Medicinal Products

BACLOFENE AGUETTANT 0.05 mg / mL

Generic drug of Lioresal 0.05 MG / 1 ML
Therapeutic class: Rheumatology
active ingredients: Baclofen
laboratory: Aguettant

Injectable solution for intrathecal infusion
Box of 10 ampoules of 1 mL
All forms

Indication

BACLOFENE AGUETTANT is indicated in patients with severe chronic spasticity resulting from trauma, multiple sclerosis or other medullary pathology that does not respond to oral baclofen or other oral antispastic drugs and / or in patients with intolerable adverse effects at effective oral doses.

BACLOFENE AGUETTANT is effective in adult patients with severe chronic spasticity of cerebral origin following, for example, cerebral palsy, traumatic brain injury or stroke; however, clinical experience is limited.

Pediatric patients

BACLOFENE AGUETTANT is indicated in patients aged 4 to 18 years with severe chronic spasticity of medullary or cerebral origin (associated with trauma, multiple sclerosis or other medullary pathology) not responding to other antispastic drugs administered orally (including oral baclofen) and / or in patients with intolerable adverse effects at effective oral doses.

Dosage BACLOFENE AGUETTANT 0.05 mg / mL Solution for injection for intrathecal infusion Box of 10 ampoules of 1 mL

BACLOFENE AGUETTANT is intended for administration as single bolus test doses (via a catheter inserted into the subarachnoid space or by lumbar puncture) and, during chronic treatment, the baclofen solution is administered intrathecally by means of an implantable pump that delivers the solution continuously in the subarachnoid space (EU certified pumps).

In order to determine the optimal dosage, each patient should undergo a test phase with an intrathecal bolus of baclofen, followed by an individual dose-setting period that will be performed with extreme caution before initiation of treatment. interview.

Intrathecal administration of baclofen using an implantable system should only be performed by an experienced physician with the required skills. It is extremely important to strictly follow the manufacturer's specific instructions regarding implantation, pump programming and / or tank filling.

The efficacy of intrathecal baclofen has been demonstrated in randomized controlled trials using an EU-certified infusion system. This is an implantable delivery system: a refillable reservoir is implanted under the skin, usually in the abdominal wall. This system is connected to a subcutaneous intrathecal catheter to the subarachnoid space.

Test phase.

Before administering baclofen as a continuous intrathecal infusion, patients should have a positive response to intrathecal administration of a test dose as part of an initial test phase. Generally, a bolus test dose is administered by lumbar puncture or an intrathecal catheter for response. Before screening, patients should be free of infection because the presence of a systemic infection may prevent a correct assessment of the response.

The initial dose is usually 25 or 50 micrograms; this dose is usually increased in increments of 25 micrograms at intervals of at least 24 hours until a response persists for about 4 to 8 hours.

The dose must be injected in at least one minute by bubbling.

Low dose ampoules (0.05 mg / ml) are available for this test phase.

Resuscitation equipment must be immediately available when the first dose is injected.

Patients are considered to respond positively if they show a significant reduction in muscle tone and / or frequency and / or severity of spasm.

There is great variability in sensitivity to intrathecal baclofen. Signs of severe overdose (coma) have been observed in an adult after a single test dose of 25 micrograms.

Patients who do not respond to a 100 microgram test dose should not receive additional doses and are not eligible for continuous intrathecal infusions. Monitoring of the respiratory and cardiac functions is essential during this phase, especially in patients suffering from cardiopulmonary disease and respiratory muscle deficiency or in patients undergoing treatment with benzodiazepine preparations or opiates, who are at increased risk of respiratory depression.

Pediatric patients

Test phase

The initial lumbar puncture test dose for patients aged 4 to 18 years should be 25 to 50 μg / day, depending on the age and size of the child. In non-responders, the dose may be increased in increments of 25 μg at intervals of at least 24 hours. The test dose should not exceed 100 μg / day in pediatric patients.

Phase of determination of the dose.

When a patient's positive response to BACLOFENE AGUETTANT has been demonstrated through test doses, intrathecal infusion will be initiated using a suitable administration system. An infection is likely to increase the risk of surgical complications and make attempts to adjust the dose more difficult.

