Lioresal intrathecal 10 mg/20 ml

Patient Information Leaflet

Keep this leaflet! The labelling on the immediate packaging is in a foreign language.
Lioresal Intrathecal 10 mg/20 ml, solution for infusion
For use in adults and children aged 4 years and older
Baclofen
Please read this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, please consult 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 adverse reactions, including any possible side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Lioresal Intrathecal 10 mg/20 ml is and what it is used for
2. Important information before using Lioresal Intrathecal 10 mg/20 ml
3. How to use Lioresal Intrathecal 10 mg/20 ml
4. Possible side effects
5. How to store Lioresal Intrathecal 10 mg/20 ml
6. Contents of the pack and other information

1. What Lioresal Intrathecal 10 mg/20 ml is and what it is used for

Lioresal Intrathecal 10 mg/20 ml contains the active substance baclofen.
Lioresal Intrathecal 10 mg/20 ml is a medicine used to treat excessive muscle stiffness.
Lioresal Intrathecal 10 mg/20 ml is used in the treatment of severe, chronic spasticity
(increased muscle tone) that cannot be effectively managed with standard medications:

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

During the patient qualification phase and the dose escalation phase, immediately after pump implantation, the patient will be closely monitored under conditions ensuring access to appropriate equipment and medical staff. The dosage, possible adverse effects or signs of infection will be regularly assessed. The functioning of the drug delivery system will also be checked.
If no improvement occurs or if the patient feels worse, consult your doctor.

2. Important information before using Lioresal Intrathecal 10 mg/20 ml

When not to use Lioresal Intrathecal 10 mg/20 ml

• if the patient is allergic to baclofen or any of the other ingredients of this medicine (listed in section 6). If the patient thinks they may be allergic, they should consult a doctor

• if the patient has treatment-resistant epilepsy.

Warnings and precautions
Consult a doctor immediately if the patient thinks the device is not working properly or if they notice symptoms of withdrawal (see symptoms of discontinuation in section 3 “How to use Lioresal Intrathecal 10 mg/20 ml”).
If any of the following apply to the patient, they must inform their doctor before starting treatment with Lioresal Intrathecal 10 mg/20 ml:

• disturbances in cerebrospinal fluid circulation due to flow obstruction
• treatable epilepsy or other convulsive seizures involving the brain
• neurological disorders caused by cranial nerve damage in the medulla oblongata (bulbar palsy symptoms) 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
• gastric 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.

If any of the following symptoms occur during treatment with Lioresal Intrathecal 10 mg/20 ml, inform the doctor immediately:

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

Children
In children, certain requirements regarding appropriate body weight must be met to allow implantation of the infusion pump. Lioresal Intrathecal 10 mg/20 ml is intended for use in children aged 4 years and older. The safety of intrathecal administration of Lioresal Intrathecal 10 mg/20 ml in children under 4 years of age has not yet been established.

Patients over 65 years of age
During clinical trials, Lioresal Intrathecal 10 mg/20 ml 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 effects. Therefore, elderly patients should be closely monitored for the occurrence of adverse effects.

Lioresal Intrathecal 10 mg/20 ml and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
The following medicines may affect the action of Lioresal Intrathecal 10 mg/20 ml, or Lioresal Intrathecal 10 mg/20 ml may affect them. Dose adjustment of Lioresal Intrathecal 10 mg/20 ml or one of the other concomitantly used medicines may be necessary:

• medicines used in Parkinson’s disease
• medicines relieving severe muscle spasms
• medicines with central nervous system depressant effects
• medicines used in the treatment of depression, such as imipramine, doxepin, amitriptyline, opipramol
• medicines used to treat high blood pressure.

Lioresal Intrathecal 10 mg/20 ml with food, drink and alcohol
Alcohol should be avoided when using Lioresal Intrathecal 10 mg/20 ml, as it may cause undesirable intensification or unpredictable changes in the drug's effects.

Pregnancy and breastfeeding
Due to lack of experience, women who are pregnant or breastfeeding should use Lioresal Intrathecal 10 mg/20 ml only if the doctor considers it absolutely necessary.

Driving and operating machinery
Do not drive, operate machinery or perform other hazardous activities, as Lioresal Intrathecal 10 mg/20 ml may significantly affect these abilities.

Lioresal Intrathecal 10 mg/20 ml contains sodium
This medicine contains 70.81 mg of sodium (the main component of table salt) per 20 ml. This corresponds to 3.5% of the maximum recommended daily dietary sodium intake for adults.

