Baclofen

Registered South African indications:

• Spasticity of the skeletal muscle due to multiple sclerosis
• Spasticity of cerebral origin

Contraindications

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients 
• Porphyria 

Recommendations in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients 
• Peptic ulceration 

Cautions

South African recommendations

• Pregnancy
• Breastfeeding
• Renal impairment (doses >5mg dly)
• Hepatic impairment
• Elderly
• Neonates after intrauterine exposure
• Pre-existing psychotic disorders
  - Schizophrenia
  - Depressive or manic disorders
  - Confusional states
• Parkinson's disease
• Risk factors for suicide
  - Alcohol use disorder
  - Depression 
  - History of previous suicide attempts
• Epilepsy
• Pre-existing or history of peptic ulcers
• History of cerebrovascular disorders
• Respiratory failure 
• Stroke
• Diabetes mellitus
• Pre-existing sphincter hypertonia
• Abrupt withdrawal
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy
• Breastfeeding
• Renal impairment (doses >5mg dly)
• Hepatic impairment
• Elderly
• Neonates after intrauterine exposure
• Children below 1 year
• Pre-existing psychotic disorders
  - Schizophrenia
  - Depressive or manic disorders
  - Confusional states
• Parkinson's disease
• Risk factors for suicide
  - Alcohol use disorder
  - Depression 
  - History of previous suicide attempts
• Epilepsy
• Respiratory impairment
• Spasticity of cerebral origin
• History of substance abuse
  - Dose escalation
  - Drug-seeking behaviour
  - Development of tolerance
• Cerebrovascular accidents
• Pre-existing sphincter hypertonia
• Abrupt withdrawal
• Spasticity is needed to sustain upright posture and balance in locomotion
• Wheat allergy (different from coeliac disease)
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Spasticity of the skeletal muscle due to multiple sclerosis
- Spastic conditions occurring in spinal-cord diseases of infectious, degenerative, traumatic, neoplastic, or unknown aetiology (e.g. spastic spinal paralysis, amyotrophic lateral sclerosis, syringomyelia, transverse myelitis, traumatic paraplegia or paraparesis, and compression of the spinal cord)
Spasticity of cerebral origin
- e.g. following cerebrovascular accidents or in the presence of neoplastic or degenerative brain disease

• Oral (tab): Initial: 5mg, 8hrly; Titrate cautiously by 5mg, 8hrly at intervals of 3 days until sufficient to suit individual patient requirements; Optimum dose range: 30mg-80mg, dly

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In patients reacting sensitively, begin with a lower daily dosage (5mg or 10mg) and gradually raise this dosage. The optimum dosage generally ranges from 30-80mg daily

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Doses of more than 80mg-100mg daily are not generally recommended although higher doses have been given to carefully supervised patients in hospital

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Treatment should always be initiated with small, gradually increasing doses of baclofen. The optimum daily dosage should be individually adapted to the patient's requirements in such a way that clonus, flexor and extensor spasms, and spasticity are reduced, but that a sufficient degree of muscle tone is maintained to permit active movements and adverse effects are avoided as far as possible

---

To prevent excessive weakness and falling, baclofen should be used with caution when spasticity is needed to sustain upright posture and balance in locomotion or whenever spasticity is used to maintain function. It may be important to maintain some degree of muscle tone and allow occasional spasms to help support circulatory function

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Baclofen should be taken during meals with a little liquid

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

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

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Abrupt discontinuation of the treatment should be avoided

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Indications and dosages registered in other jurisdictions

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
- Arising from e.g. cerebrovascular accidents, cerebral palsy, meningitis, traumatic head injury

• Oral (tab): Initial: 5mg, 8hrly; Titrate cautiously by 5mg, 8hrly at intervals of 3 days until sufficient to suit individual patient requirements; Max: 100mg/24hrs

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Patient selection is important when initiating baclofen 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

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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 should be taken. Treatment should always (unless serious adverse effects occur) be gradually discontinued by successively reducing the dosage over a period of about 1-2 weeks

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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

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Small frequent dosage may prove better in some cases than larger spaced doses. Some patients benefit from using baclofen 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, and physiotherapy, will often improve mobility

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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

