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GABLOFEN 2 MG/ML SOLUTION FOR INJECTION/INFUSION

Active substance(s): BACLOFEN

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1.

NAME OF THE MEDICINAL PRODUCT

Gablofen™ 2 mg/ml solution for injection/infusion in prefilled syringe
2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 2 mg (2000 microgram) baclofen.
Each 20 ml pre-filled syringe contains 40 mg (40000 microgram) baclofen.
Excipient with known effect:
1 ml contains 3.54 mg sodium, equivalent to 0.154 mmol Na+.
For the full list of excipients, see section 6.1.
3.

Solution for injection/infusion.
Clear, colourless solution.
pH: 5.5 – 7.5
Osmolality: 255 mOsm/kg -320 mOsm/kg
CLINICAL PARTICULARS

4.1

Therapeutic indications

Discontinuation of treatment
Except in overdose related emergencies, the treatment with baclofen should always be gradually discontinued with
successive dose reductions. Baclofen must not be abruptly discontinued (see section 4.4 “Special warnings and
precautions”).

Discontinuation symptoms can possibly be confused with poisoning symptoms. They also require inpatient
admission of the patient.
Therapy in the event of occurrence of withdrawal symptoms
A rapid correct diagnosis and treatment in an emergency medical or intensive care unit is important to prevent the
possibly life-threatening central nervous and systemic effects of withdrawal of intrathecal baclofen (see section 4.4).

Adults
Gablofen is indicated in patients with severe chronic spasticity resulting from trauma, multiple sclerosis or other
spinal cord disorders, who are unresponsive to oral baclofen or other orally administered antispastic medicinal
products and/or those patients who experience unacceptable side-effects at effective oral doses. Gablofen is
effective in patients with severe chronic spasticity of cerebral origin, resulting e.g. from cerebral palsy, brain
trauma or cerebrovascular accident.
Paediatric population
Gablofen is indicated in patients aged 4 to <18 years with severe chronic spasticity of spinal or cerebral
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 undesirable effects at
effective oral doses.
4.2

Through the treatment period, regular checks for therapeutic and adverse effects of Gablofen are appropriate. These
checks may occur more frequently during the titration phase of therapy than during the chronic maintenance
phase. The functioning of the infusion system must be checked regularly. A local infection or a malfunction of
the catheter can cause interruption of the intrathecal delivery of baclofen with life-threatening consequences (see
section 4.4).

Withdrawal symptoms
In the event of abrupt discontinuation of intrathecal administration of baclofen, sequelae such as high fever,
changes in mental state, increased spasticity as a rebound effect and muscle rigidity may occur regardless of the
cause of the discontinuation, and in rare cases these may progress to seizures/status epilepticus, rhabdomyolysis,
multiorgan failure and death (see section 4.4).

PHARMACEUTICAL FORM

4.

to avoid overdose. This should again be performed under inpatient conditions.
Caution should be exercised when switching from baclofen to morphine and vice versa (see section 4.5).

Posology and method of administration

Efficacy of baclofen intrathecal has been demonstrated in clinical studies with an EU certified pump. This is
an implantable administration system with a refillable reservoir that is implanted subcutaneously, usually in
the abdominal wall. The instrument is connected to an intrathecal catheter that passes subcutaneously into the
subarachnoid space.

Special patient groups
In patients with slowed CSF circulation due, for example, to blockage caused by inflammation or trauma, the
delayed migration of baclofen can reduce the antispastic efficacy and boost the adverse reactions (see section 4.4).

The testing, implantation and dosage-titration phases of the intrathecal administration must be performed
under in-patient conditions in centres with specific experience with close medical supervision by suitably
qualified physicians. Intensive medical care should be immediately available owing to possible lifethreatening events or serious adverse reactions.

Administration: particular specifications
Gablofen 500 microgram/ml, 1000 microgram/ml, and 2000 microgram/ml are intended for use with infusion
pumps. The concentration to be used depends on the dose requirements and size of pump reservoir.
Please refer to the manufacturer`s manual, which contains all specific recommendations.

Only pumps constructed of material known to be compatible with the product and incorporating an in-line
bacterial retentive filter should be used.

The necessary concentration of baclofen when filling the pump depends on the total daily dose and on the rate
of delivery of the pump. If baclofen concentrations other than 50 microgram/ml, 500 microgram/ml, 1000
microgram/ml or 2000 microgram/ml are required, Gablofen in vials may be diluted to a lower concentration;
dilution must be performed under aseptic conditions with sterile preservative-free sodium chloride solution for
injections. The instructions of the pump manufacturer should be observed here. For instructions on dilution of the
medicinal product before administration, see section 6.6.

The screening procedure is as follows. The usual initial test dose in adults is 25 or 50 microgram which is
administered slowly into the intrathecal space by barbotage (alternating intrathecal baclofen administration and
distraction of cerebrospinal fluid to obtain an appropriate mixture) over a period of not less than one minute.
A positive response consists of a significant decrease in muscle tone and/or frequency and/or severity of spasms.
At intervals of at least 24 hours the dosage can be increased by increments of 25 micrograms to a maximum test
dosage of 100 micrograms, if the response is less than desired.
After every bolus injection the patient must be supervised for 4 to 8 hours.
The action of a single intrathecal dose generally sets in ½ to 1 hour after administration. The maximum
spasmolytic effect sets in about 4 hours after administration and lasts about 4 to 8 hours. The time to onset of
action, the peak action and the duration of action vary from patient to patient and are dependent on the dosage,
on the severity of symptoms, and on the mode and speed of administration.
There is much variability with regard to sensitivity to intrathecal baclofen between patients. Signs of severe
overdose (coma) have been observed in an adult after a single test dose of 25 microgram.

