Baclofen Injection

Name: Baclofen Injection

Indications

Baclofen Injection (Intrathecal) is indicated for use in the management of severe spasticity. Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion of Baclofen Injection (Intrathecal) via an implantable pump should be reserved for patients unresponsive to oral baclofen therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal baclofen therapy. Baclofen Injection (Intrathecal) is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in implantable pumps approved by the FDA specifically for the administration of Baclofen Injection (Intrathecal) into the intrathecal space.

Spasticity of Spinal Cord Origin

Evidence supporting the efficacy of intrathecal baclofen was obtained in randomized, controlled investigations that compared the effects of either a single intrathecal dose or a three day intrathecal infusion of intrathecal baclofen to placebo in patients with severe spasticity and spasms due to either spinal cord trauma or multiple sclerosis. Intrathecal baclofen was superior to placebo on both principal outcome measures employed: change from baseline in the Ashworth rating of spasticity and the frequency of spasms.

Spasticity of Cerebral Origin

The efficacy of intrathecal baclofen was investigated in three controlled clinical trials; two enrolled patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. The first study, a randomized controlled cross-over trial of 51 patients with cerebral palsy, provided strong, statistically significant results; intrathecal baclofen was superior to placebo in reducing spasticity as measured by the Ashworth Scale. A second cross-over study was conducted in 11 patients with spasticity arising from brain injury. Despite the small sample size, the study yielded a nearly significant test statistic (p=0.066) and provided directionally favorable results. The last study, however, did not provide data that could be reliably analyzed. Baclofen Injection (Intrathecal) therapy may be considered an alternative to destructive neurosurgical procedures. Prior to implantation of a device for chronic intrathecal infusion of Baclofen Injection (Intrathecal), patients must show a response to Baclofen Injection (Intrathecal) in a screening trial (see DOSAGE AND ADMINISTRATION).

Overdose

Special attention must be given to recognizing the signs and symptoms of overdosage, especially during the initial screening and dos e-titration phase of treatment, but also during re-introduction of Baclofen Injection (Intrathecal) after a period of interruption in therapy.

Symptoms Of Baclofen Injection (Intrathecal) Overdose

Drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, hypothermia, seizures, rostral progression of hypotonia and loss of con-sciousness progressing to coma of up to 72 hr. duration. In most cases reported, coma was reversible without sequelae after drug was discontinued. Symptoms of intrathecal baclofen overdose were reported in a sensitive adult patient after receiving a 25 mcg intrathecal bolus.

Treatment Suggestions For Overdose

There is no specific antidote for treating overdoses of Baclofen Injection (Intrathecal); however, the following steps should ordinarily be undertaken:

  1. Residual Baclofen Injection (Intrathecal) solution should be removed from the pump as soon as possible.
  2. Patients with respiratory depression should be intubated if necessary, until the drug is eliminated.

If lumbar puncture is not contraindicated, consideration should be given to withdrawing 30 to 40 mL of CSF to reduce CSF baclofen concentration.

Clinical pharmacology

The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possiblyby decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by stimulation of the GABA receptor subtype.

Baclofen Injection (Intrathecal) when introduced directly into the intrathecal space permits effective CSF concentrations to be achieved with resultant plasma concentrations 100 times less than those occurring with oral administration.

In people, as well as in animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.

Pharmacodynamics Of Baclofen Injection (Intrathecal)

Intrathecal Bolus

Adult Patients : The onset of action is generally one-half hour to one hour after an intrathecal bolus. Peak spasmolytic effect is seen at approximately four hours after dosing and effects may last four to eight hours. Onset, peak response, and duration of action may vary with individual patients depending on the dose and severity of symptoms.

Pediatric Patients : The onset, peak response and duration of action is similar to those seen in adult patients.

Continuous Infusion: Intrathecal baclofen's antispastic action is first seen at 6 to 8 hours after initiation of continuous infusion. Maximum activity is observed in 24 to 48 hours. No additional information is available for pediatric patients.