3. How to use Lioresal Intrathecal 10 mg/20 ml

This medicine should always be used exactly as prescribed by the doctor. In case of doubt, consult the doctor or pharmacist.
Available on the market are: Lioresal Intrathecal 10 mg/5 ml, Lioresal Intrathecal 10 mg/20 ml.
Method of administration
Lioresal Intrathecal 10 mg/20 ml 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 doctor will determine whether a single injection of a lower dose of the medicine – Lioresal Intrathecal 0.05 mg/1 ml, solution for injection – will relieve muscle spasms. If possible, a special pump will be implanted under the patient's skin, which will allow continuous, patient-adjusted dosing.
It is very important that the patient attends scheduled appointments during which the doctor refills the pump .
If the patient receives too low a dose of Lioresal Intrathecal 10 mg/20 ml, increased muscle tone may return. Muscle spasms may also worsen.
Contact the doctor immediately if there is no relief from muscle spasms or if they recur.
The doctor must regularly monitor the patient's condition and pump function—at least once a month.
Duration of treatment
The duration of treatment will be determined by the doctor.
Use of a higher than recommended dose of Lioresal Intrathecal 10 mg/20 ml
Contact the doctor immediately if the patient or caregiver notices symptoms of overdose, which may occur suddenly or gradually:

• too low muscle tone
• drowsiness
• dizziness or feeling faint
• excessive salivation
• nausea or vomiting
• breathing difficulties or even respiratory arrest
• seizures
• reduced consciousness or even coma
• low body temperature

Discontinuation of Lioresal Intrathecal 10 mg/20 ml
If discontinuation of the medicine is necessary, it must be done only by the treating physician, who will gradually reduce the dose to avoid adverse effects. Sudden discontinuation of Lioresal Intrathecal 10 mg/20 ml may cause severe adverse reactions, which in some cases have resulted in death.
Contact the doctor immediately if the patient or caregivers notice the following symptoms of discontinuation of Lioresal Intrathecal 10 mg/20 ml. This is particularly important for continued administration via pump.

• worsening spasticity, excessive muscle tone
• difficulty moving muscles
• increased heart rate and faster pulse
• 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, which may be fatal if treatment is not initiated immediately.

Bear in mind that pump malfunctions, such as battery problems, catheter issues, alarm signal failure, or defective device operation, may lead to overdose or underdosing of the medicine.
In case of any doubts regarding the use of the medicine, consult the doctor.

4. Possible adverse effects

* Adverse effects marked with an asterisk occur more frequently in patients with
cerebral palsy.
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Adverse effects are more common when starting treatment in hospital, but they may also occur later.
Many of the adverse effects listed may also be related to the underlying disease being treated.
Malfunction of the implanted drug delivery device or infusion system may lead to withdrawal symptoms, which may result in death (see symptoms of interruption of treatment in section 3 "How to use Lioresal Intrathecal 10 mg/20 ml").
The following adverse effects and their frequency of occurrence have been reported:

Very common: may affect more than 1 in 10 people

• decreased muscle tone
• drowsiness

Common: may affect up to 1 in 10 people

• anxiety
• decreased appetite
• shortness of breath, slow or shallow breathing
• reduced alertness
• decreased blood pressure upon sitting or standing
• depression
• disorientation
• diarrhoea or 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 skin sensations with tingling in 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
• urinary incontinence
• nausea or vomiting*
• excessive salivation
• constipation
• slurred speech
• confusion
• respiratory depression

Uncommon: may affect up to 1 in 100 people

• decreased body fluids (dehydration)
• pale skin
• high blood pressure
• intestinal obstruction due to constipation
• memory loss / distractibility
• mood disturbances
• hair loss
• false sensory perceptions not caused by external stimuli (hallucinations)
• skin redness
• low body temperature
• difficulty swallowing
• problems with coordination
• suicidal thoughts and attempts
• excessive sweating
• nystagmus ------- slowed heart rate
• reduced sense of taste
• blockage of a blood vessel due to deep vein thrombosis
• hallucinations
• euphoria

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

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

Some adverse effects occur with unknown frequency:

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

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

5. How to store Lioresal Intrathecal 10 mg/20 ml

Keep this medicine out of sight and reach of children.
Storage conditions
Do not store above 30°C.
Do not freeze. Do not sterilize by heat.
The solution should be used immediately after opening. Any unused solution must be discarded.
The solution must be clear and colourless. Do not use this medicine if cloudiness or discoloration is observed.
Lioresal Intrathecal 10 mg/20 ml must not be used after the expiry date stated on the container. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

• The active substance is baclofen.