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Therapy-resistant epilepsy.
The medicinal product should not be administered by any route other than intrathecal. Gablofen must not be
administered by the intravenous, intramuscular, subcutaneous or epidural routes.
4.4

Special warnings and precautions for use

Baclofen may be administered only with special caution to patients with:
impaired CSF circulation due to passage constriction,
epilepsy or other cerebral seizure illnesses,
bulbar paralytic symptoms or partial paralysis of the respiratory musculature,
acute or chronic confusional states,
psychotic states, schizophrenia or Parkinson’s disease,
a history of dysreflexia of the autonomic nervous system,
cerebrovascular and respiratory failure,
pre-existing hypertension of the bladder sphincter,
impaired renal function,
peptic ulcers,
severe hepatic dysfunction.
For patients with spasticity due to head injury, it is recommended not to proceed to long-term baclofen intrathecal
therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).
The testing, implantation and dosage-titration phases of the intrathecal treatment must be performed in
hospital under close medical supervision by suitably qualified doctors in centres with specific experience
in order to ensure the continuous monitoring of the patients.

Patients who do not respond to a 100 microgram test dose should not be given further dose increments and treatment
should not progress to continuous intrathecal infusion.

Owing to possible life-threatening events or severe adverse reactions, suitable intensive medical care
facilities should be immediately available. Suitable precautionary measures must be taken before the start
of treatment.

Resuscitative equipment and trained staff must be available during screening, dose titration, and refills.
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.

After refilling the pump, the patient must be supervised for 24 hours. A doctor must be rapidly accessible
during this period.

Paediatric population screening phase
The recommended initial lumbar puncture test dose for patients 4 to <18 years of age is 25 microgram which
is administered slowly into the intrathecal space by barbotage over a period of not less than one minute.
Patients who do not experience a response may receive a 25 microgram/day dose escalation every 24 hours. The
maximum screening dose should not exceed 100 microgram/day in paediatric patients.
Dose titration phase
Once the patient’s responsiveness to baclofen has been established, an intrathecal infusion may be introduced.
Baclofen 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.
A very careful patient tailored dosage titration is necessary because of the potential for large response differences
with a given dose among patients.
Following implantation, if the duration of action of the test dose is more than 12 hours, this is taken as the
initial daily dose. If the duration of action of the test dose is shorter than 12 hours, then the initial daily dose is
double the test dose. The dose must not be increased during the first 24 hours. After the first 24 hours the dose
is adjusted slowly on a daily basis, to obtain the desired effect.
The antispastic action of baclofen sets in 6 to 8 hours after the start of continuous infusion and reaches its
maximum within 24 to 48 hours.
Adult Patients with Spasticity of Spinal Cord Origin: After the first 24 hours, for adult patients, the daily
dosage should be increased slowly by 10% to 30% increments and only once every 24 hours, until the desired
clinical effect is achieved.
Adult Patients with Spasticity of Cerebral Origin: After the first 24 hours, the daily dose should be increased
slowly by 5% to 15% only once every 24 hours, until the desired clinical effect is achieved.
When using a programmable pump, it is advisable to adjust the dosage only once in any 24-hour period. With
non-programmable pumps with a catheter length that release 1 ml of solution per day, intervals of 48 hours are
recommended in order to be able to assess the reaction to the dosage. If a considerable rise in the daily dosage
does not increase the clinical action, then the pump function and the catheter permeability should be verified.
If the dose has been significantly increased without apparent clinical effect pump function and catheter patency
should be investigated.
During the test phase, as well as during the titration period following implantation, patients should be closely
monitored at an institution with all the necessary equipment and personnel. Resuscitative equipment must be
on immediate stand-by in the event of any reaction that threatens the vital prognosis, or onset of very serious
undesirable effects. In order to limit risks in the perioperative phase, the pump must only be implanted at centres
with experienced personnel.
Adult maintenance therapy
The clinical goal is to maintain muscle tone as close to normal as possible, and to minimise the frequency and
severity of spasms without inducing intolerable undesirable 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 is normally 300 to 800 microgram of baclofen/day. The lowest and highest daily dosages recorded as
administered to individual patients during dosage titration are 12 microgram and 2003 microgram respectively
(US studies). Experience with dosages above 1000 microgram/day is limited. During the first few months of
treatment, the dosage must be checked and adjusted particularly often.
In patients with spasticity of cerebral origin maintenance the maintenance dosages reported during long-term
therapy with continuous intrathecal infusion of Gablofen range from 22 to 1400 microgram of baclofen per day,
with mean daily doses of 276 microgram after an observation period of 1 year and 307 microgram after 2 years.
Children under 12 years of age usually require lower dosages (range: 24 to 1199 microgram/day; mean: 274
microgram/day.
Paediatric population initial maintenance therapy
In children aged 4 to <18 years with spasticity of cerebral and spinal origin, the initial maintenance dose for longterm continuous infusion of baclofen ranges from 25 to 200 microgram/day (median dose: 100 microgram/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
microgram/day.
Method of administration
Baclofen 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 undesirable effects.
If a significant dose increase should suddenly be necessary, this is indicative of a catheter complication (kink, tear
or dislodgement) or pump malfunction.
In order to prevent excessive weakness the dosage of baclofen should be adjusted with caution whenever spasticity
is required to maintain function.
Around 5% of patients receiving long-term treatment become refractory to dose escalation. This may be due
to therapeutic failure. There is insufficient experience available to make any recommendations on dealing with
treatment failure. However, this phenomenon has occasionally been treated in hospitals by a “drug holiday”
consisting of the gradual reduction off baclofen intrathecal over a period of 2 to 4 weeks and switching
to alternative methods of spasticity therapy. After this period, sensitivity to baclofen intrathecal may be
re-established: treatment should be resumed at the initial continuous infusion dose, followed by a titration phase

1

What is in this leaflet
1. What Gablofen is and what it is used for
2. What you need to know before you are given Gablofen
3. How to use Gablofen
4. Possible side effects
5. How to store Gablofen
6. Contents of the pack and other information
1.

What Gablofen is and what it is used for

Gablofen is administered by injection into the spinal canal directly into the spinal fluid (intrathecal
injection) and relieves severe muscle rigidity (spasticity).

Gablofen is used in adults and children aged 4 years and above. It is used when other orally taken
medicines, including baclofen, have been unsuccessful or caused unacceptable side effects.

Elderly patients
As part of clinical studies, some patients over 65 years of age have been treated with baclofen without specific
problems being observed. Experience with baclofen tablets shows, however, that adverse reactions can occur more
frequently in this patient group. Older patients should therefore be monitored carefully for the development of
adverse reactions.