Pharmacokinetics Of Baclofen Injection (Intrathecal)

The pharmacokinetics of CSF clearance of intrathecal baclofen calculated from intrathecal bolus orcontinuous infusion studies approximates CSF turnover, suggesting elimination is by bulk-flow removal of CSF.

Intrathecal Bolus : After a bolus lumbar injection of 50 or 100 mcg intrathecal baclofen in seven patients, the average CSF elimination half-life was 1.51 hours over the first four hours and the average CSF clearance was approximately 30 mL/hour.

Continuous Infusion: The mean CSF clearance for intrathecal baclofen was approximately 30 mL/hour in a study involving ten patients on continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during intrathecal administration are expected to be low (0 to 5 ng/mL). Limited pharmacokinetic data suggest that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5 patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic efficacy; the interpatient variability was great. The gradient was not altered by position.

Six pediatric patients(age 8 to 18 years) receiving continuous intrathecal baclofen infusion at doses of 77 to 400 mcg/day had plasma baclofen levels near or below 10 ng/mL.

Patient information

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Side effects

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

In a recent clinical study, 153 adult and pediatric patients with spasticity of spinal cord or cerebral origin were treated with Gablofen 3,000 mcg/mL. The adverse reactions seen in this study were similar to that found with lower concentrations of Gablofen.

Spasticity Of Spinal Cord Origin

Most Common Adverse Reactions In Patients With Spasticity Of Spinal Origin

In pre- and post-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo-treated patients were: somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia.

Adverse Reactions Associated With Discontinuation Of Treatment

8/474 patients with spasticity of spinal cord origin receiving long term infusion of intrathecal baclofen in pre- and post-marketing clinical studies in the U.S. discontinued treatment due to adverse reactions. These include: pump pocket infections (3), meningitis (2), wound dehiscence (1), gynecological fibroids (1) and pump overpressurization (1) with unknown, if any, sequela. Eleven patients who developed coma secondary to overdose had their treatment temporarily suspended, but all were subsequently re-started and were not, therefore, considered to be true discontinuations.

Fatalities - [see WARNINGS AND PRECAUTIONS].

Incidence In Controlled Trials

Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies were of very brief duration (up to three days of infusion) and involved only a total of 63 patients. The following events occurred among the 31 patients receiving intrathecal baclofen in two randomized, placebo-controlled trials: hypotension (2), dizziness (2), headache (2), dyspnea (1). No adverse reactions were reported among the 32 patients receiving placebo in these studies.

Events Observed During The Pre- And Post-Marketing Evaluation Of Intrathecal Baclofen

Adverse events associated with the use of intrathecal baclofen reflect experience gained with 576 patients followed prospectively in the United States. They received intrathecal baclofen for periods of one day (screening) (N=576) to over eight years (maintenance) (N=10). The usual screening bolus dose administered prior to pump implantation in these studies was typically 50 mcg. The maintenance dose ranged from 12 mcg to 2,003 mcg per day. Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of intrathecal baclofen cannot be reliably assessed in many cases and many of the adverse reactions reported are known to occur in association with the underlying conditions being treated. Nonetheless, many of the more commonly reported reactions . hypotonia, somnolence, dizziness, paresthesia, nausea/vomiting and headache . appear clearly drug-related.

Adverse experiences reported during all U.S. studies (both controlled and uncontrolled) are shown in Table 1. Eight of 474 patients who received chronic infusion via implanted pumps had adverse experiences which led to a discontinuation of long term treatment in the pre- and post-marketing studies.

Table 1: Most Common (≥1%) Adverse Reactions in Patients with Spasticity of Spinal Origin in Prospectively Monitored Clinical Trials

