1 Name of Medicine
Baclofen.
2 Qualitative and Quantitative Composition
Each tablet contains 10 mg or 25 mg of baclofen.
Excipients with known effect. Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
APO-Baclofen 10 mg tablets. White, oval, flat-faced, bevel-edged tablets, scored and engraved "APO B10" on one side.
APO-Baclofen 25 mg tablets. White, round, flat-faced, bevel-edged tablets, scored on one side.
4 Clinical Particulars
4.9 Overdose
Signs and symptoms. Prominent features of overdosage are signs of central nervous depression or encephalopathy: somnolence, depressed level of consciousness, respiratory depression due to absent respiratory movement, coma.
Other signs and symptoms which are liable to occur are: confusion, hallucinations, agitation, abnormal electroencephalogram (burst suppression pattern and triphasic waves), accommodation disorders, impaired pupillary reflex; generalised muscular hypotonia, myoclonus, hyporeflexia or areflexia; convulsions; peripheral vasodilatation, hypotension or hypertension, bradycardia, tachycardia or cardiac arrhythmias, hypothermia; nausea, vomiting, diarrhoea, salivary hypersecretion; increased hepatic enzymes, sleep apnoea, rhabdomyolysis, tinnitus, 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 1125 mg of baclofen and survived. Ingestion of 1250 to 2500 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.
Supportive measures and symptomatic treatment should be given for complications such as hypotension, hypertension, convulsions, gastrointestinal disturbances, and respiratory or cardiovascular depression.
Symptomatic treatment should include the following:
elimination of the drug from the gastrointestinal tract, e.g. administration of activated charcoal or administration of saline laxatives if necessary;
administration of artificial respiration in cases of respiratory muscle weakness;
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 intravenously, paying attention to increased muscle relaxation, and possible respiratory insufficiency, if the patient is not already being artificially ventilated;
haemodialysis (sometimes unscheduled) may be useful in severe poisoning associated with renal failure (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. 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.
Animal data. In two teratogenic studies in pregnant rats, baclofen has been shown to increase the incidence of omphaloceles (ventral hernias) in foetuses, at a dose of 20 mg/kg/day, which is maternotoxic. The relevance of this finding to humans is unknown. At the same dose the incidence of incomplete sternebral ossification in the foetuses was increased.
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 foetal 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, doses of up to 10 mg/kg/day were given orally. Maternotoxicity was manifested as a sedative effect. Skeletal examination of foetuses revealed a marked increase in the absence of ossification of the phalangeal nuclei of fore limbs and hind limbs.
Carcinogenicity. 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.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Baclofen is a white or almost white powder, which is slightly soluble in water, very slightly soluble in ethanol (96%), and practically insoluble in acetone and in ether. It dissolves in dilute mineral acids and in dilute alkali hydroxides.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSBACLOF.gif Chemical name: (RS)-4 amino-3 (4-chlorophenyl) butyric acid.
Molecular formula: C10H12ClNO2.
Molecular weight: 213.7.
CAS number. 1134-47-0.
7 Medicine Schedule (Poisons Standard)
S4 - Prescription Only Medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/APOBACST.gif
