"Nov. 1, 2012 -- Two more drugs made by the New England Compounding Center (NECC) are crawling with various kinds of bacteria, FDA tests reveal.
The NECC is the Massachusetts compounding pharmacy whose drugs are the likely source of th"...
LIORESAL Intrathecal (baclofen injection) is indicated for the management of patients with severe spasticity due to spinal cord injury or multiple sclerosis who are unresponsive to oral baclofen or who experience unacceptable side effects at effective oral doses.
LIORESAL Intrathecal therapy may be considered as an alternative to destructive neurosurgical procedures.
Prior to implantation of a device for chronic intrathecal infusion, patients must demonstrate a positive clinical response to a LIORESAL Intrathecal screening trial (see DOSAGE AND ADMINISTRATION).
LIORESAL Intrathecal has been used in patients with other spasticity of cerebral origin, e.g. spasticity following hypoxic encephalopathy, head injury, or stroke; however, clinical experience is limited.
DOSAGE AND ADMINISTRATION
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. This is due to the great variability in the effective individual therapeutic dose.
The first dose should be performed with resuscitative equipment on stand-by.
Patients must be monitored closely in a fully equipped and staffed environment during the screening phase and dose titration period immediately following implant. Resuscitative equipment should be available for immediate use in case of life threatening or intolerable adverse reactions. Implantation of pumps should only be performed in experienced centres in order to minimize the risks in the perioperative phase.
Prior to initiation of chronic infusion of intrathecal baclofen, patients must demonstrate a response to intrathecal baclofen bolus in a screening trial. A test bolus dose of LIORESAL is usually administered via a lumbar puncture or an intrathecal catheter to elicit a response. For this purpose, low concentration ampoules of 0.05 mg/mL are available.
The usual initial test dose is 25 μg or 50 μg and is stepped up by 25 μg increments at least 24 hours apart, until an approximately 4- to 8-hour response is observed; the dose should be given by barbotage over at least one minute. If an adverse reaction occurs at a dose of 25 μg, a lower dose, such as 10 μg may be tested.
Patients should demonstrate a positive clinical response in order to be considered responders to treatment. A positive clinical response is characterized by a significant decrease in muscle tone and/or frequency and/or severity of spasms. There is great variability in sensitivity to intrathecal baclofen.
Patients who do not respond to a 100 μg test dose should not be given further increases of dose or be considered for continuous intrathecal infusion. However, in rare instances some patients, particularly those with spasticity of cerebral origin, have received higher test bolus doses.
Dose Titration Phase
After confirmation that the patient is responsive to LIORESAL Intrathecal (baclofen injection) by means of test bolus doses, intrathecal infusion is established using a suitable delivery system. (See Drug delivery devices)
To determine the initial total daily dose of LIORESAL Intrathecal following implant, the screening dose which gave a positive effect should be doubled and administered over a 24-hour period, unless the efficacy of the bolus dose was maintained for more than 12 hours. In this case, the starting daily dose should be the screening dose delivered over a 24-hour period. No dose increases should be administered in the first 24 hours.
After the first 24 hours, the dosage should be adjusted slowly on a daily basis to achieve the desired effect, with dosage increments limited to 10 to 30% to avoid possible overdosing. With programmable pumps, the dose should be increased only once every 24 hours. For non-programmable pumps with a 76 cm catheter delivering 1 mL/day, intervals of 48 hours are suggested for evaluation of response. If the daily dose has been significantly increased and no clinical effect is achieved, check for proper pump function and catheter patency.
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.
There is limited experience with doses greater than 1000 μg/day.
The lowest dose producing an adequate response should be used. Most patients require gradual increases in dose over time to maintain optimum response during chronic therapy due to decreased responsiveness to therapy or to progress of the disease.
The daily dose may be gradually increased by 10 to 30% to maintain adequate symptom control by adjusting the dosing rate of the pump and/or the concentration of LIORESAL Intrathecal in the reservoir. The daily dose may also be reduced by 10 to 20% if patients experience side effects. A sudden requirement for substantial dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement) or pump malfunction.
Maintenance dosage for long-term continuous infusion of intrathecal baclofen ranges from 10 μg/day to 1200 μg/day, most patients being adequately maintained on 300 μg/day to 800 μg/day. The specific concentration that should be used depends upon the total daily dose required as well as the delivery rate of the pump. Please consult pump manufacturer's manual for specific recommendations.
During long-term treatment approximately 10% of patients become refractory to increasing doses. This 'tolerance' may be treated by gradually reducing LIORESAL Intrathecal dose over a 2 to 4 week period and switching to alternative methods of spasticity management (e.g. intrathecal preservative-free morphine sulfate). After a few days the sensitivity to baclofen may be restored and treatment should be resumed at the initial continuous infusion dose and followed by a titration phase to avoid overdose accidents.
This must be performed in a hospital unit. Caution should be exercised when switching from LIORESAL Intrathecal to morphine and vice versa (see PRECAUTIONS: DRUG INTERACTIONS).
Regular clinical review remains a necessity throughout to assess dosage requirements, functioning of the delivery system, and monitoring for possible adverse drug reactions or evidence of infection.
No studies have been performed in patients with renal impairment with LIORESAL Intrathecal therapy. Since baclofen is primarily eliminated unchanged through the kidneys, accumulation of unchanged drug in patients with renal impairment cannot be excluded (see CLINICAL PHARMACOLOGY).
