Baclofen parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Solution for injection formulations of baclofen.
Drugs List
Therapeutic Indications
Uses
Severe chronic spasticity:spinal/cerebral origin unresponsive to oral drugs
Baclofen intrathecal is indicated in patients with severe chronic spasticity of spinal or cerebral origin (associated with injury, multiple sclerosis, cerebral palsy) who are unresponsive to oral baclofen or other orally administered antispastic agents and/or those patients who experience unacceptable side effects at effective oral doses.
In patients with spasticity due to head injury a delay of at least one year before treatment with baclofen intrathecal is recommended, to allow the symptoms of spasticity to stabilise.
Baclofen intrathecal may be considered as an alternative to ablative neurosurgical procedures.
Dosage
Adults
Screening Phase (Test Dose)
Initial test dose: 25micrograms or 50micrograms, slowly administered over at least a minute. Dosage can be increased in increments of 25micrograms at intervals of at least 24 hours, until a response is observed (approximately 4 to 8 hours duration).
A response is when the patient demonstrates a significant decrease in muscle tone and/or frequency and/or severity of muscle spasms. If dosage is increased to 100micrograms test dose, patients who still do not show a response should not be given further dose increments or considered for a continuous intrathecal infusion.
Dose-Titration Phase
Administer twice the bolus dose, established in the screening phase, over 24 hours.
If a prolonged effect is observed, lasting more than 12 hours, during the screening phase, the start dose should be the screening phase dose unchanged and delivered over a period of 24 hours. Increases in dose should not be attempted in the first 24 hours.
After 24 hours adjust dose, slowly to individual patient response. Adjust dose once every 24 hours if a programmable pump is use. Adjust dose once every 48 hours for non-programmable multi-dose reservoir pumps.
Recommended dose adjustments as follows:
- Patients with spasticity of spinal origin: 10% to 30% of the previous daily dose.
- Patients with spasticity of cerebral origin: 5% to 15% of the previous daily dose.
Investigate the pump function and catheter patency if dose has significantly increased without apparent clinical effect.
Doses greater than 1,000micrograms a day have limited clinical experience.
Maintenance
Patients with spasticity of spinal origin
12micrograms to 2003micrograms a day, continuous intrathecal infusions. Majority of patients are adequately maintained on 300micrograms to 800micrograms a day.
Patients with spasticity of cerebral origin
22micrograms to 1400micrograms a day. Majority of patients on long term treatment are adequately maintained on 276micrograms a day at 12 months and 307micrograms a day at 24 months.
Elderly
(See Dosage; Adult).
Children
Children aged 4 to 18 years
Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion.
For paediatric patients with spasticity due to head injury, it is recommended not to proceed to long-term baclofen therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).
Screening Phase (Test Dose)
Initial test dose: 25micrograms to 50 micrograms a day, based on individual patient. Dosage can be increased in increments of 25micrograms at intervals of at least 24 hours.
Maximum screening dose should not exceed 100micrograms a day.
Dose-Titration Phase
(See Dosage; Adults).
Maintenance
25micrograms to 200micrograms a day, continuous intrathecal infusions, adjusted based on individual response.
Additional Dosage Information
Individual titration of dosage is essential due to a high interindividual variability in response. Each patient must undergo an initial screening phase to determine the response to test bolus doses followed by dose-titration phase to determine the optimum dose schedule for maintenance therapy with an appropriate implanted delivery system.
Respiratory function should be monitored and appropriate resuscitation facilities should be available during the introduction of treatment with baclofen intrathecal. Intrathecal administration using an implanted delivery system should only be undertaken by physicians with appropriate knowledge and experience. Specific instructions for using the implantable pump should be obtained from the pump manufacturers. Only pumps constructed of material known to be compatible with the product and incorporating an in-line bacterial retentive filter should be used.
Screening Phase (Test Dose)
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 50micrograms 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 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.
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 baclofen intrathecal has been established, an intrathecal infusion may be introduced. Baclofen intrathecal 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.
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.
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.
Administration
For intrathecal injection or intrathecal infusion.
Baclofen intrathecal 50micrograms/ml is intended for administration in single bolus test injections via a lumbar puncture or intrathecal catheter. The 10mg/20ml and 10mg/5ml and 40mg/20ml preparations have been developed specifically for use with implantable pumps.
Delivery specifications
Baclofen intrathecal ampoules of 10mg/20ml and 10mg/5ml and 40mg/20ml 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 solutions obviates the need for frequent re-filling in patients with high dosage requirements.
Delivery regimen
Baclofen intrathecal 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% to 30% to maintain adequate symptom control. Where the spasticity is of cerebral origin any increase in dose should be limited to 20% (range: 5% to 20%). In both cases the daily dose may also be reduced by 10% to 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 intrathecal 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. Sensitivity to baclofen may be restored by gradual reduction of baclofen intrathecal over a 2 to 4 week period followed by switching to alternative therapy e.g. intrathecal preservative-free morphine sulfate. Baclofen intrathecal should be resumed at the initial continuous infusion dose; this should be performed in a hospital unit. Caution should be exercised when switching from baclofen intrathecal to morphine and vice versa.
