300001781

300001781-GB

Artwork Order description:

PREA LIORESAL LIAM GB

PS, CH, STEIN (STERILES), NTO

Hepatic impairment

No dosage adjustment is recommended as the liver does not play any significant role in the metabolism of baclofen after intrathecal administration of Lioresal. Therefore, hepatic impairment is not expected to impact the drug systemic exposure.

Elderly population

Several patients over the age of 65 years have been treated with Lioresal Intrathecal during the clinical trials without increased risks compared to younger patients. Problems specific to this age group are not expected as doses are individually titrated.

Special warnings and precautions for use

Intrathecal baclofen therapy is valuable but hazardous. Careful pre-operative assessment is mandatory.

The patient must be given adequate information regarding the risks of this mode of treatment, and be physically and psychologically able to cope with the pump. It is essential that the responsible physicians and all those involved in the care of the patient receive adequate instruction on the signs and symptoms of overdose, procedures to be followed in the event of an overdose and the proper home care of the pump and insertion site.

Inflammatory mass at the tip of the implanted catheter : cases of inflammatory mass at the tip of the implanted catheter that can result in serious neurological impairment, including paralysis, have been reported. Although they have been reported with Lioresal intrathecal, they have not been confirmed by contrast MRI or histopathology. The most frequent symptoms associated with inflammatory mass are: 1) decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases), 2) pain, 3) neurological deficit/dysfun­ction. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms. Clinicians should use their medical judgement regarding the most appropriate monitoring specific to their patients’ medical needs to identify prodromal signs and symptoms for inflammatory mass especially if using pharmacy compounded drugs or admixtures that include opioids. In patients with new neurological signs or symptoms suggestive of an inflammatory mass, consider a neurosurgical consultation since many of the symptoms of inflammatory mass are not unlike the symptoms experienced by patients with severe spasticity from their disease. In some cases, performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an inflammatory mass.

Pump Implantation

Patients should be infection-free prior to pump implantation because the presence of infection may increase the risk of surgical complications.

Moreover, a systemic infection may complicate attempts to adjust the dose. A local infection or catheter malplacement can also lead to drug delivery failure, which may result in sudden Lioresal Intrathecal withdrawal and its related symptoms (see “Treatment Withdrawal” section).

Reservoir refilling

Reservoir refilling must be performed by trained and qualified personnel in accordance with the instructions provided by the pump manufacturer. Refills should be timed to avoid excessive depletion of the reservoir, as this would result in the return of spasticity or potentially life-threatening symptoms of Lioresal Intrathecal withdrawal (see “Treatment Withdrawal” section).

When refilling the pump care should be taken to avoid discharging the contents of the catheter into the intrathecal space.

Strict asepsis is required to avoid microbial contamination and infection. Extreme caution must be taken when filling a pump equipped with an injection port that allows direct access to the intrathecal catheter as a direct injection into the catheter through the access port could cause a life-threatening overdose.

Precautions in paediatric patients

For patients with spasticity due to head injury, it is recommended not to proceed to long-term Lioresal Intrathecal therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).

Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Use of Lioresal Intrathecal in the paediatric population should be only prescribed by medical specialists with the necessary knowledge and experience. There is very limited clinical data regarding the safety and efficacy of the use of Lioresal Intrathecal in children under the age of four years.

Precautions in special patient populations

In patients with abnormal CSF flow the circulation of drug and hence antispastic activity may be inadequate.

Psychotic disorders, schizophrenia, confusional states or Parkinson’s di­sease may be exacerbated by treatment with oral Lioresal. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance.

Special attention should be given to patients known to suffer from epilepsy as seizures have occasionally been reported during overdose with, and withdrawal from, Lioresal Intrathecal as well as in patients maintained on therapeutic doses. Lioresal Intrathecal should be used with caution in patients with a history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt withdrawal of Lioresal Intrathecal may precipitate an autonomic dysreflexic episode.

Lioresal should be used with caution in patients with cerebrovascular or respiratory insufficiency.

An effect of Lioresal Intrathecal on underlying, non-CNS related diseases is unlikely because its systemic availability is substantially lower than after oral administration. Observations after oral baclofen therapy suggest that caution should be exercised in patients with a history of peptic ulcers and pre-existing sphincter hypertonia.

