Lioresal intrathecal 0.05 mg/1 ml

Patient Information Leaflet

Lioresal Intrathecal 0.05 mg/1 ml solution for injection
For use in adult patients and children aged 4 years and older
baclofen
Please read this leaflet carefully before using this medicine, as 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.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet Contents

1. What Lioresal Intrathecal is and what it is used for
2. What you need to know before using Lioresal Intrathecal
3. How to use Lioresal Intrathecal
4. Possible side effects
5. How to store Lioresal Intrathecal
6. Contents of the pack and other information

1. What Lioresal Intrathecal is and what it is used for

Lioresal Intrathecal contains the active substance baclofen. Lioresal Intrathecal is a medicine used to treat
excessive muscle stiffness.
Lioresal Intrathecal is used to test the response to intrathecal administration of baclofen in patients
with severe, chronic spasticity (increased muscle tone) that cannot be effectively managed with
standard treatments:

• in multiple sclerosis – a progressive neurological disease affecting the brain and spinal cord, with physical and mental symptoms
• following spinal cord injury or brain injury
• in other spinal cord disorders

If there is no improvement or if the patient feels worse, consult a doctor.

2. Important information before using Lioresal Intrathecal

When not to use Lioresal Intrathecal

• 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 their doctor.
• if the patient has treatment-resistant epilepsy.

Warnings and precautions
If any of the following apply to the patient, they must inform their doctor or
pharmacist before starting treatment with Lioresal Intrathecal:

• disturbances in cerebrospinal fluid circulation due to flow obstruction
• treatable epilepsy or other convulsive seizures involving the brain
• neurological disorders caused by damage to cranial nerves in the medulla oblongata (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 hyperreflexia (uncontrolled)
• insufficient blood flow to the brain
• breathing difficulties
• bladder sphincter hyperactivity
• heart diseases
• kidney function disorders
• stomach and intestinal ulcers
• severe liver function impairment
• increased muscle tone caused by previous head injury. Long-term treatment of increased muscle tone should be initiated only when spasticity symptoms are stable and can be reliably assessed.
• infection. Before administering a test dose of Lioresal Intrathecal, ensure the patient does not have an infection, as this may interfere with assessing the patient's response.

If any of the following symptoms occur during treatment with Lioresal Intrathecal, the patient must
inform their doctor immediately:

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

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

Patients over 65 years of age
In clinical trials, Lioresal Intrathecal was administered to several elderly patients and did not cause specific problems. However, experience with oral Lioresal tablets shows that this patient group may be more susceptible to adverse reactions. Therefore, elderly patients should be closely monitored for adverse effects.

Lioresal Intrathecal and other medicines
The patient must inform their doctor or pharmacist about all medicines they are currently taking,
have recently taken, or plan to take.
The following medicines may affect the action of Lioresal Intrathecal or Lioresal Intrathecal may
affect them. Dose adjustments of Lioresal Intrathecal or one of the other concomitantly used medicines may be necessary:

• medicines used in Parkinson's disease
• medicines used to relieve severe muscle spasms
• medicines with central nervous system depressant effects
• medicines used to treat depression, such as imipramine, doxepin, amitriptyline, opipramol
• medicines that lower blood pressure, including those used to treat high blood pressure

Lioresal Intrathecal and alcohol
When using Lioresal Intrathecal, the patient should avoid consuming alcohol simultaneously, as this may
cause undesirable, intensified, or unpredictable effects of the medicine.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor before using this medicine.
Due to lack of experience, pregnant and breastfeeding women may use Lioresal Intrathecal
only if the doctor considers it absolutely necessary.

Driving and operating machinery
The patient must not drive, operate machinery or perform other hazardous activities, as Lioresal Intrathecal may significantly impair the ability to perform such tasks.

Lioresal Intrathecal contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per 1 ml, meaning the medicine is considered "sodium-free".
If the doctor needs to dilute Lioresal Intrathecal 0.05 mg/1 ml with physiological saline solution,
the resulting sodium content will be higher.

3. How to use Lioresal Intrathecal

This medicine should always be used as directed by the physician. If in doubt, consult the doctor or pharmacist.

