BACLOFEN

Method of administration The efficacy of Baclofen SUN has been demonstrated in clinical studies using the SyncroMed infusion system. This system is a delivery system with a refillable reservoir that is implanted subcutaneously, usually in the abdominal wall.

The instrument is connected to an intrathecal catheter that also runs subcutaneously into the subarachnoid space. There is as yet no confirmed experience with other implantable pump systems. Intrathecal administration of baclofen 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. Dosage Baclofen 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 intrathecal baclofen into the intrathecal space (EU certified pumps).

Establishment of the optimum dose schedule requires that each patient undergoes an initial screening phase with intrathecal bolus, followed by a very careful individual dose titration prior to maintenance therapy 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 doctors.

Intensive medical care should be immediately available owing to possible life-threatening events or serious adverse reactions. 05 mg/1 ml during an initial test phase before starting the long-term treatment, either via an intrathecal catheter or by lumbar puncture.

This is followed by very careful patient-tailored dosage titration. This procedure is necessary because of the large differences between the therapeutically effective dosages required by different patients. Long-term administration is achieved by means of an implantable pump for continuous delivery of baclofen solution to the cerebrospinal fluid using Baclofen 10mg/20ml or Baclofen 10mg/5ml.

Before Baclofen is administered, the subarachnoid space of patients with post- traumatic spasticity should be investigated by myelography. If radiological signs of arachnoiditis are found, treatment with Baclofen should not be instituted.

Before administration of Baclofen, 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.

0. Every ampoule is intended for single use only.

Baclofen 10 mg/20 ml solution for infusion:

Baclofen 10 mg/5 ml solution for infusion: Implantation phase/dosage-titration phase (under inpatient conditions) After the action of baclofen has been confirmed in the test phase, intrathecal infusion is started using one of the implantable infusion pumps given above.

The antispastic action of baclofen sets in 6 to 8hours after the start of continuous infusion and reaches its maximum within 24 to 48hours.

The initial total daily dosage of Baclofen is calculated as follows:

If the duration of action of the test dose is more than 12hours, this is taken as the initial daily dose. If the duration of action of the test dose is shorter than 12hours, then the initial daily dose is double the test dose. The dosage should not be increased within the first 24hours.

After the first day of treatment, the dosage can slowly be titrated from day to day in order to achieve the desired action. The increase in the dosage per day should not exceed 10 to 30% of the previous dose in patients with spinal spasticity and 5 to 15% in patients with cerebral spasticity.

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 76cm catheter length that release 1ml of solution per day, intervals of 48hours 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 function of the pump and the patency of the catheter should be checked. In general, the dosage is increased to a maintenance dosage of 300 to 800microgram/day in patients with spinal spasticity.

Patients with cerebral spasticity usually require lower doses (see below). Long-term treatment phase The clinical goal is to maintain as normal a muscle tone as possible, and to minimise the frequency and severity of spasms without inducing intolerable side effects.

The lowest dose with which the spasticity can be well controlled without the appearance of unacceptable adverse reactions 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. As over the course of the treatment the therapeutic effect can diminish or the severity of the spasticity can alter, dosage titration under in-patient conditions is usually necessary in the long-term treatment phase.

Here also, the daily dosage can be increased by 10 to 30% in patients with spinal spasticity and 5 to 20% (upper limit) in patients with cerebral spasticity by altering the delivery rate of the pump or by changing the concentration of baclofen in the reservoir.

Conversely, if adverse reactions occur, the daily dosage can be reduced by 10 to 20%. If the dosage must suddenly be increased in order to achieve a sufficient effect, the possibility of a pump malfunction or a kink, […]

Some of the adverse reactions listed below have been reported in patients with spasticity of spinal origin but could also occur in patients with spasticity of cerebral origin. Adverse reactions that are more frequent in either population are indicated below.

Adverse drug reactions (Table 2) from clinical trials are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked under headings of frequency, the most frequent reactions first.

Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category 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), not known (cannot be estimated from the available data).

Table 2 Metabolism and nutrition disorders Uncommon:

Dehydration.

Psychiatric disorders Common:

Depression, Agitation, Anxiety. 4 – Precautions in special patient populations), Paranoia, Hallucinations, Euphoric mood, Dysphoria.

Nervous system disorders Very common:

Somnolence.

Common:

Convulsion, Confusional State, Disorientation, Lethargy, Dysarthria, Headache, Paraesthesia, Insomnia, Sedation, Dizziness.

Uncommon:

Ataxia, Memory impairment, Nystagmus, Hypothermia. Convulsion and headache occur more frequently in patients with spasticity of cerebral origin than in patients with spasticity of spinal origin.

Eye disorders Common:

Accommodation disorders, vision blurred, 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, Decreased appetite, Increased salivation Uncommon: Ileus, Dysphagia, Hypogeusia. Nausea and vomiting occur more frequently in patients with spasticity of cerebral origin than in patients with spasticity of spinal origin Skin and subcutaneous tissue disorders Common: Urticaria, Pruritus, Oedema peripheral and/or Face oedema.

Uncommon:

Alopecia, Hyperhidrosis.

Musculoskeletal and connective tissue disorders Very common:

Hypotonia.

Common:

Increased muscle tension Not known: Scoliosis Renal and urinary disorders Common: Urinary retention, Urinary incontinence. Urinary retention occurs more often in patients with spasticity of cerebral origin than in patients with spasticity of spinal origin.

Reproductive system and breast disorders Common:

Sexual dysfunction (Baclofen may compromise erection and ejaculation. This effect is usually reversible on withdrawal of Baclofen).

Not known:

Erectile dysfunction General disorders and administration site conditions Common: Asthenia, Pain, Pyrexia, Chills. 4). In approximately 5% of female patients with multiple sclerosis treated with baclofen tablets for more than one year, ovarian cysts were detected by palpation.

In most cases, these cysts disappeared spontaneously, although therapy was continued. Ovarian cysts are known to form spontaneously in a proportion of the healthy female population. A definite causal relationship between the observed side effects and the administration of baclofen is not always possible, since part of the observed side effects may also be symptoms of the underlying disease being treated.

In particular, frequently occurring side effects such as dizziness, drowsiness, somnolence, headache, nausea, drop in blood pressure and muscle weakness are mostly caused by the drug. 4). 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

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 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.

e. at least one year after the injury). Precautions in paediatric patients Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion. Use of baclofen 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 baclofen in children under the age of four years. 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.

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. 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.

Before the start of treatment with Baclofen, any unsatisfactory treatment with other antispastic medications should be tailed off. 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 baclofen, 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. 05 mg/1 ml, as systemic infections may increase the risk of surgical complications. Moreover, a systemic infection may complicate attempts to adjust the dose.

4 – Special Precautions for Use “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. 4 – Special Precautions for Use “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.

Medical environment Initial intrathecal administration, infusion system implantation, and initial infusion and dose adjustments of baclofen are associated with risks such as CNS attenuation, cardiovascular collapse, and respiratory failure, respectively.

Therefore, these steps must be taken under inpatient conditions when intensive care measures are available and dosing instructions are followed. Necessary equipment should be available to perform […]

1,) - therapy-resistant epilepsy. Baclofen should be administered only into the subarachnoid space. Baclofen must not be administered by the intravenous, intramuscular, subcutaneous or epidural routes.