Adverse Reactions Percent
N=576
Screening*
Percent
N=474
Titration†
Percent
N=430
Maintenance‡
Hypotonia 5.4 13.5 25.3
Somnolence 5.7 5.9 20.9
Dizziness 1.7 1.9 7.9
Paresthesia 2.4 2.1 6.7
Nausea and Vomiting 1.6 2.3 5.6
Headache 1.6 2.5 5.1
Constipation 0.2 1.5 5.1
Convulsion 0.5 1.3 4.7
Urinary Retention 0.7 1.7 1.9
Dry Mouth 0.2 0.4 3.3
Accidental Injury 0.0 0.2 3.5
Asthenia 0.7 1.3 1.4
Confusion 0.5 0.6 2.3
Death 0.2 0.4 3.0
Pain 0.0 0.6 3.0
Speech Disorder 0.0 0.2 3.5
Hypotension 1.0 0.2 1.9
Ambylopia 0.5 0.2 2.3
Diarrhea 0.0 0.8 2.3
Hypoventilation 0.2 0.8 2.1
Coma 0.0 1.5 0.9
Impotence 0.2 0.4 1.6
Peripheral Edema 0.0 0.0 2.3
Urinary Incontinence 0.0 0.8 1.4
Insomnia 0.0 0.4 1.6
Anxiety 0.2 0.4 0.9
Depression 0.0 0.0 1.6
Dypsnea 0.3 0.0 1.2
Fever 0.5 0.2 0.7
Pneumonia 0.2 0.2 1.2
Urinary Frequency 0.0 0.6 0.9
Urticaria 0.2 0.2 1.2
Anorexia 0.0 0.4 0.9
Diplopia 0.0 0.4 0.9
Dysautonomia 0.2 0.2 0.9
Hallucinations 0.3 0.4 0.5
Hypertension 0.2 0.6 0.5
* Following administration of test bolus
† Two month period following implant
‡ Beyond two months following implant
N=Total number of patients entering each period
%=% of patients evaluated

In addition to the more common (1% or more) adverse reactions reported in the prospectively followed 576 domestic patients in pre- and post-marketing studies, experience from an additional 194 patients exposed to intrathecal baclofen from foreign studies has been reported. The following adverse reactions, not described in the table, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Abnormal gait, thinking abnormal, tremor, amnesia, twitching, vasodilatation, cerebrovascular accident, nystagmus, personality disorder, psychotic depression, cerebral ischemia, emotional lability, euphoria, hypertonia, ileus, drug dependence, incoordination, paranoid reaction and ptosis.

Digestive System: Flatulence, dysphagia, dyspepsia and gastroenteritis.

Cardiovascular: Postural hypotension, bradycardia, palpitations, syncope, arrhythmia ventricular, deep thrombophlebitis, pallor and tachycardia.

Respiratory: Respiratory disorder, aspiration pneumonia, hyperventilation, pulmonary embolus and rhinitis.

Urogenital: Hematuria and kidney failure.

Skin and Appendages: Alopecia and sweating.

Metabolic and Nutritional Disorders: Weight loss, albuminuria, dehydration and hyperglycemia.

Special Senses: Abnormal vision, abnormality of accommodation, photophobia, taste loss and tinnitus.

Body as a Whole: Suicide, lack of drug effect, abdominal pain, hypothermia, neck rigidity, chest pain, chills, face edema, flu syndrome and overdose.

Hemic and Lymphatic System: Anemia.

Spasticity Of Cerebral Origin

Most Common Adverse Reactions

In pre-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo-treated patients included: agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia.

Adverse Reactions Associated with Discontinuation of Treatment

Nine of 211 patients receiving intrathecal baclofen in pre-marketing clinical studies in the U.S. discontinued long-term infusion due to adverse reactions associated with intrathecal therapy.

The nine adverse reactions leading to discontinuation were: infection (3), CSF leaks (2), meningitis (2), drainage (1), and unmanageable trunk control (1).

Fatalities

Three deaths, none of which were attributed to intrathecal baclofen, were reported in patients in clinical trials involving patients with spasticity of cerebral origin. See Warnings on other deaths reported in spinal spasticity patients.

Incidence In Controlled Trials

Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies involved a total of 62 patients exposed to a single 50 mcg intrathecal bolus. The following adverse reactions occurred among the 62 patients receiving intrathecal baclofen in two randomized, placebocontrolled trials involving cerebral palsy and head injury patients, respectively: agitation, constipation, somnolence, leukocytosis, nausea, vomiting, nystagmus, chills, urinary retention, and hypotonia.

