LIORESAL® Intrathecal Injection 50 micrograms/1 ml

LIORESAL® Intrathecal Infusion 10 mg/5 ml

LIORESAL® Intrathecal Infusion 10 mg/20 ml

(baclofen)

Patient Information Leaflet

The product will be called Lioresal Intrathecal in this leaflet What you need to know about Lioresal Intrathecal

Your doctor has decided that you or your child need this medicine to help treat your condition.

Please read this leaflet carefully before you start treatment. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don't understand, please ask your doctor or nurse.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

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

2.    Things to consider before you have Lioresal Intrathecal

3.    Having Lioresal Intrathecal

4.    Possible side effects

5.    How to store Lioresal Intrathecal

6.    Further information

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

Lioresal Intrathecal contains the active ingredient, baclofen. It is administered by intrathecal injection directly into the spinal fluid. It is available in three different sizes and strengths containing either 50 micrograms in 1 ml, 10 mg in 5 ml or 10 mg in 20 ml of baclofen.

Baclofen is a muscle-relaxant drug. Lioresal Intrathecal is intended for adults and children of 4 years and above and is used to reduce and relieve the excessive tension in your muscles (spasms) occurring in various illnesses such as cerebral palsy, multiple sclerosis, spinal cord diseases, cerebrovascular accidents, and other nervous system disorders.This injection is used in people who haven't responded to oral medicines or who get unacceptable side effects when they take baclofen by mouth.

2. Things to consider before you have Lioresal Intrathecal

Some people MUST NOT have Lioresal Intrathecal. Talk to your doctor if:

•    you think you may be allergic to baclofen or to any of the other ingredients of the injection. (These are listed at the end of the leaflet.)

You should also ask yourself these questions before having Lioresal Intrathecal:

•    Have you understood everything the doctor or nurse has told you about the risks associated with Lioresal Intrathecal?

•    Do you understand how to use the injection pump?

If you are at all confused about either of these points, please ask the doctor or nurse.

•    Are you having any other injections into the spine?

•    Are you suffering from any infection?

•    Have you had a head injury within the last year?

•    Have you ever had a crisis caused by a condition called autonomic dysreflexia? (Your doctor will be able to explain this to you.)

•    Have you had a stroke?

•    Do you have epilepsy?

•    Do you have a stomach ulcer or any other problem with your digestion?

•    Do you suffer from any mental illness?

•    Are you being treated for high blood pressure?

•    Do you have Parkinson's disease?

•    Do you suffer from any liver, kidney or lung disease?

•    Do you have diabetes?

•    Do you have difficulties in urinating?

•    Are you pregnant or breast feeding?

If the answer to any of this second list of questions Is YES, tell your doctor or nurse because Lioresal Intrathecal may not be the right medicine for you.

Are you taking other medicines?

Some medicines can interfere with your treatment. Remind your doctor or nurse if you are taking any of the following:

•    Other medicines for your spastic condition e.g. tizanidine or diazepam

•    Antidepressants e.g. imipramine or amitriptyline

•    Medicines for high blood pressure e.g. diltiazem or moxonidine

•    Other drugs which also affect the kidney, e.g. ibuprofen

•    Medicines for Parkinson's disease e.g. levodopa or carbidopa

•    Medicines for epilepsy e.g. carbamazepine or clonazepam

•    Opiates for pain relief e.g. morphine

•    Medicines which slow down the nervous system,

e.g. anti-histamines such as promethazine and sedatives such as temazepam. (Some of these can be bought over-the-counter.)

Always tell your doctor or nurse about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Will there be any problems with driving or using machinery?

Some people may feel drowsy and/or dizzy or have problems with their eyes while they are being treated with Lioresal Intrathecal. If this happens, you should not drive or do anything that requires you to be alert (such as operate tools or machinery) until these effects have worn off.

Other special warnings

•    Be careful when drinking alcohol - it may affect you more than usual.

•    Contact your doctor immediately if you think that Lioresal Intrathecal is not working as well as usual. It is important to make sure that there are no problems with the pump.

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•    Treatment with Lioresal Intrathecal must not stop suddenly because of the risk of withdrawal effects. You must make sure that you do not miss those hospital visits when the pump reservoir is being refilled.

•    Your doctor may want to give you a check up from time to time while you are being treated with Lioresal Intrathecal.

•    If you are going to have an operation of any kind, make sure that the doctor knows that you are being treated with Lioresal Intrathecal. Anaesthetics such as propofol may increase the risk of side effects.

Children and adolescents:

Lioresal Intrathecal formulation is intended for children of 4 years and above.

3. Having Lioresal Intrathecal

Lioresal Intrathecal is administered by intrathecal injection.