Paed. forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Spasticity of the skeletal muscle due to multiple sclerosis
- Spastic conditions occurring in spinal-cord diseases of infectious, degenerative, traumatic, neoplastic, or unknown aetiology (e.g. spastic spinal paralysis, amyotrophic lateral sclerosis, syringomyelia, transverse myelitis, traumatic paraplegia or paraparesis, and compression of the spinal cord)
Spasticity of cerebral origin
- e.g. following cerebrovascular accidents or in the presence of neoplastic or degenerative brain disease

Younger than 10 years

• Oral (tab): Initial: 0.3mg/kg/day, in 3-4 divided doses; Titrate cautiously at 1-2 week intervals until sufficient for individual requirements.; Maintenance: 0.75-2mg/kg body mass/day; Max: 2mg/kg/24hrs

Older than 10 years

• Oral (tab): Initial: 0.3mg/kg/day, in 3-4 divided doses; Titrate cautiously at 1-2 week intervals until sufficient for individual requirements.; Maintenance: 0.75-2mg/kg body mass/day; Max: 2.5mg/kg/24hrs

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Daily dosage should be given in at least 3-4 divided doses in children

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Treatment should always be initiated with small, gradually increasing doses of baclofen. The optimum daily dosage should be individually adapted to the patient's requirements in such a way that clonus, flexor and extensor spasms, and spasticity are reduced, but that a sufficient degree of muscle tone is maintained to permit active movements and adverse effects are avoided as far as possible

---

To prevent excessive weakness and falling, baclofen should be used with caution when spasticity is needed to sustain upright posture and balance in locomotion or whenever spasticity is used to maintain function. It may be important to maintain some degree of muscle tone and allow occasional spasms to help support circulatory function

---

Baclofen is taken during meals with a little liquid

---

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

---

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

---

Abrupt discontinuation of the treatment should be avoided

---

Indications and dosages registered in other jurisdictions

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
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

Younger than 8 years

• Oral (tab): ≥33kg: Initial dose: 0.3mg/kg/day, in 2-4 divided doses (preferably in 4 divided doses); Titrate cautiously at approx. 1 week intervals until it becomes sufficient for the individual requirements; Maintenance: 0.75-2mg/kg/day; Max: 40mg/24hrs 

Older than 8 years

• Oral (tab): ≥33kg: Initial dose: 0.3mg/kg/day, in 2-4 divided doses (preferably in 4 divided doses); Titrate cautiously at approx. 1 week intervals until it becomes sufficient for the individual requirements; Maintenance: 0.75-2mg/kg/day; Max: 60mg/24hrs

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Treatment should usually be started with a very low dose in 2-4 divided doses, preferably in 4 divided doses

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 Baclofen tablets are not suitable for use in children below 33kg body weight

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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 should be taken. Treatment should always (unless serious adverse effects occur) be gradually discontinued by successively reducing the dosage over a period of about 1-2 weeks

---

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

---

Patient selection is important when initiating baclofen 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

Pregnancy

South African recommendations

• Caution; not recommended
• There are no adequate and well-controlled studies in pregnant women. Baclofen crosses the placental barrier and should not be used during pregnancy. Drug withdrawal reactions including postnatal seizures in neonates have been reported after intrauterine exposure to oral baclofen

Recommendations in other jurisdictions

• Caution
• During pregnancy, especially in the first 3 months, baclofen 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
• Drug withdrawal reactions including postnatal convulsions in neonates have been reported after intrauterine exposure to oral baclofen

Breastfeeding

• Caution
• In mothers taking baclofen at 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

Fertility

South African recommendations

• There are no data available on the effect of baclofen on fertility in humans

Recommendations in other jurisdictions

• No information available

Renal Impairment

South African recommendations

• Caution; dose adjustment recommended 
  Baclofen should be given with caution and at lower doses. Closely monitor for prompt diagnosis of early signs and/or symptoms of toxicity (e.g. somnolence, lethargy). Patients undergoing chronic haemodialysis, baclofen concentrations in plasma are elevated and therefore a particularly low dosage of baclofen should be selected
  Oral (tab): Approx. 5mg, dly