Method of administration
Lioresal Intrathecal 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 physician will determine whether a single injection of undiluted Lioresal Intrathecal, solution for injection, relieves muscle spasms. The recommended dose is ½ to 1 vial. The dose may be increased by ½ vial every 24 hours, up to a maximum dose of 2 vials.
After each injection, the patient must be monitored for 4 to 8 hours.
If significant relief of muscle spasms is possible, a special pump will be implanted under the patient's skin. This will allow continuous administration of higher doses of Lioresal Intrathecal, solution for infusion. The dose will be individually adjusted for the patient.
Determining the optimal dose may take several days. After the optimal treatment has been established, the physician will regularly monitor treatment progress and pump function.

Inform the doctor immediately if there is no improvement in muscle spasms or if they recur.

Duration of treatment
The duration of treatment will be determined by the physician.

Use of a higher than recommended dose of Lioresal Intrathecal
Contact the doctor immediately if the patient or caregiver observes symptoms of overdose, which may occur suddenly or gradually:

• too little muscle tone
• drowsiness
• dizziness or feeling faint
• excessive salivation
• nausea or vomiting
• breathing difficulties or even respiratory arrest
• seizures
• reduced level of consciousness or even coma
• low body temperature
• rapid heartbeat (tachycardia)
• ringing in the ears (tinnitus)

Discontinuation of Lioresal Intrathecal
If discontinuation of the medication is necessary, it must be performed only by the treating physician, who will gradually reduce the dose to avoid adverse effects. Sudden discontinuation of Lioresal Intrathecal may cause severe adverse reactions, which in a few cases have resulted in death.

Contact the doctor immediately if the patient or caregivers notice the following symptoms of withdrawal from Lioresal Intrathecal. This is particularly important when further administration of the drug is via a pump.

• worsening spasticity, excessive muscle tone
• difficulty moving muscles
• rapid heartbeat (tachycardia)
• 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 more severe adverse reactions if treatment is not immediately initiated.

If you have any doubts regarding the use of this medicine, consult your doctor.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
Adverse reactions are more common when treatment is initiated in hospital, but they may also occur later.
Many of the adverse reactions listed below may also be related to the underlying disease being treated.
The following adverse reactions and their frequency of occurrence have been reported:

Very common: may affect more than 1 in 10 patients

• reduced muscle tone
• drowsiness

Common: may affect up to 1 in 10 patients

• anxiety
• decreased appetite
• shortness of breath, slow or shallow breathing
• reduced alertness
• decreased blood pressure when sitting or standing up
• depression
• disorientation
• diarrhoea and 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 sensations of the skin such as tingling in the hands and feet
• dry mouth
• muscle weakness
• stupor
• 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 patients

• decreased body fluids (dehydration)
• pale skin
• high blood pressure
• intestinal obstruction
• memory loss/distraction
• 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
• slow heart rate
• reduced sense of taste
• blockage of a blood vessel due to a deep vein thrombosis
• hallucinations
• euphoria

Rare: may affect up to 1 in 1,000 patients

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

Not known: frequency cannot be estimated from the available data

• progression of lateral curvature of the spine (scoliosis)
• inability to achieve or maintain erection (erectile dysfunction)
• allergic reaction (hypersensitivity)

* Adverse reactions marked with an asterisk occur more frequently in patients with cerebral palsy.

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

5. How to store Lioresal Intrathecal

Keep this medicine out of sight and reach of children.
Do not store above 30 °C.
Do not freeze. Do not sterilize by heat.
The medicine should be used immediately after opening. Any unused solution should be discarded.
The solution must be clear and colourless. Do not use this medicine if cloudiness or discolouration is observed.
Do not use this medicine after the expiry date stated on the ampoule and carton. The expiry date refers to the last day of the month indicated.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

• The active substance is baclofen. One ampoule containing 1 ml of injection solution contains 0.05 mg of baclofen.
• Other ingredients are: sodium chloride, water for injections.

What Lioresal Intrathecal looks like and contents of the pack
Lioresal Intrathecal is a clear, colourless solution in a transparent, colourless ampoule.
Lioresal Intrathecal 0.05 mg/1 ml solution for injection is available in packs containing 5 ampoules.