The initial test phase must only be performed with low concentration solution containing 50 microgram baclofen
in 1 ml.

Read all of this leaflet carefully before you are given this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.

Renal impairment
No studies have been performed in patients with renal impairment receiving baclofen therapy. In patients with
impaired renal function, the dosage may need to be reduced to take account the clinical condition and the level of
reduced renal function (see section 5.2).

Gablofen 50 microgram/1ml 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 Gablofen
500 microgram/ml, 1000 microgram/ml, or 2000 microgram/ml 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 individualized dose titration prior to maintenance therapy.

Adult screening phase
Prior to pump implantation and initiation of chronic infusion of baclofen, patients must demonstrate a positive
response to intrathecal test dose in an initial test phase. Usually, a bolus test dose is administered via lumbar
puncture or an intrathecal catheter, in order to provoke a response. Patients should be infection-free prior to
screening, as the presence of a systemic infection may prevent an accurate assessment of the response.

Baclofen

Gablofen is used to treat severe, long-lasting muscle tension (spasticity) occurring in various
illnesses, such as:

brain or spinal cord injuries or diseases

multiple sclerosis, which is a progressive brain and spinal cord nerve disease with physical and
mental symptoms

Intrathecal administration of Gablofen 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.

Before administration of Gablofen, the solution should be checked for clarity and colourlessness. Only clear
solutions practically free from particles should be used. If clouding or discoloration is evident, then the solution
should not be used and should be discarded.
The solution it contains is stable, isotonic, pyrogen and antioxidant free and has a pH-value of 5.5–7.5.
Every pre-filled syringe is intended for single use only.

Package leaflet: Information for the user
Gablofen™ 2 mg/ml solution for injection/infusion in pre-filled syringe

Hepatic impairment
No studies have been performed in patients with hepatic impairment receiving baclofen therapy. No dosage
adjustment is recommended as the liver does not play any significant role in the metabolism of baclofen after
intrathecal administration of baclofen. Therefore, hepatic impairment is not expected to impact the systemic
exposure of baclofen (see section 5.2).

Paediatric population
The safety and efficacy of baclofen for the treatment of severe spasticity of cerebral or spinal origin in children
younger than 4 years of age have not been established.
The implantation of the pump requires a certain body size.
Use of intrathecal baclofen in the paediatric population should only be prescribed by medical specialists with the
necessary knowledge and experience.
The experience in children under 4 years of age is limited.

Before Gablofen is administered, the subarachnoid space of patients with post-traumatic spasticity should be
investigated by an appropriate imaging technique as clinically indicated. If radiological signs of arachnoiditis are
found, treatment with Gablofen should not be instituted.

Gablofen 2000-United Kingdom-syringe-06-2015 INS0157GB-0615

Gablofen 2000-United Kingdom-syringe-06-2015 INS0157GB-0615

SUMMARY OF PRODUCT CHARACTERISTICS

In the event of abrupt discontinuation of intrathecal administration of baclofen, sequelae such as
high fever, changes in mental state, increased spasticity as a rebound effect, and muscle rigidity may
occur regardless of the cause of the discontinuation, and in rare cases may progress to seizures / status
epilepticus, rhabdomyolysis, multiple organ failure and death.
In order to prevent abrupt discontinuation of intrathecal administration of baclofen, special attention
should be paid to the correct programming and monitoring of the infusion system, to the time schedules
and procedures for refilling the pump and to the alarm signals of the pump. The patients and their
caregivers must be instructed about the need to observe the set appointments for refilling and about the
early symptoms of baclofen withdrawal. Particular attention must be paid to patients with an evident
risk (e.g., patients with spinal cord injuries in the region of the sixth thoracic vertebra or higher, patients
who have difficulty making themselves understood, or patients who already have a history of exhibiting
withdrawal symptoms after discontinuing oral or intrathecal baclofen).
The manufacturers of infusion systems give specific instructions for the programming and refilling of the
pumps, and these must be followed exactly. Experience with continuous intrathecal baclofen infusion is
available only for the use of one particular pump model. Confirmed experience with other implantable
pump systems is not available.
Preconditions for treatment with intrathecal baclofen include the ability to tolerate and respond to the single
intrathecal injection of a dose of up to 100 microgram of baclofen as a bolus injection in the form of intrathecal
solution containing 50 microgram baclofen in 1 ml.
Before the start of treatment with baclofen, any unsatisfactory treatment with other antispastic medications should
be tailed off.
Medical Support
The infusion system should not be implanted before the reaction of the patient to the single intrathecal injections
of baclofen 50 microgram/1 ml is sufficiently established. The first intrathecal administration, the implantation
of the infusion system, and the first infusion and dosage-titration of baclofen are associated with risks such as
CNS suppression, cardiovascular collapse and respiratory failure. These steps must therefore be performed under
in-patient conditions with the availability of intensive medical care, and the instructions on dosage must be
observed. The necessary facilities and support for immediate resuscitation in cases of life-threatening symptoms
should be available. The treating physician must have specific experience in dealing with intrathecal administration
and related infusion systems.
Monitoring the patients
After surgical implantation of the pump and particularly during the initial phase of pump activity and on changing
the baclofen concentration or the infusion rate, the patient must be monitored closely until his/her condition is
stable. The treating doctor, the patient and the hospital staff as well as other persons involved in the care of the
patient must be adequately informed about the risks of this method of treatment. In particular, the symptoms of
overdosing or sudden withdrawal, the measures to be taken in these cases, and the care of the pump and of the
implantation site must be known.
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,
have been reported. However, a causal relationship with intrathecal baclofen could not be established. 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, 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.
Implantation of the pump
Prior to implantation of the pump, patients should be free from infection, since an infection increases the risks of
surgical complications. Moreover, a systemic infection may complicate attempts to adjust the dose.
Refilling the pump reservoir
The pump reservoir is to be re-filled by specially trained doctors according to the instructions given by the pump
manufacturer. Re-fill intervals should be carefully calculated to prevent depletion of the reservoir, as this would
result in recurrence of severe spasticity (see Discontinuation phenomena section).
This re-filling should be performed under strictly aseptic conditions in order to prevent contamination by
microorganisms and infections. Every re-filling and every manipulation of the pump reservoir should be followed
by an observation phase appropriate for the clinical situation. Extreme caution is indicated when filling an
implanted pump that possesses an access port with direct access to the intrathecal catheter. Injection via the access
port directly into the catheter can cause life-threatening overdosing.
Additional notes on dose adjustment
Occasionally a certain level of spasticity is necessary to maintain body posture and balance or other functions.
In order to avoid excessive weakness and thus to prevent the patient from falling over, baclofen should be
administered with care in these cases. A certain level of muscle tone and occasional spasms may also be necessary to
support circulatory function and prevent deep-vein thrombosis.
Discontinuation phenomena
Abrupt discontinuation of baclofen, regardless of cause, may manifest itself in increased spasticity as a rebound
effect, pruritis, paraesthesia (tingling or burning) and hypotension. This can lead to sequelae such as a hyperactive
state with rapid and uncontrolled spasms, to elevated body temperature, and to symptoms similar to those of a
malignant neuroleptic syndrome such as changes in mental state and muscle rigidity. In rare cases these symptoms
have developed further to seizures/status epilepticus, muscle degradation (rhabdomyolysis), clotting disorders
(coagulopathy), multiple organ failure and death.
All patients receiving intrathecal baclofen therapy are potentially at risk for abrupt withdrawal. For this reason, the
patients and their caregivers must be informed about the need to observe the set appointments for re-filling the
pump and be instructed about the signs and symptoms of baclofen withdrawal, especially those that occur in an
early phase.
The early symptoms of baclofen withdrawal include recurrence of the spasticity originally present, itching, low
blood pressure and paraesthesia. Some clinical signs of advanced withdrawal syndrome resemble those of autonomic
dysreflexia, infection or sepsis, malignant hyperthermia, malignant neuroleptic syndrome or other conditions that
accompany a hypermetabolic state or extensive rhabdomyolysis.

