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ALPHA-BACLOFEN 10mg tablets are white to off-white, oval shaped tablets with bevelled edges, engraved APO B10 on one side. Each tablet contains 10mg of baclofen and typically weighs 200mg.
ALPHA-BACLOFEN 20mg tablets are white to off white, capsule shaped tablets with a breakline and engraved APO-B20 on one side. Each tablet contains 20mg of baclofen and typically weighs 400mg.
Baclofen is an effective muscle relaxant and antispastic agent with a spinal site of action. Its mode of action is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level by stimulating the GABAB-receptors, which inhibits the release of glutamate and aspartate. It may also act at intraspinal sites producing CNS depression. Neuromuscular transmission is not affected by baclofen. Baclofen also exerts an antinoceptive effect but the clinical significance of this is unknown.
Baclofen is beneficial in neurological diseases associated with spasm of the skeletal muscles by providing relief from painful spasms, clonus and automatism as well as reflex muscle contractions. With the use of baclofen the patient's mobility improves. Indirect effects of treatment with baclofen include, improved sleep patterns, improvement in bladder and sphincter function and helps in the prevention and healing of decubitus ulcers. Baclofen also stimulates gastric acid secretion.
Baclofen is rapidly and almost completely absorbed from the gastrointestinal tract. The peak plasma concentration occurs 1 to 3 hours following ingestion, but the rate and extent of absorption vary between patients. The volume of distribution is 0.7L/kg and the protein-binding rate is about 30%. Some baclofen does cross the blood-brain barrier with concentrations in the CSF of approximately 12% of those found in the plasma. Within 72 hours, 70 to 80% of the dose is excreted in urine mainly as unchanged baclofen while approximately 15% is metabolised in the liver by deamination to β- (p-chlorophenyl)-γ-hydroxybutyric acid which is pharmacologically inactive. The elimination half-life of baclofen is 3 to4 hours in plasma and about 5 hours in CSF. In patients with severely impaired renal function a marked increase in serum concentrations of baclofen and toxic symptoms have been observed although a moderate reduction in renal function does not adversely affect the disposition of baclofen. Moderate hepatic dysfunction has no major effect of the pharmacokinetics of baclofen.
ALPHA-BACLOFEN is indicated for the alleviation of spasticity resulting from multiple sclerosis, spinal cord diseases, muscle spasm of cerebral origin especially infantile cerebral palsy, cerebrovascular accidents or neoplastic or degenerative brain disease.
ALPHA-BACLOFEN should be taken during meals with a little liquid.
The determination of optimal dosage of ALPHA-BACLOFEN requires titration to individual requirements to ensure that clonus, flexor and extensor spasms and spasticity are reduced but adverse effects are minimised. Baclofen should be used with caution where spasticity is needed to sustain upright posture and balance or maintain function. Baclofen should be given in divided doses preferably 3 times daily for adults and 4 times daily for children. The lowest dose compatible with an optimal response is recommended.
If benefits are not evident after a 6 to 8 week trial period, patients should be slowly withdrawn from the drug.
Start therapy at low dosage and increase gradually until optimum effect is achieved (usually between 30 - 80mg daily).
The following dosage titration schedule is suggested:
5mg three times a day for 3 days
10mg three times a day for 3 days
15mg three times a day for 3 days
20mg three times a day for 3 days
Thereafter additional increases may be necessary, but the total daily dose should usually not exceed a maximum of 80mg, although in hospitalised patients daily doses of 100 - 120mg may occasionally be necessary.
Treatment should be started at a very low dose e.g. 0.3mg/kg per day in divided doses. The dosage should be raised cautiously at 1-2 week intervals until it is sufficient for the child's individual needs. The usual dosage range for maintenance therapy is 0.75 to 2 mg/kg body weight per day. In children aged over 10 years a maximum daily dose of 2.5mg/kg bodyweight may be given.
Dosages should be cautiously administered and the patient kept under appropriate surveillance. Toxicity due to baclofen may be mistaken for uraemic encephalopathy.
Baclofen should be used with caution. Lower doses (approximately 5mg per day) should be used for patients with impaired renal function or those undergoing chronic haemodialysis.
Known hypersensitivity to baclofen.
Patients suffering not only from spasticity but also from psychotic disorders, schizophrenia, depressive or manic disorders or confusional states should be treated cautiously and closely monitored as exacerbations of these disorders may occur.
In patients with epilepsy and muscle spasticity, baclofen may be used under appropriate supervision and provided that adequate anticonvulsive therapy is continued. Lowering of the convulsion threshold may occur and seizures have been reported after the cessation of baclofen therapy or with overdose.
Baclofen should be used with caution in patients with or with a history of peptic ulcers, cerebrovascular diseases, or hepatic, renal or respiratory failure.
Careful monitoring of respiratory and cardiovascular function is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.
During treatment with baclofen, neurogenic disturbances affecting emptying of the bladder may improve. However in patients with pre-existing sphincter hypertonia, acute retention of urine may occur. Baclofen should be used with caution in these circumstances.
Baclofen has not significantly benefited patients with stroke. These patients have also shown poor tolerance to the medicine.
Elevated laboratory test results for SGOT, alkaline phosphatase and glucose levels in the serum have been reported, therefore appropriate laboratory tests should be performed periodically in patients with hepatic diseases or diabetes mellitus to ensure that no medicine induced changes in these underlying diseases have occurred.
Following abrupt withdrawal of baclofen, visual and auditory hallucinations, convulsions (status epilepticus), dyskinesia, confusion, psychotic, manic or paranoid states, anxiety with tachycardia and sweating, insomnia and worsening of spasticity have occurred. Therefore, except for serious adverse reactions or overdose-related emergencies, the dose of baclofen should be reduced slowly until the drug is discontinued. This should be over a period of one to two weeks.
