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

Baclofen 5mg/5mL Oral Solution is given orally in either tablet or liquid form. These two formulations are bioequivalent. The liquid may be particularly suitable for children or those adults who are unable to take tablets. Dosage titration can be more precisely managed with the liquid. The lowest dose compatible with an optimal response is recommended.

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.

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.

Discontinuation of the treatment should always be gradual by successively reducing the dosage over a period of approximately 1 to 2 weeks, except in overdose-related emergencies, or where serious adverse effects have occurred (see section 4.4).

Adults:

Treatment should be started with a dosage of 15 mg daily, preferably in divided doses. 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.

Special populations

Elderly patients (aged 65 years or above):

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.

Maximum daily dose

The maximum daily dose should not exceed 2 mg/kg/day. 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.

Baclofen 5mg/5mL Oral Solution are not suitable for use in children below 33kg body weight

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.

Baclofen 5mg/5mL Oral Solution should be administered to end stage renal failure patients only if the expected benefit outweighs the potential risk. These patients should be closely monitored for prompt diagnosis of early signs and/or symptoms of toxicity (e.g. somnolence, lethargy) (see section 4.4 and section 4.9).

Patients with hepatic impairment:

No studies have been performed in patients with hepatic impairment receiving Baclofen 5mg/5mL Oral Solution therapy. The liver does not play a significant role in the metabolism of baclofen after oral administration of Baclofen 5mg/5mL Oral Solution (see section 5.2). However, Baclofen 5mg/5mL Oral Solution has the potential of elevating liver enzymes. Baclofen 5mg/5mL Oral Solution should be prescribed with caution in patients with hepatic impairment

Patients with spastic states of cerebral origin:

Unwanted effects are more likely to occur in these patients. It is therefore recommended that a cautious dosage schedule be adopted and that patients be kept under appropriate surveillance.

Method of administration

Baclofen 5mg/5mL Oral Solution should be taken during meals with a little liquid.

4.3. Contraindications

• Hypersensitivity to baclofen or to any of the excipients listed in section 6.1

• Peptic ulceration.

4.4. Special warnings and precautions for use

Psychiatric and nervous system disorders

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.

Suicide and suicide-related events have been reported in patients treated with baclofen. In most cases, the patients had additional risk factors associated with an increased risk of suicide including alcohol use disorder, depression and/or a history of previous suicide attempts. Close supervision of patients with additional risk factors for suicide should accompany drug therapy. Patients (and caregivers of patients) should be alerted about the need to monitor for clinical worsening, suicidal behaviour or thoughts or unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Cases of misuse, abuse and dependence have been reported with baclofen. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of baclofen misuse, abuse or dependence e.g. dose escalation, drug-seeking behaviour, development of tolerance.

Epilepsy

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.

Encephalopathy

Cases of encephalopathy have been reported in patients receiving baclofen at therapeutic doses, which were reversible after treatment discontinuation. Symptoms included somnolence, depressed level of consciousness, confusion, myoclonus and coma. (see sections 4.8 and 4.9)

If signs of encephalopathy are observed, baclofen should be discontinued.

Others

Baclofen 5 mg/5 mL Oral Solution should be used with extreme care in patients already receiving antihypertensive therapy, (see section 4.5).

Baclofen 5 mg/5 mL Oral Solution should be used with caution in patients suffering from cerebrovascular accidents or from respiratory or hepatic impairment.

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).

Renal impairment

Baclofen should be used with caution in patients with renal impairment and should be administered to end-stage renal failure patients only 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 and at doses of 5mg per day in patients with end-stage renal failure being treated with chronic haemodialysis. Patients with impaired renal function should be closely monitored for prompt diagnosis of early symptoms of toxicity.

Particular caution is required when combining Baclofen 5 mg/5 mL Oral Solution to drugs or medicinal products that can significantly affect renal function. Renal function should be closely monitored and Baclofen 5 mg/5 mL Oral Solution daily dosage adjusted accordingly to prevent baclofen toxicity.

Cases of baclofen toxicity have been reported in patients with acute renal failure (see section 4.9).

Besides discontinuing treatment, unscheduled haemodialysis might be considered as a treatment alternative in patients with severe baclofen toxicity. Haemodialysis effectively removes baclofen from the body, alleviates clinical symptoms of overdose and shortens the recovery time in these patients.

Urinary disorders

Under treatment with Baclofen 5 mg/5 mL Oral Solution 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.

Laboratory tests

In rare instances elevated aspartate aminotransferase, blood alkaline phosphatase and blood 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.

Excipients

Baclofen Oral Solution syrup contains methyl para hydroxybenzoate (E218) and propyl para hydroxybenzoate (E216), which may cause allergic reactions (possibly delayed). Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

Baclofen Oral Solution syrup contains 3275 mg sorbitol in each 5ml of syrup. If your doctor has told you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take or receive this medicine. Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

Information on Sodium content

This medicine contains less than 1 mmol sodium (23mg) per 5ml, that is to say essentially 'sodium free'. When the dose is greater than 14ml it cannot be considered 'sodium free' and it should be taken into consideration by patients on a controlled sodium diet. At maximum daily dose (120ml) this medicine contains 194.4mg of sodium. This is equivalent to 9.72% of the recommended maximum daily dietary intake of sodium for an adult.

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 state, delirium, hallucination, psychotic disorder, mania or paranoia, convulsion (status epilepticus), dyskinesia, tachycardia, hyperthermia, rhabdomyolysis and temporary aggravation of spasticity and hypertonia have been reported with abrupt withdrawal of baclofen, especially after long term medication.

Drug withdrawal reactions including postnatal convulsions in neonatal have been reported after intrauterine exposure to oral Baclofen 5 mg/5 mL Oral Solution (See Section 4.6).

