Baclofen
Alphapharm Pty Ltd
MIMS Abbreviated Prescribing Information
Section: 5(c) Muscle relaxants
Consumer Medicine Information: Available
Pregnancy Category: B3
Sport Category: Permitted in sport
Uses/Indications: Suppression of voluntary muscle spasm in multiple sclerosis, spinal lesions causing skeletal hypertonus, spastic and dyssynergic bladder dysfunction
Precautions: Psychiatric disorders; epilepsy, other convulsive disorders; cortical, subcortical brain damage, significant EEG abnormalities; peptic ulcer, history of; cerebrovascular disease; respiratory, hepatic, renal failure; porphyria; alcoholism; diabetes; urinary sphincter hypertonia; spasticity dependent posture, balance; abrupt withdrawal; elderly; pregnancy, lactation, children < 16 yrs
Adverse Reactions: Daytime sedation, drowsiness; GI upset; CNS, psychiatric disturbances; hypotension; tinnitus; pruritus; lowered seizure threshold; hypotonia; paradoxical spasticity; others, see full PI
Drug Interactions: Alcohol; agents acting on CNS; TCAs; MAOIs; lithium; insulin, oral hypoglycaemics; antihypertensives; levodopa + carbidopa; diazepam
CLOFEN (Tablets) Prescription required. S4 This product may cause drowsiness.
Baclofen; lactose; white; gluten free;
Dose: Should be taken with food. Adults: initially 15 mg/day in 3 divided doses; incr by 15 mg every 3 days according to response; optimum dose usually 30-75 mg/day; max 100 mg/day, see full PI
Pack: 10 mg [100] Brand substitution is permitted. : PBS/RPBS (Rp 5) PBS: $38.50
Pack: 25 mg [100] Brand substitution is permitted. : PBS/RPBS (Rp 5) PBS: $78.64
MIMS Full Prescribing Information
Section: 5(c) Muscle relaxants SECTION NOTES
topComposition
Active. Baclofen.
Inactive. Lactose, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, sodium starch glycollate, colloidal anhydrous silica, magnesium stearate.
topDescription
Chemical name: (3RS)-4-amino-3- (4-chlorophenyl) butanoic acid. Molecular formula: C10H12ClNO2. MW: 213.7. CAS: 1134-47-0. It is a white or almost white powder which is slightly soluble in water, very slightly soluble in ethanol (96%), practically insoluble in acetone and in ether. It dissolves in dilute mineral acids and in dilute alkali hydroxides.
topActions
Antispastic agent. Baclofen is a derivative of gamma-aminobutyric acid (GABA).
Pharmacology. Baclofen is an effective antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from those of other antispastic agents.
Baclofen also has central sites of action given the adverse event profile and general central nervous system (CNS) depressant properties.
Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by various actions, including stimulation of GABAB receptors. This stimulation in turn inhibits the release of excitatory amino acids (glutamate and aspartate) in guinea pig preparations. Neuromuscular transmission is not affected by baclofen.
Baclofen exerts an antinociceptive effect. The clinical significance of this awaits clarification. In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen take the form of a beneficial action on reflex muscle contractions and of marked relief from painful spasm, automatism and clonus. Baclofen, where indicated, improves the patient's mobility, making for greater independence and facilitating passive and active physiotherapy. Baclofen stimulates gastric acid secretion.
Pharmacokinetics. Absorption. Baclofen is rapidly and completely absorbed from the gastrointestinal tract. Maximum concentrations of unchanged drug are achieved in plasma in two to four hours after an oral dose.
The onset of action is highly variable and may range from hours to weeks.
Distribution. The distribution volume of baclofen amounts to 0.7 L/kg. In cerebrospinal fluid, the active substance attains concentrations approximately 8.5 times lower than in the plasma.
Baclofen is bound to plasma proteins to the extent of approximately 30%.
Metabolism. About 15% of the baclofen dose is metabolised in the liver. Deamination yields the main metabolite, beta-(chlorophenyl)- gamma-hydroxybutyric acid, which is pharmacologically inactive.
