BACLOFEN AGUETTANT

Intrathecal 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 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. 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. Efficacy of intrathecal baclofen has been demonstrated in controlled randomised studies with an EU certified pump.

This is an implantable administration system: a refillable reservoir is implanted beneath the skin, mostly into the abdominal wall. This system is connected to an intrathecal catheter that passes subcutaneously into the subarachnoid space.

Before administering Baclofen Aguettant, a myelography of the subarachnoid space should be performed in patients with post-traumatic spasticity. In the event of radiological signs of arachnoiditis, treatment with Baclofen Aguettant should not be initiated.

Posology Due to the highly variable inter-individual sensitivity to baclofen, an optimal dosage should be determined for the treatment of each patient, according to a defined protocol, in three phases: • Test phase: initial selection using the intrathecal bolus technique (test dose), • Titration phase: determination of the dose, • Maintenance phase Test phase.

Prior to administering baclofen as a continuous intrathecal infusion, patients must show a positive response to administration of an 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. The initial dose is generally 25 or 50 micrograms; the dose is generally increased in increments of 25 micrograms at intervals of at least 24 hours, until a response lasting approximately 4 to 8 hours is obtained.

The dose must be injected over at least one minute via barbotage. 05 mg/ml, corresponding to 50 micrograms/ml) are available for this test phase. Resuscitative equipment must be on hand during injection of the first dose. Patients are considered to be positive responders if they show a significant decrease in muscle tone and/or frequency and/or severity of spasms.

There is much variability with regard to 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 must not be given further doses and are not eligible for continuous intrathecal infusions..

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 depressions.

Titration phase Once the patient's response to Intrathecal Baclofen has been established as positive via test doses, intrathecal infusion with a suitable administration system is introduced. Infection may increase the risk of surgical complications and complicate attempts to adjust the dose.

Following implantation, the initial total daily dose should be determined by doubling the dose that gave a positive effect in the test phase and administering it over a 24-hour period, unless the effect of the bolus dose is maintained for more than 12 hours.

In this latter case, the initial daily dose should be similar to the dose in the test phase and should be administered over a 24 hour period. 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.

To avoid any overdose, increments must not exceed l0-30%.

Patients with spasticity of cerebral origin:

After the first 24 hours the dose is adjusted slowly on a daily basis, to obtain the desired effect. To avoid any overdose, increments must not exceed 5 - 15%. If a programmable pump is used, dosage should only be increased once every 24 hours.

For non-programmable pumps attached to a 76 cm catheter and with a delivery rate of 1 ml/day, it is recommended that the response should only be evaluated at 48 hour intervals. If the daily dosage has been significantly increased without any clinical effect having been observed, pump functioning and catheter permeability should be verified.

Only limited experience is available with doses exceeding 1,000 micrograms/day. 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.

Maintenance therapy. The clinical goal is to maintain as normal a muscle tone as possible, and to minimize the frequency and severity of spasms without inducing intolerable side effects. The lowest dose producing an adequate response should be used.

Due to a decreasing response to treatment or due to disease progression, patients on chronic treatment gradually require higher doses to maintain an optimal long-term response. In the majority of […]

The most common reactions observed during baclofen Aguettant administration are: somnolence, hypotonia, depression, convulsions, hypotension and diarrhoea Adverse drug reactions are listed according to MedDRA system organ classes in table 1.

Undesirable effects are ranked according to system class and frequency, within each frequency grouping, undesirable effects are presented in order of decreasing seriousness, according to 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).

4 special warning and precautions for use), hallucinations, paranoia, euphoric mood Not known Dysphoria Nervous system disorders Very common Somnolence (especially during the test phase) Common Convulsion, headache, dysarthria, dizziness/ light-headedness, sedation, epileptic seizures (especially upon abrupt discontinuation of treatment), lethargy, paraesthesia, confusion/ disorientation.

Uncommon Ataxia, impaired memory nystagmus Convulsion and headache occur more often in patients with spasticity of cerebral origin than in patients with spasticity of spinal origin Eye disorders Common Diplopia, vision blurred, accommodation disorders Cardiac disorders Uncommon Bradycardia Vascular disorders Common Hypotension.

Uncommon Hypertension, deep vein thrombosis, flushing, pallor. Respiratory, thoracic and mediastinal disorders Common Respiratory depression, pneumonia, dyspnoea Not known Bradypnoea Gastrointestinal disorders Common Diarrhoea, vomiting, nausea, constipation, decreased appetite, dry mouth, increased salivation.

Uncommon Ileus, dysphagia, hypogeusia. Nausea and vomiting occur more often in patients with spasticity of cerebral origin than in patients with spasticity of spinal origin Skin and subcutaneous tissue disorders Common Urticaria, pruritus, facial or peripheral oedema.

Uncommon Hyperhidrosis, alopecia. Musculoskeletal and connective tissue disorders Very common Muscular hypotonia (especially during the test phase – transient effects). Common Muscular hypertonia. 4 special warning and precautions for use) 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 (Intrathecal Baclofen may compromise erection and ejaculation.

g. inflammatory mass at the tip of the implanted catheter, catheter dislodgement with possible complications, local infection, meningitis, overdose due to incorrect manipulation of the system) have been mentioned and in some of these cases a causal link with baclofen cannot be excluded.

