Baclopar Tablets 10 mg

4 CLINICAL PARTICULARS

4.4 Special warnings and precautions for use

Abrupt withdrawal
Treatment should always, (unless serious adverse effects occur), be gradually discontinued by successively reducing the dosage over a period of about 1-2 weeks. Anxiety and confusional states, delirium, hallucinations, psychotic disorder, manic mania or paranoia, d sates, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia, rhabdomyolysis and temporary aggravation of spasticity as a rebound phenomenon have been reported with abrupt withdrawal of baclofen, especially after long-term medication.

Renal impairment
Baclofen should be used with caution in patients with renal insufficiency impairment and should only be administered to end stage renal failure patients only when if the expected benefit outweighs the potential risk (see section 4.2 Posology and method of administration). Neurological signs and symptoms of overdose including clinical manifestations of toxic encephalopathy (e.g. confusion, disorientation, somnolence and depressed level of consciousness) have been observed in patients with renal impairment taking oral baclofen at doses of more than 5mg per day. Patients with impaired renal function should be closely monitored for prompt diagnosis of early symptoms of toxicity.

Particular caution is required when combining baclofen with to drugs or medicinal products that can significantly impact renal function. Renal function should shall be closely monitored and baclofen daily dosage adjusted accordingly to prevent baclofen toxicity.

4.8 Undesirable effects

Nervous system disorders:
Unknown: Sleep apnoea syndrome*

General disorders and administration site disorders:
Very rare: Hypothermia
Not known: Drug withdrawal syndrome (see section 4.4).
Investigations
Not known: Blood glucose increased

* Cases of central sleep apnoea syndrome have been observed with baclofen at high doses (≥ 100 mg) in patients who are alcohol dependent

4.9 Overdose

Symptoms: Central nervous depression: drowsiness, somnolence, depressed level of consciousness, respiratory depression and coma.

Other possible symptoms are Also liable to occur are: confusion, hallucinations, agitation, convulsion, abnormal electroencephalogram (burst suppression pattern and triphasic waves), accommodation disorders, impaired pupillary reflex; generalised muscular hypotonia, myoclonia, hyporeflexia or areflexia; : convulsions; abnormal electroencephalogram (EEG) changes (burst suppression pattern and triphasic waves); peripheral vasodilatation, hypotension or hypertension, bradycardia or tachycardia, or cardiac arrhythmias; hypothermia; nausea, vomiting, diarrhoea, salivary hypersalivationhypersecretion; elevated increased heapatic enzymes, SGOT and AP values, rhabdomyolysis.

10. DATE OF REVISION OF THE TEXT

December 2015July 2017

4.1 Therapeutic Indications

 

 

 

 

Baclopar is indicated for the relief of voluntary muscle spasticity as occurs in conditions such as multiple sclerosis and spinal cord lesions including syringomyelia, transverse myelitis and motor neurone disease.
Baclopar is also indicated in adults for the management of spasticity of cerebral origin including meningitis, cerebral palsy, traumatic head injury, cerebrovascular accident.

 

 

Patient selection is important when initiating

 

 

Baclopar therapy. It is of most benefit in relief of spasticity which is seriously interfering with activity. Treatment should not be commenced until the spastic state has been stabilised.

 

 

 

 

 

4.2 Posology and method of administration

 

 

 

 

Posology

Titration of the dose is necessary to meet the individual patients requirements while avoiding adverse effects or interference with function depending on the activity of voluntary muscles e.g. bladder, central posture support. The lowest dose compatible with an optimal response is recommended.

 

 

 

 

Adults:

 

Treatment should be started with a dosage of 15 mg daily, preferably in 2 to 4 divided doses. Dose should be titrated upwards cautiously by 15 mg /day increments at 3-day intervals until the requisite daily dosage has been attained. In certain patients reacting sensitively to drugs, it may be advisable to begin with a lower daily dosage (5 or 10 mg) and to raise the dosage more gradually (see section 4.4). The optimum dosage generally ranges from 30 to 80 mg daily.