Excretion. Approximately 70% of baclofen is eliminated in the urine in the unchanged form. The plasma elimination half-life of baclofen averages three to four hours. Within 72 hours, approximately 75% of the dose is excreted via the kidneys, approximately 5% of this quantity being in the form of metabolites. The remainder of the dose, including 5% as metabolites, is excreted in the faeces.
topIndications
Suppression of voluntary muscle spasm in multiple sclerosis and in spinal lesions of traumatic, infectious, degenerative, neoplastic and unknown origin, causing skeletal hypertonus and spastic and dyssynergic bladder dysfunction.
Baclofen is not recommended in Parkinson's disease or spasticity arising from strokes, cerebral palsy or rheumatoid disorders.
topContraindications
Known hypersensitivity to baclofen or any of the components of the formulation.
topPrecautions
Abrupt discontinuation. Anxiety and confusional states, hallucinations, psychotic, manic or paranoid states, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia and, as a rebound phenomenon, temporary aggravation of spasticity, have been reported upon the abrupt withdrawal of baclofen, especially after long-term medication. Except in overdose related emergencies or where serious adverse effects have occurred, treatment should therefore always be gradually withdrawn by successive dosage reduction over a period of approximately one to two weeks.
If withdrawal symptoms occur, restarting baclofen therapy and withdrawing over a longer period may help to resolve withdrawal problems.
Mental disorders. Patients suffering not only from spasticity but also from psychotic disorders, schizophrenia, depressive or manic disorders or confusional states should be treated cautiously with baclofen and kept under careful surveillance, because exacerbations of these conditions may occur.
Epilepsy or other potential convulsive conditions. Caution is needed in patients with epilepsy or other convulsive conditions, cortical or subcortical brain damage or significant EEG abnormalities, since ingestion of baclofen may cause deterioration of seizure control and EEG changes, and may precipitate convulsions. In patients with epilepsy and muscle spasticity, baclofen can be used under appropriate supervision, provided adequate anticonvulsive therapy is continued.
Lowering of the convulsion threshold may occur and seizures have been reported occasionally after cessation of baclofen or with overdosage.
Other concomitant conditions. Baclofen should be used with caution in patients with the following.
Peptic ulcers or with a history of peptic ulcers;
cerebrovascular diseases or respiratory, hepatic or renal failure (due to increased risk of central nervous system, respiratory and cardiovascular depression);
porphyria;
history of alcoholism;
diabetes mellitus (baclofen may increase blood glucose concentrations); and
hypertension (see Interactions).
Changes in muscle tone. Baclofen should be used with caution in patients who use spasticity to maintain an upright posture and balance in moving. If an undesirable degree of muscular hypotonia occurs, making it more difficult for patients to walk or fend for themselves, this can usually be relieved by adjusting the dosage (i.e. by reducing the doses given during the day and possibly increasing the evening dose).
During treatment with baclofen, neurogenic disturbances affecting emptying of the bladder may improve, whereas in patients with pre-existing sphincter hypertonia, acute retention of urine may occur; the drug should therefore be used with caution in such cases.
Impaired renal function. Since baclofen is largely eliminated by the kidneys, a dosage reduction is advised to avoid drug accumulation (see Dosage and Administration).
Impaired hepatic function. Because baclofen is partially metabolised in the liver, patients with impaired hepatic function should be periodically monitored with laboratory tests (see Dosage and Administration).
Use in the elderly. See Dosage and Administration.
Carcinogenesis, mutagenesis, impairment of fertility. A two year carcinogenicity study in rats found no evidence that baclofen had carcinogenic potential at oral doses up to 100 mg/kg/day. An apparently dose related increase in the incidence of ovarian cysts and of enlarged and/or haemorrhagic adrenals at the highest two doses (50 and 100 mg/kg/day) was observed in female rats. The clinical relevance of these findings is not known.
Ovarian cysts have been found by palpation in about 5% of the multiple sclerosis patients who were treated with oral baclofen for up to one year. In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are known to occur spontaneously in a proportion of the normal female population.
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.