Renal impairment

After oral Lioresal dosing severe neurological outcomes have been reported in patients with renal impairment. Thus caution should be exercised while administering Lioresal Intrathecal in patients with renal impairment.

In rare instances elevated SGOT, alkaline phosphatase and glucose levels in the serum have been recorded when using oral Lioresal.

Treatment withdrawal

Abrupt discontinuation of Lioresal Intrathecal, regardless of cause, manifested by increased spasticity, pruritus, paraesthesia and hypotension, has resulted in sequelae including a hyperactive state with rapid uncontrolled spasms, hyperthermia and symptoms consistent with neuroleptic malignant syndrome, e.g. altered mental status and muscle rigidity. In rare cases this has advanced to seizures/status epilepticus, rhabdomyolysis, coagulopathy, multiple organ failure and death. All patients receiving intrathecal baclofen therapy are potentially at risk for withdrawal.

Some clinical characteristics associated with intrathecal baclofen withdrawal may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.

Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the signs and symptoms of baclofen withdrawal particularly those seen early in the withdrawal syndrome (e.g. priapism). In most cases, symptoms of withdrawal appeared within hours to a few days following interruption of baclofen therapy. Common reasons for abrupt interruption of intrathecal baclofen therapy included malfunction of the catheter (especially disconnection), low volume in the pump reservoir and end of pump battery life. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. The suggested treatment for intrathecal Lioresal withdrawal is the restoration of intrathecal Lioresal at or near the same dosage as before therapy was interrupted. However, if restoration of intrathecal delivery is delayed, treatment with GABA-ergic agonist drugs such as oral or enteral Lioresal, or oral, enteral, or intravenous benzodiazepines may prevent potentially fatal sequelae. Oral or enteral Lioresal alone should not be relied upon to halt the progression of intrathecal baclofen withdrawal.

Scoliosis

The onset of scoliosis or worsening of a pre-existing scoliosis has been reported in patient treated with Lioresal Intrathecal. Signs of scoliosis should be monitored during treatment with Lioresal Intrathecal.

Incompatibilities

If alternative baclofen concentrations are required Lioresal Intrathecal may be diluted under aseptic conditions with sterile preservative-free sodium chloride for injections. The ampoules should not be mixed with other solutions for injection or infusion (dextrose has proved to be incompatible due to a chemical reaction with baclofen).

The compatibility of Lioresal Intrathecal with the components of the infusion pump (including the chemical stability of baclofen in the reservoir) and the presence of an in-line bacterial retentive filter should be confirmed with the pump manufacturer prior to use.

Shelf life

LIORESAL® Intrathecal Injection 50 micrograms/1 ml: 3 years

LIORESAL® Intrathecal Infusion 10 mg/5 ml: 3 years

LIORESAL® Intrathecal Infusion 10 mg/20 ml: 3 years

Special precautions for storage

Keep this medicine out of the sight and reach of children.

Store below 30°C.

Nature and content of container

Colourless glass ampoules, glass type I, according to Ph. Eur.

Instructions for use / handling

Each ampoule is intended for single use only, and any unused solution should be discarded. Ampoules should not be either frozen or autoclaved.

Date of revision: December 2020 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 run out. The pump must always be filled by a doctor or nurse, and you must make sure that you do not miss your clinic appointments.

You should not stop treatment suddenly. If the doctor decides to stop your treatment, the dose will be reduced gradually to prevent withdrawal symptoms such as muscle spasms and increased muscle rigidity, fast heart rate, fever, confusion, hallucinations, changes in mood and emotion, mental disorders, feeling persecuted or convulsions (fits), persistent painful erection of the penis (priapism). On rare occasions these symptoms could be life-threatening. If you or your carers notice any of these symptoms, contact your doctor immediately just in case something has gone wrong with the pump or delivery system.

During long-term treatment some patients find that Lioresal becomes less effective. You may require occasional breaks in treatment. Your doctor will advise you what to do.

Lioresal Intrathecal is not suitable for all children. The doctor will decide.

Overdose

It is very important that you, and anyone caring for you, can recognise the signs of overdose. These may appear if the pump is not working properly, and you must tell the doctor straight away.