 

Symptoms are usually adequately controlled with doses up to 60 mg daily. However, in order to meet individual patient needs, dosage adjustments should be slow and careful. The dose may be increased slowly if required, but the dose should not exceed 100 mg per day unless the patient is in hospital under medical supervision. In such cases 100 mg - 120 mg may occasionally be necessary. If therapeutic effect is not achieved within 6 weeks of reaching the maximum recommended dose, a decision should be taken whether to continue with therapy.

 

 

If no benefit is apparent within 6 to 8 weeks of achieving the maximum dosage, a decision should be taken whether to continue with Baclopar.

 

 

 

 

Elderly

 

: Side effects are more common in elderly and are noticed most particularly at the beginning of baclofen therapy. Elderly patients should be treated under careful medical supervision and initially receive a low dose of baclofen which can gradually be titrated upwards according to the therapeutic response. Most elderly patients are able to tolerate the same average maximum dose as for younger patientsThere is no evidence that the eventual average maximum dose differs from that in younger patients.

 

 

 

 

Patients with

 

impaired renal functionrenal impairment: A particularly low dosage of baclofen should be used, i.e. 5 mg daily, in patients with impaired renal function or those undergoing haemodialysis.

 

 

 

 

Epilepsy

Baclofen should only be used with great caution in patients with a history of convulsions since exacerbation of such conditions may occur and seizures have occasionally been reported in connection with the discontinuation of baclofen or with overdosage. Adequate anticonvulsive therapy should be continued and the patient carefully monitored.

 

 

 

Baclofen should be used with extreme care in patients already receiving antihypertensive therapy.

 

 

 

 

Others

Patients with cerebrovascular disease, a history of/or existent peptic ulcers, or those with respiratory or hepatic impairment should receive baclofen only under careful supervision. Since unwanted effects are more likely to occur, a cautious dosage schedule should be adopted in elderly and patients with spasticity of cerebral origin (see section 4.2).

 

 

 

Baclofen should be used with extreme care in patients already receiving antihypertensive therapy.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine.

 

 

 

 

Abrupt withdrawal

 

 

 

Use of the drug

 

 

Treatment should always, (unless adverse effects occur), be gradually discontinued by successively reducing the dosage over a period of 1-2 weeks. Anxiety and confusional states, hallucinations, psychotic, manic or paranoid sates, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia and temporary aggravation of spasticity as rebound phenomenon have been reported with abrupt withdrawal of baclofen, especially after long-term medication.

 

 

 

 

Urinary disorders

 

 

 

Baclofen may interfere with micturition and associated functions.

 

 

Patients with neurogenic disturbances affecting emptying may show improvement. but those In patients with pre-existing sphincter hypertonia may experience acute urinary retention, baclofen should be used with caution in such cases.

 

Laboratory tests

 

 

 

Raised AST, AP and blood glucose levels

 

 

Elevated aspartate aminotransferase, blood alkaline phosphatase and blood glucose levels in serum have been noted rarely. Liver function tests should be performed in patients with liver disease and diabetic patients monitored to ensure that no underlying drug induced changes have occurred in these diseases.

 

Paediatric population

There is very limited clinical data on the use of baclofen in children under the age of one year. Use in this patient population should be based on the physician’s consideration of individual benefit and risk of therapy.

 

 

 

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucosegalactose malabsorption should not take this medicine.

 

 

 

 

4.5 Interaction with other medicinal products and other forms of interaction

 

 

 

Drugs causing Central Nervous System (CNS) depression

In concomitant administration with other drugs acting on the CNS including other muscle relaxants (such as tizanidine) with synthetic opiates or with alcohol, increased sedation may occur (see section 4.4).

The risk of respiratory depression is also increased. In addition, hypotension has been reported with concomitant use of morphine and intrathecal baclofen. Careful monitoring of respiratory and cardiovascular functions is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.

Concurrent use of baclofen with MAO inhibitors may result in increased CNS-depressant and hypotensive effects; caution is recommended and dosage of one or both agents may require reduction.

 

 

 

Prolongation of fentanyl induced anaesthesia may occur in patients pre-treated with baclofen.

 

 

 

 

4.8 Undesirable effects

 

 

 

Nervous system disorders:

 

 

 

Very common: Sedation, somnolence.