2

2.

What you need to know before you are given Gablofen

Do not use Gablofen

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

if you have untreatable epilepsy

by any other route of administration than via the spinal canal
Warnings and precautions
Talk to your doctor before you are given Gablofen if you are/have:

any infection

had a head injury; for patients with spasticity due to head injury, it is recommended not to
proceed to intrathecal Gablofen therapy until the symptoms of spasticity are stable and can be
reliably assessed

had autonomic dysreflexia: a reaction of the nervous system to overstimulation, causing
sudden severe high blood pressure

reduced circulation of liquid contained in the brain and spinal cord as a result of obstructed
passage, for example caused by inflammation or injuries

treatable epilepsy

had a stomach or intestinal ulcer

overactive bladder sphincter muscle

acute or chronic confusional states

psychotic disorder, or schizophrenia (mental disease)

Parkinson’s disease

reduced kidney function or a liver disease

inadequate blood flow in the brain (cerebrovascular insufficiency)

heart or breathing difficulties

Monitoring of heart and breathing function is essential during the initial test phase,
particularly if you have heart or breathing difficulties.

diabetes

to undergo an operation
Contact your doctor immediately if you think that Gablofen is not working as well as usual. It is
important to make sure that there are no problems with the pump.
You will be monitored closely in a fully equipped and staffed environment during the screening phase
and dose-finding period immediately following pump implant. You will regularly be assessed for your
dosage requirements, for possible side effects or evidence of infection. The functioning of the delivery
system will also be checked.
Treatment with Gablofen must not stop suddenly because of the risk of withdrawal effects. Make
sure that you do not miss hospital visits when the pump reservoir is being refilled.
Children
Gablofen is not recommended for children under 4 years. Older children must have sufficient
body mass to accommodate the implantable pump. There is limited clinical data in children under
the age of four.
Elderly patients
Some patients over the age of 65 years have been treated with intrathecal baclofen during the
clinical trials without specific problems. Experience with baclofen tablets shows however, that this
patient group may be more susceptible to side effects. Older patients should therefore be carefully
monitored for the occurrence of side effects.
Other medicines and Gablofen
Tell your doctor or pharmacist if you are using or have recently used or might use any other
medicines, including medicines obtained without a prescription.
Inform your doctor if you are using any of the following medicines as they can affect or be affected
by Gablofen:

other medicines to treat muscle spasm condition
If possible, your doctor may slowly discontinue other medicines which treat muscle spasm.

medicines to treat depression

medicines to treat high blood pressure

levodopa, carbidopa: medicines to treat Parkinson’s disease

strong pain relief medicines, such as morphine

medicines which slow down the function of the central system, such as sleep inducing
medicines

other medicines administered into the spine

Administration of other medicines into the spine is not recommended during Gablofen
treatment.
Concomitant use of general anaesthetics may increase the risk of cardiac disturbances and seizures.
Gablofen with alcohol
Avoid drinking alcohol during treatment with Gablofen as this may lead to an undesirable
intensification or unpredictable change in the effects of the medicine.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby,
ask your doctor or pharmacist for advice before using this medicine.
There is limited experience on the use of intrathecal baclofen during pregnancy or while breastfeeding. Gablofen should not be used during pregnancy or while breast-feeding, unless the expected
benefit for the mother outweighs the potential risk for the child. Gablofen passes into breast milk,
but low levels are expected after intrathecal administration. Consequently, Gablofen can be used
during breast-feeding.
Driving and using machines
During treatment with Gablofen your ability to drive or use machines may be considerably
impaired.
Some people may feel drowsy, dizzy, have problems with their eyes, difficulties in controlling
movements or have hallucinations while being treated with Gablofen. Do not drive or anything that
requires you to be alert until these effects have worn off, if this applies to you. Before driving or
using machines you should consult your physician.
Gablofen contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per maximum daily dose i.e. essentially
“sodium-free”.
3.