After implantation, the initial total daily dose should be determined by doubling the dose that produced a positive effect during the test phase and administering this dose over a 24-hour period, unless the effect of the bolus dose 'is maintained for more than 12 hours. In the latter case, the initial daily dose will be identical to the dose administered during the test phase and will be administered over a 24-hour period. The dose should not be increased during the first 24 hours. After the first 24 hours, the dose is slowly adjusted daily until the desired effect is achieved. To avoid an overdose, the increment should not exceed 10 to 30%.

Patients with cerebral spasticity: After the first 24 hours, the dose should be adjusted slowly each day until the desired effect is achieved. To avoid an overdose, the increment should not exceed 5 to 15%.

If a programmable pump is used, the dose should be increased once every 24 hours. For non-programmable pumps connected to a 76 cm catheter and with a flow rate of 1 ml / day, it is recommended to evaluate the response only at 48 hour intervals. If the daily dose has been significantly increased without observing any clinical effect, check that the pump is working properly and that the catheter is permeable.

There is only limited experience with doses above 1, 000 micrograms / day.

During the test phase, as well as during the post-implantation dose-setting period, patients should be carefully monitored in a hospital facility with all equipment and necessary staff. Resuscitation equipment must be readily available in the event of a life-threatening reaction or the appearance of very serious adverse reactions. To limit risks during the perioperative phase, the pump must only be installed in centers with experienced staff.

Maintenance treatment.

The clinical objective is to maintain a muscle tone as close as possible to normal and to limit the frequency and severity of spasms without causing intolerable side effects. The lowest dose required should therefore be used to obtain a satisfactory response. Maintaining a certain degree of spasticity is desirable in order to avoid a feeling of "paralysis" by the patient.

In addition, some degree of muscle clonicity and occasional spasms may be important in supporting circulatory function and possibly preventing deep vein thrombosis.

In patients with spasticity of spinal origin, the daily dose should be increased gradually from 10 to 30% in order to maintain adequate control of symptoms. When the spasticity is of brain origin, any increase in the dose should be limited to 20% (range: 5 to 20%).

In both cases, the daily dose should also be reduced by 10 to 20% if the patient has adverse effects.

If a significant increase in dose is suddenly needed, this should be a problem with the catheter (kinking or shifting) or pump malfunction.

For long-term continuous infusion maintenance therapy, the intrathecal baclofen dose in patients with spasticity of spinal origin is between 10 and 1000 micrograms / day, a satisfactory response being obtained in most patients with 300 to 800 micrograms / day.

In patients with cerebral spasticity, the maintenance dose is between 22 and 1400 micrograms / day, with an average daily dose of 276 micrograms per day after 12 months and 307 micrograms per day after 24 months.

Pediatric population

In children aged 4 to 18 years with spasticity of cerebral and spinal origin, the initial maintenance dose for long-term continuous infusion is in the range of 25 to 200 μg / day (median dose: 100 μg / day). The total daily dose tends to increase during the first year of treatment, therefore the maintenance dose should be adjusted according to the individual clinical response. There is little data available for doses above 1000 micrograms / day.

The safety and efficacy of intrathecal baclofen in the treatment of cerebral and medullary spasticity in children under 4 years of age have not been established (see Warnings and Precautions ). .

About 5% of long-term treated patients become refractory to an increase in the dose. This phenomenon could be the consequence of a therapeutic failure. There is not enough experience to make recommendations on what to do when treatment fails. However, this phenomenon has occasionally been treated in hospital by a "therapeutic window" consisting of a progressive reduction of the intrathecal baclofen dose over a period of 2 to 4 weeks and the transition to another method of treatment of spasticity (for example morphine sulfate without preservative intrathecally). After this period, sensitivity to intrathecal baclofen may be reestablished: treatment should be resumed at the initial dose as a continuous infusion, followed by a dose-setting phase to avoid overdose.

Caution should be exercised when switching from intrathecal baclofen to morphine and vice versa (see "Interactions").

