a head injury: in patients with spasticity due to a head injury, it is recommended not to initiate long-term therapy with Lioresal via intrathecal until the spasticity symptoms are stable (i.e., at least one year after the injury),
• it is essential to closely monitor cardiovascular function during the initial testing phase, especially if you have respiratory or cardiac problems,
• before undergoing any surgical intervention (including dental procedures) or emergency treatment, inform your doctor that you are receiving Lioresal via intrathecal.

If you are in any of these circumstances, inform your doctor before starting Lioresal via intrathecal.

After the pump implantation, you will be closely monitored in a well-equipped environment with trained personnel during the testing and dosage selection phase. Regular assessments of adverse effects or suspected infections will be performed according to your needs. The system's functioning will be periodically evaluated. It is essential to check for any problems with the pump.

Consult your doctor immediatelyif you experience any of the following symptoms during treatment with Lioresal intrathecal:

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

Children and adolescents

Lioresal intrathecal formulation is indicated for children aged 4 years or older.

It is not recommended to use Lioresal via intrathecal in children under 4 years old.

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

Lioresal via intrathecal administration in the pediatric population should only be performed by specialized doctors.

Older adults

During clinical trials, some patients over 65 years old were treated with intrathecal baclofen without observing specific problems. However, experience with baclofen tablets indicates that this age group may be more prone to adverse effects. Therefore, it is essential to closely monitor older adults for the appearance of adverse effects.

Using Lioresal with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

The simultaneous treatment of Lioresal via intrathecal requires special attention in the following cases:

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

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

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

Using Lioresal with food, drinks, and alcohol

Avoid drinking alcohol during treatment with Lioresal, as this may lead to undesirable intensification or unpredictable changes in the medication's effects.

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 no data or these are limited regarding the use of baclofen in pregnant women.

Your doctor will evaluate the possible risk of using Lioresal via intrathecal during pregnancy.

As a precaution, it is preferable to avoid using Lioresal via intrathecal during pregnancy.

Breastfeeding

Lioresal via intrathecal passes in very small amounts into breast milk.

No adverse effects are expected in infants/young children since systemic exposure to baclofen in lactating mothers is insignificant. You can breastfeed your child if your doctor allows it and always monitor the child for possible adverse 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 operating machinery

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

Lioresal contains sodium

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

Only a specially qualified doctor can administer Lioresal intrathecally.

Lioresal administered intrathecally is only given in the hospital through a pump placed under the skin of the abdomen. It can only be administered in the spinal canal (intrathecally). It should 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 testing phase, the appropriate dose of Lioresal for this chronic phase will have been determined. For the prior testing phase, another presentation 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 an appropriate 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 for 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 being emptied. The refill should always be done in aseptic conditions to prevent possible microbial contamination.

It is very important that your doctor monitors the pump's functioning during regular visits.

It is essential to maintain scheduled visits for pump refills, as if you do not, your muscle spasms could reappear due to not receiving a sufficient dose of Lioresal.As a result, muscle spasticity may not improve and could 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 muscle spasticity does not improve or if you start experiencing muscle spasms again, either gradually or suddenly,contact your doctor immediately..

If you are administered more Lioresal intrathecally than you should

You could experience an overdose. It is very important that you and your caregivers are able to recognize the symptoms of an overdose. These could appear suddenly, or slowly because the pump is not functioning correctly.

Themainsymptoms of an overdose are:

- excessive muscle weakness (too low muscle tone),

- drowsiness,

- dizziness or vertigo,

- excessive salivation,

- nausea or vomiting,

- difficulty breathing,

- convulsions,

- loss of consciousness,

- abnormal decrease in body temperature,

- rapid heart rate (tachycardia),

- ringing in the ears (tinnitus).

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

If you interrupt treatment with Lioresal by intrathecal administration

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

The abrupt interruption or reduction of Lioresal intrathecal dose can cause withdrawal symptoms that in some cases have been fatal. It is very important that you and your caregivers are able to recognize the withdrawal symptoms of Lioresal intrathecal. These can appear suddenly, or slowly due to, for example, pump battery problems, catheter problems, alarm malfunction, or device malfunction.

Therefore:

• Attend scheduled regular visits with your doctor for pump refills.
• Do not stop taking Lioresal suddenly.

Withdrawal symptoms are:

- severe and uncontrolled muscle spasms (too high muscle tone),

- difficulty moving muscles,

- rapid heart rate (tachycardia),

- low blood pressure,

- numbness or tingling in your hands or feet,

- anxiety,

- high fever,

- altered mental states such as agitation, confusion, hallucinations, abnormal behavior or thought, or convulsions.