How to use Gablofen

Gablofen may only be administered by a specially qualified doctor.
The dose varies, dependent upon each person’s condition. The doctor will decide your dose after
testing your response to this medicine.
Firstly, the doctor will give you single doses of Gablofen, to find out if 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 continuously delivers Gablofen will be implanted into your chest or abdominal
wall. The doctor will provide you with all necessary instructions for using the pump and dosage
information. Make sure that you understand everything.
Your dose depends upon your response to the medicine. Beginning with a low dose, this is gradually
increased over a few days under doctor’s supervision, until you have the right dose.
Side effects are more likely if the starting dose is too high or the dose is increased too quickly. To
avoid these effects, which may be serious, it is important that your pump does not run out. Ensure
that you do not miss your hospital appointments.
It is extremely important that you keep your appointments with the doctor to refill the pump,
otherwise spasms may recur because you are not getting a high enough dose of Gablofen. Your
muscle spasms may worsen as a result.
If your muscle spasticity is not improving or if you start having spasms again, either gradually or
suddenly, contact your doctor immediately.
If treatment with Gablofen is interrupted
It is very important that you, and those caring for you, are able to recognise signs of Gablofen
withdrawal. These may appear suddenly or slowly for example because the pump is not working
properly due to battery problems, catheter problems or alarm dysfunction.
The signs of withdrawal are:
increased spasticity, too much muscle tone
difficulty with muscle movements

1

-

increase in heart rate or pulse
itching, tingling, burning sensation or numbness (paraesthesia) in your hands or feet
palpitations
anxiety
high body temperature
low blood pressure
altered mental conditions for example agitation, confusion, hallucinations, abnormal thinking
and behaviour, convulsions

Other symptoms of abrupt discontinuation can be: hallucinations, psychotic, manic or paranoid states, severe
headaches and sleeplessness. An autonomic crisis with heart failure has been observed in one case of a patient with a
syndrome resembling stiff-man syndrome.

The patient must be closely monitored for any signs and symptoms of overdose throughout the entire treatment,
particularly during the initial test phase and titration phase, but also during reintroduction of baclofen after an
interruption of therapy.

In most cases the withdrawal symptoms set in within hours or a few days after interruption of the intrathecal
administration. Common reasons for the abrupt interruption of intrathecal administration are malfunctions of the
catheter (especially problems with the connection), low volume in the pump reservoir, or a discharged battery in
the pump. In order to prevent abrupt interruption of intrathecal administration of baclofen, particular care should
be paid to the programming and the monitoring of the infusion system, the time schedule and procedure for
re-filling the pump and the alarm signals of the pump.

Signs of overdose may appear suddenly or insidiously.

Duration of use
To be decided by the doctor.

Therapy of discontinuation/withdrawal symptoms
Rapid and correct confirmation of the diagnosis and treatment in an emergency medical or intensive care unit
are important to prevent the possibly life-threatening CNS and systemic effects of withdrawal of baclofen. The
recommended treatment is resumption of the baclofen administration at the same or approximately the same
dosage as before interruption of the baclofen delivery. However, if baclofen administration can be resumed
only after a delay, treatment with GABA-agonists such as oral or enteral baclofen or oral, enteral or intravenous
benzodiazepines can prevent the potentially fatal sequelae. However, there is no guarantee that mere administration
of oral or enteral baclofen is sufficient to prevent the progression of the symptoms of withdrawal of baclofen.

During long-term treatment, some patients find that Gablofen becomes less effective. Your doctor
may recommend occasional breaks in treatment to counteract this.

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

If you have any of the above signs, tell your doctor straight away. These signs may be followed by
more serious side effects unless you are treated immediately.
Route of administration
Gablofen may only be administered into the spinal canal (intrathecal use).

If you are given more Gablofen than you should
It is very important that you and your carer can recognise the signs of overdose. This may occur if the
pump is not working properly.
Inform your doctor immediately if this applies to you or you experience any overdose signs, such as:

unusual muscle weakness

sleepiness, clouding or loss of consciousness

dizziness, light-headedness

excessive salivation, abnormal low body temperature

nausea or vomiting

breathing difficulties, respiratory arrest

seizures
If you stop using Gablofen
If this medicine must be stopped, this may only be done by your doctor who will reduce the
dose gradually to avoid side effects. Suddenly stopping intrathecal Gablofen can cause withdrawal
symptoms which in some cases have proven fatal.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
These occur more often at the start of treatment during your hospital stay, but they may also occur
later. Many of these side effects are also known to be associated with the specific medical condition for
which you are being treated.
Side effects can occur with the following frequencies:
Very common, may affect more than 1 in 10 people

drowsiness

reduced muscle tension
Common, may affect up to 1 in 10 people

sedation, dizziness, light-headedness

pain, fever, chills

abnormal sensation such as tingling

problems with eyesight with vision blurred or double-vision

slurred speech

lethargy, weakness

breathing difficulties (respiratory depression, dyspnoea, bradypnoea), lung inflammation
(aspiration pneumonia)

sleeplessness

confusion, disorientation, anxiety, restlessness, depression

low blood pressure

constipation, diarrhoea

dry mouth, decreased appetite, excessive saliva

rash, itching

tissue swelling in the face, hands or feet

urinary incontinence

increased muscle tension, muscle weakness

sexual problems, such as impotence
The following side effects occur more frequently in patients with cerebral spasticity:
Seizures, headache, nausea, vomiting and difficulties in urinating
Uncommon, may affect up to 1 in 100 people

feeling abnormally cold

involuntary eye movement (nystagmus)

difficulties in controlling movements (ataxia)

reduced memory

disturbed mood, euphoria, paranoia, hallucinations, suicidal thoughts and attempts

bowel obstruction, difficulty in swallowing, loss of taste, dehydration

high blood pressure, slow heartbeat

deep vein thrombosis

flushed or pale skin, excessive sweating

hair loss
Rare, may affect up to 1 in 1000 people

Life-threatening withdrawal symptoms due to drug delivery failure.
For a description of the signs of withdrawal, see “If treatment with Gablofen is interrupted”.
For a description of the signs of overdose, see “If you are given more Gablofen than you should”.
There have been reports of problems associated with the pump and delivery system such as infections,
inflammation of the lining around the brain and spinal cord (meningitis) or inflammation at the tip of
the delivery tube.
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 Yellow Card Scheme, Website: www.mhra.gov.uk/
yellowcard. By reporting side effects, you can help provide more information on the safety of this
medicine.
5.