Contraindications
Children under 4 years
Precautions and Warnings
Children under 18 years
Infection
Autonomic dysreflexia
Breastfeeding
Cerebrovascular insufficiency
Confusional states
Epileptic disorder
History of peptic ulcer
Hypertonic bladder sphincter
Parkinson's disease
Pregnancy
Psychosis
Renal impairment
Respiratory impairment
Schizophrenia
Response may be modified by abnormal CSF flow
Advise patient drowsiness may affect ability to drive or operate machinery
Treatment to be administered only by an experienced intrathecal clinician
Reservoir refilling of the pump must be done by trained personnel
Resuscitation facilities must be immediately available
Individual assessment instruction and monitoring required
Monitor cardiac function
Monitor for signs of scoliosis during treatment
Monitor neurological function
Monitor respiratory function
Potential for withdrawal symptoms
Risk of inflammatory mass formation at tip of implanted catheter
Tolerance may develop with continued use
Avoid abrupt withdrawal
Progressive withdrawal recommended
Ensure patient is informed of risks of treatment
Intrathecal baclofen therapy is valuable but hazardous. Careful pre-operative assessment is mandatory.
The patient should be given adequate information regarding the risks of this mode of treatment, and be physically and psychologically able to cope with the pump. It is essential that the responsible physician and all those involved in the care of the patient receive adequate instruction on the signs and symptoms of overdose, procedures to be followed in the event of an overdose and the proper home care of the pump and insertion site.
Cases of inflammatory mass at the tip of the implanted catheter can result in serious neurological impairment, including paralysis. Patients should be monitored carefully for any new neurological signs or symptoms. In some cases, performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an inflammatory mass.
Infection - Patients should be infection free prior to pump implantation, as the presence of infection may lead to surgical complications. A systemic infection may complicate attempts to adjust the dose. A local infection or catheter misplacement can also lead to drug delivery failure.
For paediatric patients with spasticity due to head injury, it is recommended not to proceed to long-term baclofen therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).
In patients with abnormal cerebrospinal fluid flow the circulation of drug and hence antispastic activity may be inadequate.
In rare instances elevated AST, alkaline phosphatase and glucose levels in the serum have been recorded when using oral baclofen.
The co-administration of other intrathecal agents with intrathecal baclofen is not recommended. An attempt should be made to reduce or discontinue concomitant oral antispastic medications, preferably before initiating baclofen infusion. However, abrupt reduction or discontinuation during chronic intrathecal baclofen therapy should be avoided.
Except in overdose-related emergencies or where serious adverse effects occur, treatment should always be discontinued gradually with successive reductions in dosage. Sudden cessation of treatment, especially after doses exceeding the normal dose range, may result in a hyperactive state with rapid uncontrolled spasms and increased rigidity to intolerable levels, lasting for several days.
Pregnancy and Lactation
Pregnancy
Use baclofen with caution during pregnancy.
Baclofen crosses the placental barrier. However, the intrathecal route is probably low risk because of the expected very low systemic exposure. If a woman requires baclofen, it should not be withheld because of pregnancy, but the lowest dose possible should be used and offspring should be monitored for late-onset seizures (Briggs, 2015).
Lactation
Use baclofen with caution during breastfeeding.
The manufacturer states that it is unknown if measurable levels of baclofen are present in breastmilk following intrathecal administration, however with oral doses exposure is minimal.
Side Effects
Abdominal pain
Agitation
Alopecia
Anxiety
Asthenia
Ataxia
Bradycardia
Bradypnoea
Changes in hepatic function
Chills
Confusion
Constipation
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Depression
Diaphoresis
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dry mouth
Dysarthria
Dysphagia
Dysphoria
Dyspnoea
Erectile dysfunction
Euphoria
Facial oedema
Fever
Flushing
Hallucinations
Headache
Hyperhidrosis
Hypersalivation
Hypertension
Hypertonia
Hypotension
Hypothermia
Ileus
Insomnia
Lethargy
Light-headedness
Memory disturbances
Muscle hypotonia
Myalgia
Nausea
Nightmares
Nystagmus
Pain
Pallor
Paraesthesia
Paranoia
Peripheral oedema
Pneumonia
Pruritus
Rash
Respiratory depression
Scoliosis progression
Sedation
Seizures
Sexual dysfunction
Slurred speech
Suicidal tendencies
Taste disturbances
Tremor
Urinary incontinence
Urinary retention
Urticaria
Visual disturbances
Vomiting
Withdrawal symptoms
Withdrawal Symptoms and Signs
Sudden cessation of treatment, especially after doses exceeding the normal dose range, may result in a hyperactive state with rapid uncontrolled spasms and increased rigidity to intolerable levels, lasting for several days. Autonomic dysfunction including hyperthermia has also been reported following sudden withdrawal of intrathecal baclofen. In rare cases abrupt discontinuation has resulted in seizures, rhabdomyolysis, coagulopathy, multiple organ failure and death.
Confusional states, hallucinations, psychotic, manic or paranoid states, convulsions (status epilepticus), and, as a rebound phenomenon, temporary aggravation of spasticity have been reported upon the abrupt withdrawal of oral baclofen, especially after long-term treatment.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: October 2021
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Baclofen 2mg/ml solution for infusion. Aguettant Ltd. Revised October 2014.
Summary of Product Characteristics: Lioresal Intrathecal. Novartis Pharmaceuticals UK Ltd. Revised June 2017.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Baclofen. Last revised: June 03, 2019
Last accessed: 08 October 2021
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 October 2021
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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