Lioresal 0.5 mg/ml solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Lioresal 0.5 mg/ml solution for infusion

baclofen

Read all of this leaflet carefully before you are given 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, ask your doctor or pharmacist.

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

Contents of the 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. How to store Lioresal 0.5 mg/ml solution for infusion
6. Contents of the pack and other information

1. What Lioresal 0,5 mg/ml infusion solution is and what it is used for

The active substance of Lioresal is baclofen.

Lioresal for intrathecal use is used in adults and children aged 4 years and older to reduce and relieve excessive muscle stiffness (spasms) caused by certain conditions such as cerebral palsy, multiple sclerosis, stroke, spinal cord diseases, and certain disorders of the nervous system.

Due to muscle relaxation and the resulting relief of pain, Lioresal improves mobility, helps patients become more independent in daily activities, and facilitates physiotherapy.

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

The ampoules contain a solution that is injected or infused into the back (around the spinal cord) by means of a special pump implanted under the skin of the abdomen. The medication is continuously delivered to the spinal cord through a thin tube.

2. What you need to know before Lioresal 0.5 mg/ml solution for infusion is administered to you

Do not be administered Lioresal by intrathecal route:

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

Warnings and precautions

Seek urgent medical help if you notice that your implanted device is not working and you experience any withdrawal symptoms (see “If you interrupt treatment with Lioresal by intrathecal route”).

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

• • any infection,
  • reduced circulation of the fluid surrounding the brain and spinal cord due to an obstruction in its flow caused, for example, by inflammation or injury,
  • inadequate blood flow to the brain (cerebrovascular insufficiency),
  • acute or chronic confusional states,
  • a psychotic disorder or schizophrenia (mental illness),
  • Parkinson’s disease,
  • epilepsy (seizures),
  • any history of heart problems,
• if you have acute stomach (ulcer) or intestinal pain, breathing difficulties, liver disease, or disorders of cerebral circulation,
• if you have kidney disease. Your doctor will decide whether Lioresal is the appropriate 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 medicines),
• if you have difficulty urinating,
• if you are diabetic,
• if you have experienced sudden high blood pressure, anxiety, excessive sweating, chills, severe headaches, or abnormally slow heart rate due to overstimulation of your nervous system caused by a full bladder or bowel, skin irritation, or pain,
• if you have suffered a head injury: in patients with spasticity due to head injury, long-term intrathecal Lioresal therapy should not be initiated until spasticity symptoms are stable (i.e., at least one year after the injury),
• it is essential to closely monitor cardiorespiratory 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 the doctor that you are receiving intrathecal Lioresal.

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

After pump implantation, you will be closely monitored in a properly equipped setting with trained personnel during the test phase and dose selection. You will undergo regular assessments for adverse effects or suspected infections as needed. The system’s function will be evaluated periodically. It is important to ensure there are no problems with the pump.

Contact your doctor immediately if you experience any of the following symptoms during treatment with intrathecal Lioresal:

• back, shoulder, neck, or buttock pain during treatment (a type of spinal deformity called scoliosis).
• if at any time you think about harming yourself or suicide, speak to your doctor or go to a 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

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

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

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

Administration of intrathecal Lioresal in the pediatric population should only be performed by specialist physicians.

Elderly patients

During clinical trials, some patients over 65 years of age were treated with intrathecal baclofen without specific problems being observed. However, experience with baclofen tablets indicates that this patient group may be more prone to adverse effects. Therefore, elderly patients should be carefully monitored for the emergence of adverse effects.

Use of Lioresal with other medicines

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

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

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

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

Your doctor may decide to adjust the dose, temporarily discontinue one of the medications, or take other precautions if necessary.

Use of Lioresal with food, beverages, and alcohol

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

Pregnancy

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

Your doctor will assess the potential risk of using intrathecal Lioresal during pregnancy.