How to store Gablofen

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the outer carton and on the pre-filled
syringe.
The expiry date refers to the last day of that month.
Do not store above 30°C. Do not freeze.
After first opening: the product should be used immediately.
Do not use this medicine if you notice that the solution is not clear or free from particles.
As it is limited to hospital use the disposal of unused medicine is carried out directly by the hospital.
6.

Contents of the pack and other information

What Gablofen contains

The active substance is baclofen.

Each ml contains 2 mg (2000 microgram) baclofen.
Each 20 ml pre-filled syringe contains 40 mg (40000 microgram) baclofen.

The other ingredients are sodium chloride and water for injection.
What Gablofen looks like and contents of the pack
Gablofen is a clear, colourless solution for injection.
Gablofen is available in packs containing one syringe of 20 ml.
Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Mallinckrodt UK Commercial Ltd., Building 1000, Lakeside, Portsmouth, PO6 3EZ, United
Kingdom


Manufacturer
Mallinckrodt Medical Imaging Ireland, Damastown, Mulhuddart, Dublin 15, Ireland

This medicinal product is authorised in the Member States of the EEA under the following
names:
Belgium
Baclofen Mallinckrodt
Denmark
Gablofen
France
BACLOFENE Mallinckrodt
Germany
Gablofen
Italy
Baclofene Mallinckrodt
Netherlands
Gablofen
Spain
Baclofeno Mallinckrodt
Sweden
Gablofen
United Kingdom
Gablofen
This leaflet was last revised in July 2015.

Elderly patients >65 years
Elderly patients may be more susceptible to the undesirable effects of oral baclofen in the titration stage and this
may also apply to intrathecal baclofen.
Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per maximum daily dose, i.e. essentially
“sodium free”.
4.5

Interaction with other medicinal products and other forms of interaction

No interactions studies have been performed.
There is little experience with the use of intrathecal baclofen in combination with systemic medicinal products to
predict specific drug-drug interactions, although it is suggested that the low baclofen systemic exposure observed
after intrathecal administration could reduce the potential for pharmacokinetic interactions (see section 5.2).
Whenever possible, all concomitant oral antispastic medications should be discontinued, to prevent a possible
overdose or undesirable interactions; preferably prior to initiating the baclofen infusion and under close medical
surveillance. However, any abrupt reduction or discontinuation of the concomitant antispastic medication should
be avoided during chronic treatment with baclofen.
Alcohol and other compounds affecting the CNS
The concomitant administration of baclofen and other medicinal products that have a suppressing effect on
functions of the central nervous system (e.g. analgesics, neuroleptics, barbiturates, benzodiazepines, anxiolytics)
can enhance the action of baclofen. In particular, the concomitant intake of alcohol should be avoided as the
interactions with alcohol are unpredictable.
Tricyclic Antidepressants
When taken concomitantly with baclofen tablets, some specific medicinal products for the treatment of depression
(tricyclic antidepressants) can potentiate the effect, and as a result considerable muscle relaxation may occur. For
this reason, such an interaction during concomitant administration of baclofen and tricyclic antidepressants cannot
be excluded.
Antihypertensives
As concomitant use of oral baclofen and antihypertensive medicinal products may increase any fall in blood
pressure, it may prove necessary to monitor blood pressure. If applicable, the dosage of the antihypertensive
medication must be reduced.
Levodopa/Dopa decarboxylase inhibitor
Concomitant use of oral baclofen and levodopa/Dopa decarboxylase inhibitor resulted in increased risk of
adverse events like visual hallucinations, confusional state, headache and nausea. Worsening of the symptoms of
Parkinsonism has also been reported. Thus, caution should be exercised when intrathecal baclofen is administered
to patients receiving levodopa/Dopa decarboxylase inhibitor therapy.
Morphine
The combined use of morphine and intrathecal baclofen has been responsible for hypotension in one patient.
It cannot be excluded that in such cases respiratory disturbances or CNS disturbances may also occur. For this
reason, an increased risk of these disturbances should be borne in mind during concomitant administration of
opiates or benzodiazepines.
Anaesthetics
Concomitant use of intrathecal baclofen and general anaesthetics (e.g. fentanyl, propofol) may increase the risk of
cardiac disturbances and seizures. Thus, caution should be exercised when anaesthetics are administered to patients
receiving intrathecal baclofen.
There is hitherto no information on the concomitant administration of baclofen with other intrathecally
administered medications.
4.6

Fertility, pregnancy and lactation

Pregnancy
There is limited data on the use of intrathecal baclofen in pregnant women. After intrathecal administration, small
amounts of baclofen can be detected in maternal plasma (see section 5.2). Baclofen crosses the placenta and has
shown reproduction toxicity (see section 5.3). Baclofen should not be used during pregnancy, unless the expected
benefit for the mother outweighs the possible risks for the child.
Breastfeeding
Baclofen is excreted in breast milk, however clinically relevant levels are not expected due to the low plasma
concentration of baclofen in mothers treated with intrathecal baclofen. Gablofen can be used during breast-feeding.
Fertility
Animal studies have shown that intrathecal baclofen is unlikely to have an adverse effect on fertility (see section
5.3).
4.7

Effects on ability to drive and use machines

The ability to drive or use machines may be considerably impaired during treatment with intrathecal baclofen.
Alcohol consumption increases this impairment still further.
Central nervous system (CNS) depressant effects such as somnolence and sedation have been reported in some
patients on intrathecal baclofen. Other listed events include ataxia, hallucinations, diplopia and withdrawal
symptoms.
In Patients treated with intrathecal baclofen, the ability to continue driving or operating complex machinery should
be routinely evaluated by the treating physician.
4.8

