Severe chronic spasticity of cerebral origin

Adult screening phase

Prior to initiation of a chronic infusion, the patient’s response to intrathecal bolus doses administered via a catheter or lumbar puncture must be assessed. Low concentration ampoules containing 50 micrograms baclofen in 1ml are available for the purpose. Patients should be infection-free prior to screening, as the presence of a systemic infection may prevent an accurate assessment of the response.

The usual initial test dose in adults is 25 or 50 micrograms, increasing step-wise by 25 microgram increments at intervals of not less than 24 hours until a response of approximately 4 to 8 hours duration is observed. Each dose should be given slowly (over at least one minute). In order to be considered a responder the patient must demonstrate a significant decrease in muscle tone and/or frequency and/or severity of muscle spasms.

The variability in sensitivity to intrathecal baclofen between patients is emphasised. Signs of severe overdose (coma) have been observed in an adult after a single test dose of 25 micrograms. It is recommended that the initial test dose is administered with resuscitative equipment on hand.

Patients who do not respond to a 100 micrograms test dose should not be given further dose increments or considered for continuous intrathecal infusion.

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.

Dose-titration phase

Once the patient’s responsiveness to intrathecal baclofen has been established, an intrathecal infusion may be introduced. Intrathecal 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.

The initial total daily infused dose is determined by doubling the bolus dose which gave a significant response in the initial screening phase and administering it over a 24 hour period.

However, if a prolonged effect (i.e. lasting more than 12 hours) is observed during screening the starting dose should be the unchanged screening dose delivered over 24 hours. No dose increases should be attempted during the first 24 hours.

After the initial 24 hour period dosage should be adjusted slowly to achieve the desired clinical effect. If a programmable pump is used the dose should be increased only once every 24 hours; for non-programmable multi-dose reservoir pumps intervals of 48 hours between dose adjustments are recommended. In either case increments should be limited as follows to avoid possible overdosage:

Patients with spasticity of cerebral origin: 5-15% of the previous daily dose.

If the dose has been significantly increased without apparent clinical effect pump function and catheter patency should be investigated.

There is limited clinical experience using doses greater than 1000 micrograms/day.

It is important that patients are monitored closely in an appropriately equipped and staffed environment during screening and immediately following pump implantation. Resuscitative equipment should be available for immediate use in case of life-threatening adverse reactions.

Adult maintenance therapy

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 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 cerebral origin maintenance dosage has been found to range from 22 to 1400 micrograms/day, with a mean daily dosage of 276 micrograms per day at 12 months and 307 micrograms per day at 24 months.

Discontinuation

Except in overdose-related emergencies, the treatment with intrathecal baclofen should always be gradually discontinued by successively reducing the dosage. Intrathecal baclofen should not be discontinued suddenly.

Paediatric population screening phase

The initial lumbar puncture test dose for patients 4 to <18 years of age should be 25-50 micrograms/day based upon age and size of the child. 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 micrograms/day in paediatric patients.

Dose-titration phase

Once the patient’s responsiveness to intrathecal baclofen has been established, an intrathecal infusion may be introduced. Intrathecal 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.

The initial total daily infused dose is determined by doubling the bolus dose which gave a significant response in the initial screening phase and administering it over a 24 hour period.

However, if a prolonged effect (i.e. lasting more than 12 hours) is observed during screening the starting dose should be the unchanged screening dose delivered over 24 hours. No dose increases should be attempted during the first 24 hours.

After the initial 24 hour period dosage should be adjusted slowly to achieve the desired clinical effect. If a programmable pump is used the dose should be increased only once every 24 hours; for non-programmable multi-dose reservoir pumps intervals of 48 hours between dose adjustments are recommended. In either case increments should be limited as follows to avoid possible overdosage:

Patients with spasticity of cerebral origin: 5-15% of the previous daily dose.

If the dose has been significantly increased without apparent clinical effect pump function and catheter patency should be investigated.

There is limited clinical experience using doses greater than 1000 micrograms/day.

It is important that patients are monitored closely in an appropriately equipped and staffed environment during screening and immediately following pump implantation. Resuscitative equipment should be available for immediate use in case of life-threatening adverse reactions.

Paediatric population maintenance therapy

In children aged 4 to <18 years with spasticity of cerebral origin, the initial maintenance dosage for long-term continuous infusion of intrathecal baclofen ranges from 25 to 200 micrograms/day (median dose: 100 micrograms/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 micrograms/day.

The safety and efficacy of intrathecal baclofen for the treatment of severe spasticity of cerebral origin in children younger than 4 years of age have not been established.