Package Insert: Information for the User

Lioresal 0.05 mg/ml Injectable Solution

baclofen

Read this entire package insert carefully before this medicine is administered to you, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Lioresal 0.05 mg/ml Injectable Solution and what it is used for

2. What you need to know before Lioresal 0.05 mg/ml Injectable Solution is started

3. How to use Lioresal 0.05 mg/ml Injectable Solution

4. Possible side effects

5. Storage of Lioresal 0.05 mg/ml Injectable 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 by the intrathecal route:

• if you are allergic to baclofen or to 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 symptoms of withdrawal (see “If you interrupt treatment with Lioresal by the intrathecal route”).

Consult your doctor or pharmacist before Lioresal by the intrathecal route is started if you have:

• • any infection,
  • a reduced circulation of the fluid that contains the brain and spinal cord as a result of an obstruction to its passage caused, for example, by inflammation or injury,
  • inadequate blood flow to the brain (cerebrovascular insufficiency),
  • acute or chronic confusion states,
  • psychotic disorder or schizophrenia (mental illness),
  • if you haveparkinson's disease,
  • if you suffer from epilepsy (seizures),
  • if you have ever had heart problems,
• if you have acute stomach or intestinal pain(ulcer) orproblems with breathing, 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 for 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, stabbing headaches, and abnormally slow heart rate due to overstimulation of your nervous system caused by having 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 by the intrathecal route until the symptoms of spasticity 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) or emergency treatment, inform your doctor that you are receiving Lioresal by the intrathecal route.

If you are in any of these circumstances, inform your doctor before Lioresal by the intrathecal route is started.

After the pump is implanted, you will be closely monitored in an equipped environment with trained personnel during the testing and dosage selection phase. Regular assessments of adverse effects or suspected infections will be made according to your needs. The system's function will be periodically evaluated. It is essential to check that there are no problems with the pump.

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

• if you have back, shoulder, neck, and buttock pain during treatment (a type of spinal deformity 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 in children aged 4 years or older.

The use of Lioresal by the intrathecal route is not recommended in children under 4 years.

Children must have sufficient body mass to be able to implant the infusion pump.

Lioresal by the intrathecal route should only be administered in pediatric populations by specialist doctors.

Older adults

During clinical trials, some patients over 65years old were treated with intrathecal baclofen without observing specific problems. However, experience with baclofen tablets indicates that this group of patients may have a higher tendency to experience adverse effects. Therefore, patients over 65 years old should be closely monitored to rule out the occurrence of adverse effects.

Use of 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 Lioresalby the intrathecal routerequires special attention in the following cases:

• other medications for treating muscle spasms
  if possible, your doctor will gradually discontinue other medications for treating muscle spasms
• medications for treating depression,
• medicationsthat reduce blood pressure, including medicationsfor treating high blood pressure (hypertension),
• levodopa, carbidopa: medications for treating Parkinson's disease,
• strong 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,
• do not recommend the administration of 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.

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, or if you think you may be 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 by the intrathecal route during pregnancy.

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

Breastfeeding

Lioresal by the intrathecal route 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 the possible appearance of adverse effects.

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

Fertility

Studies in animals have shown that intrathecal baclofen is unlikely to produce adverse effects on fertility.

Driving and operating machinery

Lioresal by the intrathecal route 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 less than 1 mmolof sodium (23 mg) per ampoule (1 ml); this is essentially “sodium-free”.

If your doctor needs to dilute Lioresal with a saline solution, the sodium dose received would be higher.

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, the Lioresal 0.05 mg/ml presentation is used, which is administered in a single bolus via 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 that you maintain regular visits for the pump refill, 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,

- abnormally low body temperature,

- rapid heart rate (tachycardia),

- ringing in the ears (tinnitus).

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

If you interrupt the treatment with Lioresal intrathecally

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, battery problems, catheter problems, alarm malfunction, or device malfunction.

Therefore :

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

The 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 can 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 medicines, this medicine may cause side effects, although not everyone will experience them.,.

Side effects occur more frequently at the beginning of treatment during your stay in the hospital, but they may also occur later. Many of these side effects are associated with the medical condition for which you are being treated.

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

Some side effects can be serious

If you experience any of the side 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 side effects,inform your doctor immediately.

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

• drowsiness,
• abnormal muscle tone.

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

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

• feeling of sadness,
• feeling 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 side effects severely,inform your doctor.

Some side 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,
• uncontrolled and continuous eye movements,
• unusually slow heart rate,
• decreased sense of taste,
• difficulty swallowing,
• abdominal pain,
• hair loss,
• increased sweating.

Some side 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 side effects may be related to the pump delivery 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 side effects:

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

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 drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Lioresal 0.05 mg/ml injectable solution

• The active ingredient is baclofen. Each ampoule of 1 ml contains 0.05 mg of baclofen. Each ml contains 0.05 mg (50 micrograms) of baclofen.
• The other components (excipients) are: sodium chloride and water for injection preparations.

Appearance of the product and contents of the package

Lioresal 0.05 mg/ml is presented in the form of a clear and colorless solution for bolus administration.

Each package contains 5 ampoules.

Other presentations

Lioresal 0.5 mg/ml infusion solution. Package with 1 ampoule

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

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 leaflet:August 2024

The detailed and updated information on 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 data sheet for more details on the medication, its dosage, and administration method.

Dosage

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 is observed that lasts approximately 4-8 hours. The dose will be administered 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 intratecal to 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 1,000 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 2,000 micrograms/ml, Lioresal Intratecal must be diluted, in aseptic conditions, with sterile sodium chloride for injection and free of preservatives.

As a general rule, Lioresal 0.05 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 infusion pump 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 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 Intratecal has been shown to be stable in the SynchroMed infusion pump system for 11 weeks. No stability data are available for Lioresal Intratecal when using other infusion systems.