Signs of overdose are:

Unusual muscle weakness (too little muscle tone) Sleepiness

Dizziness or light-headedness

Excessive salivation

Nausea or vomiting

Difficulty in breathing

Convulsions

Loss of consciousness

Abnormally low body temperature.

4. possible side effects

Lioresal Intrathecal is suitable for most people, but, like all medicines, it can sometimes cause side effects. Implanted drug delivery device or infusion system malfunction can lead to withdrawal symptoms including death.

The side effects listed below have been reported:

More than 1 in 10 people have experienced:

Feeling tired, drowsy or weak.

Up to 1 in 10 people have experienced:

Feeling lethargic (having no energy)

Headache, dizziness or light-headedness

Pain, fever or chills

Seizures

Tingling hands or feet

Problems with eyesight

Slurred speech

Insomnia

Breathing difficulties, pneumonia

Feeling confused, anxious, agitated or depressed

Low blood pressure (fainting)

Feeling or being sick, constipation and diarrhoea

Loss of appetite, dry mouth or excessive saliva

Rash and itching, swelling of the face or hands and feet Urinary incontinence, or problems when urinating Cramps

Sexual problems in men, e.g. impotence.

Up to 1 in 100 people have experienced:

Feeling abnormally cold

Memory loss

Mood swings and hallucinations, feeling suicidal

Stomach ache, difficulty in swallowing, loss of taste, dehydration

Loss of muscle control

Raised blood pressure

Slow heart beat

Deep vein thrombosis

Flushed or pale skin, excessive sweating Hair loss.

Other side effects (how often they happen is not known) Restlessness (dysphoria)

Abnormally slow breathing rate (bradypnoea)

Increase in sideways curvature of the spine (scoliosis) Inability to achieve or maintain an erection (erectile dysfunction).

There have been rare reports of problems associated with the pump and delivery system e.g. infections, inflammation of the lining around the brain and spinal cord (meningitis) or a collection of immune cells at the tip of the delivery tube.

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to adjust the dose or give you a different medicine.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme () or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store lioresal intrathecal

300001781

300001781-GB

Artwork Order description:

PREA LIORESAL LIAM GB

PS, CH, STEIN (STERILES), NTO

Hepatic impairment

No dosage adjustment is recommended as the liver does not play any significant role in the metabolism of baclofen after intrathecal administration of Lioresal. Therefore, hepatic impairment is not expected to impact the drug systemic exposure.

Elderly population

Several patients over the age of 65 years have been treated with Lioresal Intrathecal during the clinical trials without increased risks compared to younger patients. Problems specific to this age group are not expected as doses are individually titrated.

Special warnings and precautions for use

Intrathecal baclofen therapy is valuable but hazardous. Careful pre-operative assessment is mandatory.

The patient must be given adequate information regarding the risks of this mode of treatment, and be physically and psychologically able to cope with the pump. It is essential that the responsible physicians and all those involved in the care of the patient receive adequate instruction on the signs and symptoms of overdose, procedures to be followed in the event of an overdose and the proper home care of the pump and insertion site.

Inflammatory mass at the tip of the implanted catheter : cases of inflammatory mass at the tip of the implanted catheter that can result in serious neurological impairment, including paralysis, have been reported. Although they have been reported with Lioresal intrathecal, they have not been confirmed by contrast MRI or histopathology. The most frequent symptoms associated with inflammatory mass are: 1) decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases), 2) pain, 3) neurological deficit/dysfun­ction. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms. Clinicians should use their medical judgement regarding the most appropriate monitoring specific to their patients’ medical needs to identify prodromal signs and symptoms for inflammatory mass especially if using pharmacy compounded drugs or admixtures that include opioids. In patients with new neurological signs or symptoms suggestive of an inflammatory mass, consider a neurosurgical consultation since many of the symptoms of inflammatory mass are not unlike the symptoms experienced by patients with severe spasticity from their disease. In some cases, performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an inflammatory mass.

Pump Implantation

Patients should be infection-free prior to pump implantation because the presence of infection may increase the risk of surgical complications.

Moreover, a systemic infection may complicate attempts to adjust the dose. A local infection or catheter malplacement can also lead to drug delivery failure, which may result in sudden Lioresal Intrathecal withdrawal and its related symptoms (see “Treatment Withdrawal” section).