As a precautionary measure, it is preferable to avoid the use of intrathecal Lioresal during pregnancy.

Breastfeeding

Intrathecal Lioresal passes into breast milk in very small amounts.

No effects are expected in breastfed infants, as systemic exposure to baclofen in breastfeeding mothers is negligible. You may breastfeed your baby if your doctor allows it, while closely monitoring the infant for possible adverse effects.

Baclofen may reduce breast milk production if used long-term.

Fertility

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

Driving and use of machines

Intrathecal Lioresal may cause drowsiness, dizziness, vision problems, clumsiness, or instability in some people. If this happens to you, do not drive or operate dangerous tools or machinery.

Lioresal contains sodium

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

3. How to use Lioresal 0.5 mg/ml solution for infusion

Only a specially qualified physician may administer Lioresal intrathecally.

Lioresal for intrathecal use is administered exclusively in a hospital setting via an implanted pump placed under the skin of the abdomen. It must only be administered into the spinal canal (intrathecal route). It must not be administered intravenously, intramuscularly, epidurally, or subcutaneously.

Lioresal is intended for chronic administration by intrathecal infusion via a continuous-delivery pump implanted in the abdomen. Prior to chronic administration, a test phase will have determined the appropriate Lioresal dose for this long-term phase. For the preliminary test phase, another formulation of Lioresal (Lioresal 0.05 mg/ml) is used, administered as a single bolus dose via an intrathecal spinal catheter or lumbar puncture. Determining the appropriate dose for you may take several days under medical supervision.

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

After the pump is implanted, the reservoir must be monitored regularly to prevent it from becoming empty. Refilling must always be performed under sterile conditions to avoid possible microbial contamination.

It is very important that your doctor regularly monitors the proper functioning of the pump.

You must keep all scheduled appointments for pump refills, because if you do not, your muscle spasms may return due to insufficient Lioresal dosing.

As a result, muscle spasticity may fail to improve or even worsen.

The duration of treatment will be determined by your doctor. During long-term treatment, some patients may experience a gradual decrease in baclofen efficacy. Your doctor may recommend occasional treatment breaks to counteract this effect.

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

If you receive more intrathecal Lioresal than prescribed

You may experience an overdose. It is very important that you and your caregivers are able to recognize the symptoms of overdose. These may appear suddenly or gradually due to improper pump function.

Main symptoms of overdose include:

• Excessive muscle weakness (muscle tone too low),
• Somnolence,
• Dizziness or vertigo,
• Excessive salivation,
• Nausea or vomiting,
• Difficulty breathing,
• Seizures,
• Loss of consciousness,
• Abnormally low 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 intrathecal Lioresal

If you need to discontinue treatment with this medication for any reason, your doctor will gradually reduce your dose to avoid withdrawal effects.

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

For this reason:

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

Withdrawal symptoms include:

• Severe, uncontrolled muscle spasms (muscle tone too high),
• Difficulty performing muscular movements,
• Rapid heart rate (tachycardia),
• Low blood pressure,
• Numbness or tingling in hands or feet,
• Anxiety,
• High fever,
• Altered mental status such as agitation, confusion, hallucinations, abnormal thoughts or seizures,
• Persistent and painful penile erection (priapism),
• Infection (sepsis).

If you experience any of the above symptoms, seek medical attention immediately. These symptoms may progress to more serious adverse effects (including death) if not treated promptly.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Adverse effects occur more frequently at the beginning 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 experience any of the adverse effects listed below, inform your doctor immediately:

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

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

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

• drowsiness,
• muscle tone too low.

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

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

• feeling of sadness,
• anxiety,
• sedation or exhaustion (tiredness),
• dizziness or vertigo,
• headache,
• tingling in hands and feet,
• insomnia,
• blurred vision, visual disturbances, double vision,
• low blood pressure,
• pneumonia,
• rapid or very slow breathing or breathing difficulties,
• weakness, sedation, fatigue,
• pain,
• muscle tone too high,
• 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 above effects severely, inform your doctor.