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.

Paediatric patients

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.

Posture and balance

Baclofen 5 mg/5 mL Oral Solution should be used with caution when spasticity is needed to sustain upright posture and balance in locomotion (see section 4.2).

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

Levodopa/dopa decarboxylase (DDC) inhibitor (Carbidopa)

In patients with Parkinson's disease receiving treatment with Baclofen 5 mg/5 mL Oral Solution and levodopa (alone or in combination with DDC inhibitor, carbidopa), there have been reports of mental confusion, hallucinations, nausea and agitation. Worsening of the symptoms of Parkinsonism has also been reported. Hence, caution should be exercised during concomitant administration of Baclofen 5 mg/5 mL Oral Solution and levodopa/carbidopa.

Drugs causing Central Nervous System (CNS) depression

Increased sedation may occur when Baclofen 5 mg/5 mL Oral Solution is taken concomitantly with other drugs causing CNS depression including other muscle relaxants (such as tizanidine), with synthetic opiates or with alcohol(see section 4.7).

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.

Antidepressants

During concomitant treatment with tricyclic antidepressants, the effect of Baclofen 5 mg/5 mL Oral Solution may be potentiated, resulting in pronounced muscular hypotonia.

Lithium

Concomitant use of oral Baclofen 5mg/5mL Oral Solution and lithium resulted in aggravated hyperkinetic symptoms. Thus, caution should be exercised when Baclofen 5 mg/5 mL Oral Solution is used concomitantly with lithium.

Antihypertensives and other drugs known to lower blood pressure

Since concomitant treatment with Baclofen 5 mg/5 mL Oral Solution and drugs that lower blood pressure is likely to increase the fall in blood pressure, the dosage of concomitant medications should be adjusted accordingly.

Agents reducing renal function

Drugs or medicinal products that can significantly affect renal function may reduce baclofen excretion leading to toxic effects (see Section 4.4).

4.6. Fertility, pregnancy and lactation

Pregnancy

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 crosses the placental barrier.

Foetal/neonatal adverse reactions

Drug withdrawal reactions including postnatal convulsions in neonates have been reported after intra-uterine exposure to oral baclofen (see section 4.4).

Breast-feeding

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 in the infant are to be expected.

4.7. Effects on ability to drive and use machines

Baclofen 5mg/5mL Oral Solution may be associated with adverse effects such as dizziness, sedation, somnolence and visual impairment (See section 4.8) which may impair the patient's reaction. Patients experiencing these adverse reactions should be advised to refrain from driving or using machines.

4.8. Undesirable effects

Adverse effects occur mainly at the start of treatment (e.g. sedation, somnolence and nausea) 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.

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).

Adverse reactions (Table 1) are ranked under heading of frequency, the most frequent first, using the following convention: very common (≥ 1/10); common (≥1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000) very rare (< 1/10,000) and Not known (cannot be estimated from the available data).

Table 1 Tabulated summary of adverse drug reactions

Immune system disorders

Not known:

Hypersensitivity

Nervous system disorders

Very common:

Sedation, somnolence

Common:

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

Rare:

Paraesthesia, dysarthria, dysgeusia

Unknown

Sleep Apnoea syndrome*

Not known:

Encephalopathy

Eye Disorders

Common:

Visual impairment, accommodation disorder

Cardiac disorders

Common:

Cardiac output decreased

Not known:

Bradycardia

Vascular disorders

Common:

Hypotension

Gastrointestinal disorders

Very common:

Nausea

Common:

Gastrointestinal disorder, constipation, diarrhoea, retching, vomiting

Rare:

Abdominal pain

Hepatobiliary disorders

Rare:

Hepatic function abnormal

Skin and subcutaneous tissue disorders

Common:

Rash, hyperhidrosis

Not known

Urticaria, alopecia

Renal and urinary disorders

Common:

Pollakiuria, enuresis, dysuria

Rare:

Urinary retention

Reproductive system and breast disorders

Rare:

Erectile dysfunction

Not known:

Sexual dysfunction

General disorders and administration site conditions

Very rare

Hypothermia

Not known

Drug withdrawal syndrome* (see section 4.4), swelling face and peripheral oedema

Investigations

Not known:

Blood glucose increased

*Drug withdrawal syndrome including postnatal convulsions in neonates has also been reported after intra-uterine exposure to oral baclofen.

*Cases of central sleep apnoea syndrome have been observed with baclofen at high doses (more than or equal to 100 mg) in patients who are alcohol dependent.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms:

Prominent features are signs of central nervous depression or encephalopathy: somnolence, depressed level of consciousness, coma, respiratory depression, coma and tinnitus.

Also liable to occur are: confusion, hallucination, agitation, convulsion, abnormal electroencephalogram (burst suppression pattern and triphasic waves, generalised slowing on EEG); accommodation disorder, impaired pupillary reflex; generalised muscular hypotonia, myoclonus, hyporeflexia or areflexia; convulsion, peripheral vasodilatation, hypotension or hypertension, bradycardia, tachycardia or cardiac arrhythmia; hypothermia; nausea, vomiting, diarrhoea, salivary hypersecretion; increased hepatic enzymes, sleep apnoe rhabdomyolysis. 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 and section 4.4)

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.

Supportive measures and symptomatic treatment should be given for complications such as hypotension, hypertension, convulsions, gastrointestinal disorders and respiratory or cardiovascular depression.

Since the drug is excreted chiefly via the kidneys, generous quantities of fluid should be given, possibly together with a diuretic. Haemodialysis (sometimes unscheduled) may be useful in severe poisoning associated with renal failure (see Section 4.4).