Reservoir refilling

Reservoir refilling must be performed by trained and qualified personnel in accordance with the instructions provided by the pump manufacturer. Refills should be timed to avoid excessive depletion of the reservoir, as this would result in the return of spasticity or potentially life-threatening symptoms of Lioresal Intrathecal withdrawal (see “Treatment Withdrawal” section).

When refilling the pump care should be taken to avoid discharging the contents of the catheter into the intrathecal space.

Strict asepsis is required to avoid microbial contamination and infection. Extreme caution must be taken when filling a pump equipped with an injection port that allows direct access to the intrathecal catheter as a direct injection into the catheter through the access port could cause a life-threatening overdose.

Precautions in paediatric patients

For patients with spasticity due to head injury, it is recommended not to proceed to long-term Lioresal Intrathecal therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).

Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Use of Lioresal Intrathecal in the paediatric population should be only prescribed by medical specialists with the necessary knowledge and experience. There is very limited clinical data regarding the safety and efficacy of the use of Lioresal Intrathecal in children under the age of four years.

Precautions in special patient populations

In patients with abnormal CSF flow the circulation of drug and hence antispastic activity may be inadequate.

Psychotic disorders, schizophrenia, confusional states or Parkinson’s di­sease may be exacerbated by treatment with oral Lioresal. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance.

Special attention should be given to patients known to suffer from epilepsy as seizures have occasionally been reported during overdose with, and withdrawal from, Lioresal Intrathecal as well as in patients maintained on therapeutic doses. Lioresal Intrathecal should be used with caution in patients with a history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt withdrawal of Lioresal Intrathecal may precipitate an autonomic dysreflexic episode.

Lioresal should be used with caution in patients with cerebrovascular or respiratory insufficiency.

An effect of Lioresal Intrathecal on underlying, non-CNS related diseases is unlikely because its systemic availability is substantially lower than after oral administration. Observations after oral baclofen therapy suggest that caution should be exercised in patients with a history of peptic ulcers and pre-existing sphincter hypertonia.

Renal impairment

After oral Lioresal dosing severe neurological outcomes have been reported in patients with renal impairment. Thus caution should be exercised while administering Lioresal Intrathecal in patients with renal impairment.

In rare instances elevated SGOT, alkaline phosphatase and glucose levels in the serum have been recorded when using oral Lioresal.

Treatment withdrawal

Abrupt discontinuation of Lioresal Intrathecal, regardless of cause, manifested by increased spasticity, pruritus, paraesthesia and hypotension, has resulted in sequelae including a hyperactive state with rapid uncontrolled spasms, hyperthermia and symptoms consistent with neuroleptic malignant syndrome, e.g. altered mental status and muscle rigidity. In rare cases this has advanced to seizures/status epilepticus, rhabdomyolysis, coagulopathy, multiple organ failure and death. All patients receiving intrathecal baclofen therapy are potentially at risk for withdrawal.

Some clinical characteristics associated with intrathecal baclofen withdrawal may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.

Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the signs and symptoms of baclofen withdrawal particularly those seen early in the withdrawal syndrome (e.g. priapism). In most cases, symptoms of withdrawal appeared within hours to a few days following interruption of baclofen therapy. Common reasons for abrupt interruption of intrathecal baclofen therapy included malfunction of the catheter (especially disconnection), low volume in the pump reservoir and end of pump battery life. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. The suggested treatment for intrathecal Lioresal withdrawal is the restoration of intrathecal Lioresal at or near the same dosage as before therapy was interrupted. However, if restoration of intrathecal delivery is delayed, treatment with GABA-ergic agonist drugs such as oral or enteral Lioresal, or oral, enteral, or intravenous benzodiazepines may prevent potentially fatal sequelae. Oral or enteral Lioresal alone should not be relied upon to halt the progression of intrathecal baclofen withdrawal.

Scoliosis

The onset of scoliosis or worsening of a pre-existing scoliosis has been reported in patient treated with Lioresal Intrathecal. Signs of scoliosis should be monitored during treatment with Lioresal Intrathecal.