Recommendations in other jurisdictions

• Caution; dose adjustment recommended 
  In patients with impaired renal function or undergoing chronic haemodialysis, a particularly low dosage of baclofen should be selected. Baclofen 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)
  Oral (tab): Approx. 5mg, dly

Hepatic Impairment

• Caution; no dose adjustment recommended
  No studies have been performed in patients with hepatic impairment under baclofen therapy. The liver does not play a significant role in the metabolism of baclofen after oral administration of baclofen. However, baclofen has the potential of elevating liver enzymes

Elderly

South African recommendations

• Caution; no dose adjustment recommended 
  Since unwanted effects are more likely to occur in elderly patients or in patients with spastic states of cerebral origin, in such cases it is recommended that a very cautious dosage schedule be adopted and that the patient be kept under appropriate surveillance

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended  
  Elderly patients may be more susceptible to side effects, particularly in the early stages of introducing baclofen. 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

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Probably not porphyrinogenic (PNP) 

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders 

• Sedation
• Somnolence
• Drowsiness
• Mental confusion
• Confusional state
• Dizziness
• Hallucinations
• Depression
  -  Depressive states
• Fatigue
• Exhaustion
• Insomnia
• Euphoric mood
• Ataxia
• Tremor
• Nightmare
• Headache
• Paraesthesia
• Dysarthria
• Lowering of the seizure threshold and seizures
• Dysarthria

Respiratory Disorders 

• Respiratory depression
• Central sleep apnoea syndrome

Cardiovascular Disorders

• Decreased cardiac output
• Bradycardia
• Hypotension

Gastrointestinal Disorders  

• Dry mouth
• Nausea and vomiting
• Constipation
• Diarrhoea
• Retching
• Abdominal pain

Hepatobiliary Disorders

• Abnormal hepatic function 

Genitourinary Disorders

• Pollakiuria
• Enuresis
• Dysuria
• Urinary retention
• Erectile dysfunction

Endocrine and Metabolic Disorders 

• Increased blood glucose

Musculoskeletal Disorders 

• Myalgia
• Muscular weakness
• Increased muscle spasticity (paradoxical reaction) 
• Muscular hypotonia

Skin and Subcutaneous Tissue Disorders

• Rash
• Hyperhidrosis
• Urticaria

Sensory Disorders

• Visual impairment
• Accommodation disorder
• Dysgeusia
• Nystagmus
• Tinnitus

Others

• Hypothermia
• Drug withdrawal syndrome
  - Postnatal seizures (in neonates)

• Levodopa (alone or in combination with carbidopa)
• Central nervous system depressants
• Other muscle relaxants
• Tizanidine
• Synthetic opiates
• Morphine 
• Intrathecal baclofen
• Tricyclic antidepressants
• Lithium
• Antihypertensives
• Medicinal agents that significantly affect renal function

Other interactions

• Alcohol

None routine. Specific cases may require

• Electroencephalogram (EEG) (in patients with epilepsy)
• Respiratory function
• Cardiovascular function
• Renal function
• Hepatic function
• Blood glucose

Additional observations

• Signs and symptoms of baclofen withdrawal (oral or intrathecal)
   - Altered mental status
  - Exaggerated rebound spasticity
  - Hallucination
  - High fever
  - Hypertension
  - Hyperthermia
  - Muscle rigidity
  - Tachycardia
  - Seizure
  - Agitation
  - Confusion
  - Delusions
  - Insomnia
  - Paranoid ideation
• Signs and symptoms of overdose (during the initial screening, dose-titration phase, and reintroduction of therapy)
  - Drowsiness
  - Dizziness
  - Somnolence
  - Hypothermia
  - Respiratory depression
  - Seizures
  - Rostral progression of hypotonia
  - Loss of consciousness progressing to coma

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 GABA_B-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 his 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 agents. Baclofen stimulates gastric acid secretion.

Tablet 10mg

• Aspen Baclofen 10mg (Pharmacare)
• Bio-Baclofen (Biotech Laboratories)
• Lioresal  (Novartis) originator
• Teva Baclofen 10 (Teva Pharmaceuticals)

Tablet 25mg

• Aspen Baclofen 25mg (Pharmacare)
• Baclofen 25 Biotech (Biotech Laboratories)
• Lioresal (Novartis) originator

Also available in the following forms: infusion and injection.