Baclofen 5mg/5ml Oral Solution
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Baclofen 5 mg/5 mL Oral Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5 ml contains 5 mg Baclofen.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Oral Solution
A colourless to pale yellow solution with a raspberry flavour.
4.1. Therapeutic indications
Baclofen 5 mg/5 mL Oral Solution is indicated for the relief of spasticity of voluntary muscle resulting from such disorders as: multiple sclerosis, other spinal lesions, e.g. tumours of the spinal cord, syringomyelia, motor neurone disease, transverse myelitis, traumatic partial section of the cord.
Baclofen 5 mg/5 mL Oral Solution is also indicated in adults and children for the relief of spasticity of voluntary muscle arising from e.g. cerebrovascular accidents, cerebral palsy, meningitis, traumatic head injury.
Patient selection is important when initiating Baclofen 5 mg/5 mL Oral Solution therapy; it is likely to be of most benefit in patients whose spasticity constitutes a handicap to activities and/or physiotherapy. Treatment should not be commenced until the spastic state has become stabilised.
Paediatric population
Baclofen 5 mg/5 mL Oral Solution 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 5 mg/5 mL Oral Solution 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
Before starting treatment with Baclofen 5 mg/5 mL Oral Solution it is prudent to realistically assess the overall extent of clinical improvement that the patient may be expected to achieve. Careful titration of dosage is essential (particularly in the elderly) until the patient is stabilised. If too high a dose is initiated or if the dosage is increased too rapidly side effects may occur. This is particularly relevant if the patient is ambulant in order to minimise muscle weakness in the unaffected limbs or where spasticity is necessary for support.
Adults:
The following gradually increasing dosage regimen is suggested, but should be adjusted to suit individual patient requirements.
5 mg three times a day for three days 10 mg three times a day for three days 15 mg three times a day for three days 20 mg three times a day for three days
Satisfactory control of symptoms is usually obtained with doses of up to 60 mg daily, but a careful adjustment is often necessary to meet the requirements of each individual patient. The dose may be increased slowly if required, but a maximum daily dose of more than 100 mg is not advised unless the patient is in hospital under careful medical supervision. Small frequent dosage may prove better in some cases than larger spaced doses. Also some patients benefit from the use of Baclofen 5 mg/5 mL Oral Solution only at night to counteract painful flexor spasm. Similarly a single dose given approximately 1 hour prior to performance of specific tasks such as washing, dressing, shaving, physiotherapy, will often improve mobility.
Once the maximum recommended dose has been reached, if the therapeutic effect is not apparent within 6 weeks a decision whether to continue with Baclofen 5 mg/5 mL Oral Solution should be taken.
Elderly:
Elderly patients may be more susceptible to side effects, particularly in the early stages of introducing Baclofen 5 mg/5 mL Oral Solution. Small doses should therefore be used at the start of treatment, the dose being titrated gradually against the response, under careful supervision. There is no evidence that the eventual average maximum dose differs from that in younger patients.
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.
The dosage should be cautiously raised 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 2mg/kg body weight. The total daily dose should not exceed a maximum of 40mg/day in children below 8 years of age. In children over 8 years of age, a maximum daily dosage of 60mg/day may be given.
Patients with impaired renal function:
In patients with impaired renal function or undergoing chronic haemodialysis, a particularly low dosage of Baclofen 5 mg/5 mL Oral Solution should be selected i.e. approx. 5 mg daily. Signs of overdose have been observed in patients with renal impairment taking oral Baclofen at doses of more than 5 mg per day.
Patients with spastic states of cerebral origin:
Unwanted effects are more likely to occur in these patients. It is therefore recommended that a very cautious dosage schedule be adopted and that patients be kept under appropriate surveillance.
4.3 Contraindications
Hypersensitivity to baclofen, peptic ulceration.
4.4. Special warnings and precautions for use
Psychotic disorders, schizophrenia, depressive or manic disorders, confusional states or Parkinson's disease may be exacerbated by treatment with Baclofen 5 mg/5 mL Oral Solution. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance.
Baclofen 5 mg/5 mL Oral Solution may also exacerbate epileptic manifestations but can be employed provided appropriate supervision and adequate anticonvulsive therapy are maintained. Baclofen 5 mg/5 mL Oral Solution should be used with extreme care in patients already receiving antihypertensive therapy, (see Interactions).
Baclofen 5 mg/5 mL Oral Solution should be used with caution in patients suffering from cerebrovascular accidents or from respiratory, hepatic or renal impairment.
Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Signs of overdose have been observed in patients with renal impairment taking oral baclofen at doses of more than 5 mg per day.
Under treatment with Baclofen 5 mg/5 mL Oral Solution neurogenic disturbances affecting emptying of the bladder may show an improvement. In patients with preexisting sphincter hypertonia, acute retention of urine may occur; the drug should be used with caution in such cases.
Abrupt withdrawal:
Anxiety and confusional states, hallucinations, psychotic, manic or paranoid states, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia and as rebound phenomenon temporary aggravation of spasticity have been reported with abrupt withdrawal of baclofen, especially after long term medication. Treatment should always, (unless serious adverse effects occur), therefore be gradually discontinued by successively reducing the dosage over a period of about 1-2 weeks.
Since in rare instances elevated SGOT, alkaline phosphatase and glucose levels in serum have been recorded, appropriate laboratory tests should be performed in patients with liver diseases or diabetes mellitus in order to ensure that no drug induced changes in these underlying diseases have occurred.
There is very limited clinical data on the use of Baclofen 5 mg/5 mL Oral Solution 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.
4.5 Interaction with other medicinal products and other forms of interaction
Where Baclofen 5 mg/5 mL Oral Solution is taken concomitantly with other drugs acting on the CNS with synthetic opiates or with alcohol, increased sedation may occur.
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.
During concurrent treatment with tricyclic antidepressants, the effect of Baclofen 5 mg/5 mL Oral Solution may be potentiated, resulting in pronounced muscular hypotonia.
Since concomitant treatment with Baclofen 5 mg/5 mL Oral Solution and antihypertensives is likely to increase the fall in blood pressure, the dosage of antihypertensive medication should be adjusted accordingly. Hypotension has been reported in one patient receiving morphine and intrathecal baclofen.
Drugs that may produce renal insufficiency e.g. ibuprofen may reduce baclofen excretion leading to toxic effects. In patients with Parkinson's disease receiving treatment with baclofen and levodopa plus carbidopa, there have been reports of mental confusion, hallucinations, nausea and agitation.
4.6 Pregnancy and lactation
During pregnancy, especially in the first 3 months, Baclofen 5 mg/5 mL Oral Solution should only be employed if its use is of vital necessity. The benefits of the treatment for the mother must be carefully weighed against the possible risks for the child. Baclofen 5 mg/5 mL Oral Solution crosses the placental barrier.
In mothers taking Baclofen 5 mg/5 mL Oral Solution in therapeutic doses, the active substance passes into the breast milk, but in quantities so small that no undesirable effects on the infant are to be expected.
4.7 Effects on ability to drive and use machines
The patient's reactions may be adversely affected by Baclofen 5 mg/5 mL Oral Solution induced sedation or decreased alertness, patients should therefore exercise due caution. Operating equipment or machinery may be hazardous.
4.8 Undesirable effects
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 Baclofen 5 mg/5 mL Oral Solution be ingested with food or a milk beverage.
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.
Frequency estimates: frequent > 10%, occasional > 1% - 10%, Rare > 0.001% - 1%, isolated cases < 0.001%.
Central Nervous System:
Frequent: particularly at the start of treatment daytime sedation, drowsiness, and nausea may frequently occur.
Occasional: respiratory depression, light-headedness, lassitude, exhaustion, mental confusion, dizziness, headache, insomnia, euphoria, depression, muscular weakness, ataxia, tremor, hallucinations, nightmares, myalgia, nystagmus, dry mouth.
Rare: paraesthesia, dysarthria. Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients.
Sense organs:
Occasional: accommodation disorders, visual disturbance.
Rare: dysgeusia.
Gastro-intestinal tract:
Frequent: nausea.
Occasional: mild gastro-intestinal disturbances, constipation, diarrhoea, retching and vomiting.
Rare: abdominal pain
Cardiovascular system:
Occasional: hypotension, diminished cardiovascular function.
Urogenital system:
Frequent: frequency of micturition, enuresis, dysuria.
Rare: urinary retention, impotence.
Liver:
Rare: disorders of hepatic function.
Skin:
Occasional: hyperhydrosis, skin rash.
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:
Prominent features are signs of central nervous depression: drowsiness, impairment of consciousness, respiratory depression, coma. Also liable to occur are: confusion, hallucinations, agitation, accommodation disorders, absent pupillary reflex; generalised muscular hypotonia, myoclonia, hyporeflexia or areflexia; convulsions; peripheral vasodilatation, hypotension, bradycardia; hypothermia; nausea, vomiting, diarrhoea, hypersalivation; elevated LDH, SGOT and AP values. Patients with renal impairment can develop signs of overdose even on low doses of oral Baclofen 5 mg/5 mL Oral Solution (see section 4.2 Posology and Method of administration and 4.4 Special warnings and special precautions for use.)