4 special warnings and precautions for use). In a screening trial the presence of a PEG tube increased the incidence of deep infections in children. 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

Medical management The pump should only be implanted after strict evaluation of the patient's response to intrathecal baclofen bolus injections and/or dose titration. Given the risks associated with initial administration and dose adjustment of intrathecal baclofen (general depression of CNS functions, cardiovascular collapse and/or respiratory depression), these steps must only be performed under medical surveillance at a centre with the required equipment, in compliance with the directives given in section "Posology and method of administration".

Resuscitative equipment must be on immediate stand-by in the event of overdose symptoms that threaten the vital prognosis. Doctors must be adequately experienced in the chronic treatment with intrathecal infusions. Patient surveillance The patient must be closely monitored after surgical implantation of the pump, especially during the initial phase of pump use and each time that its delivery rate and/or the baclofen concentration in the reservoir are readjusted, until the patient's response to the infusion is acceptable and stabilised within reasonable limits.

It is essential that the risks of such a method of treatment are precisely known by the patient, doctors in charge of him/her and all caregivers. All persons participating in the treatment or care given to the patient must be clearly informed about the symptoms of under- and overdosing, procedures to be implemented in the event of intoxication, as well as the measures to be taken at home with regard to the pump and the insertion site.

. Test phase. Close monitoring of respiratory and cardiovascular functions is essential during the initial test phase, particularly in the presence of a cardiopulmonary condition or respiratory muscle weakness, as well as in patients concomitantly receiving benzodiazepine- or opiate-type medications, as the risk of respiratory depression is increased in such cases.

Any infection must be excluded prior to the test phase with Intrathecal Baclofen, as a systemic infection might falsify the evaluation of the patient's response to the Intrathecal Baclofen injection. Pump implantation. The patient must be free from infection prior to pump implantation, as the risk of postoperative complications would be increased.

Furthermore, a systemic infection could complicate dose adjustment. A local infection or catheter misplacement can also cause interruption of drug delivery, which may result in abrupt Intrathecal Baclofen withdrawal, accompanied by its symptoms (see "Interruption of treatment").

Filling the reservoir. This must be performed by trained and fully qualified personnel, in accordance with the manufacturer's instructions. Intervals between each refill should be carefully calculated to avoid depletion of the reservoir, which would lead to severe recurrence of spasticity or potentially life-threatening symptoms of Intrathecal Baclofen withdrawal (see "Interruption of treatment").

Filling should be performed under strictly aseptic conditions, in order to avoid any microbial contamination or any serious CNS infection. There should be an observation period, adapted to the clinical situation, after each refill or handling of the reservoir.

Extreme caution is required when filling an implantable pump fitted with a port with direct access to the intrathecal catheter, as direct injection into the catheter may lead to an overdose threatening the vital prognosis. Dose adjustment: additional comments.

Intrathecal Baclofen must be used with caution to avoid excessive weakness or a fall when a certain degree of spasticity is needed for standing up and gait balance, or whenever spasticity contributes to functional maintenance. It may be important to retain a certain amount of muscle tone and to tolerate occasional spasms, in order to facilitate circulatory function and prevent possible formation of deep vein thrombosis.

Whenever possible, all concomitant oral antispasmodic medications should be discontinued to avoid a possible overdose or undesirable interactions; preferably prior to initiating the Intrathecal Baclofen infusion and under close medical surveillance.

However, any abrupt reduction or discontinuation of the concomitant antispasmodic medication should be avoided during chronic treatment with Intrathecal Baclofen. Precaution for patients driving or using machines Patients should be especially vigilant when driving vehicles, handling dangerous machinery and performing activities made dangerous in case of loss of attention.

Precautions in special populations. In patients with slowed CSF circulation due, for example, to blockage caused by inflammation or trauma, the delayed migration of Intrathecal Baclofen can reduce the antispastic efficacy and boost the adverse reactions.

Patients with psychotic disorders, schizophrenia, confusional states or Parkinson's disease must be cautiously treated with Intrathecal Baclofen and undergo strict surveillance whenever exacerbation of such conditions has been observed following oral baclofen administration.

Close supervision of patients with additional risk factors for suicide should accompany drug therapy with Baclofen Aguettant. 8). Patients with epilepsy must be particularly monitored, as seizures may occasionally occur in the event of an overdose or withdrawal of the medication and even during maintenance treatment at therapeutic doses of Intrathecal Baclofen.

Intrathecal Baclofen must be used with caution in patients with a history of autonomic dysreflexia. Nociceptive stimulation or abrupt withdrawal of Intrathecal Baclofen may precipitate such episodes. The same caution is required in the presence of cerebrovascular or respiratory insufficiency as baclofen can aggravate such […]

1. Pharmaco-resistant epilepsy. The drug should not be administered by any route other than intrathecal.