Common: Respiratory depression, fatigue, confusional state, dizziness, headache, insomnia, euphoria mood, depression, muscular weakness, ataxia, tremor, hallucination, nightmare, myalgia, nystagmus, dry mouth.

Rare: Paraesthesia, dysarthria, dysgeusia. Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients.

 

 

 

Certain patients have shown increased spasticity as a paradoxical reaction to the medication. An undesirable degree of muscular hypotonia - making it more difficult for patients to walk or fend for themselves - may occur and can usually be relieved by re-adjusting the dosage (i.e. by reducing the doses given during the day and possibly increasing the evening dose).

 

 

 

 

General disorders and administration site disorders:

 

 

 

Very rare: Hypothermia

Not known: Drug withdrawal syndrome (see section 4.4).

 

 

 

Investigations

 

 

 

Not known: Blood glucose increased

 

 

 

 

 

 

Certain patients have shown increased spasticity as a paradoxical reaction to the medication. An undesirable degree of muscular hypotonia - making it more difficult for patients to walk or fend for themselves - may occur and can usually be relieved by re-adjusting the dosage (i.e. by reducing the doses given during the day and possibly increasing the evening dose).

 

 

 

 

4.9 Overdose

 

 

 

Symptoms: Central nervous depression: drowsiness,

 

somnolence, impairment depressed level of consciousness, respiratory depression and coma.

 

Other possible symptoms are: confusion, hallucinations, agitation, accommodation disorders,

 

absent impaired pupillary reflex; generalised muscular hypotonia, myoclonia, hyporeflexia or areflexia:convulsions; abnormal electroencephalogram (EEG) changes (burst suppression pattern and triphasic waves); peripheral vasodilatation, hypotension or hypertension, bradycardia or tachycardia or cardiac arrhythmias; hypothermia; nausea, vomiting, diarrhoea, salivary hypersalivation; elevated LDH, AST hapatic enzymes, SGOT and AP values.

 

 

 

 

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

 

 

 

Pharmacotherapeutic group: Muscle relaxants, centrally acting agents, other centrally acting agents, ATC code M03BX01

 

 

 

Baclofen is a chlorophenyl analogue of gamma-aminobutyric acid (GABA) and is chemically unrelated to other antispastic agents.

 

 

 

 

Mechanism of action

 

 

 

Baclofen is a highly effective antispastic agent

 

 

It acts acting at the spinal level. A gamma-aminobutyric acid (GABA) derivative, and chemically unrelated to other antispastic agent.

 

Baclofen

 

 

depressing depresses monosynaptic and polysynaptic reflex transmission, most probably by stimulating the GABAß receptors. This, in turn inhibits the release of the excitatory amino acids (glutamate and aspartate). Baclofen does not affect neuromuscular transmission.

 

 

 

 

Special populations

 

 

 

 

Elderly patients (aged 65 years or above)

The pharmacokinetics of baclofen in older patients aged 65 years or above are virtually the same as in young subjects below 65 years of age. Following a single oral dose, older patients have slower elimination but with a similar systematic exposure of baclofen compared to adults below 65 years of age.
Extrapolation of these results to multi-dose treatment suggests no significant pharmacokinetic difference between patients below 65 years of age and elderly patients.

 

 

 

10. DATE OF REVISION OF THE TEXT

 

 

 

February

 

 

December 2015

 

 

 

 

4.1       Therapeutic indications
Added:
Paediatric Population
Baclofen is indicated in patients 0 to <18 years for the symptomatic treatment of spasticity of cerebral origin, especially where due to infantile cerebral palsy, as well as following cerebrovascular accidents or in the presence of neoplastic or degenerative brain disease.
Baclofen is also indicated for the symptomatic treatment of muscle spasms occurring in spinal cord diseases of infectious, degenerative, traumatic, neoplastic, or unknown origin such as multiple sclerosis, spastic spinal paralysis, amyotrophic lateral sclerosis, syringomyelia, transverse myelitis, traumatic paraplegia or paraparesis, and compression of the spinal cord.