Incompatibilities

If alternative baclofen concentrations are required Lioresal Intrathecal may be diluted under aseptic conditions with sterile preservative-free sodium chloride for injections. The ampoules should not be mixed with other solutions for injection or infusion (dextrose has proved to be incompatible due to a chemical reaction with baclofen).

The compatibility of Lioresal Intrathecal with the components of the infusion pump (including the chemical stability of baclofen in the reservoir) and the presence of an in-line bacterial retentive filter should be confirmed with the pump manufacturer prior to use.

Shelf life

LIORESAL® Intrathecal Injection 50 micrograms/1 ml: 3 years

LIORESAL® Intrathecal Infusion 10 mg/5 ml: 3 years

LIORESAL® Intrathecal Infusion 10 mg/20 ml: 3 years

Special precautions for storage

Keep this medicine out of the sight and reach of children.

Store below 30°C.

Nature and content of container

Colourless glass ampoules, glass type I, according to Ph. Eur.

Instructions for use / handling

Each ampoule is intended for single use only, and any unused solution should be discarded. Ampoules should not be either frozen or autoclaved.

Date of revision: December 2020 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 run out. The pump must always be filled by a doctor or nurse, and you must make sure that you do not miss your clinic appointments.

You should not stop treatment suddenly. If the doctor decides to stop your treatment, the dose will be reduced gradually to prevent withdrawal symptoms such as muscle spasms and increased muscle rigidity, fast heart rate, fever, confusion, hallucinations, changes in mood and emotion, mental disorders, feeling persecuted or convulsions (fits), persistent painful erection of the penis (priapism). On rare occasions these symptoms could be life-threatening. If you or your carers notice any of these symptoms, contact your doctor immediately just in case something has gone wrong with the pump or delivery system.

During long-term treatment some patients find that Lioresal becomes less effective. You may require occasional breaks in treatment. Your doctor will advise you what to do.

Lioresal Intrathecal is not suitable for all children. The doctor will decide.

Overdose

It is very important that you, and anyone caring for you, can recognise the signs of overdose. These may appear if the pump is not working properly, and you must tell the doctor straight away.

Signs of overdose are:

Unusual muscle weakness (too little muscle tone) Sleepiness

Dizziness or light-headedness

Excessive salivation

Nausea or vomiting

Difficulty in breathing

Convulsions

Loss of consciousness

Abnormally low body temperature.

4. possible side effects

Lioresal Intrathecal is suitable for most people, but, like all medicines, it can sometimes cause side effects. Implanted drug delivery device or infusion system malfunction can lead to withdrawal symptoms including death.

The side effects listed below have been reported:

More than 1 in 10 people have experienced:

Feeling tired, drowsy or weak.

Up to 1 in 10 people have experienced:

Feeling lethargic (having no energy)

Headache, dizziness or light-headedness

Pain, fever or chills

Seizures

Tingling hands or feet

Problems with eyesight

Slurred speech

Insomnia

Breathing difficulties, pneumonia

Feeling confused, anxious, agitated or depressed

Low blood pressure (fainting)

Feeling or being sick, constipation and diarrhoea

Loss of appetite, dry mouth or excessive saliva

Rash and itching, swelling of the face or hands and feet Urinary incontinence, or problems when urinating Cramps

Sexual problems in men, e.g. impotence.

Up to 1 in 100 people have experienced:

Feeling abnormally cold

Memory loss

Mood swings and hallucinations, feeling suicidal

Stomach ache, difficulty in swallowing, loss of taste, dehydration

Loss of muscle control

Raised blood pressure

Slow heart beat

Deep vein thrombosis

Flushed or pale skin, excessive sweating Hair loss.

Other side effects (how often they happen is not known) Restlessness (dysphoria)

Abnormally slow breathing rate (bradypnoea)

Increase in sideways curvature of the spine (scoliosis) Inability to achieve or maintain an erection (erectile dysfunction).

There have been rare reports of problems associated with the pump and delivery system e.g. infections, inflammation of the lining around the brain and spinal cord (meningitis) or a collection of immune cells at the tip of the delivery tube.

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to adjust the dose or give you a different medicine.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme () or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store lioresal intrathecal

Keep this medicine out of the sight and reach of children. Store below 30°C.

It should not be used after the expiry date which is printed on the outside of the pack.

• 6. Further information