Use in pregnancy. (Category B3)
In two teratogenic studies in pregnant rats, baclofen has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses, at a dose of 20 mg/kg/day, which is maternotoxic. The relevance of this finding to humans is unknown. At the same dose there was also an increased incidence of incomplete sternebral ossification in the fetuses.
In mice, no teratogenic effects were observed at a dose of 81.5 mg/kg/day given via the diet or up to 40 mg/kg/day given by gavage. At 40 mg/kg/day by gavage, a delay in fetal growth was associated with maternal anorexia. The lack of maternotoxicity seen in the dietary study suggests that the dose used was inadequate.
In pregnant rabbits, oral doses up to 10 mg/kg/day were manifested as a sedative effect. Skeletal examination of fetuses revealed a marked increase in the absence of ossification of the phalangeal nuclei of fore limbs and hind limbs.
There are no studies in pregnant women.
Use in lactation. Studies in lactating women are limited to one patient. In this particular case, available evidence suggests that baclofen is found in quantities so small that undesirable effects in the infant would have been unlikely.
Use in children. Baclofen should be given with extreme caution to children under 16 years, as only limited data are available.
Effect on ability to drive or operate machinery. The patient's ability to react may be adversely affected by sedation and decreased alertness caused by baclofen; patients should therefore exercise due caution when driving a vehicle or operating machinery.
topAdverse Reactions
Unwanted effects mainly occur at the start of treatment, if the dosage is increased too quickly, if large doses are used, or if the patient is elderly. They are often transitory and can be attenuated or eliminated by reducing the dosage; they may necessitate withdrawal of the medication.
In patients with a history of psychiatric illness, cortical or organic brain disorders, or with cerebrovascular disorders (such as stroke), as well as elderly patients, adverse reactions may be more serious.
It is often difficult to distinguish whether some of these are drug effects or manifestations of the diseases under treatment. Psychiatric manifestations can occur in acute or chronic toxicity due to baclofen.
Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients (see Precautions).
Certain patients have shown increased spasticity as a paradoxical reaction to the medication.
The following frequency estimates apply. Very common: greater than or equal to 10%; common: greater than or equal to 1% to < 10%; uncommon: greater than or equal to 0.1% to < 1%; rare: greater than or equal to 0.01% to < 0.1%; very rare: < 0.01%.
Cardiovascular. Common: hypotension, diminished cardiovascular functions.
Rare: arrhythmias, dyspnoea, palpitations, chest pain, ankle oedema.
Gastrointestinal. Very common: nausea (particularly at the start of treatment).
Common: constipation, diarrhoea, retching, vomiting, dryness of the mouth.
Rare: colicky abdominal pain, anorexia.
Hepatic. Rare: disorders of hepatic function (e.g. increased AST and glucose).
Musculoskeletal system. Common: myalgia, muscular weakness.
Nervous system. Very common: daytime sedation and drowsiness (particularly at the start of treatment).
Common: respiratory depression, lightheadedness, lassitude, exhaustion, dizziness, mental confusion, personality changes, vertigo, headache, insomnia, euphoria, depressive states, ataxia, tremor, hallucinations, nightmares.
Rare: paresthesiae, dysarthria, syncope, dyskinesia, coma.
Sense organs. Common: tinnitus, nystagmus, accommodation disorders, visual disturbances.
Rare: taste disturbances.
Dermatological. Common: hyperhidrosis, rash, pruritus.
Urogenital system. Common: dysuria, frequency of micturition, enuresis.
Rare: retention of urine, impotence, inability to ejaculate, nocturia, haematuria.
Miscellaneous. Rare: nasal congestion, weight gain.
topInteractions
Where baclofen is taken concomitantly with other drugs acting on the central nervous system, or with alcohol, increased sedation may occur (see Precautions).
The risk of respiratory depression is also increased.
During concurrent treatment with tricyclic antidepressants, the effect of baclofen may be potentiated, resulting in pronounced muscular hypotonia.
The use of concurrent baclofen with monoamine oxidase inhibitors (MAOIs) may result in increased CNS depressant and hypotensive effects. Caution is recommended and dosage of one or both agents may require reduction.
Aggravation of hyperkinetic symptoms may possibly occur in patients taking lithium.