1 ml of infusion solution contains 0.5 mg of baclofen.
One 20 ml vial of infusion solution contains 10 mg of baclofen.

• Other ingredients are: sodium chloride, water for injections.

What Lioresal Intrathecal 10 mg/20 ml looks like and contents of the pack
Lioresal Intrathecal 10 mg/20 ml is a clear, colourless solution in a transparent, colourless vial.
Lioresal Intrathecal 10 mg/20 ml infusion solution is available in packs containing 1, 2 or 5 vials.
For further information, please contact the Marketing Authorisation Holder or the Parallel Importer.
Marketing Authorisation Holder in Germany, the country of export:
Novartis Pharma GmbH
Roonstr. 25
D-90429 Nuremberg
Germany
Manufacturer:
Novartis Pharma GmbH
Roonstr. 25
D-90429 Nuremberg
Germany
Parallel Importer:
InPharm Sp. z o.o.
ul. Strumykowa 28/11
03-138 Warsaw
Repackaged in:
Pharma Innovations Sp. z o.o.
ul. Jagiellońska 76
03-301 Warsaw
InPharm Sp. z o.o. Services sp. k.
ul. Chełmżyńska 249
04-458 Warsaw
Marketing Authorisation number in Germany, the country of export: 39917.01.01
Parallel Import Authorisation number: 282/19
This medicinal product has been authorised in the Member States of the European Economic Area under the following names:
Germany: Lioresal Intrathecal 10 mg/20 ml Infusionslösung
Poland: Lioresal Intrathecal 10 mg/20 ml, infusion solution

Information intended solely for healthcare professionals:

How to prepare and administer the medicinal product Lioresal Intrathecal 10 mg/20 ml
Administration of a test dose, implantation of the infusion pump, and dose escalation of the intrathecally administered medicinal product must be performed in a hospital setting, within centers possessing appropriate expertise and under the close supervision of suitably qualified physicians. Immediate access to an intensive care unit must be ensured due to the potential for severe or life-threatening adverse reactions to the medicinal product.

To determine the optimal dosing regimen for the medicinal product Lioresal Intrathecal 10 mg/20 ml, each patient must first receive a trial dose prior to initiating long-term treatment: Lioresal Intrathecal 0.05 mg/1 ml administered as an intrathecal bolus injection via an intrathecal catheter or lumbar puncture. Subsequently, the dose must be carefully and individually adjusted for each patient, due to considerable inter-individual variation in therapeutically effective doses.

In long-term therapy, the medicinal product Lioresal Intrathecal 10 mg/20 ml is administered via an implanted pump, enabling continuous infusion of baclofen solution into the cerebrospinal fluid.

The efficacy of the medicinal product Lioresal Intrathecal 10 mg/20 ml has been demonstrated in clinical studies using the SynchroMed infusion system. This drug delivery system includes refillable reservoirs implanted subcutaneously in the patient (typically in the abdominal wall tissues) and connected to an intrathecal catheter, which runs from the subcutaneous implantation site into the subarachnoid space. Experience with other implanted infusion systems is currently lacking.

Prior to initiating treatment with Lioresal Intrathecal 10 mg/20 ml, myelographic evaluation of the subarachnoid space is required in patients with traumatic spasticity. If radiological signs of meningitis are detected, treatment with Lioresal Intrathecal 10 mg/20 ml must not be initiated.

Before administration of Lioresal Intrathecal 10 mg/20 ml, the solution must 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 within is stable, isotonic, pyrogen-free, antioxidant-free, and has a pH of 5.0–7.0.

Implantation of the infusion pump / dose escalation phase (in hospital setting)
After confirming the patient's response to Lioresal Intrathecal 10 mg/20 ml during the trial phase, intrathecal infusion of the medicinal product may be initiated using the aforementioned infusion pump. The antispastic effect of baclofen begins 6 to 8 hours after the start of continuous infusion, with maximum effect observed after 24 to 48 hours.

The initial total daily dose of Lioresal Intrathecal 10 mg/20 ml is calculated as follows: if the effect of the test dose lasts longer than 12 hours, this dose is used as the initial dose. If the effect lasts less than 12 hours, the test dose should be doubled and administered as the initial dose. The dose should not be increased during the first 24 hours of therapy.

