Muscle Relaxant – Antispastic
Action And Clinical Pharmacology: Baclofen’s precise mechanisms of action are not fully known. It inhibits both monosynaptic and polysynaptic reflexes at the spinal level, probably by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Although baclofen is an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA), there is no conclusive evidence that actions on GABA systems are involved in the production of its clinical effects.
Peak plasma concentrations of baclofen are achieved within 2 hours and the plasma half-life is 2 to 4 hours.
In man, a single 10 mg oral dose of baclofen is rapidly and almost completely absorbed whereas absorption of 20 mg and 40 mg doses is less complete. Animal studies indicate rapid distribution throughout the body except to the CNS where concentrations are lower than average. The decay in CNS concentration is, however, slower than the decay from other tissues.
About 85% of a single oral dose is excreted unchanged in the urine. The remaining 15% is mainly deaminated to b-(p-chlorophenyl)-g-hydroxybutyric acid within 24 hours. Baclofen is about 30% bound to serum proteins.
Indications And Clinical Uses: The alleviation of signs and symptoms of spasticity resulting from multiple sclerosis. May also be of some value in patients with spinal cord injuries and other spinal cord diseases.
Contra-Indications: Baclofen hypersensitivity.
Manufacturers’ Warnings In Clinical States: Abrupt Drug Withdrawal: 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, reduce the dose slowly when the drug is discontinued (over a period of approximately 1 to 2 weeks).
Impaired Renal Function: Because baclofen is primarily excreted unchanged through the kidneys, it should be given with caution and it may be necessary to reduce the dosage.
Stroke: Baclofen has not significantly benefited patients with stroke. These patients have also shown poor tolerability to the drug.
Pregnancy and Lactation: Safe use of baclofen during pregnancy or lactation has not been established. Baclofen crosses the placental barrier. High doses are associated with an increased incidence of abdominal hernias in the fetuses of rats and of ossification defects in those of rats and rabbits. Therefore, the drug should be administered to pregnant patients or women of childbearing potential only when the potential benefits outweigh the possible hazards.
Precautions: Children: Safe use of baclofen in children under age 12 has not been established and it is, therefore, not recommended for use in children.
Occupational Hazards: Because of the possibility of sedation, patients should be cautioned regarding the operation of automobiles or dangerous machinery and activities made hazardous by decreased alertness.
Patients should also be cautioned that baclofen’s CNS effects may be additive to those of alcohol and other CNS depressants.
Use baclofen with caution where spasticity is utilized to sustain upright posture and balance in locomotion, or whenever spasticity is utilized to obtain increased function.
Exercise extreme caution in patients with epilepsy or a history of convulsive disorders. In such patients, monitor the clinical state and EEG at regular intervals during therapy, as deterioration in seizure control and EEG has been reported occasionally in patients taking baclofen.
Use caution in treating patients with, or with a history of, peptic ulceration, elderly patients with cerebrovascular disorders and in patients with respiratory, hepatic, or renal failure.
Baclofen should be used with caution in patients with underlying bladder sphincter hypertonia, since acute retention of urine may occur.
Patients with psychiatric disorders such as psychosis, schizophrenia, or confusional states should be treated cautiously with baclofen and kept under close surveillance, since exacerbation of these conditions may occur with baclofen treatment.
The following laboratory tests have been found to be abnormal in a few patients receiving baclofen: AST, alkaline phosphatase and blood sugar (all elevated). Therefore, in patients with liver diseases or diabetes mellitus, appropriate laboratory tests should be performed periodically in order to ensure that no drug-induced changes in these underlying diseases have occurred.
Drug Interactions: The concomitant administration of baclofen and tricyclic antidepressants may potentiate the pharmacological effects of baclofen, resulting in pronounced muscular hypotonia.
The concurrent use of MAO inhibitors and baclofen may result in increased CNS depressant effects; therefore, caution is advised and the dosage of one or both agents should be adjusted accordingly.