This means that the medicine is injected directly into the spinal fluid. The dose needed varies from person to person depending on their condition, and the doctor will decide what dose you need after he/she has tested your response to the drug.

First of all the doctor will find out, by giving you single doses of Lioresal Intrathecal, whether it is suitable for you. During this period your heart and lung functions will be closely monitored. If your symptoms improve, a special pump which can deliver the drug continuously, will be implanted into your chest or abdominal wall. The doctor will give you all of the information you need to use the pump and to get the correct dosage. Make sure that you understand everything.

The final dose of Lioresal Intrathecal depends on how each person responds to the drug. You will be started on a low dose, and this will be increased gradually over a few days, under the supervision of the doctor, until you are having the dose which is right for you. If the starting dose is too high, or if the dose is increased too quickly, you are more likely to experience side effects.

To avoid unpleasant side effects which may be serious and even life-threatening, it is important that your pump does not

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Information for the healthcare professional

Please see the SPC for full details.

Therapeutic indications

Lioresal Intrathecal is indicated in patients with severe chronic spasticity of spinal or cerebral origin (associated with injury, multiple sclerosis, cerebral palsy) who are unresponsive to oral baclofen or other orally administered antispastic agents and/or those patients who experience unacceptable side-effects at effective oral doses.

In patients with spasticity due to head injury a delay of at least one year before treatment with Lioresal Intrathecal is recommended, to allow the symptoms of spasticity to stabilise.

Lioresal Intrathecal may be considered as an alternative to ablative neurosurgical procedures.

Paediatric population

Lioresal Intrathecal is indicated in patients aged 4 to <L8years with severe chronic spasticity of cerebral origin or of spinal origin (associated with injury, multiple sclerosis, or other spinal cord diseases) who are unresponsive to orally administered antispastics (including oral baclofen) and/or who experience unacceptable side effects at effective oral doses.

Posologv and method of administration Intrathecal administration of Lioresal through an implanted delivery system should only be undertaken by physicians with the necessary knowledge and experience. Specific instructions for implantation, programming and/or refilling of the implantable pump are given by the pump manufacturers, and must be strictly adhered to.

Lioresal Intrathecal 50 micrograms/lml is intended for administration in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, in implantable pumps suitable for continuous administration of Lioresal Intrathecal L0mg/20ml and L0mg/5ml into the intrathecal space (EU certified pumps). Establishment of the optimum dose schedule requires that each patient undergoes an initial screening phase with intrathecal bolus, followed by a very careful individual dose titration prior to maintenance therapy.

Respiratory function should be monitored and appropriate resuscitation facilities should be available during the introduction of treatment with Lioresal Intrathecal. Intrathecal administration using an implanted delivery system should only be undertaken by physicians with appropriate knowledge and experience. Specific instructions for using the implantable pump should be obtained from the pump manufacturers. Only pumps constructed of material known to be compatible with the product and incorporating an in-line bacterial retentive filter should be used.

2173455 Adult Screening Phase

Prior to initiation of a chronic infusion, the patient's response to intrathecal bolus doses administered via a catheter or lumbar puncture must be assessed. Low concentration ampoules containing 50 micrograms baclofen in Lml are available for the purpose. Patients should be infection-free prior to screening, as the presence of a systemic infection may prevent an accurate assessment of the response.

The usual initial test dose in adults is 25 or 50 micrograms, increasing step-wise by 25 microgram increments at intervals of not less than 24 hours until a response of approximately 4 to 8 hours duration is observed. Each dose should be given slowly (over at least one minute). In order to be considered a responder the patient must demonstrate a significant decrease in muscle tone and/or frequency and/or severity of muscle spasms.

The variability in sensitivity to intrathecal baclofen between patients is emphasised. Signs of severe overdose (coma) have been observed in an adult after a single test dose of 25 micrograms. It is recommended that the initial test dose is administered with resuscitative equipment on hand.

Patients who do not respond to a LOO micrograms test dose should not be given further dose increments or considered for continuous intrathecal infusion. Monitoring of respiratory and cardiac function is essential during this phase, especially in patients with cardiopulmonary disease and respiratory muscle weakness or those being treated with benzodiazepine-type preparations or opiates, who are at higher risk of respiratory depression.

Paediatric population Screening Phase

The initial lumbar puncture test dose for patients 4 to < L8 years of age should be 25-50 micrograms/day based upon age and size of the child. Patients who do not experience a response may receive a 25 micrograms/day dose escalation every 24 hours. The maximum screening dose should not exceed LOO micrograms/day in paediatric patients.

Dose-Titration Phase

Once the patient's responsiveness to Lioresal Intrathecal has been established, an intrathecal infusion may be introduced. Lioresal Intrathecal is most often administered using an infusion pump which is implanted in the chest wall or abdominal wall tissues. Implantation of pumps should only be performed in experienced centres to minimise risks during the perioperative phase.

