Active ingredient: Baclofen
Baclofen is indicated for the relief of spasticity of voluntary muscle resulting from such disorders as multiple sclerosis, other spinal lesions e.g. tumours of the spinal cord, syringomyelia, motor neurone disease, transverse myelitis, traumatic partial section of the cord.
Baclofen is also indicated in adults and children for the relief of spasticity of voluntary muscle arising from e.g. cerebrovascular accidents, cerebral palsy, meningitis, traumatic head injury.
Patient selection is important when initiating baclofen therapy; it is likely to be of most benefit in patients whose spasticity constitutes a handicap to activities and/or physiotherapy. Treatment should not be commenced until the spastic state has become stabilized.
For this indication, competent medicine agencies globally authorize below treatments:
15 - 100 mg
From 5 To 33.333 mg 3 time(s) per day every day
The following gradually incremented dosage regime is suggested but may need adjustment to suit individual patient requirements.
Satisfactory control of symptoms is usually obtained with doses up to 60mg daily but a careful adjustment is often necessary to meet the requirements of each individual patient. Dosage may be slowly increased where necessary to a maximum daily dose of not more than 100mg unless the patient is in hospital under careful medical supervision. Small frequent dosage regimes may prove to be more beneficial in some cases than larger spaced doses. Additionally, some patients may benefit from the administration of baclofen at night only in order to counteract painful flexor spasm. Similarly, a single dose given approximately 1 hour prior to the performance of specific tasks such as washing, shaving, dressing and physiotherapy will often improve mobility.
Baclofen should be taken during meals with a little liquid.
25 - 1,400 ug
From 25 To 1,400 ug once every day
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 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.
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.
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 spinal origin: 10-30% of the previous daily dose
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.
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 spinal origin maintenance dosing for long-term continuous infusions of baclofen has been found to range from 12 to 2003 micrograms/day, with most patients being adequately maintained on 300 to 800 micrograms/day.
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.
In children aged 4 to <18 years with spasticity of cerebral and spinal 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 baclofen for the treatment of severe spasticity of cerebral or spinal origin in children younger than 4 years of age have not been established.
Baclofen ampoules of 20ml containing 500 micrograms/ml and 5ml containing 2mg (2000micrograms)/ml are intended for use with infusion pumps. The concentration to be used depends on the dose requirements and size of pump reservoir. Use of the more concentrated solution obviates the need for frequent re-filling in patients with high dosage requirements.
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 side effects.
A sudden requirement for substantial dose escalation is indicative of a catheter complication (i.e. a kink 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.
During long-term treatment approximately 5% of patients become refractory to increasing doses due to tolerance or drug delivery failure. This “tolerance” may be treated by gradually reducing baclofen dose over 2 to 4 week period and switching to alternative methods of spasticity management (e.g. preservative-free morphine sulphate). Baclofen should be resumed at the initial continuous infusion dose. Caution should be exercised when switching from baclofen to morphine and vice versa.
Except in overdose-related emergencies, the treatment with baclofen should always be gradually discontinued by successively reducing the dosage. Baclofen should not be discontinued suddenly.
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