Events Observed During The Pre-Marketing Evaluation Of Intrathecal Baclofen

Adverse events associated with the use of intrathecal baclofen reflect experience gained with a total of 211 U.S. patients with spasticity of cerebral origin, of whom 112 were pediatric patients (under age 16 at enrollment). They received intrathecal baclofen for periods of one day (screening) (N=211) to 84 months (maintenance) (N=1). The usual screening bolus dose administered prior to pump implantation in these studies was 50 mcg to 75 mcg. The maintenance dose ranged from 22 mcg to 1,400 mcg per day. Doses used in this patient population for long-term infusion are generally lower than those required for patients with spasticity of spinal cord origin.

Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of intrathecal baclofen cannot be reliably assessed in many cases. Nonetheless, many of the more commonly reported reactions . somnolence, dizziness, headache, nausea, hypotension, hypotonia and coma . appear clearly drug-related.

The most frequent (≥1%) adverse reactions reported during all clinical trials are shown in Table 2. Nine patients discontinued long term treatment due to adverse reactions.

Table 2: Most Common (≥1%) Adverse Reactions in Patients with Spasticity of Cerebral Origin

Adverse Reactions Percent
N=211
Screening*
Percent
N=153
Titration†
Percent
N=150
Maintenance‡
Hypotonia 2.4 14.4 34.7
Somnolence 7.6 10.5 18.7
Headache 6.6 7.8 10.7
Nausea and Vomiting 6.6 10.5 4.0
Vomiting 6.2 8.5 4.0
Urinary Retention 0.9 6.5 8.0
Convulsion 0.9 3.3 10.0
Dizziness 2.4 2.6 8.0
Nausea 1.4 3.3 7.3
Hypoventilation 1.4 1.3 4.0
Hypertonia 0.0 0.7 6.0
Paresthesia 1.9 0.7 3.3
Hypotension 1.9 0.7 2.0
Increased Salivation 0.0 2.6 2.7
Back Pain 0.9 0.7 2.0
Constipation 0.5 1.3 2.0
Pain 0.0 0.0 4.0
Pruritus 0.0 0.0 4.0
Diarrhea 0.5 0.7 2.0
Peripheral Edema 0.0 0.0 3.3
Thinking Abnormal 0.5 1.3 0.7
Impotence 0.5 0.0 1.3
Agitation 0.0 0.0 2.0
Asthenia 0.5 0.0 1.3
Chills 0.5 0.0 1.3
Coma 0.5 0.0 1.3
Dry Mouth 0.0 0.0 2.0
Pneumonia 0.5 0.7 0.7
Speech Disorder 0.5 0.0 1.3
Tremor 0.0 0.0 2.0
Urinary Incontinence 0.0 0.0 2.0
Urination Impaired 2.4 14.4 34.7
* Following administration of test bolus
† Two month period following implant
‡ Beyond two months following implant
N=Total number of patients entering each period. 211 patients received drug; (1 of 212) received placebo only

The more common (1% or more) adverse reactions reported in the prospectively followed 211 patients exposed to intrathecal baclofen have been reported. In the total cohort, the following adverse reactions, not described in Table 2, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Akathisia, ataxia, confusion, depression, opisthotonos, amnesia, anxiety, hallucinations, hysteria, insomnia, nystagmus, personality disorder, reflexes decreased, and vasodilitation.

Digestive System: Dysphagia, fecal incontinence, gastrointestinal hemorrhage and tongue disorder.

Cardiovascular: Bradycardia.

Respiratory: Apnea, dyspnea and hyperventilation.

Urogenital: Abnormal ejaculation, kidney calculus, oliguria and vaginitis.

Skin and Appendages: Rash, sweating, alopecia, contact dermatitis and skin ulcer.

Special Senses: Abnormality of accommodation.

Body as a Whole: Death, fever, abdominal pain, carcinoma, malaise and hypothermia.

Hemic and Lymphatic System: Leukocytosis and petechial rash.

Warnings

Because of the possibility of potential life-threatening CNS depression, cardiovascular collapse and/or respiratory failure, physicians must be adequately trained in intrathecal infusion therapy.

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.