4.2       Posology and method of administration
updated:
Paediatric population (0 to <18 years):  Treatment should usually be started with a very low dose (corresponding to approximately 0.3 mg/kg a day), in 2-4 divided doses (preferably in 4 divided doses). Baclofen tablets are not suitable for use in children below 33 kg body weight.
The dosage should be raised cautiously, at about 1 week intervals, until it becomes sufficient for the child's individual requirements. The usual daily dosage for maintenance therapy ranges between 0.75 and 2 mg/kg body weight. The total daily dose should not exceed a maximum of 40 mg/day in children below 8 years of age. In children over 8 years of age a maximum daily dose of 60 mg/day may be given.

4.4       Special warnings and precautions for use
Added:
There is very limited clinical data on the use of Baclofen in children under the age of one year. Use in this patient population should be based on the physician’s consideration of individual benefit and risk of therapy.

10.       DATE OF REVISION OF THE TEXT
July 2012

 

4.3 Contraindications

Hypersensitivity to baclofen and pulmonary insufficiency.

Use in patients with pulmonary insufficiency.

4.4 Special warnings and precautions for use

Baclofen should only be used with great caution in patients with porphyria, history of alcoholism, hypertension, epilepsy, history of convulsions, psychotic disorders, schizophrenia depressive or manic disorders or confusional states since exacerbation of such conditions may occur.

Patients with acute cerebrovascular ischaemia, a history of/or existent peptic ulcers, or those on anti-hypertensive therapy or with renal impairment should receive baclofen only under careful supervision.

Baclofen should be used with extreme care in patients already receiving antihypertensive therapy.

Use of the drug, particularly if it has been prolonged, should not be terminated abruptly to avoid precipitation of paranoia, hallucinations, and withdrawal syndrome. Treatment should be gradually discontinued by reducing the dosage over 1-2 weeks. should always, (unless adverse effects occur), be gradually discontinued by successively reducing the dosage over a period of 1-2 weeks. Anxiety and confusional states, hallucinations, psychotic, manic or paranoid sates, convulsions (state epilepticus), dyskinesia, tachycardia, hyperthermia and temporary aggravation of spasticity as rebound phenomenon have been reported with abrupt withdrawal of Baclofen, especially after long-term medication.

For the intrathecal formulation of Lioresal, it has been reported that clinical characteristics of withdrawal may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabodomyolysis.

4.5 Interaction with other medicinal products and other forms of interaction

In concomitant administration with other drugs acting on the CNS or with alcohol, increased sedation may occur.

Concurrent use of baclofen with MAO inhibitors may result in increased CNS-depressant and hypotensive effects; caution is recommended and dosage of one or both agents may require reduction.

Prolongation of fentanyl induced anaesthesia may occur in patients pre-treated with baclofen.

The effect of baclofen may be prolonged if co-administered with tricyclic anti-depressants resulting in marked muscle hypotonia.

The risk of respiratory depression is also increased. Careful monitoring of respiratory and cardiovascular functions is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.

The risk of hypotension occurring is increased in patients receiving both baclofen and anti-hypertensive therapy.  Adjustments to the dosage of anti-hypertensive medication should be made accordingly.

Mental confusion, hallucinations and agitation has been reported in patients concurrently treated with baclofen and levodopa plus carbidopa for Parkinson's Disease.

Drugs which may produce renal insufficiency e.g. ibuprofen may reduce baclofen excretion leading to toxic effects.

Since balcofen may increase blood glucose concentrations, dosage adjustments of insulin and/or oral hypoglycemic agents may be necessary during and after concurrent therapy.

Aggravation of hyperkinetic symptoms may possibly occur in patients taking lithium.

 

4.8 Undesirable effects

These are most common at the start of baclofen therapy; if the dose is raised too rapidly; at high doses and also in the elderly. They are usually temporary and can be relieved or removed by reducing the dose. It is rare for the side effects to require withdrawal of therapy.

Central nervous system:  At the start of treatment frequent effects have included day time sedation, drowsiness, and nausea.  Occasionally dryness of the mouth, respiratory depression, lightheadedness, lassitude, exhaustion, mental confusion, dizziness, retching, vomiting, headache and insomnia are reported.

If nausea persists despite dosage reduction, it is recommended that baclofen be taken with food or a milk beverage.