- persistent and painful erection of the penis (priapism)

- infection (sepsis)

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

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

Like all medications, this medication may have adverse effects, although not all people may experience them.

Adverse effects occur more frequently at the beginning of treatment during your stay in the hospital, but they may 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 severe

If you experience any of the adverse effects listed below, inform your doctor immediately:

• malfunction of the implanted device or infusion system that may cause withdrawal symptoms including death (see “If you interrupt treatment with Lioresal by intrathecal route”)
• suicidal thoughts or attempts,
• confusion, disorientation,
• extreme feeling of happiness (euphoria),
• mood changes or mental changes (paranoia),
• feeling of sadness,
• muscle coordination dysfunction (ataxia),
• hallucinations (seeing or hearing things that are not real),
• blurred vision, visual disturbances,
• shortness of breath or abnormally slow or difficult breathing,
• neumonia,
• fever,
• sedation and lethargy (excessive drowsiness),
• low blood pressure (hypotension),
• high blood pressure (hypertension),
• seizures,
• abnormal muscle tone.

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

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

• drowsiness,
• abnormal muscle tone.

If you experience any of the mentioned effects severely,inform your doctor.

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

• feeling of sadness,
• sensation of anxiety,
• sedation or fatigue (exhaustion),
• dizziness or vertigo,
• headache,
• tingling in hands and feet,
• insomnia,
• blurred vision, visual disturbances, double vision,
• low blood pressure,
• neumonia,
• agitated or very slow breathing or breathing difficulties,
• weakness, sedation, fatigue,
• pain,
• abnormal muscle tone,
• dry mouth,
• skin rash or itching,
• swelling of ankles, feet, lower legs, facial swelling,
• 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 mentioned effects severely,inform your doctor.

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

• suicidal thoughts, attempts,
• hallucinations (seeing or hearing things that are not real),
• mood changes or mental changes (paranoia),
• extreme feeling of happiness (euphoria),
• abnormal muscle coordination (ataxia),
• abnormal decrease in body temperature,
• memory disorders,
• continuous and uncontrolled eye movements,
• unusually slow heart rate,
• 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 pump release system.

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 by intrathecal route than you should”.

Reporting adverse effects:

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

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

Do not use this medication 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 disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medication that you no longer need. This will help protect the environment.

Composition of Lioresal 0.5 mg/ml solution for intrathecal infusion

• The active ingredient is baclofen. Each ampoule of 20 ml 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 injection.

Aspect of the product and content of the package

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

Holder of the Marketing Authorization

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes 764

08013 Barcelona

Spain

Responsible for manufacturing

Novartis Pharma GmbH

Roonstrasse 25

90429 Nürnberg

Germany

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

Spain

Last review date of this prospectus: August 2024

The detailed and updated information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es

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This information is intended solely for healthcare professionals: Consult the technical file for more details on the medication, its dosage and administration.

Dosage

Recommended dose:

Test phase:

Adults

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

Pediatric population

The initial lumbar puncture in 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 an increase in dose of 25 micrograms every 24 hours. The maximum test dose should not exceed 100 micrograms/day in pediatric patients.

Dose determination phase:

The initial daily dose of Lioresal intrathecal that should be administered through the pump is determined by doubling the effective dose in the test phase and administering it for a period of 24 hours. If the effect of the test dose has been maintained for more than 12 hours, the initial dose should be the same as the test dose but administered for a period of 24 hours. No dose increases should be made during the first 24 hours of treatment. After the first 24 hours, the dose will be adjusted daily to achieve the desired clinical effect. Experience is limited with doses above 1000 micrograms/day.

Maintenance phase:

The minimum dose required to achieve an adequate response should be used. Many patients need gradual increases in dose to maintain optimal response during chronic therapy due to reduced response to treatment or progression of the disease.

Preparation and handling of the product

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

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

To patients who require concentrations other than 50 micrograms/ml, 500 micrograms/ml or 2000 micrograms/ml, Lioresal Intratecal must be diluted, in aseptic conditions, with sterile sodium chloride for injection without preservatives.

As a general rule, ampoules of Lioresal 0.5 mg/ml 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 infusion system, which is an implantable drug delivery system with refillable reservoirs, which, after general or local anesthesia, are implanted in a subcutaneous cavity, usually in the abdominal wall.

This device is connected to an intrathecal catheter that passes subcutaneously to the subarachnoid space. Further details can be obtained from its 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 Intratecal has been shown to be stable in the SynchroMed infusion system for 11 weeks. No stability data are available for Lioresal Intratecal when other infusion systems are used.