Marketing Authorisation Holder
Novartis Poland Sp. z o.o.
ul. Marynarska 15
02-674 Warsaw
tel.: +48 22 37 54 888

Manufacturer/Importer
Novartis Pharma GmbH
Roonstrasse 25
D-90429 Nuremberg
Germany
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Poland Sp. z o.o.
ul. Marynarska 15
02-674 Warsaw

This medicinal product has been authorised in the member states of the European Economic Area under the following names:
Germany: Lioresal Intrathecal 0.05 mg/1 ml Injektionslösung
Poland: Lioresal Intrathecal 0.05 mg/1 ml, solution for injection

Information intended exclusively for medical professionals:

How to prepare and administer the medicinal product Lioresal Intrathecal?
Administration of a test dose, implantation of an infusion pump, and dose escalation of the intrathecally administered medicinal product must be performed in a hospital setting, within centers with appropriate experience and under very close supervision of adequately qualified physicians. Immediate access to an intensive care unit must be ensured due to the possibility of severe or life-threatening adverse reactions associated with the medicinal product.

To determine the optimal dosing regimen for Lioresal Intrathecal, each patient must first receive a test dose of the medicinal product Lioresal Intrathecal 0.05 mg/1 ml administered intrathecally as a bolus injection via an intrathecal catheter or lumbar puncture prior to initiating long-term treatment. Subsequently, the dose must be carefully and individually titrated according to the patient's needs. This is necessary due to considerable inter-individual differences in therapeutically effective doses.

For long-term therapy, the medicinal product Lioresal Intrathecal 10 mg/20 ml or Lioresal Intrathecal 10 mg/5 ml is administered via an implanted pump, which enables continuous infusion of baclofen into the cerebrospinal fluid.

The efficacy of the medicinal product Lioresal Intrathecal has been demonstrated in clinical studies using the SynchroMed infusion system. This drug delivery system includes refillable reservoirs implanted subcutaneously in the patient (usually in the abdominal wall tissues). The device is also connected to an intrathecal catheter, which runs from the subcutaneous implantation site into the subarachnoid space. There is currently no experience with other implanted drug infusion systems.

Prior to administering Lioresal Intrathecal, a myelographic examination of the subarachnoid space should be performed in patients with post-traumatic spasticity. If radiological signs of meningitis are detected, treatment with Lioresal Intrathecal should not be initiated.

Before administering Lioresal Intrathecal, the solution should be inspected visually for clarity and colorlessness. The medicinal product must not be administered if the solution is cloudy or discolored.

Each ampoule is intended for single use only. The solution contained therein is stable, isotonic, pyrogen-free, and contains no antioxidants, with a pH of 5.0–7.0.

Test dose (in a hospital setting).
Prior to initiating long-term infusion of Lioresal Intrathecal, the patient's response to baclofen should first be assessed during a test phase. For this purpose, the medicinal product Lioresal Intrathecal 0.05 mg/1 ml is used. The test dose is usually administered undiluted via an intrathecal catheter or lumbar puncture. The initial test dose typically ranges from 25 micrograms to 50 micrograms of baclofen, corresponding to the content of ½ to 1 ampoule of Lioresal Intrathecal 0.05 mg/1 ml. In children, the recommended test dose is 25 micrograms. The dose should be administered by mixing it with cerebrospinal fluid (CSF) (barbotage) over 1 minute (or longer). The dose may be increased at intervals of at least 24 hours by increments of 25 micrograms, up to a maximum test dose of 100 micrograms, as follows:

After each injection (bolus), the patient should remain under observation for 4 to 8 hours.
The effect of a single intrathecal dose usually begins within ½ to 1 hour after administration.
The maximum spasmolytic effect is typically observed 4 hours after administration of the medicinal product and lasts for approximately 4 to 8 hours. The onset of action, maximum effect, and duration of action may vary between individual patients and depend on the dose, severity of symptoms, and method and speed of solution administration. A clinically significant reduction in muscle tone and/or a decrease in the frequency or intensity of spasms must be documented to consider that the patient is responding to treatment. If administration of a test dose equal to the content of 2 vials of Lioresal Intrathecal 0.05 mg/1 ml (corresponding to 100 micrograms of baclofen) is insufficient, the dose should not be further increased, and transition to continuous intrathecal infusion should not be performed.
Tolerance to the test dose may vary among individual patients. In the past, overdose symptoms (coma) occurred in one patient after administration of a single test dose of 25 micrograms of baclofen; therefore, treatment must be initiated exclusively in a hospital setting with immediate access to intensive medical care.

Pharmaceutical incompatibilities
The medicinal product Lioresal Intrathecal 0.05 mg/1 ml injection solution must be administered undiluted.
A chemical incompatibility between dextrose and baclofen has been demonstrated.
Do not freeze. Do not sterilize at high temperature.