After the first day of treatment, the dose may be gradually increased to achieve the desired therapeutic effect. The daily dose should not be increased by more than 10% to 30% of the previous dose in patients with spinal spasticity, and by 5% to 15% in patients with cerebral spasticity. When using a programmable pump, dose adjustments should be made no more than once every 24 hours. For non-programmable pumps equipped with a 76 cm catheter delivering 1 ml per day, the patient's response to a new dose should be evaluated after 48 hours. If a significant increase in the daily dose does not result in enhanced clinical effect, the proper functioning of the pump and catheter patency should be verified.

In general, the dose is escalated until a maintenance dose in the range of 300 µg to 800 µg per day is achieved in patients with spinal spasticity. Patients with cerebral spasticity typically require lower doses (see below).

Long-term therapy phase
The goal of treatment is to use the lowest dose that provides adequate control of spasticity without unacceptable adverse effects. Since therapeutic response may diminish over time and spasticity severity may change, dose adjustments in a hospital setting are usually necessary during long-term therapy.

In this phase, the daily dose may be increased by 10% to 30% in patients with spinal spasticity and by 5% to 20% (upper limit) in patients with cerebral spasticity, by adjusting the infusion rate or the baclofen concentration in the pump reservoir. Conversely, if adverse effects occur, the daily dose may be reduced by 10% to 20%.

The need for sudden dose escalation to achieve adequate therapeutic effect may indicate pump malfunction or catheter kinking, fracture (abrasion), or displacement.

The maintenance dose of Lioresal Intrathecal 10 mg/20 ml in long-term treatment of patients with spinal spasticity typically ranges from 300 µg to 800 µg of baclofen per day. The lowest and highest recorded daily doses administered to individual patients during the titration phase were 12 µg and 2003 µg, respectively (studies conducted in the United States). Experience with doses exceeding 1000 µg per day is limited. During the first several months of treatment, the dose should be verified and modified particularly frequently.

In patients with cerebral spasticity, maintenance doses used during long-term continuous infusion of Lioresal Intrathecal 10 mg/20 ml range from 22 µg to 1400 µg of baclofen per day. Mean daily doses are 276 µg after one year of observation and 307 µg after two years. Children under 12 years of age typically require lower doses (range: 24 µg to 1199 µg per day; mean: 274 µg per day).

If the technical parameters of the pump allow, after establishing the daily dose and stabilizing the antispastic effect, attempts may be made to adjust drug delivery to the patient's circadian spasticity pattern. For example, if spasms occur more frequently at night, a 20% increase in the hourly infusion rate may be required. Changes in infusion rate should be programmed to occur two hours before the desired clinical effect is needed.

Throughout the treatment period, regular monitoring—at least monthly—is required at the treating center to assess tolerance to Lioresal Intrathecal 10 mg/20 ml and to detect any signs of infection. The proper functioning of the infusion system must be checked regularly. Local infection or catheter malfunction may interrupt intrathecal administration of Lioresal Intrathecal 10 mg/20 ml, with potentially life-threatening consequences for the patient.

The baclofen concentration required for pump refilling depends on the total daily dose of the medicinal product and the infusion rate of the pump. If baclofen concentrations other than 0.05 mg/ml, 0.5 mg/ml, or 2 mg/ml are required, the medicinal product Lioresal Intrathecal 10 mg/20 ml must be diluted under aseptic conditions using sterile sodium chloride solution for injection, free of preservatives. In such cases, the manufacturer's instructions for the infusion pump must be followed.

Approximately 5% of patients may require higher doses due to reduced treatment efficacy ("development of tolerance") during long-term therapy. As described in the literature, tolerance development may be prevented by a 10- to 14-day interruption of baclofen administration, during which preservative-free morphine sulfate should be administered. After this period, the patient may again respond to treatment with Lioresal Intrathecal 10 mg/20 ml. Therapy should be resumed with the initial dose used in continuous infusion, followed by gradual dose escalation to avoid adverse effects due to overdose. This procedure must be performed in a hospital setting.

Pharmaceutical incompatibilities
The medicinal product Lioresal Intrathecal 10 mg/20 ml, solution for infusion, must not be mixed with other injectable or infusion solutions except sterile sodium chloride solution free of preservatives, diluted under aseptic conditions.

Chemical incompatibility between dextrose and baclofen has been demonstrated.

Do not freeze. Do not sterilize by high temperature.