Regular clinical follow-up is necessary to assess the patient's dosage needs, to ensure that the administration system is functioning properly and to detect any adverse effects or the presence of an infection.

Stop treatment.

Except in the case of an emergency associated with an overdose, treatment should be discontinued progressively with successive reductions in dose. BACLOFENE AGUETTANT must not be stopped abruptly (see "Special warnings and precautions for use").

Administration: special specifications.

Ampoules of 10 mg / 5 ml, 40 mg / 20 ml and 10 mg / 20 ml of BACLOFENE AGUETTANT have been specifically developed for use with infusion pumps.

The exact concentration to choose will depend on the total daily dose required, as well as the minimum infusion rate of the pump. Refer to the manufacturer's instruction manual, which contains all specific recommendations.

Administration mode.

In the majority of cases, BACLOFENE AGUETTANT is administered as a continuous infusion directly after implantation. As soon as the patient is stabilized in terms of daily dose and in terms of functional aspects and to the extent that the pump allows, we can move to a more complex mode of administration to allow optimal control of the spasticity to different times of the day. For example, patients who experience more spasm during the night may require a 20% increase in the hourly infusion rate.

This change in infusion rate should be scheduled about 2 hours before the desired clinical effect is achieved.

Each bulb is exclusively for single use. Do not resterilize.

The drug must be visually inspected before use. Only clear solutions that are practically free of particles can be used.

For instructions on product dilution before administration, see section Instructions for use, handling and disposal .

Against indications

Hypersensitivity to the active substance or to any of the excipients.

Epilepsy refractory to treatment.

The drug should not be administered by any route other than the intrathecal route.

Adverse effects Baclofene Aguettant

In a large number of cases, it was not possible to establish a causal relationship between the observed effects and the administration of baclofen as most of the undesirable effects described may also be associated with the underlying disease. However, some commonly reported reactions (drowsiness, dizziness, headache, nausea, hypotension, hypotonia) appear to be associated with the drug. These effects are mostly transient and occur mainly during the test phase or when the concentration changes.

Table 1

Adverse effects are classified by organ system class and frequency; within each frequency group, adverse effects are presented in order of decreasing severity according to the following convention: very common (≥1 / 10), frequent (≥1 / 100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥1 / 10, 000, <1/1000), very rare (<1 / 10, 000).

Nervous system disorders

Very common

drowsiness (especially during the test phase)

Frequent

sedation, dizziness / vertigo, epileptic seizures (especially during abrupt cessation of treatment), headache, paresthesia, accommodation / vision disorder / diplopia, dysarthria, lethargy, asthenia, respiratory depression, insomnia, confusion / disorientation, anxiety, agitation, depression.

Rare

hypothermia, nystagmus, dysphagia, ataxia, memory problems, suicidal thoughts and suicide attempts, euphoria, dysphoria, hallucinations, paranoia.

Heart conditions

Frequent

hypotension.

Rare

hypertension, bradycardia, deep vein thrombosis, congestive flushing, pallor.

Respiratory, thoracic and mediastinal disorders

Frequent

dyspnoea, bradypnea, pneumonia.

Gastrointestinal disorders

Frequent

nausea / vomiting, constipation, dry mouth, diarrhea, lack of appetite, excessive salivation.

Rare

dehydration, ileus, ageusia.

Skin and subcutaneous tissue disorders

Frequent

urticaria, pruritus, facial or peripheral edema.

Rare

alopecia, diaphoresis.

Musculoskeletal and systemic disorders

Very common

Muscle hypotonia (especially during the test phase - transient effects).

Frequent

muscular hypertonia.

Renal and urinary disorders

Frequent

urinary incontinence, urinary retention

Disorders of reproductive organs and breast

Frequent

sexual dysfunction

General disorders and administration site conditions

Frequent

pain, fever / chills.

Rare

potentially life-threatening withdrawal symptoms following abrupt discontinuation of medication (see "Discontinuation of Treatment")

Adverse effects related to the administration system (eg catheter displacement, local infection, meningitis, overdose due to improper handling of the system) are not mentioned here.

In a screening study, the presence of a percutaneous endoscopic gastrostomy tube increased the incidence of deep infections in children.

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