Because of the risks associated with the screening procedure and the adjustment of dosage following pump implantation, these procedures must be conducted in a medically supervised and adequately equipped environment (see DOSAGE AND ADMINISTRATION).

Resuscitative equipment should be available.

The pump system should not be implanted until the patient's response to bolus intrathecal injection of LIORESAL Intrathecal (baclofen injection) has been properly evaluated and found to be clinically safe and effective.

Following surgical implantation of the pump, particularly during the initial phase of pump use the patient should be monitored closely until it is certain that the patient's response to the infusion is acceptable and reasonably stable.

Whenever the dosing rate of the pump and/or the concentration of LIORESAL Intrathecal in the reservoir is adjusted, close medical monitoring is required until it is certain that the patient's response to the infusion is acceptable and reasonably stable.

It is mandatory that the patient and all those involved in the care of the patient receive adequate information regarding the risks of LIORESAL Intrathecal treatment. All medical personnel and care givers should be instructed in 1) the signs and symptoms of overdose, 2) procedures to be followed in the event of overdose and 3) proper home care of the pump and insertion site.

Inflammatory mass at the tip of implanted catheter with LIORESAL Intrathecal

Cases of inflammatory mass at the tip of the implanted catheter, have been reported in patients receiving LIORESAL Intrathecal monotherapy. The most frequent symptom associated with these masses is decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases). It is known that inflammatory mass at intrathecal tip can result in pain and serious neurological impairment. Clinicians should monitor patients on LIORESAL Intrathecal therapy carefully for any new neurological signs or symptoms. In patients with new neurological signs or symptoms suggestive of an inflammatory mass, consider a neurosurgical consultation since many of the symptoms of inflammatory mass are similar to the symptoms experienced by patients with severe spasticity from their disease. A diagnostic imaging procedure may be appropriate to confirm or rule-out inflammatory mass. Inflammatory masses have also been reported in patients receiving pharmacy compounded drugs or admixtures, including opioids. Diagnosis and management of inflammatory mass in these patients should take into consideration the pharmacology of the drugs in addition to LIORESAL.

Abrupt Drug Withdrawal

Abrupt discontinuation of LIORESAL Intrathecal, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure and death.

Prevention of abrupt discontinuation of LIORESAL Intrathecal requires careful attention to proper programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of LIORESAL withdrawal. Special attention should be given to patients at apparent risk (e.g. spinal cord injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from oral or LIORESAL Intrathecal). Consult the technical manual of the implantable infusion system for additional postimplant clinician and patient information. (see WARNINGS).

In the first 9 years of post-marketing experience, 27 cases of withdrawal temporally related to the cessation of LIORESAL Intrathecal therapy were reported; six patients died. In most cases, symptoms of withdrawal appeared within hours to a few days following interruption of LIORESAL Intrathecal therapy. Common reasons for abrupt interruption of LIORESAL Intrathecal therapy included malfunction of the catheter (especially disconnection), low volume in the pump reservoir, and end of pump battery life; human error may have played a causal or contributing role in some cases.

All patients receiving LIORESAL Intrathecal therapy are potentially at risk for withdrawal. Early symptoms of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension, and paresthesias. Some clinical characteristics of the advanced LIORESAL Intrathecal withdrawal syndrome may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.

Rapid, accurate diagnosis and treatment in an emergency room or intensive care setting are important in order to prevent the potentially life-threatening central nervous system and systemic effects of LIORESAL Intrathecal withdrawal. The suggested treatment for LIORESAL Intrathecal withdrawal is the restoration of LIORESAL Intrathecal at or near the same dosage as before therapy was interrupted. However, if restoration of intrathecal delivery is delayed, treatment with GABA-ergic agonist drugs such as oral baclofen, or oral, enteral, or intravenous benzodiazepines may prevent potentially fatal sequelae. Oral baclofen alone should not be relied upon to halt the progression of the effects of LIORESAL Intrathecal withdrawal.

Seizures have been reported during overdose and with withdrawal from LIORESAL Intrathecal as well as in patients maintained on therapeutic doses of LIORESAL Intrathecal.