A deterioration in the condition may occur if various substances or drugs acting on the central nervous system (e.g. alcohol, diazepam, tricyclic antidepressants) have been taken at the same time.
Treatment:
No specific antidote is known.
Elimination of the drug from the gastro-intestinal tract (induction of vomiting, gastric lavage; comatose patients should be intubated prior to gastric lavage), administration of activated charcoal; if necessary, saline aperient; in respiratory depression, administration of artificial respiration, also measures in support of cardiovascular functions. Since the drug is excreted chiefly via the kidneys, generous quantities of fluid should be given, possibly together with a diuretic. In the event of convulsions diazepam should be administered cautiously i.v.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Baclofen is an antispastic agent acting at the spinal level. A gamma-aminobutyric acid (GABA) derivative, baclofen is chemically unrelated to other antispastic agents.
Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by stimulating the GABAb receptors, this stimulation in turn inhibiting the release of the excitatory amino acids glutamate and aspartate. Neuromuscular transmission is unaffected by baclofen.
The major benefits of baclofen stem from its ability to reduce painful flexor spasms and spontaneous clonus thereby facilitating the mobility of the patient, increasing independence and helping rehabilitation.
Baclofen also exerts an antinociceptive effect. General well being is often improved and sedation is less often a problem than with centrally acting drugs.
Baclofen stimulates gastric acid secretion.
5.2 Pharmacokinetic properties
Absorption:
Baclofen is rapidly and completely absorbed from the gastro-intestinal tract. No significant difference between the solution and tablet formulations is observed in respect of tmax, cmax and bioavailability. Following oral administration of single doses (10-30mg) peak plasma concentrations are recorded after 0.5 to 1.5 hours and areas under the serum concentration curves are proportional to the dose.
Distribution:
The volume of distribution of baclofen is 0.7 l/kg and the protein binding rate is approximately 30%. In cerebrospinal fluid active substance concentrations are approximately 8.5 times lower than in the plasma.
Biotransformation:
Baclofen is metabolised to only a minor extent. Deamination yields the main metabolite, -(p-chlorophenyl)-4-hydroxybutyric acid, which is pharmacologically inactive.
Elimination/excretion:
The plasma elimination half-life of baclofen averages 3 to 4 hours. The serum protein binding rate is approximately 30%.
Baclofen is eliminated largely in unchanged form. Within 72 hours, about 75% of the dose is excreted via the kidneys with about 5% of this amount as metabolites.
Elderly:
The pharmacokinetics of baclofen in elderly patients are virtually the same as in young subjects. The peak plasma concentrations of baclofen in elderly patients are slightly lower and occur later than in healthy young subjects but the AUCs are similar in the two groups.
5.3 Preclinical safety data
Baclofen increases the incidence of omphaloceles (ventral hernias) in the foetuses of rats given approximately 13 times the maximum oral dose (on a mg/kg basis) recommended for human use. This was not seen in mice or rabbits.
An apparently dose related increase in the incidence of ovarian cysts, and a less marked increase in enlarged and/or haemorrhagic adrenals have been observed in female rats treated for 2 years. The clinical relevance of these findings is not known.
Experimental evidence to date suggests that baclofen does not possess either carcinogenic or mutagenic properties.
6.1. List of excipients
Methylparahydroxybenzoate (E218)
Propylparahydroxyb enzoate (E216)
Raspberry flavour (containing propylene glycol (E490/E1520)) Hydroxyethylcellulose (E1525)
Propylene glycol (E490/E1520)
Sorbitol (E420)
Sodium hydroxide (for pH-adjustment)
Purified water
6.2 Incompatibilities
Not Applicable
6.3 Shelf life
2 years
In Use Shelf Life
60 days
6.4 Special precautions for storage
Protect from light. Do not store above 25°C. Do not refrigerate.
6.5. Nature and Contents of Container
Amber 300 mL Type III glass bottles with polypropylene/polyethylene tamper evident caps.
Pack size: 300 mL.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Waymade Plc Trading as Sovereign Medical Sovereign House Miles Gray Road Basildon Essex SS14 3FR
8 MARKETING AUTHORISATION NUMBER(S)
PL 06464/2354
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 19/11/2008
10 DATE OF REVISION OF THE TEXT
11/02/2013