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

• suicidal thoughts, suicide attempts,
• hallucinations (seeing or hearing things that are not real),
• mood or mental changes (paranoia),
• feeling of extreme happiness (euphoria),
• impaired muscle coordination (ataxia),
• abnormally low body temperature,
• memory disturbances,
• continuous, uncontrolled eye movements,
• unusually slow heart rate,
• reduced sense of taste,
• difficulty swallowing,
• abdominal pain,
• hair loss,
• increased sweating.

Some adverse effects have unknown frequency:

• restlessness (agitation),
• 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 delivery system.

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

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

Reporting of adverse effects:

If you experience any adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaRAM.es. By reporting adverse effects, you can help provide 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 expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Store below 30°C. Do not freeze.

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

6. Contents of the pack and other information

Composition of Lioresal 0.5 mg/ml solution for intrathecal infusion

• The active substance is baclofen. Each 20 ml vial 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 injections.

Appearance of the product and contents of the pack

Lioresal 0.5 mg/ml is presented as a clear, colourless solution for intrathecal infusion.

Each pack contains 1 vial.

Other presentations

Lioresal 2 mg/ml solution for infusion. Pack with 1 vial

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

Marketing Authorization Holder

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes 764

08013 Barcelona

Spain

Manufacturer

Novartis Farmacéutica, S.A.
Gran Vía de les Corts Catalanes, 764
08013 Barcelona
Spain

Date of the most recent review of this leaflet: August 2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS): http://www.aemps.gob.es

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This information is intended for healthcare professionals only: Refer to the Summary of Product Characteristics for further details on the medicinal product, its posology, and administration.

Posology

Recommended dose:

Test phase:

Adults

In adults, the initial test dose is 25 or 50 micrograms, which may be increased by 25 micrograms every 24 hours until a response lasting approximately 4–8 hours is observed. The dose will be administered via pump over at least 1 minute. Ampoules containing 0.05 mg/mL are available for this test dose.

Pediatric population

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

Dose determination phase:

The initial daily dose of Lioresal Intrathecal to be administered via pump is determined by doubling the effective test dose and administering it over a 24-hour period. If the effect of the test dose lasted longer than 12 hours, the initial dose should be the same as the test dose, administered over a 24-hour period. Dose increases should not be made during the first 24 hours of treatment. After the first 24 hours, the dose should be adjusted gradually on a daily basis until the desired clinical effect is achieved. Experience with doses exceeding 1000 micrograms/day is limited.

Maintenance phase:

The lowest effective dose achieving an adequate response should be used. Many patients require gradual dose increases to maintain an optimal response during chronic therapy, due to diminished response to treatment or disease progression.

Preparation and handling of the product

Lioresal Intrathecal is intended for intrathecal injection and continuous infusion, as specified by the infusion system manufacturer's instructions.

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

For patients requiring concentrations other than 50 micrograms/mL, 500 micrograms/mL, or 2000 micrograms/mL, Lioresal Intrathecal must be diluted under aseptic conditions with sterile, preservative-free sodium chloride for injection.

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 occurring with baclofen.

Administration devices

Various delivery systems have been used for prolonged intrathecal administration of Lioresal. These include the Medtronic SynchroMed® Programmable Infusion System, an implantable drug delivery system with refillable reservoirs, implanted under general or local anesthesia into a subcutaneous cavity, usually in the abdominal wall.

This device is connected to an intrathecal catheter that runs subcutaneously into the subarachnoid space. Further details are available from the manufacturer.

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

Each ampoule is intended for single use only. Any unused portion should be discarded. Do not freeze. Do not sterilize by heat.

Stability

Lioresal Intrathecal has been shown to be stable in the SynchroMed® Programmable Infusion System for 11 weeks. Stability data for Lioresal Intrathecal in other infusion systems are not available.