Therefore, except for serious adverse reactions and overdose related emergencies, the dose should always be reduced slowly when the drug is discontinued (over a period of approximately 1-2 weeks).

Neonatal Withdrawal

Convulsions have been reported in neonates after intrauterine exposure to oral baclofen (See PRECAUTIONS, Pregnant Women).

Patient information

PrLIORESAL Intrathecal
(baclofen) Injection 0.05 mg/mL, 0.5 mg/mL and 2 mg/mL

For intrathecal injection and infusion only

This leaflet is part III of a three-part “Product Monograph” published when LIORESAL IT was approved for sale in Canada and is designed specifically for Consumers. This leaflet is a summary and will not tell you everything about LIORESAL IT. Contact your doctor or pharmacist if you have any questions about the drug.

ABOUT THIS MEDICATION

What the medication is used for:

LIORESAL Intrathecal belongs to a group of medicines called muscle relaxants. It is used to reduce and relieve the excessive stiffness and/or spasms occurring in various illnesses such as, for example, multiple sclerosis, diseases or injuries of the spinal cord, and certain brain disorders.

What it does:

The solution is injected or infused into the fluid space around the spinal cord by use of a special pump which is implanted under the skin of your abdomen. From the pump a constant amount of the solution is delivered into the fluid space around the spinal cord through a tiny tube.

Due to the beneficial effect on muscle contractions and the consequent relief from pain, LIORESAL Intrathecal improves your mobility and your ability to manage your daily activities without aid. LIORESAL also helps you to benefit more from physiotherapy.

When it should not be used:

You should not be treated with LIORESALIT if you:

  • are allergic (hypersensitivity) to LIORESAL Intrathecal or any of the other ingredients of LIORESAL Intrathecal listed below.

What the medicinal ingredient is:

baclofen.

What the nonmedicinal ingredients are:

LIORESAL IT contains: sodium chloride and water for injection

What dosage forms it comes in:

LIORESAL Intrathecal (baclofen injection) 0.05 mg/mL: Each 1 mL ampoule contains 0.05 mg baclofen for intrathecal administration.

LIORESAL Intrathecal (baclofen injection) 0.5 mg/mL: Each 20 mL ampoule contains 10 mg baclofen for intrathecal administration.

LIORESAL Intrathecal (baclofen injection) 2 mg/mL: Each 5 mL ampoule contains 10 mg baclofen for intrathecal administration.

WARNINGS AND PRECAUTIONS

LIORESAL Intrathecal is suitable for many, but not all, patients with muscle spasms.

BEFORE you use LIORESALIT talk to your doctor or pharmacist if you:

  • have any kind of infection
  • have Parkinson's disease or certain mental illnesses accompanied by confusion
  • have epilepsy (seizures)
  • have diabetes
  • ever had heart problems
  • ever had kidney problems
  • have breathing problems
  • have acute pain in your stomach or intestine
  • have disturbed blood circulation in your brain
  • have ever experienced sudden episodes of high blood pressure, anxiety, excessive sweating, “goose flesh”, pounding headache, and unusually slow heartbeat due to an overreaction of your nervous system to stimuli such as distension of the bladder and intestine, skin irritation and pain

If any of these apply to you, your doctor may not want to give you this medicine or may want to take special precautions. If you have not told your doctor about any of these things, tell him/her before you start LIORESAL Intrathecal treatment.

If you think you may be allergic, ask your doctor for advice.

Driving and using machines: LIORESAL Intrathecal may make you feel sleepy or dizzy. Be careful when driving a car or using a machine or doing things that need careful attention until you are feeling normal again.

INTERACTIONS WITH THIS MEDICATION

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including herbal and non- prescription medicines (over the counter). Some other medicines may interact with LIORESALIT. Your doctor may change the dosage or sometimes stop one of the medicines. This is particularly important for the following medicines:

  • other medicines for your spastic condition
  • medicines for Parkinson' disease
  • medicines for epilepsy
  • medicines used to treat mood disorders such as antidepressants and lithium
  • medicines for high blood pressure
  • other drugs which affect the kidney, e.g. ibuprofen
  • opiates for pain relief
  • medicines used to help you sleep or calm you down
  • medicines which slow down the central nervous system, e.g. anti-histamines and sedatives (some of these can be bought over the counter)

Always tell your doctor or nurse about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Be careful if you drink alcoholic beverages during treatment with LIORESAL Intrathecal as you may feel more sleepy or dizzy than usual.