Infection may increase the risk of surgical complications and complicate attempts to adjust the dose.

The initial total daily infused dose is determined by doubling the bolus dose which gave a significant response in the initial screening phase and administering it over a 24 hour period. However, if a prolonged effect (i.e. lasting more than L2 hours) is observed during screening the starting dose should be the unchanged screening dose delivered over 24 hours. No dose increases should be attempted during the first 24 hours.

After the initial 24 hour period dosage should be adjusted slowly to achieve the desired clinical effect. If a programmable pump is used the dose should be increased only once every 24 hours; for non-programmable multi-dose reservoir pumps intervals of 48 hours between dose adjustments are recommended. In either case increments should be limited as follows to avoid possible overdosage:

Patients with spasticity of spinal origin: 10-30% of the previous daily dose Patients with spasticity of cerebral origin: 5-15% of the previous daily dose.

If the dose has been significantly increased without apparent clinical effect pump function and catheter patency should be investigated.

There is limited clinical experience using doses greater than 1000 micrograms/day.

It is important that patients are monitored closely in an appropriately equipped and staffed environment during screening and immediately following pump implantation. Resuscitative equipment should be available for immediate use in case of life-threatening adverse reactions.

Adult Maintenance Therapy

The clinical goal is to maintain as normal a muscle tone as possible, and to minimise the frequency and severity of spasms without inducing intolerable side effects. The lowest dose producing an adequate response should be used. The retention of some spasticity is desirable to avoid a sensation of "paralysis" on the part of the patient. In addition, a degree of muscle tone and occasional spasms may help support circulatory function and possibly prevent the formation of deep vein thrombosis.

In patients with spasticity of spinal origin: maintenance dosing for long-term continuous infusions of intrathecal baclofen has been found to range from 12 to 2003 micrograms/day, with most patients being adequately maintained on 300 to 800 micrograms/day.

In patients with spasticity of cerebral origin: maintenance dosage has been found to range from 22 to 1400 micrograms/day, with a mean daily dosage of 276 micrograms per day at 12 months and 307 micrograms per day at 24 months.

Paediatric population Maintenance Therapy

In children aged 4 to <18 years with spasticity of cerebral and spinal origin, the initial maintenance dosage for long-term continuous infusion of Lioresal Intrathecal ranges from 25 to 200 micrograms/day (median dose: 100 micrograms/day). The total daily dose tends to increase over the first year of therapy, therefore the maintenance dose needs to be adjusted based on individual clinical response.

There is limited experience with doses greater than 1,000 micrograms/day.

The safety and efficacy of Lioresal Intrathecal for the treatment of severe spasticity of cerebral or spinal origin in children younger than 4 years of age have not been established.

Delivery specifications

Lioresal Intrathecal ampoules of 20ml containing 500 micrograms/ml and 5ml containing 2mg (2000micrograms)/ml are intended for use with infusion pumps. The concentration to be used depends on the dose requirements and size of pump reservoir. Use of the more concentrated solution obviates the need for frequent refilling in patients with high dosage requirements.

Delivery regimen

Lioresal Intrathecal is most often administered in a continuous infusion mode immediately following implant. After the patient has stabilised with regard to daily dose and functional status, and provided the pump allows it, a more complex mode of delivery may be started to optimise control of spasticity at different times of the day. For example, patients who have increased spasm at night may require a 20% increase in their hourly infusion rate. Changes in flow rate should be programmed to start two hours before the desired onset of clinical effect.

Most patients require gradual dose increases to maintain optimum response during chronic therapy due to decreased responsiveness or disease progression. In patients with spasticity of spinal origin the daily dose may be increased gradually by 10-30% to maintain adequate symptom control. Where the spasticity is of cerebral origin any increase in dose should be limited to 20% (range: 5-20%). In both cases the daily dose may also be reduced by 10-20% if patients suffer side effects.

A sudden requirement for substantial dose escalation is indicative of a catheter complication (i.e. a kink or dislodgement) or pump malfunction.

In order to prevent excessive weakness the dosage of Lioresal Intrathecal should be adjusted with caution whenever spasticity is required to maintain function.

During long-term treatment approximately 5% of patients become refractory to increasing doses due to tolerance or drug delivery failure (see Special Warnings and Precautions for Use "Treatment Withdrawal" section). This "tolerance" may be treated by gradually reducing Lioresal Intrathecal dose over 2 to 4 week period and switching to alternative methods of spasticity management (e.g. Intrathecal preservative-free morphine sulphate). Lioresal Intrathecal should be resumed at the initial continuous infusion dose. Caution should be exercised when switching from Lioresal Intrathecal to morphine and vice versa.

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