SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Lyflex 5mg/5ml Oral Solution Baclofen 5mg/5ml Sugar Free Oral Solution

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5ml of oral solution contains 5mg Baclofen.

For excipients see Section 6.1

3. PHARMACEUTICAL FORM

Oral Solution

Clear yellowish liquid with an odour and flavour of raspberry

4.1 Therapeutic indications

Baclofen is indicated for the relief of voluntary muscle spasticity resulting from disorders such 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 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 treatment with Baclofen Oral Solution; 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 is indicated in patients 0 to <18 years for the symptomatic treatment of spasticity of celebral 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

Baclofen Oral Solution is particularly suitable for children or those adults who are unable to take tablets. Dosage titration can be achieved more precisely with the oral solution.

Before initiating treatment with Baclofen Oral Solution it is advisable to assess realistically the overall extent of clinical improvement that the patient may be expected to achieve with treatment. Careful titration of dosage is essential (particularly in the elderly) until the patient is stabilised. If too high a dose is used initially or if increases in dosage are too rapid 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:

It is recommended that treatment is started with a gradually increasing dosage regimen as follows. However this may be adjusted to meet individual patient requirements:

5mg three times a day for three days 10mg three times a day for three days 15mg three times a day for three days 20mg three times a day for three days

Satisfactory control of symptoms is usually obtained with doses of up to 60mg 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 100mg is not advised unless the patient is in hospital under careful medical supervision. Small frequent doses may prove better in some cases than larger spaced doses. Also some patients benefit from the use of Baclofen 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 consideration should be made by the physician as to whether to continue treatment with Baclofen Oral Solution .

Elderly:

Elderly patients may be more susceptible to side effects, particularly in the early stages of starting treatment with Baclofen 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 raised cautiously, at about 1 week intervals, until it becomes sufficient for the child’s individual requirements. The usual daily dose 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.

Patients with impaired renal function:

In patients with impaired renal function or undergoing chronic haemodialysis, a particularly low dosage of Baclofen should be selected i.e. approx. 5mg daily.

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 or any of the ingredients of the oral solution, peptic ulceration.

4.4 Special warning and precautions for use

Psychotic disorders, schizophrenia, depressive or manic disorders, confusional states or Parkinson’s disease may be exacerbated by treatment with baclofen. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance.

Baclofen may also exacerbate epileptic manifestations but can be used provided appropriate supervision and adequate anticonvulsive therapy are maintained. Baclofen should be used with extreme care in patients already receiving antihypertensive therapy, (see Interactions).

Baclofen should be used with caution in patients suffering from cerebrovascular accidents or from respiratory, hepatic or renal impairment.

During treatment with baclofen, neurogenic disturbances affecting emptying of the bladder may show an improvement. In patients with pre-existing sphincter hypertonia, acute retention of urine may occur; the drug should be used with caution in such cases.

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.

This medicine contains sorbitol. Patients with rare hereditary problems should not take this medicine. Calorific value 2.6kcal/g sorbitol”.

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), 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.

4.5. Interactions with other medicinal products and other forms of interaction

Where baclofen 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 may be potentiated, resulting in pronounced muscular hypotonia.

Since concomitant treatment with baclofen and anti-hypertensives 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 which 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 should only be used 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 crosses the placental barrier.

In mothers taking baclofen in therapeutic doses, the active substance passes into the breast milk, but in quantities so small that no undesirable effects on the infant would be expected.

4.7. Effects on ability to drive and use machines

The patient’s reactions may be adversely affected by baclofen induced sedation or decreased alertness. Patients should therefore exercise due caution. Operating equipment or machinery may be hazardous.

4.8 Undesirable 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 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.

Central nervous system:

Frequent (>10%): particularly at the start of treatment daytime sedation, drowsiness, and nausea.

Occasional (> 1%,<10%): respiratory depression, light-headedness, lassitude, exhaustion, mental confusion, dizziness, headache, insomnia, euphoria, depression, muscular weakness, ataxia, tremor, hallucinations, nightmares, myalgia, nystagmus, dry mouth.

Rare (> 0.001%,<1%): paraesthesia, dysarthria. Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients.

Sense organs:

Occasional (> 1%,<10%): accommodation disorders, visual disturbance.

Rare (> 0.001%,<1%): dysgeusia.

Gastro-intestinal tract:

Frequent (>10%): nausea.

Occasional (> 1%,<10%): mild gastro-intestinal disturbances constipation, diarrhoea, retching and vomiting.

Rare (> 0.001%,<1%): abdominal pain

Cardiovascular system:

Occasional (> 1%,<10%): hypotension, diminished cardiovascular function. Urogenital system:

Frequent (>10%): frequency of micturition, enuresis, dysuria.

Rare (> 0.001%,<1%): urinary retention, impotence.

Liver:

Rare (> 0.001%,<1%): disorders of hepatic function.

Skin:

Occasional (> 1%,<10%): hyperhydrosis, skin rash.

General disorders and administration site conditions:

Very rare: hypothermia.

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).

The excipient sorbitol may have a mild laxative effect when taken in large amounts and hydroxybenzoates may cause allergic reactions which may be possibly delayed.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Overdose

Symptoms:

Prominent features of overdosage 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.

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. It is a gamma-aminobutyric acid (GABA) derivative, with a similar chemical structure, but differing in action.

Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by stimulating the GABA beta 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 their 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 liquid and tablet formulations is observed in respect of t_max c_max and bioavailability.

Following oral administration of single doses (10-30mg) peak plasma concentrations are reached after 0.5 to 3.0 hours and the 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.

A 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. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

70% Sorbitol Solution Methyl hydroxybenzoate,

Propyl hydroxybenzoate,

Raspberry flavour (contains propylene glycol), Carmellose Sodium,

Purified water.

Baclofen Oral Solution is sugar free.

6.2. Incompatibilities

None known.

6.3. Shelf life

24 months

Once opened use within 56 days of first opening

Baclofen Oral Solution may be diluted with purified water. The shelf life of the diluted solution is 14 days when stored not above 25°C.

Special precautions for storage

Do not store above 25°C Store in the original container Do not refrigerate or freeze

6.5    Nature and contents of container

Pharmaceutical grade type III amber glass bottle with child resistant and tamper evident polypropylene faced cap with an EPE liner.

6.6    Special precautions for disposal

There is no specific instruction for use/handling.

7.    MARKETING AUTHORISATION HOLDER

Chemidex Pharma Limited Trading as Chemidex Generics Egham Business Village Crabtree Road Egham

Surrey TW20 8RB United Kingdom

8. MARKETING AUTHORISATION NUMBER

PL 17736/0061

9.    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

24 May 2004

10 DATE OF REVISION OF THE TEXT

23/03/2016