PROPER USE OF THIS MEDICATION

Usual dose

LIORESAL Intrathecal can only be given by experienced doctors using special medical equipment. You will need to stay in hospital, at least at the beginning of treatment.

Your doctor will inject a small amount of LIORESAL Intrathecal into your spinal cord to see if it improves your muscle spasms. If it does, then a special pump will be implanted under your skin. The pump will give you a small amount of medicine all the time.

It may take several days to find out the amount of medicine that suits you best, your doctor will keep a close watch on you during this time.

After that, your doctor will still want to see you regularly to check your progress and make sure your pump is working well.

IT IS OF UTMOST IMPORTANCE THAT APPOINTMENTS TO REFILL THE PUMP ARE KEPT, OTHERWISE SPASMS MAY RECUR BECAUSE YOU ARE NOT GETTING A HIGH ENOUGH DOSE OF LIORESAL INTRATHECAL. MUSCLE SPASTICITY MAY NOT IMPROVE OR MAY WORSEN AS A RESULT.

If muscle spasticity is not improving or if you start having spasms again, either gradually or suddenly, contact your doctor immediately.

Please consult the pump manufacturer's literature for information regarding proper home care of the pump and the insertion site.

Monitoring during treatment with LIORESAL Intrathecal

You will be monitored closely in a fully equipped and staffed environment during the screening phase and dose-titration period immediately following pump implant. You will regularly be assessed for your dosage requirements, for possible side effects or evidence of infection. The functioning of the delivery system will also be checked.

Pregnancy and breast-feeding

You should tell your doctor if you are pregnant, or planning to become pregnant as LIORESAL Intrathecal should not be used during pregnancy, or if you are breast-feeding. Ask your doctor or pharmacist for advice before taking any medicine.

Your doctor will discuss with you the potential risk of taking LIORESAL Intrathecal during pregnancy.

The doctor will decide if you may receive LIORESAL Intrathecal in these special situations. Only very small quantities of LIORESAL pass into the breast milk. Ask your doctor if you want to breast-feed.

Overdose

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Signs of overdose may appear suddenly or insidiously e.g. by a malfunctioning of the pump. It is very important that you and those caring for you recognize signs of overdosage. If you experience any one or a combination of the following symptoms, tell your doctor without delay as the amount of drug you receive may be too high:

  • unusual muscular weakness (too little muscle tone)
  • sleepiness
  • lightheadedness or dizziness
  • excessive salivation
  • nausea or vomiting
  • difficulties in breathing, seizures or loss of consciousness
  • abnormal low body temperature

Missed Dose

Abruptly stopping LIORESAL Intrathecal can result in serious medical problems and in rare cases has been fatal.

Signs that your pump is not functioning properly or that it is not delivering the right amount of medication include an increase or return in spasticity, itching, low blood pressure, lightheadedness, tingling sensation, high fever, altered mental status, and muscle rigidity or new muscle weakness or paralysis. It is important to tell your doctor right away if you experience any of the above symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

As with all medicines, patients treated with LIORESAL Intrathecal, may experience some side effects, although not everybody gets them. These occur more often at the start of treatment during your hospital stay but they may also occur later and should be checked with your doctor.

Very common: Drowsiness, muscle weakness

Common: Feeling of anxiety, sedation and weariness (exhaustion), weakness in the legs, stiffness in the muscles, dizziness/light-headedness, headache, sleepiness, feeling sick and/or vomiting, tingling in hands and feet, insomnia, slurred speech, pneumonia, weakness, chills, fatigue, pain, dry mouth, skin rash and/or itching, swelling of the ankles, feet, or lower legs, puffy face, unusual nervousness or restlessness, confusion/disorientation, constipation, diarrhea, decreased appetite, excessive salivation, fever/shivering, urinary problems, sexual difficulties.