LIORESAL Intrathecal should only be administered to end stage renal failure patients when benefit outweighs risk. These patients should be closely monitored for prompt diagnosis of early signs and/or symptoms of toxicity (see PRECAUTIONS, Renal Impairment).
Since unwanted effects are more likely to occur in elderly patients or in patients with spastic states of cerebral origin, it is recommended that a very cautious dosage schedule be adopted in such cases and that the patient should be kept under appropriate surveillance. Patients should be monitored for signs of overdose, central nervous system depression and toxic encephalopathy such as drowsiness, impairment of consciousness, coma, respiratory depression, hallucinations, agitation, and convulsions (see Symptoms And Treatment Of Overdosage).
No studies have been performed in patients with hepatic impairment receiving LIORESAL Intrathecal therapy. No dosage adjustment is recommended as the liver does not play any significant role in the metabolism of baclofen after intrathecal administration of LIORESAL.
Therefore, hepatic impairment is not expected to impact the drug systemic exposure (see CLINICAL PHARMACOLOGY). However, patients with severe hepatic impairment should be treated with caution, as they are in general more sensitive to therapeutic effects/adverse effects of drugs.
Several patients over the age of 65 years have been treated with LIORESAL Intrathecal during the clinical trials without increased risks compared to younger patients. Problems specific to this age group are not expected as doses are individually titrated (see WARNINGS, PRECAUTIONS and CLINICAL PHARMACOLOGY).
LIORESAL Intrathecal is most often administered in a continuous infusion mode immediately following implant. After the patient has stabilized with regard to daily dose and functional status, and provided the pump allows it, a more complex mode of delivery may be started to optimize 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 time of desired clinical effect.
Drug Delivery Devices
Intrathecal administration of LIORESAL through an implanted delivery system should only be undertaken by physicians with the necessary knowledge and experience. Specific instructions for programming and/or refilling the implantable pump are given by the pump manufacturers, and must be strictly adhered to. Consult pump manufacturer's literature for information on the appropriate use and care of these devices.
Evidence demonstrating the efficacy of LIORESAL Intrathecal was obtained using the Medtronic SynchroMed Programmable Infusion System. Other pumps proven to be suitable for intrathecal baclofen administration may be used.
The Medtronic SynchroMed Programmable Infusion System is an implantable drug delivery system with refillable reservoirs which, after general or local anesthesia, is implanted in a subcutaneous pocket usually on the abdominal wall. This device is connected to an intrathecal catheter that passes subcutaneously to the subarachnoid space.
The Medtronic SynchroMed Programmable Infusion System has an 18 mL drug reservoir and may be programmed to different flow rates such as single bolus, periodic boluses, continuous and complex continuous. However, the lithium battery of the pump has a life span of 3 to 4 years and therefore requires replacement.
LIORESAL Intrathecal proved to be stable in the implanted SynchroMed Programmable Infusion System for 11 weeks.
Details regarding the availability and use of this drug delivery device can be obtained from the manufacturer.
Medtronic of Canada Ltd. 6733 Kitimat Road Mississauga, Ontario L5N 1W3 1 (800) 268 5346 Fax: 1 (416) 826 6620
General guidelines regarding the use of all implantable systems are located under PRECAUTIONS.
Before using other systems, it must be confirmed that the technical specifications, including chemical stability of baclofen in the reservoir fulfil the requirements for safe and effective use of LIORESAL Intrathecal. Please consult pump manufacturer's manual for this information.
Availability Of Dosage Forms
PrLIORESAL Intrathecal (baclofen injection) 0.05 mg/mL:
Each 1 mL ampoule of clear, colorless solution contains 0.05 mg baclofen for intrathecal administration.
PrLIORESAL Intrathecal (baclofen injection) 0.5 mg/mL:
Each 20 mL ampoule of clear, colorless solution contains 10 mg baclofen for intrathecal administration.
PrLIORESAL Intrathecal (baclofen injection) 2 mg/mL:
Each 5 mL ampoule of clear, colourless solution contains 10 mg baclofen for intrathecal administration.
PrLIORESAL Intrathecal 0.05 mg/ml and 2 mg/ml are provided in cartons of 5 ampoules.
PrLIORESAL Intrathecal 0.5 mg/ml is provided in cartons of 1 ampoule.
Stability And Storage Recommendations
Protect from heat (store at 15-30°C). Do not freeze. Do not heat sterilize.
LIORESAL Intrathecal must be kept out of the reach and sight of children.
Instructions for use/handling:
LIORESAL Intrathecal is intended for intrathecal injection and continuous intrathecal infusion as indicated by the delivery specifications of the infusion system.
Each ampoule is intended for single use only. Discard any unused portion.
Parenteral drug products should be inspected for particulate matter and discoloration prior to administration whenever solution and container permit.
The concentration to be used depends upon the total daily dose required as well as the delivery rate of the pump. Please consult manufacturer's manual for specific recommendations.
For patients who require concentrations other than 0.05 mg/mL, 0.5 mg/mL or 2.0 mg/mL, LIORESAL Intrathecal must be diluted, under aseptic conditions, with sterile preservative-free sodium chloride injection and used immediately.
This leaflet was prepared by Novartis Pharmaceuticals Canada Inc., 385 Bouchard, Dorval, Quebec, H9S 1A9. Last Revised: September 18, 2013
Last reviewed on RxList: 1/10/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Lioresal Intrathecal Information
Report Problems to the Food and Drug Administration
Chronic Pain/Back Pain
Find tips and advances in treatment.