It is often difficult to distinguish between neurological and/or psychiatric manifestations and those of the disease under treatment.  Those which have occasionally or rarely been reported include:  euphoria, depressive states, paraesthesiae, myalgia, muscular weakness, ataxia, tremor, nystagmus, accommodation disorders, hallucinations, nightmares.  Lowering of the convulsion threshold and seizures may possibly occur, particularly in epileptic patients.

Gastro-Intestinal Tract:  Occasionally, mild gastro-intestinal disturbances (constipation, diarrhoea).

Cardio-vascular System:  Occasionally, hypotension, diminished cardiovascular function.

Urogenital System:  Occasionally or rarely, dysuria, frequency of micturition, enuresis and impotence and ejaculation problems.  It is often difficult to distinguish between these manifestations and those of the disease under treatment.

Miscellaneous Unwanted Effects:  In rare or isolated cases, alterations in the taste sensation, hyperhidrosis, skin rash, hepatic dysfunction.

Paradoxical increased spasticity has been noted in some patients.

An undesirable degree of muscular hypotonia may occur.  This can usually be relieved by dosage re-adjustments (i.e. by reducing the doses given during the day and possibly increasing the evening dose).

Side-effects: Unwanted effects occur mainly at the start of treatment, if the dosage is raised too rapidly, if large doses are employed, or in elderly patients. They are often transitory and can be attenuated or eliminated by reducing the dosage; they are seldom severe enough to necessitate withdrawal of the medication.

Should nausea persist following a reduction in dosage, it is recommended that Lioresal be ingested with food or a milk beverage.

Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients.

Certain patients have shown increased muscle spasticity as a paradoxical reaction to the medication.

In patients with a case history of psychiatric illness or with cerebrovascular disorders (e.g. stroke) as well as in elderly patients, adverse reactions may assume a more serious form.

Adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: very common (1/10); common (1/100, < 1/10); uncommon (1/1,000, <1/100); rare (1/10,000, < 1/1,000) very rare (< 1/10,000), including isolated reports.

Nervous System Disorders:
Very common: Sedation, somnolence.
Common: Respiratory depression, light-headedness, lassitude, exhaustion, mental confusion, dizziness, headache, insomnia, euphoria mood, depression, muscular weakness, ataxia, tremor, hallucinations, nightmares, myalgia, nystagmus, dry mouth.
Rare: Paraesthesia, dysarthria, dysgeusia. Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients.
Very rare: Hypothermia

Eyes disorders:
Certain patients have shown increased spasticity as a paradoxical reaction to the medication. An undesirable degree of muscular hypotonia - making it more difficult for patients to walk or fend for themselves - may occur and can usually be relieved by re-adjusting the dosage (ie. By reducing the doses given during the day and possibly increasing the evening dose).
Common: Accommodation disorders, visual disturbance.

Gastro-intestinal disorders:
Very common: Nausea.
Common: Mild gastro-intestinal disturbances constipation, diarrhoea, retching and vomiting.
Rare: Abdominal pain

Cardiac Disorders:
Common: Diminished cardiovascular function.

Vascular disorders:
Common: Hypotension

Renal and urinaire disorders:
Common:, Pollakiuria, enuresis, dysuria
Rare: Urinary retention

Reproductive system and brest disorders:
Rare: Erectile dysfunction

Hepatobiliary disorders:
Rare: Hepatic function abnormal.

Skin and subcutaneous tissue disorders:
Common: Hyperhidrosis, skin rash.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 21st November 1989
Date of last renewal: 21st November 2004 2009

10. DATE OF REVISION OF THE TEXT

March 2010 June 2011

 

3.   PHARMACEUTICAL FORM

 

Tablets.

White flat bevel-edge tablet, marked “BN” breakline “10” on one side and “G” on the reverse.

 

The tablet can be divided into equal halves.

1. NAME OF THE MEDICINAL PRODUCT

 

Baclopar Tablets 10 mg tablets

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains 10 mg of Baclofen.

Excipients: Each tablets contains 40mg of lactose monohydrate

For a full list of excipients, see section 6.1.

 

 

3. PHARMACEUTICAL FORM

 

Tablets.

A white tablet White flat bevel-edge tablet, marked “BN” breakline “10” on one side and “G” on the reverse.

 

 

10. DATE OF REVISION OF THE TEXT

 

July 2005 March 2010