Uncommon: Mood or mental changes, paranoia, feeling extreme happiness (euphoria), loss of muscle coordination (ataxia), abnormally low body temperature, memory loss, continuous uncontrollable eye movements, decreased sense of taste, difficulty in swallowing, abdominal pain, hair loss, excessive sweating.

Rare: Restlessness, abnormally slow breathing rate.

Tell your doctor if you notice any other effect. Some side effects could be associated with the delivery system.

SERIOUS SIDE EFFECTS, HOW OFTEN THEY HAPPEN AND WHAT TO DO ABOUT THEM

Symptom / effect Talk with your doctor or pharmacist Stop taking drug and immediately seek assistance
Only if severe In all cases
Common Low Blood Pressure   √   
  Shortness of breath or unusually slow or troubled breathing   √   
Uncommon Unusually slow heartbeat   √   
  Feeling of depression   √   
  Suicidal ideas and suicide attempt   √   
  Hallucina-tions: seeing or hearing things that are not there   √   
  Visual Disturbance: blurred vision, double vision √     

This is not a complete list of side effects. For any unexpected effects while taking LIORESAL IT contact your doctor or pharmacist.

HOW TO STORE IT

Store LIORESAL IT ampoules between 15-30°C (protect from heat). Do not freeze. Do not heat sterilize.

Keep all medicines out of the reach and sight of children.

This medicine is prescribed for your specific medical problem and for your own use only. Do not give to other people.

Do not use outdated medicines. Discard them safely out of the reach of children or take them to your pharmacist who will dispose of them for you.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

  • Report online at www.healthcanada.gc.ca/medeffect
  • Call toll-free at 1-866-234-2345
  • Complete a Canada Vigilance Reporting Form and:
    • Fax toll-free to 1-866-678-6789, or
    • Mail to: Canada Vigilance Program, Health Canada, Postal Locator 0701E, Ottawa, Ontario, K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect™ Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found at: http://www.novartis.ca or by contacting the sponsor, Novartis Pharmaceuticals Canada Inc, at: 1-800-363-8883

.05 mg/mL ampule label

mg/20 mL ampule label

mg/20mL ampule label

BACLOFEN 
Baclofen Injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68055-415
Route of Administration INTRATHECAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BACLOFEN (BACLOFEN) BACLOFEN 10 mg  in 20 mL
Inactive Ingredients
Ingredient Name Strength
SODIUM CHLORIDE  
WATER  
Packaging
# Item Code Package Description
1 NDC:68055-415-01 1 AMPULE in 1 PACKAGE
1 20 mL in 1 AMPULE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091193 05/09/2016
BACLOFEN 
Baclofen Injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68055-416
Route of Administration INTRATHECAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BACLOFEN (BACLOFEN) BACLOFEN 40 mg  in 20 mL
Inactive Ingredients
Ingredient Name Strength
WATER  
SODIUM CHLORIDE  
Packaging
# Item Code Package Description
1 NDC:68055-416-01 1 AMPULE in 1 PACKAGE
1 20 mL in 1 AMPULE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091193 05/09/2016
BACLOFEN 
Baclofen Injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68055-346
Route of Administration INTRATHECAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BACLOFEN (BACLOFEN) BACLOFEN 0.05 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
WATER  
SODIUM CHLORIDE  
Packaging
# Item Code Package Description
1 NDC:68055-346-10 10 AMPULE in 1 PACKAGE
1 1 mL in 1 AMPULE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091193 05/09/2016
Labeler - Sintetica S.A. (480895478)
Establishment
Name Address ID/FEI Operations
Sintetica S.A. 480895478 manufacture(68055-346, 68055-415, 68055-416), label(68055-346, 68055-415, 68055-416), pack(68055-346, 68055-415, 68055-416), analysis(68055-346, 68055-415, 68055-416)
Establishment
Name Address ID/FEI Operations
Sintetica-Bioren SA 483148768 analysis(68055-346, 68055-415, 68055-416)
Revised: 12/2016   Sintetica S.A.
(web3)