Since combined treatment with baclofen and antihypertensives is likely to increase the fall in blood pressure, the dosage of antihypertensive medication should be adjusted accordingly.
In patients with Parkinson’s disease receiving treatment with baclofen and levodopa plus carbidopa, there have been several reports of mental confusion, hallucinations and agitation.
Isolated cases of increased blood glucose concentrations have reported with baclofen; dosage adjustments of antidiabetic agents (oral and insulin) may therefore be necessary with combined baclofen treatment.
Caution should be exercised when administering baclofen and magnesium sulfate (or other neuromuscular blocking agents), since a synergistic effect may theoretically occur.
Lactation: Baclofen is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug.
Adverse Reactions: Adverse effects most frequently occur at the start of treatment, particularly if the dosage is increased too rapidly, if large doses are administered, and in the elderly patient. However, 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 disorder 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. Others reported:
Gastrointestinal: nausea (approx. 10%), constipation
Genitourinary: urinary frequency
Other: instances of rash, pruritus, ankle edema, 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 dose may be reduced and the evening dose increased.
Some of the CNS and genitourinary symptoms reported may be related to the underlying disease rather than to drug therapy.
Symptoms And Treatment Of Overdose: Symptoms: Symptoms of overdosage are predominantly those of CNS depression and include drowsiness, impairment of consciousness, respiratory depression, coma, seizures, confusion, hallucinations, agitation, accommodation disorders, absent pupillary reflexes, muscular hypotonia, myoclonia, hyporeflexia or areflexia, hypotension, bradycardia, hypothermia, peripheral vasodilatation, nausea, vomiting, diarrhea, increased salivation, and elevated LDH, AST, AP and blood glucose values.
The signs and symptoms may be further aggravated by coadministration of a variety of other agents including alcohol, diazepam and tricyclic antidepressants.
Treatment: There is no specific antidote. The treatment is symptomatic. In the alert patient, empty the stomach promptly by induced emesis followed by lavage. Administer activated charcoal and if necessary, saline laxatives. In the obtunded 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. Maintain a high urinary output 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 i.v. with caution.
Dosage And Administration: The determination of baclofen’s optimal dosage requires individual titration. Start therapy at a low dosage and increase gradually until optimum effect is achieved (usually between 40 to 80 mg daily).
The following dosage titration schedule is suggested: 5 mg 3 times daily for 3 days; 10 mg 3 times daily for 3 days; 15 mg 3 times daily for 3 days; 20 mg 3 times daily for 3 days.
Thereafter, additional increases may be necessary but the total daily dose should not exceed a maximum of 80 mg daily (20 mg 4 times daily).
Utilize the lowest dose compatible with an optimal response. If benefits are not evident after a reasonable trial period, withdraw patients slowly from the drug (see Warnings).
Availability And Storage: 10 mg: Each white to off-white, oval, flat-faced, bevel-edged tablet, engraved GEIGY on one side and engraved KJ on the other (fully bisected between the K and J), contains: baclofen 10 mg. Nonmedicinal ingredients: cellulose compounds, cornstarch, magnesium stearate and polyvinylpyrrolidone. Energy: 8.6 kJ (2.05 kcal). Alcohol-, bisulfite-, gluten-, lactose-, parabens-, sodium- and tartrazine-free. Bottles of 100 and 500.
D.S. 20 mg: Each white to off-white, capsule-shaped tablet, engraved GEIGY on one side and engraved GW on the other, (fully bisected between the G and W), contains: baclofen 20 mg. Nonmedicinal ingredients: cellulose compounds, cornstarch, magnesium stearate and polyvinylpyrrolidone. Energy: 1.7 kJ (0.41 kcal). Alcohol-, bisulfite-, gluten-, lactose-, parabens-, sodium- and tartrazine-free. Bottles of 100.
LIORESAL® Novartis Pharmaceuticals Baclofen Muscle Relaxant – Antispastic