Undesirable effects

Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to
<1/1,000); very rare (<1/10,000).
Metabolism and nutrition disorders
Common:
Decreased appetite.
Uncommon:
Dehydration.
Psychiatric disorders
Common:
Depression, Confusional state, Disorientation, Agitation, Anxiety.
Uncommon:
Suicidal ideation, Suicide attempt, Paranoia, Hallucinations, Dysphoria, Euphoric
mood.
Nervous system disorders
Very common:
Somnolence.
Common:
Convulsion, Lethargy, Dysarthria, Headache, Paraesthesia, Insomnia, Sedation,
Dizziness.
Convulsion and headache occur more frequently in patients with cerebral spasticity.
Uncommon:
Ataxia, Hypothermia, Dysphagia, Memory impairment, Nystagmus.
Eye disorders
Common:
Accommodation disorders with vision blurred or diplopia.
Cardiac disorders
Uncommon:
Bradycardia.
Vascular disorders
Common:
Orthostatic hypotension
Uncommon:
Deep vein thrombosis, Hypertension, Flushing, Pallor.
Respiratory, thoracic and mediastinal disorders
Common:
Respiratory depression, Aspiration Pneumonia, Dyspnoea, Bradypnoea.
Gastrointestinal disorders
Common:
Vomiting, Constipation, Diarrhoea, Nausea, Dry mouth, Salivary hypersecretion.
Nausea and vomiting occur more frequently in patients with cerebral spasticity
Uncommon:
Ileus, Hypogeusia.
Skin and subcutaneous tissue disorders
Common:
Urticaria, Pruritus.
Uncommon:
Alopecia, Hyperhidrosis.
Musculoskeletal and connective tissue disorders
Very common:
Hypotonia.
Common:
Hypertonia, Asthenia.
Renal and urinary disorders
Common:
Urinary retention, Urinary incontinence.
Urinary retention occurs more frequently in patients with cerebral spasticity.
Reproductive system and breast disorders
Common:
Sexual dysfunction.
General disorders and administration site conditions
Common:
Oedema peripheral, Face oedema, Pain, Pyrexia, Chills.
Rare:
Life-threatening withdrawal symptoms due to drug delivery failure
A reliable causal connection between the observed adverse events and the administration of intrathecal baclofen is
not always possible as some of the observed adverse events could also be symptoms of the underlying illness being
treated. Particularly frequently occurring adverse events such as dizziness, light-headedness, somnolence, headache,
nausea, drop in blood pressure, and muscle weakness are usually due to the medication.
Seizures, headache, nausea, vomiting and urinary retention occur more often in patients with spasticity of cerebral
origin than in patients with spasticity of spinal origin).
Ovarian cysts have been found by palpation in about 5% of the multiple sclerosis patients who were treated with
oral baclofen for up to one year. In most cases these cysts disappeared spontaneously while patients continued to
receive the medicinal product. Ovarian cysts are known to occur spontaneously in a proportion of the normal
female population.
Adverse events due to the infusion system
These can include inflammatory mass at the tip of the catheter, dislocation/kinking/rupture (tearing) of the
catheter with possible complications, infection of the implantation site, meningitis, septicaemia, pump-pocket
seroma and haematoma with a possible risk of inflammation, failure of the pump function and CSF leakage, as well
as skin perforation after a long time, and overdosing or underdosing due to incorrect handling, whereby in some
cases a causal relationship with baclofen cannot be excluded (see section 4.4).

Symptoms of overdose: excessive muscular hypotonia, light-headedness, dizziness, somnolence, sedation, convulsions,
loss of consciousness, hypothermia, excessive salivation, nausea and vomiting.
Respiratory depression, apnoea and coma occur in the event of a major overdose. Seizures may occur with
increasing dosage or, more commonly, during recovery from an overdose.
Treatment
There is no specific antidote for the treatment of overdosing with baclofen. In general, the following steps should
be undertaken:

Residual intrathecal baclofen solution should be removed from the pump as soon as possible.

Patients with respiratory depression should be intubated if necessary until baclofen is eliminated.

If lumbar puncture is not contraindicated, 30 to 40 ml of CSF may be drawn off in the early stage of
intoxication in order to reduce the concentration of baclofen in the CSF.

Maintenance of cardiovascular function.

If spasms occur, diazepam intravenous should be administered carefully.
5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Musculo-skeletal system; Muscle-relaxants, centrally acting agents; other centrally
acting agents
ATC code: M03BX01
Mechanism of action
The precise mechanism of action of baclofen as a muscle relaxant and antispasticity medicinal product is not
fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflex transmission in the spinal cord
by stimulating the GABAB receptors. Baclofen is a chemical analogue of the inhibitory neurotransmitter gammaaminobutyric acid (GABA).
Neuromuscular transmission is not affected by baclofen. Baclofen exerts an antinociceptive effect. In neurological
diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen take the form of a beneficial
action on reflex muscle contractions and of marked relief from painful spasm, automatism, and clonus. Baclofen
improves patient mobility, providing them with greater autonomy, and facilitates physiotherapy. In humans, as
well as in animals, baclofen has been shown to have general depressant properties on the central nervous system,
causing sedation, somnolence, and respiratory and cardiovascular depression.
Intrathecal bolus
The onset of action is generally one-half hour to one hour after an intrathecal bolus. Peak spasmolytic effect is
seen at approximately 4 hours after dosing and effects may last 4 to 8 hours. Onset, peak response, and duration of
action may vary with individual patients depending on the dose and severity of symptoms.
Continuous infusion
Intrathecal baclofen’s antispastic action is first seen at 6 to 8 hours after initiation of continuous infusion.
Maximum activity is observed in 24 to 48 hours.
5.2