Because baclofen is primarily excreted unchanged through the kidneys it should be given with caution to patients with impaired renal function and it may be necessary to reduce the dosage.
A 2 year carcinogenicity study in rats found no evidence that baclofen had carcinogenic potential at oral doses up to 100mg/kg/day. An apparently dose related increase in the incidence of ovarian cysts and of enlarged and/or haemorrhagic adrenals at doses of 50 and 100mg/kg/day was observed in female rats. The clinical relevance of these findings is not known.
Baclofen did not induce mutations in bacterial or mammalian cells in vitro, lacked DNA damaging activity in the sister chromatid exchange assay and had no clastogenic activity in the nuclear anomaly test.
Category B3
Safe use of baclofen during pregnancy has not been established. Baclofen crosses
the placental barrier. High doses are associated with an increased incidence of
abdominal hernias in the foetuses of rats and of ossification defects in those
of rats and rabbits. Baclofen should only be administered to pregnant women,
when in the judgement of the physician, the potential benefits outweigh the
possible hazards.
Baclofen is excreted in breast milk however evidence to date suggests that the quantities are so small that no undesirable effects on the infant would be expected.
The patients ability to react may be adversely affected by sedation and decreased alertness caused by ALPHA-BACLOFEN. Patients should exercise due caution when driving a vehicle or operating machinery.
Adverse effects most frequently occur at the start of treatment, if the dosage is increased too rapidly, if large doses are administered and in the elderly patient. These effects are often transient and can be alleviated or eliminated by decreasing the dosage. They are seldom severe enough to warrant withdrawal of the medication. In elderly patients or those patients with cerebrovascular disorders or a history of psychiatric illness, more serious adverse reactions may occur such as hallucinations and confusion.
The most common adverse reactions associated with baclofen are transient drowsiness, daytime sedation, dizziness, weakness and fatigue.
Headache (<10%), insomnia (<10%), and rarely, euphoria, excitement, depression, confusion, hallucinations, paraesthesia, nightmares, muscle pain, tinnitus, slurred speech, co-ordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizures, respiratory depression .
Hypotension (<10%), rare instances of dyspnoea, palpitation, chest pain, syncope.
Nausea (approximately 10%), constipation (<10%) and rarely, dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhoea and positive test for occult blood in stool.
Urinary frequency (<10%) and rarely, enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, haematuria.
Instances of rash, pruritus, ankle oedema, excessive perspiration, weight gain, nasal congestion, visual disturbances, hepatic function disorders and paradoxical increase in spasticity.
Muscular hypotonia of a degree sufficient to make walking or movement difficult may occur but is usually relieved by readjusting the dosage. For this purpose, the daytime dosage may be reduced and the evening dosage increased.
Some of the CNS and genitourinary symptoms reported may be related to the underlying disease rather than to baclofen therapy.
Increased sedation may occur if baclofen is taken with agents acting on the central nervous system, alcohol or synthetic opiates. The risk of respiratory depression is also increased.
Combined treatment with baclofen and antihypertensives is likely to increase the fall in blood pressure; therefore the dosage of antihypertensive medication should be adjusted accordingly.
The concomitant administration of baclofen and tricyclic antidepressants may potentiate the pharmacological effects of baclofen resulting in pronounced muscular hypotonia.
In patients with Parkinsons disease receiving treatment with baclofen and levodopa plus carbidopa there have been several reports of mental confusion, hallucinations, headaches, nausea and agitation.
The concurrent use of MAO inhibitors and baclofen may result in increased CNS depressant effects. Caution is advised and the dosage of one or both agents should be adjusted accordingly.
Caution should be exercised when administering baclofen and magnesium sulphate or other neuromuscular blocking agents since a synergistic effect may theoretically occur.
Symptoms of overdosage are predominately those of central nervous system depression and include drowsiness, impairment of consciousness, respiratory depression and coma. Seizures, confusion, hallucinations, agitation, accommodation disorders, absent pupillary reflexes, muscular hypotonia, myoclonia, hyporeflexia or areflexia, hypotension, bradycardia, hypothermia, peripheral vasodilation, nausea, vomiting, diarrhoea, increased salivation, elevated LDH, SGOT, AP and blood glucose values may also occur.
The signs and symptoms may be further aggravated by co-administration of a variety of other agents which act on the CNS including alcohol, diazepam and tricyclic antidepressants.
There is no specific antidote. The treatment is symptomatic. In the alert patient, empty the stomach promptly by induced emesis followed by gastric lavage. Administer charcoal and if necessary saline laxatives. In the comatose patient, secure the airway with a cuffed endotracheal tube before beginning lavage (do not induce emesis). Maintain adequate respiratory exchange. Do not use respiratory stimulants. Muscular hypotonia may involve the respiratory muscles and require assisted respiration. Institute measures to support cardiovascular function. A high urinary output should be maintained since baclofen is excreted mainly by the kidneys. For this purpose, generous quantities of fluid should be administered, possibly together with a diuretic. Dialysis is indicated in severe poisoning associated with renal failure. In the event of convulsions, administer diazepam IV with caution.
Store below 30°C. Protect from heat, light, and moisture.
Keep container tightly closed.
Prescription Only Medicine.
ALPHA-BACLOFEN 10mg:
Bottles of 50, 100, 250 and 500 tablets
ALPHA-BACLOFEN 20mg:
Bottles of 50, 100, 250 and 500 tablets
Tablets contain Lactose and Cornstarch.
ALPHA PHARMACEUTICALS LTD
Melville House
150 Broadway Avenue
PO Box 705
Palmerston North
Tel: (06) 355-1066
Fax: (06) 356-6293
27 May 1999