Since baclofen may increase blood glucose concentrations, dosage adjustments of insulin and/or oral hypoglycaemic agents may be necessary during and after concurrent therapy.
Since concomitant treatment with baclofen and antihypertensive agents is likely to increase the risk of hypotension, the dosage of antihypertensive medication should be adjusted accordingly.
In patients with Parkinson's disease receiving treatment with levodopa plus carbidopa, who additionally required use of baclofen, there have been reports of mental confusion, hallucinations, headaches, nausea and agitation.
Studies in rats indicate that the agonistic effects of baclofen on gastric acid secretion are potentiated by diazepam.
topDosage and Administration
Treatment with baclofen should always be started in hospital using small doses which are then gradually increased stepwise. The optimum daily dosage should be individually adapted to each patient's requirements, so that clonus, flexor and extensor spasms, and spasticity are reduced, at the same time retaining enough muscle tone to permit active movements, and avoiding adverse effects as far as possible.
Abrupt discontinuation of treatment should be avoided (see Precautions).
Clofen should be taken during meals with a little liquid.
Adults. In adults, Clofen should be given in at least three divided doses daily.
As a rule, treatment should be started with a dose of 5 mg three times daily, subsequently increased at three day intervals by 5 mg three times daily (i.e. the dosage regimen is 5 mg three times a day for three days, then 10 mg three times a day for three days) until the optimum response has been attained. In certain patients reacting sensitively to drugs, it may be advisable to begin with a lower daily dose (5 or 10 mg), increased by smaller steps at longer intervals. The optimum dosage generally ranges from 30 to 75 mg daily, although occasionally in hospitalised patients daily doses up to 100 mg may be necessary.
If no benefit is apparent with six to eight weeks of achieving the maximum dosage, a decision whether or not to continue treatment with baclofen should be made.
Impaired renal function. In patients with impaired renal function or undergoing chronic haemodialysis, low doses (i.e. approximately 5 mg daily) should be used.
Use in the elderly. Since unwanted effects are more likely to occur in elderly patients (due to increased risk of renal function impairment and CNS toxicity), a very cautious dosage schedule should be adopted and the patient kept under appropriate surveillance.
Toxicity due to baclofen may be taken for uraemic encephalopathy.
Children. Baclofen should be given with extreme caution to children under 16 years, as only limited data are available.
Monitoring advice. Since in rare instances elevated AST, alkaline phosphatase or glucose levels in the serum have been recorded, appropriate laboratory tests should be performed periodically in patients with liver diseases or diabetes mellitus, in order to ensure that no drug induced changes in these underlying diseases have occurred.
Careful monitoring of respiratory and cardiovascular function is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.
topOverdosage
Symptoms. Prominent features are signs of central nervous depression: drowsiness, impairment of consciousness, respiratory depression due to absent respiratory movement, 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 lactate dehydrogenase (LDH), aspartate transaminase (AST) and alkaline phosphatase (ALP) 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.
Adult patients have ingested up to 1,125 mg of baclofen and survived. Ingestion of 1,250 to 2,500 mg by one patient was fatal. Serious poisoning has occurred with doses of 150 and 300 mg in adults.
Treatment. No specific antidote is known. Symptomatic treatment should include the following.
Elimination of the drug from the gastrointestinal tract, e.g. administration of activated charcoal; if necessary, saline laxatives;
Since the drug is excreted chiefly via the kidneys, generous quantities of fluid should be given, possibly together with a diuretic.
Measures in support of cardiovascular functions.
In the case of respiratory muscle weakness, administration of artificial respiration.
In the event of convulsions, diazepam should be administered cautiously intravenously, paying attention to increased muscle relaxation, and possible respiratory insufficiency, if the patient is not already being artificially ventilated.
topPresentation
Tablets, 10 mg (white, marked BN/10, G on reverse): 100's; 25 mg (white, marked BN/25, G on reverse): 100's.
Clofen 10 mg; Clofen 25 mg.
Storage Store below 30 deg. C. The tablets should be kept out of reach of children.
Poison Schedule S4.
Date of TGA Approval or Manufacturer's Last Amendment 17/12/2004