Pharmacokinetic properties

When considering the pharmacokinetic data on baclofen intrathecal, the effects of the slow CSF circulation should
be taken into account.
Absorption
Infusion directly into the spinal subarachnoid space circumvents absorption processes and allows access to the
receptor sites in the posterior horn of the spinal cord.
Baclofen when introduced directly into the intrathecal space permits effective CNS concentrations to be achieved
with resultant plasma concentrations at least 100 times lower than those occurring with oral administration.
Distribution
After a single intrathecal bolus injection/rapid infusion, the distribution volume calculated from the concentration
in the CSF ranges from 22 to 157 ml. The mean of about 75 ml corresponds approximately to the human CSF
volume, and indicates that it is this in which the baclofen is mainly distributed.
With continuous intrathecal infusion of daily doses of between 50 to 1200 microgram, steady-state concentrations
of baclofen in the CSF of the lumbar region of 130 to 1240 nanogram/ml are reached within 1 to 2 days.
During continuous intrathecal infusion of daily doses between 95 to 190 microgram, once steady state has been
reached, a baclofen concentration gradient is built up in the range between 1.8 : 1 and 8.7 : 1 (mean = 4 : 1)
between lumbar CSF and subarachnoid cisternal CSF. This is of clinical importance, as spasticity of the lower
extremities can be effectively treated without greatly influencing the upper limbs, with fewer adverse central
nervous effects due to the medicinal product’s action on the brain centres.
The baclofen plasma concentrations under intrathecal infusion of clinically used doses of baclofen are below 5
nanogram/ml (≤ 10 nanogram/ml in children) and are thus below the analytical quantitation limits. During
intrathecal infusion the plasma concentrations do not exceed 5 ng/ml, confirming that baclofen passes only slowly
across the blood-brain barrier.
Elimination
The elimination half-life from the CSF after administration of a single intrathecal bolus injection/ rapid infusion of
50 to 135 microgram of baclofen ranges from 1 to 5 hours. Both after a single bolus injection and after continuous
infusion into the spinal subarachnoid space using an implanted pump, the mean clearance from the CSF is about
30 ml/hour (corresponding to the physiological turnover rate of the CSF).
Thus the amount of baclofen infused over 24 hours is eliminated almost completely with the CSF over the
same period of time. Systemic baclofen is eliminated almost completely renally in the unaltered form. A
metabolite (beta-(p-chlorophenyl)-gamma-hydroxybutyric acid) formed in small amounts in the liver by oxidative
desamination is inactive. Investigations suggest baclofen is not metabolised in the CSF. Other routes of elimination
are not considered significant according to the information currently available.
From animal experiments it is evident that the active substance cumulates in the CSF after administration of high
doses. It has not been investigated to what extent this finding is relevant for humans and what consequences should
be expected.
Elderly Patients
No pharmacokinetic data is available in elderly patients after administration of intrathecal baclofen. When a single
dose of the oral formulation is administered, data suggest that elderly patients have a slower elimination but a
similar systemic exposure to baclofen compared to young adults. However, the extrapolation of these results to
multi-dose treatment suggests no significant pharmacokinetics difference between young adults and elderly patients.
Paediatric population
In paediatric patients, respective plasma concentrations are at or below 10 ng/ml.
Hepatic impairment
No pharmacokinetic data is available in patients with hepatic impairment after administration of baclofen.
However, as liver does not play a significant role in the disposition of baclofen it is unlikely that its
pharmacokinetics would be altered to a clinically significant level in patients with hepatic impairment.
Renal impairment
No pharmacokinetic data is available in patients with renal impairment after administration of baclofen. Since
baclofen is majorly eliminated unchanged through the kidneys, accumulation of unchanged active substance in
patients with renal impairment cannot be excluded.
5.3

Preclinical safety data

Local tolerance
Histological investigations in studies with continuous intrathecal infusion of baclofen to rats (2-4 weeks) and dogs
(2-4 months) have revealed no signs of a local reaction or inflammation due to baclofen.
Following 3 months intrathecal infusion in sheep, a mild inflammatory mass was observed during histopathological
examination without resulting in any clinical observations.
Genotoxicity and carcinogenicity
In vivo and in vitro genotoxicity tests have shown no mutagenic effect.
A 2-year study in rats (oral route) has shown that baclofen is not carcinogenic. This study showed a dosedependent increase in the incidence of ovarian cysts and a less marked increase in the incidence of hypertrophic
and/or haemorrhagic adrenal glands. The clinical relevance of these findings is not known.
Reproduction toxicity
Baclofen had no effect on the fertility of female rats. Possible effects on male fertility have not been investigated.
Baclofen is not teratogenic in mice, rats, and rabbits at doses at least 125-times the maximum intrathecal mg/kg
dose. Orally administered baclofen has been shown to increase the incidence of omphaloceles (ventral hernias)
in foetuses of rats given approximately 500-times the maximum intrathecal dose expressed as a mg/kg dose. This
abnormality was not observed in mice or rabbits.
Oral baclofen has been shown to delay foetal growth (ossification of bones) at doses that also caused maternal
toxicity in rats and rabbits. Baclofen caused widening of the vertebral arch in rat foetuses at a high intraperitoneal
dose.
Intrathecal baclofen is unlikely to have adverse effects on prenatal or postnatal development based on oral studies
in rats.
6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Sodium chloride
Water for injections
6.2

Incompatibilities

Glucose has been shown to be incompatible with baclofen, as a chemical reaction occurs between the two
substances.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3

Shelf life

3 years
After first opening: the product should be used immediately.
6.4

Special precautions for storage

Do not store above 30°C.
Do not freeze.
For storage conditions after first opening of the medicinal product, see section 6.3.
6.5

Nature and contents of container

Clear, colourless pre-filled syringes of glass type I (Ph. Eur.). Stoppers are made from halobutyl rubber. Each
syringe is packed into a plastic tray (intermediate packaging).
Pack size
1 pre-filled syringe of 20 ml.
6.6

Special precautions for disposal and other handling

Each syringe is intended for single use only. Any unused medicinal product or waste material should be disposed of
in accordance with local requirements.
7.

MARKETING AUTHORISATION HOLDER

Mallinckrodt UK Commercial Ltd.
Building 1000
Lakeside
Portsmouth, PO6 3EZ
United Kingdom

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued
monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard

8.

4.9

Date of first authorisation: DD month YYYY

Overdose

At the first signs of overdosing with intrathecal baclofen, the patient should be admitted to inpatient care if being
treated as an outpatient.

2

Overdosing can occur, for example, as a result of accidental delivery of the contents of the catheter during checking
of the patency or position of the catheter. Other possible causes are errors in the programming, extremely rapid
dosage increment, concurrent oral administration of baclofen or malfunction of the pump.
In one case, an adult patient showed signs of severe overdosing (coma) after injection of a single dose of
25 microgram of intrathecal baclofen.

3

MARKETING AUTHORISATION NUMBER(S)

PL 41744/0026
9.

10.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

DATE OF REVISION OF THE TEXT

30 July 2015

4

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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